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  1. Intrauterine growth restriction

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    Bernardita Donoso Bernales

    2012-07-01

    Full Text Available It is estimated that the true prevalence of intrauterine growth restriction is 3-10% of all pregnancies, making this fetal condition one of the most frequent obstetric problems, together with premature labor and premature rupture of membranes. The article stresses the importance of early diagnosis because of the associated risks.

  2. Experimental intrauterine growth retardation.

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    van Marthens, E; Harel, S; Zamenshof, S

    1975-01-01

    The effects of experimental intrauterine growth retardation on subsequent fetal development, especially with respect to brain development, were studied in a new animal model. The rabbit was chosen since it has a perinatal pattern of brain development similar to that of the human. Experimental ischemia was induced during the last trimester by ligation of spiral arterioles and the differential effects on fetal development at term (30th gestational day) are reported. Specific brain regions were examined for wet weight, total cell number (DNA) and total protein content. Highly significant decreases in all these parameters were found in both the cortex and cerebellum following experimental intrauterine growth retardation; these two organs were differentially affected. The prospects and advantages of using this animal model for the study of the postnatal "catch-up growth" are discussed.

  3. Intrauterine Growth Restriction

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    ... org editorial staff Categories: Family Health, Infants and Toddlers, Pregnancy and Childbirth, WomenTags: Amniocentesis, Delivery - Cesarean, female, Growth and Development, Obstetrical, Obstetrical ultrasound, Pregnant Women, prenatal care September ...

  4. Impact of hydroxychloroquine on preterm delivery and intrauterine growth restriction in pregnant women with systemic lupus erythematosus: a descriptive cohort study.

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    Leroux, M; Desveaux, C; Parcevaux, M; Julliac, B; Gouyon, J B; Dallay, D; Pellegrin, J L; Boukerrou, M; Blanco, P; Lazaro, E

    2015-11-01

    The aim of this study was to evaluate the effect of hydroxychloroquine (HCQ) on fetal preterm delivery and intrauterine growth restriction (IUGR) in a cohort of pregnant women with systemic lupus erythematosus (SLE). Over an 11-year period (January 1, 2001 to December 31, 2011), all women with SLE and admitted to deliver after 22 weeks of gestation to Bordeaux University Hospital (France), were retrospectively enrolled in the present study. The population was then split into two groups based on the treatment they received: HCQ exposed (HCQ+) versus HCQ non-exposed (HCQ-) group. 118 pregnancies were included, 41 in the HCQ+ group and 77 in the HCQ- group. The rate of adverse fetal outcome was significantly lower in the HCQ+ group (p = 0.001), particularly in terms of preterm delivery, 15.8% versus 44.2% (p = 0.006), and IUGR, 10.5% versus 28.6% (p = 0.03). No adverse outcomes were reported in the HCQ+ group. HCQ reduces neonatal morbidity in women with SLE by significantly decreasing the rate of prematurity and intrauterine growth restriction. © The Author(s) 2015.

  5. Strategies in intrauterine growth restriction at term

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    Boers, Kim Esther

    2012-01-01

    To establish consensus and to collect evidence on the best management policy in intrauterine growth restriction (IUGR) at term, the DIGITAT-trial (Disproportionate Intrauterine Growth Intervention Trial At Term) was designed. The aim of the DIGITAT study was to compare the effect of induction of

  6. Monitoring of fetuses with intrauterine growth restriction: a longitudinal study

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    Hecher, K.; Bilardo, C. M.; Stigter, R. H.; Ville, Y.; Hackelöer, B. J.; Kok, H. J.; Senat, M. V.; Visser, G. H.

    2001-01-01

    To describe the time sequence of changes in fetal monitoring variables in intrauterine growth restriction and to correlate these findings with fetal outcome at delivery. This was a prospective longitudinal observational multicenter study on 110 singleton pregnancies with growth-restricted fetuses

  7. Intrauterine growth restriction - part 2.

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    Sharma, Deepak; Farahbakhsh, Nazanin; Shastri, Sweta; Sharma, Pradeep

    2016-12-01

    Small for gestational age (SGA) infants have been classically defined as having birth weight less than two standard deviations below the mean or less than the 10th percentile of a population-specific birth weight for specific gestational age, whereas intrauterine growth restriction (IUGR) has been defined as a rate of foetal growth that is less than normal for the population and for the growth potential of a specific infant. SGA infants have more frequent problems such as perinatal asphyxia, hypothermia, hypoglycaemia, polycythaemia and many more when compared with their appropriate for gestational age counterpart. They too have growth retardation and various major and subtle neurodevelopmental handicaps, with higher rates of perinatal and neonatal mortality. With the advent of newer technologies, even though the perinatal diagnosis of these SGA/IUGR foetuses has increased, but still perinatal morbidity and mortality rates are higher than normal foetuses and infants. In this part, we have covered neonatal IUGR classification, postnatal diagnosis, short-term and long-term complications faced by these IUGR infants.

  8. Folic acid protects against lipopolysaccharide-induced preterm delivery and intrauterine growth restriction through its anti-inflammatory effect in mice.

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    Mei Zhao

    Full Text Available Increasing evidence demonstrates that maternal folic acid (FA supplementation during pregnancy reduces the risk of neural tube defects, but whether FA prevents preterm delivery and intrauterine growth restriction (IUGR remains obscure. Previous studies showed that maternal lipopolysaccharide (LPS exposure induces preterm delivery, fetal death and IUGR in rodent animals. The aim of this study was to investigate the effects of FA on LPS-induced preterm delivery, fetal death and IUGR in mice. Some pregnant mice were orally administered with FA (0.6, 3 or 15 mg/kg 1 h before LPS injection. As expected, a high dose of LPS (300 μg/kg, i.p. on gestational day 15 (GD15 caused 100% of dams to deliver before GD18 and 89.3% of fetuses dead. A low dose of LPS (75 μg/kg, i.p. daily from GD15 to GD17 resulted in IUGR. Interestingly, pretreatment with FA prevented LPS-induced preterm delivery and fetal death. In addition, FA significantly attenuated LPS-induced IUGR. Further experiments showed that FA inhibited LPS-induced activation of nuclear factor kappa B (NF-κB in mouse placentas. Moreover, FA suppressed LPS-induced NF-κB activation in human trophoblast cell line JEG-3. Correspondingly, FA significantly attenuated LPS-induced upregulation of cyclooxygenase (COX-2 in mouse placentas. In addition, FA significantly reduced the levels of interleukin (IL-6 and keratinocyte-derived cytokine (KC in amniotic fluid of LPS-treated mice. Collectively, maternal FA supplementation during pregnancy protects against LPS-induced preterm delivery, fetal death and IUGR through its anti-inflammatory effects.

  9. Intrauterine fetal death and risk of shoulder dystocia at delivery.

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    Larsen, Sandra; Dobbin, Joanna; McCallion, Oliver; Eskild, Anne

    2016-12-01

    Vaginal delivery is recommended after intrauterine fetal death. However, little is known about the risk of shoulder dystocia in these deliveries. We studied whether intrauterine fetal death increases the risk of shoulder dystocia at delivery. In this population-based register study using the Medical Birth Registry of Norway, we included all singleton pregnancies with vaginal delivery of offspring in cephalic presentation in Norway during the period 1967-2012 (n = 2 266 118). Risk of shoulder dystocia was estimated as absolute risk (%) and odds ratio with 95% confidence interval. Adjustment was made for offspring birthweight (in grams). We performed sub-analyses within categories of birthweight (dystocia occurred in 1.1% of pregnancies with intrauterine fetal death and in 0.8% of pregnancies without intrauterine fetal death (p dystocia occurred in 14.6% of pregnancies with intrauterine fetal death and in 2.8% of pregnancies without intrauterine fetal death (p dystocia occurred in 57.1% of pregnancies with intrauterine fetal death and 9.6% of pregnancies without intrauterine fetal death (p dystocia at delivery, and the absolute risk of shoulder dystocia was particularly high if offspring birthweight was high and the mother had diabetes. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

  10. Intrauterine Intervention for the Treatment of Fetal Growth Restriction.

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    Spiroski, A-M; Oliver, M H; Harding, J E; Bloomfield, F H

    2016-01-01

    Fetal growth restriction (FGR) is associated with an increased incidence of fetal and neonatal death, and of neonatal morbidity. Babies born following FGR also are at risk of a range of postnatal complications, which may contribute to an increased incidence of disease later in life. There currently are no effective clinical interventions which improve perinatal survival, intrauterine growth and later outcomes of the FGR baby. Postnatal interventions aimed at promoting or accelerating growth in FGR babies to improve outcome, particularly neurodevelopmental outcomes, may further increase the risk of metabolic dysregulation and, therefore, the risk of developing chronic disease in adulthood. An intrauterine intervention to improve nutrition and growth in the FGR fetus may have the potential to decrease mortality and improve long-term outcomes by delaying preterm delivery and mitigating the need for and risks of accelerated postnatal growth.

  11. Screening, diagnosis, and management of intrauterine growth restriction.

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    Lausman, Andrea; McCarthy, Fergus P; Walker, Melissa; Kingdom, John

    2012-01-01

    To provide comprehensive background knowledge relevant to the SOGC Maternal-Fetal Medicine Committee-approved guideline entitled "Intrauterine Growth Restriction: Screening, Diagnosis, and Management." Publications in English were retrieved through searches of PubMed or Medline, CINAHL, and the Cochrane Library in January 2011 using appropriate controlled vocabulary via MeSH terms (fetal growth restriction and small for gestational age) and any key words (fetal growth, restriction, growth retardation, intrauterine growth restriction [IUGR], low birth weight, small for gestational age). Results were restricted to systematic reviews, randomized controlled trials or controlled clinical trials, and high-quality prospective and retrospective observational studies. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Evidence obtained from at least one properly randomized controlled trial, Cochrane Reviews, and high quality cohort data have been combined to provide clinicians with evidence to optimize their practice for screening, diagnosis, and management of intrauterine growth restriction. Considerable advances have been made to improve clinicians' ability to screen, diagnose, and manage pregnancies with suspected IUGR more effectively, including several properly randomized controlled trials. Pregnancies with late-onset IUGR may be managed equally effectively by early delivery or delayed delivery (with increased surveillance) anticipating favourable outcomes. By contrast, many aspects of the management of early-onset IUGR require further clinical trials.

  12. Maternal morbidity and mortality associated with delivery after intrauterine death

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    Ifnan, F.; Jameel, M.B.

    2006-01-01

    To determine the maternal morbidity and mortality associated with delivery after intrauterine fetal death (IUFD) and to find out the place of fetal destructive procedures and cesarean section. All women were included in the present study who presented before the onset of labour pains, after intrauterine fetal death at 26 weeks or onward with singleton pregnancy. Assessment of maternal demographic characteristics, gestational age at fetal demise, delivery-IUFD interval, mode of delivery; vaginal with or without fetal destructive procedures/cesarean section and maternal complications were the main outcome measures. There were 1834 live birth and 63 deliveries with intrauterine fetal death. Mode of delivery was vaginal in 87.4% and cesarean section in 12.6% of the cases. Twelve (21%) of the vaginal deliveries were complicated by lower urogenital tract injuries in certain cases, whereas 75% (6/8) of patients delivered by cesarean section developed major postoperative complications like postpartum haemorrhage, shock, endometritis, peritonitis and wound dehiscence. No maternal death was identified. Rate of delivery with intrauterine fetal death was 34.3/1000 live-birth deliveries. (author)

  13. Predictive factors for intrauterine growth restriction.

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    Albu, A R; Anca, A F; Horhoianu, V V; Horhoianu, I A

    2014-06-15

    Reduced fetal growth is seen in about 10% of the pregnancies but only a minority has a pathological background and is known as intrauterine growth restriction or fetal growth restriction (IUGR / FGR). Increased fetal and neonatal mortality and morbidity as well as adult pathologic conditions are often associated to IUGR. Risk factors for IUGR are easy to assess but have poor predictive value. For the diagnostic purpose, biochemical serum markers, ultrasound and Doppler study of uterine and spiral arteries, placental volume and vascularization, first trimester growth pattern are object of assessment today. Modern evaluations propose combined algorithms using these strategies, all with the goal of a better prediction of risk pregnancies.

  14. Antenatal taurine reduces cerebral cell apoptosis in fetal rats with intrauterine growth restriction.

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    Liu, Jing; Wang, Xiaofeng; Liu, Ying; Yang, Na; Xu, Jing; Ren, Xiaotun

    2013-08-15

    From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12(th) day of pregnancy, 300 mg/kg rine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neonatal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neonatal rats with intrauterine growth restriction undergoing taurine supplement were obtained for further experiments. The terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cells in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cell apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. nohistochemical staining revealed that taurine supplement increased glial cell line-derived neurotrophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cell apoptosis through the glial cell line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain.

  15. Consequences in Infants That Were Intrauterine Growth Restricted

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    Erich Cosmi

    2011-01-01

    Full Text Available Intrauterine growth restriction is a condition fetus does not reach its growth potential and associated with perinatal mobility and mortality. Intrauterine growth restriction is caused by placental insufficiency, which determines cardiovascular abnormalities in the fetus. This condition, moreover, should prompt intensive antenatal surveillance of the fetus as well as follow-up of infants that had intrauterine growth restriction as short and long-term sequele should be considered.

  16. Can extrauterine growth approximate intrauterine growth? Should it?

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    Sauer, Pieter J. J.

    Most studies evaluating the growth of preterm infants use the so-called intrauterine growth curve and reference fetus as standards. These curves might not be the optimal standards, however, for several reasons. The curves were constructed from small numbers of infants with uncertainty about

  17. Maternal determinants of intrauterine growth restriction in Goa, India: a case-control study

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    DD Motghare

    2014-01-01

    Full Text Available Objective: To study the maternal determinants of intrauterine growth restriction. Methods: A case-control study was conducted at a tertiary care Hospital in the year 2009. Ninety eight cases of intrauterine growth restriction were compared to 98 controls, matched for newborns sex and type of delivery. Data was collected by interviewing the mother using a structured pretested schedule and perusal of antenatal records. Intrauterine growth restriction was defined as occurring if birth weight of the newborn is below 10th percentile for gestational age on the intrauterine growth curve. Data was analyzed using SPSS software version 17 package. Percentages, odds ratios with 95% CI and multiple logistic regression analysis were used wherever appropriate. Results: Maternal age, education, socioeconomic status and number of antenatal visits were found to be the significant socio-demographic factors associated with Intrauterine growth restriction while, maternal height, parity, previous spontaneous abortion, direct obstetric morbidity, indirect obstetric morbidity and anemia were the maternal biological factors found to be significantly associated on bivariate analysis. Multiple logistic regression analysis identified parity, previous spontaneous abortion, direct obstetric morbidity, indirect obstetric morbidity and antenatal visits as significant maternal determinants of intrauterine growth restriction. Conclusions: A focus on good antenatal care, especially on high risk pregnancies would go a long way in reducing the problem of intrauterine growth restriction in the community thereby ensuring a safe and healthy future for our youngest generation.

  18. Cardiovascular adaptation to extrauterine life after intrauterine growth restriction.

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    Rodriguez-Guerineau, Luciana; Perez-Cruz, Miriam; Gomez Roig, María D; Cambra, Francisco J; Carretero, Juan; Prada, Fredy; Gómez, Olga; Crispi, Fátima; Bartrons, Joaquim

    2018-02-01

    Introduction The adaptive changes of the foetal heart in intrauterine growth restriction can persist postnatally. Data regarding its consequences for early circulatory adaptation to extrauterine life are scarce. The aim of this study was to assess cardiac morphometry and function in newborns with late-onset intrauterine growth restriction to test the hypothesis that intrauterine growth restriction causes cardiac shape and functional changes at birth. A comprehensive echocardiographic study was performed in 25 neonates with intrauterine growth restriction and 25 adequate-for-gestational-age neonates. Compared with controls, neonates with intrauterine growth restriction had more globular ventricles, lower longitudinal tricuspid annular motion, and higher left stroke volume without differences in the heart rate. Neonates with intrauterine growth restriction also showed subclinical signs of diastolic dysfunction in the tissue Doppler imaging with lower values of early (e') diastolic annular peak velocities in the septal annulus. Finally, the Tei index in the tricuspid annulus was higher in the intrauterine growth restriction group. Neonates with history of intrauterine growth restriction showed cardiac remodelling and signs of systolic and diastolic dysfunction. Overall, there was a significant tendency to worse cardiac function results in the right heart. The adaptation to extrauterine life occurred with more globular hearts, higher stroke volumes but a similar heart rate compared to adequate-for-gestational-age neonates.

  19. Consequences of intrauterine growth restriction for the kidney

    NARCIS (Netherlands)

    M.F. Schreuder; A. van Wijk (Ans); H.A. Delemarre-van de Waal (Henriette)

    2006-01-01

    textabstractLow birth weight due to intrauterine growth restriction is associated with various diseases in adulthood, such as hypertension, cardiovascular disease, insulin resistance and end-stage renal disease. The purpose of this review is to describe the effects of intrauterine growth restriction

  20. Review: Neuroinflammation in intrauterine growth restriction.

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    Wixey, Julie A; Chand, Kirat K; Colditz, Paul B; Bjorkman, S Tracey

    2017-06-01

    Disruption to the maternal environment during pregnancy from events such as hypoxia, stress, toxins, inflammation, and reduced placental blood flow can affect fetal development. Intrauterine growth restriction (IUGR) is commonly caused by chronic placental insufficiency, interrupting supply of oxygen and nutrients to the fetus resulting in abnormal fetal growth. IUGR is a major cause of perinatal morbidity and mortality, occurring in approximately 5-10% of pregnancies. The fetal brain is particularly vulnerable in IUGR and there is an increased risk of long-term neurological disorders including cerebral palsy, epilepsy, learning difficulties, behavioural difficulties and psychiatric diagnoses. Few studies have focused on how growth restriction interferes with normal brain development in the IUGR neonate but recent studies in growth restricted animal models demonstrate increased neuroinflammation. This review describes the role of neuroinflammation in the progression of brain injury in growth restricted neonates. Identifying the mediators responsible for alterations in brain development in the IUGR infant is key to prevention and treatment of brain injury in these infants. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Molecular mechanisms of intrauterine growth restriction.

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    Gurugubelli Krishna, Rao; Vishnu Bhat, B

    2017-07-10

    Intrauterine growth restriction (IUGR) is a pregnancy specific disease characterized by decreased growth rate of fetus than the normal growth potential at particular gestational age. In the current scenario it is a leading cause of fetal and neonatal morbidity and mortality. In the last decade exhilarating experimental studies from several laboratories have provided fascinating proof for comprehension of molecular basis of IUGR. Atypical expression of enzymes governed by TGFβ causes the placental apoptosis and altered expression of TGFβ due to hyper alimentation causes impairment of lung function. Crosstalk of cAMP with protein kinases plays a prominent role in the regulation of cortisol levels. Increasing levels of NOD1 proteins leads to development of IUGR by increasing the levels of inflammatory mediators. Increase in leptin synthesis in placental trophoblast cells is associated with IUGR. In this review, we emphasize on the regulatory mechanisms of IUGR and its associated diseases. They may help improve the in-utero fetal growth and provide a better therapeutic intervention for prevention and treatment of IUGR.

  2. Intrauterine Growth Restriction: Antenatal and Postnatal Aspects

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    Sharma, Deepak; Shastri, Sweta; Sharma, Pradeep

    2016-01-01

    Intrauterine growth restriction (IUGR), a condition that occurs due to various reasons, is an important cause of fetal and neonatal morbidity and mortality. It has been defined as a rate of fetal growth that is less than normal in light of the growth potential of that specific infant. Usually, IUGR and small for gestational age (SGA) are used interchangeably in literature, even though there exist minute differences between them. SGA has been defined as having birth weight less than two standard deviations below the mean or less than the 10th percentile of a population-specific birth weight for specific gestational age. These infants have many acute neonatal problems that include perinatal asphyxia, hypothermia, hypoglycemia, and polycythemia. The likely long-term complications that are prone to develop when IUGR infants grow up includes growth retardation, major and subtle neurodevelopmental handicaps, and developmental origin of health and disease. In this review, we have covered various antenatal and postnatal aspects of IUGR. PMID:27441006

  3. Intrauterine Growth Restriction: Hungry for an Answer

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    Chu, Alison

    2016-01-01

    Intrauterine growth restriction (IUGR) has been defined in several ways, but in general describes a condition in which the fetus exhibits poor growth in utero. This complication of pregnancy poses a significant public health burden as well as increased morbidity and mortality for the offspring. In human IUGR, alteration in fetal glucose and insulin homeostasis occurs in an effort to conserve energy and survive at the expense of fetal growth in an environment of inadequate nutrient provision. Several animal models of IUGR have been utilized to study the effects of IUGR on fetal glucose handling, as well as the postnatal reprogramming of energy metabolite handling, which may be unmasked in adulthood as a maladaptive propensity for cardiometabolic disease. This developmental programming may be mediated in part by epigenetic modification of essential regulators of glucose homeostasis. Several pharmacological therapies and nonpharmacological lifestyle modifications have shown early promise in mitigating the risk for or severity of adult metabolic phenotypes but still require further study of unanticipated and/or untoward side effects. PMID:26889018

  4. Intrauterine growth restriction: screening, diagnosis, and management.

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    Lausman, Andrea; Kingdom, John

    2013-08-01

    Intrauterine growth restriction (IUGR) is an obstetrical complication, which by definition would screen in 10% of fetuses in the general population. The challenge is to identify the subset of pregnancies affected with pathological growth restriction in order to allow intervention that would decrease morbidity and mortality. The purpose of this guideline is to provide summary statements and recommendations and to establish a framework for screening, diagnosis, and management of pregnancies affected with IUGR. Affected pregnancies are compared with pregnancies in which the fetus is at an appropriate weight for its gestational age. History, physical examination, and laboratory investigations including biochemical markers and ultrasound characteristics of IUGR are reviewed, and a management strategy is suggested. Published literature in English was retrieved through searches of PubMed or MEDLINE, CINAHL, and The Cochrane Library in January 2013 using appropriate controlled vocabulary via MeSH terms (fetal growth restriction and small for gestational age) and key words (fetal growth, restriction, growth retardation, IUGR, low birth weight, small for gestational age). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table). Implementation of the recommendations in this guideline should increase clinician recognition of IUGR and guide intervention where appropriate. Optimal long-term follow-up of neonates diagnosed as IUGR may improve their long-term health.

  5. [Associated factors in newborns with intrauterine growth retardation].

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    Thompson-Chagoyán, Oscar C; Vega-Franco, Leopoldo

    2008-01-01

    To identify the risk factors implicated in the intrauterine growth retardation (IUGR) of neonates born in a social security institution. Case controls design study in 376 neonates: 188 with IUGR (weight RCIU in the population.

  6. Alteration of placental haemostatic mechanisms in idiopathic intrauterine growth restriction

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    Jaime Eduardo Bernal Villegas

    2012-08-01

    Full Text Available Intrauterine growth restriction is a complication of pregnancy with a high probability of perinatal morbidity and mortality. It appears tobe caused by abnormal development of placental vasculature. Haemostatic processes are important for the development of the placenta,and an imbalance between procoagulant and anticoagulant factors has been associated with risk of intrauterine growth restriction.Objective. To evaluate coagulation abnormalities in placenta of pregnancies complicated with idiopathic intrauterine growth restriction.Materials and methods. Five placentas from pregnancies with idiopathic intrauterine growth restriction were compared to 19 controls.We performed gross and histological examination of the placenta. Analysis was made of both mRNA expression by real-time PCRand protein by ELISA of tissue factor and thrombomodulin in placental tissue. Results. Results based on histological evaluation wereconsistent with an increased prothrombotic state in placentas from pregnancies with idiopathic intrauterine growth restriction, andthrombosis of chorionic vessels was the most important finding. The study showed an increased expression of tissue factor protein(p=0.0411 and an increase in the ratio of tissue factor/thrombomodulin mRNA (p=0.0411 and protein (p=0.0215 in placentas frompregnancies with idiopathic intrauterine growth restriction. There were no statistically significant differences neither between cases andcontrols in the mRNA levels of tissue factor or thrombomodulin nor at the protein level of thrombomodulin. Conclusion. Evidence ofalteration of local haemostatic mechanisms at the level of the placenta, including abnormal expression of tissue factor and tissue factor/thrombomodulin ratio, in pregnancies that occur with idiopathic intrauterine growth restriction is presented.

  7. Disproportionate Intrauterine Growth Intervention Trial At Term: DIGITAT

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    Huisjes Anjoke JM

    2007-07-01

    Full Text Available Abstract Background Around 80% of intrauterine growth restricted (IUGR infants are born at term. They have an increase in perinatal mortality and morbidity including behavioral problems, minor developmental delay and spastic cerebral palsy. Management is controversial, in particular the decision whether to induce labour or await spontaneous delivery with strict fetal and maternal surveillance. We propose a randomised trial to compare effectiveness, costs and maternal quality of life for induction of labour versus expectant management in women with a suspected IUGR fetus at term. Methods/design The proposed trial is a multi-centre randomised study in pregnant women who are suspected on clinical grounds of having an IUGR child at a gestational age between 36+0 and 41+0 weeks. After informed consent women will be randomly allocated to either induction of labour or expectant management with maternal and fetal monitoring. Randomisation will be web-based. The primary outcome measure will be a composite neonatal morbidity and mortality. Secondary outcomes will be severe maternal morbidity, maternal quality of life and costs. Moreover, we aim to assess neurodevelopmental and neurobehavioral outcome at two years as assessed by a postal enquiry (Child Behavioral Check List-CBCL and Ages and Stages Questionnaire-ASQ. Analysis will be by intention to treat. Quality of life analysis and a preference study will also be performed in the same study population. Health technology assessment with an economic analysis is part of this so called Digitat trial (Disproportionate Intrauterine Growth Intervention Trial At Term. The study aims to include 325 patients per arm. Discussion This trial will provide evidence for which strategy is superior in terms of neonatal and maternal morbidity and mortality, costs and maternal quality of life aspects. This will be the first randomised trial for IUGR at term. Trial registration Dutch Trial Register and ISRCTN

  8. Prognosis and risk factors for intrauterine growth retardation

    DEFF Research Database (Denmark)

    Sehested, Line Thousig; Pedersen, Pernille

    2014-01-01

    INTRODUCTION: Intrauterine growth retardation (IUGR) is the term describing a foetus that has not reached its genetic growth potential. There is no international consensus on the definition of IUGR. The aim of this study was to describe a cohort of weight-restricted neonates and their mothers...

  9. Retardo del crecimiento intrauterino Intrauterine growth retardation

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    Adriana Cuartas Calle

    1995-01-01

    Full Text Available

    El crecimiento fetal anormal es un aspecto de gran interés en la obstetricia actual y un dilema clínico relativamente frecuente. La falla del crecimiento sigue siendo un enigma a pesar de los adelantos que ha habido en su conocimiento: el diagnóstico temprano y preciso del retardo del crecimiento puede aminorar la incidencia de complicaciones y muerte en fetos con este problema. Por ello es necesario mejorar las técnicas para identificar esta entidad y asegurar una atención apropiada durante el embarazo y el parto. En este artículo se resumen datos acerca de la definición del retardo del crecimiento fetal, su fisiopatología, clasificación, etiología, diagnóstico y manejo.

    Abnormal fetal growth is a very important aspect In present-day obstetrics and a frequent clinical dilemma. Fetal failure to grow continues to be puzzling, despite advances in its knowledge; early and precise diagnosis of growth retardation can diminish the incidence of complications and death of fetuses with this problem. It becomes therefore necessary, in the presence of growth retardation, to improve diagnostic techniques and assure proper attention during pregnancy and delivery. Information is summarized in this review on the definition, pathophysiology, classification, etiology, diagnosis and handling of fetal growth retardation.

  10. Growth hormone in intra-uterine growth retarded newborns.

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    Setia, Sajita; Sridhar, M G; Bhat, Vishnu; Chaturvedula, Latha

    2007-11-01

    To study growth hormone levels in IUGR and healthy controls and its association with birth weight and ponderal index. We studied 50 Intra uterine growth retarded (IUGR) and 50 healthy newborns born at term by vaginal delivery in JIPMER, Pondicherry, India. Cord blood was collected at the time of delivery for measurement of growth hormone. When compared with healthy newborns, IUGR newborns had higher growth hormone levels (mean +/- SD, 23.5 +/- 15.6 vs 16.2 +/- 7.61 ngm/ml, P = 0.019). A negative correlation was identified between growth hormone levels and birth weight (r2 = - 0.22, P = 0.03) and ponderal index (r2 = - 0.36, P = 0.008). Correlation of growth hormone levels was much more confident with ponderal index than with birth weight. At birth IUGR infants display increased growth hormone levels which correlate with ponderal index much more confidently than with birth weight.

  11. Induction versus expectant monitoring for intrauterine growth restriction at term : randomised equivalence trial (DIGITAT)

    NARCIS (Netherlands)

    Boers, K. E.; Vijgen, S. M. C.; Bijlenga, D.; van der Post, J. A. M.; Bekedam, D. J.; Kwee, A.; van der Salm, P. C. M.; van Pampus, M. G.; Spaanderman, M. E. A.; de Boer, K.; Duvekot, J. J.; Bremer, H. A.; Hasaart, T. H. M.; Delemarre, F. M. C.; Bloemenkamp, K. W. M.; van Meir, C. A.; Willekes, C.; Wijnen, E. J.; Rijken, M.; le Cessie, S.; Roumen, F. J. M. E.; Thornton, J. G.; van Lith, J. M. M.; Mol, B. W. J.; Scherjon, S. A.

    2010-01-01

    Objective To compare the effect of induction of labour with a policy of expectant monitoring for intrauterine growth restriction near term. Design Multicentre randomised equivalence trial (the Disproportionate Intrauterine Growth Intervention Trial At Term (DIGITAT)). Setting Eight academic and 44

  12. Induction versus expectant monitoring for intrauterine growth restriction at term: randomised equivalence trial (DIGITAT)

    NARCIS (Netherlands)

    Boers, K.E.; Vijgen, S.M.C.; Bijlenga, D.; van der Post, J.A.M.; Bekedam, D.J.; Kwee, A.; van der Salm, P.C.M.; van Pampus, M.G.; Spaanderman, M.E.A.; Boer, K.; Duvekot, J.J.; Bremer, H.A.; Hasaart, T.H.M.; Delemarre, F.M.C.; Bloemenkamp, K.W.M.; van Meir, C.A.; Willekes, C.; Wijnen, E.J.; Rijken, M.; le Cessie, S.; Roumen, F.J.M.E.; Thornton, J.G.; van Lith, J.M.M.; Mol, B.W.J.; Scherjon, S.A.

    2010-01-01

    Objective To compare the effect of induction of labour with a policy of expectant monitoring for intrauterine growth restriction near term. Design Multicentre randomised equivalence trial (the Disproportionate Intrauterine Growth Intervention Trial At Term (DIGITAT)). Setting Eight academic and 44

  13. Growth patterns in children with intrauterine growth retardation and their correlation to neurocognitive development.

    Science.gov (United States)

    Fattal-Valevski, Aviva; Toledano-Alhadef, Hagit; Leitner, Yael; Geva, Ronny; Eshel, Rina; Harel, Shaul

    2009-07-01

    The relationship between somatic growth and neurocognitive outcome was studied in a cohort of 136 children with intrauterine growth retardation. The children were followed up from birth to 9 to 10 years of age by annual measurements of growth parameters, neurodevelopmental evaluations, and IQ. The rate of catch-up for height between 1 and 2 years of age was significantly higher than the catch-up for weight (P importance for prediction of subsequent neurodevelopmental outcome in children with intrauterine growth retardation.

  14. ACR Appropriateness Criteria® growth disturbances - risk of intrauterine growth restriction.

    Science.gov (United States)

    Zelop, Carolyn M; Javitt, Marcia C; Glanc, Phyllis; Dubinsky, Theodore; Harisinghani, Mukesh G; Harris, Robert D; Khati, Nadia J; Mitchell, Donald G; Pandharipande, Pari V; Pannu, Harpreet K; Podrasky, Ann E; Shipp, Thomas D; Siegel, Cary Lynn; Simpson, Lynn; Wall, Darci J; Wong-You-Cheong, Jade J

    2013-09-01

    Fetal growth disturbances include fetuses at risk for intrauterine growth restriction. These fetuses may have an estimated fetal weight at less than the 10% or demonstrate a plateau of fetal growth with an estimated fetal growth greater than the 10%. Uteroplacental insufficiency may play a major role in the etiology of intrauterine growth restriction. Fetuses at risk for intrauterine fetal growth restriction are susceptible to the potential hostility of the intrauterine environment leading to fetal hypoxia and fetal acidosis. Fetal well-being can be assessed using biophysical profile, Doppler velocimetry, fetal heart rate monitoring, and fetal movement counting.Fetal growth disturbances include fetuses at risk for intrauterine growth restriction. These fetuses may have an estimated fetal weight at less than the 10% or demonstrate a plateau of fetal growth with an estimated fetal growth greater than the 10%. Uteroplacental insufficiency may play a major role in the etiology of intrauterine growth restriction. Fetuses at risk for intrauterine fetal growth restriction are susceptible to the potential hostility of the intrauterine environment leading to fetal hypoxia and fetal acidosis. Fetal well-being can be assessed using biophysical profile, Doppler velocimetry, fetal heart rate monitoring, and fetal movement counting.The ACR Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

  15. Inherited thrombophilia in pregnant women with intrauterine growth restriction.

    Science.gov (United States)

    Coriu, Letitia; Copaciu, Elena; Tulbure, Dan; Talmaci, Rodica; Secara, Diana; Coriu, Daniel; Cirstoiu, Monica

    2014-12-01

    Intrauterine growth restriction (IUGR) is a major cause of fetal morbidity and mortality during pregnancy. The role of mutation in the factor V gene, prothrombin gene, MTHFR gene, as risk factors for intrauterine growth restriction during pregnancy, is not very well known so far. This is a retrospective study of 151 pregnant women with a history of complicated pregnancy: intrauterine growth restriction, preeclampsia, recurrent pregnancy loss or maternal venous thromboembolism, who were admitted in Bucharest Emergency University Hospital, during the period January 2010 to July 2014. Genetic testing was performed for all the cases to detect: factor V Leiden mutation, G20210A mutation in the prothrombin gene, C677T mutation and A1298C mutation in methylenetetrahydrofolate reductase (MTHFR) gene. Blood samples were obtained as soon as the diagnosis of intrauterine growth restriction was established with ultrasonography. The following gene mutations were associated with increased risk of IUGR: G20210A prothrombin gene mutation (OR 4.81, 95% CI 1.05 - 2.22, p= 0.043), G1691A factor V gene mutation (factor V Leiden) (OR 1.58, 95% CI 0.61 - 4.080, p= 0.347), C677T MTHFR gene mutation (OR 1.61, 95% CI 0.79 to 3.26, p= 0.186), compound heterozygous MTHFR C677T and A1298C (OR 1.66, 95% CI 0.81- 3.42, p= 0.169). Particularly, for G20210A prothrombin gene mutation we found statistically significant risk (p≤0.05) of IUGR.

  16. Immediate metabolic consequences of intrauterine growth restriction and low birthweight.

    Science.gov (United States)

    Bhatia, Jatinder; Gates, Amy

    2013-01-01

    Optimal fetal growth resulting in a 'normally grown' term infant is of paramount importance for assuring a healthy start for postnatal growth and development. Fetal, infant and childhood growth restriction is an important clinical problem for obstetricians, neonatologists, pediatricians and globally, for public health. Worldwide, an estimated 20 million infants are born with low birthweight and a substantial proportion are small for gestational age. Many advances have been made in defining growth restriction by prenatal techniques, thus allowing the recognition of intrauterine growth restriction. Distinguishing infants who are small but have appropriate growth potential from those with growth restriction is important in order to apply obstetric surveillance, anticipate neonatal problems and plan for postneonatal guidance. It is clear that the fetus in growth-restricted pregnancies has limited supply of nutrients and oxygen. The resultant changes, if involving the placenta as well, can lead to circulatory and metabolic changes affecting both short- and long-term survival and development. In this paper, the causes and immediate consequence of being born with low birthweight, intrauterine growth restriction or small for gestational age will be discussed. Copyright © 2013 Nestec Ltd., Vevey/S. Karger AG, Basel.

  17. Final height and intrauterine growth retardation.

    Science.gov (United States)

    Tauber, Maïthé

    2017-06-01

    Approximately 10% of small for gestational age (SGA) children maintain a small body size throughout childhood and often into adult life with a decreased pubertal spurt. Growth hormone (GH) therapy increases short-term growth in a dose-dependent manner and adult height had now been well documented. Shorter children might benefit from a higher dose at start (50μg/kg/day). The response to GH treatment was similar for both preterm and term short SGA groups and the effect of GH treatment on adult height showed a wide variation in growth response. As a whole, mean adult height is higher than -2 SDS in 60% of patients and 70% reached an adult height in their target height with better results with higher doses and combined GnRH analog therapy in those who were short at onset of puberty. Copyright © 2017. Published by Elsevier Masson SAS.

  18. [ANTITHROMBOTIC MEDICATION IN PREGNANT WOMEN WITH PREVIOUS INTRAUTERINE GROWTH RESTRICTION].

    Science.gov (United States)

    Neykova, K; Dimitrova, V; Dimitrov, R; Vakrilova, L

    2016-01-01

    To analyze pregnancy outcome in patients who were on antithrombotic medication (AM) because of previous pregnancy with fetal intrauterine growth restriction (IUGR). The studied group (SG) included 21 pregnancies in 15 women with history of previous IUGR. The patients were on low dose aspirin (LDA) and/or low molecular weight heparin (LMWH). Pregnancy outcome was compared to the one in two more groups: 1) primary group (PG) including the previous 15 pregnancies with IUGR of the same women; 2) control group (CG) including 45 pregnancies of women matched for parity with the ones in the SG, with no history of IUGR and without medication. The SG, PG and CG were compared for the following: mean gestational age (g.a.) at birth, mean birth weight (BW), proportion of cases with early preeclampsia (PE), IUGR (total, moderate, and severe), intrauterine fetal death (IUFD), neonatal death (NND), admission to NICU, cesarean section (CS) because of chronic or acute fetal distress (FD) related to IUGR, PE or placental abruption. Student's t-test was applied to assess differences between the groups. P values < 0.05 were considered statistically significant. The differences between the SG and the PG regarding mean g. a. at delivery (33.7 and 29.8 w.g. respectively) and the proportion of babies admitted to NICU (66.7% vs. 71.4%) were not statistically significant. The mean BW in the SG (2114,7 g.) was significantly higher than in the PG (1090.8 g.). In the SG compared with the PG there were significantly less cases of IUFD (14.3% and 53.3% respectively), early PE (9.5% vs. 46.7%) moderate and severe IUGR (10.5% and 36.8% vs. 41.7% and 58.3%). Neonatal mortality in the SG (5.6%) was significantly lower than in the PG (57.1%), The proportion of CS for FD was not significantly different--53.3% in the SG and 57.1% in the PG. On the other hand, comparison between the SG and the CG demonstrated significantly lower g.a. at delivery in the SG (33.7 vs. 38 w.g.) an lower BW (2114 vs. 3094 g

  19. New Approaches to Treatment of Severe Intrauterine Growth Restriction

    Directory of Open Access Journals (Sweden)

    Zhanar Kurmangali

    2014-12-01

    Full Text Available Introduction. Intrauterine growth restriction (IUGR is a leading cause of perinatal morbidity and mortality due to placental insufficiency. Currently, one of the new approaches to treating this disease is the injection of nutrients to the fetus through intravascular port-systems (catheters.Objective. To assess the impact of nutrient injections as treatment to fetuses with severe growth retardation.Materials and methods. Pregnant women with IUGR (abdominal circumference (AC < 5th percentile with the absence of diastolic flow in the umbilical artery and a fetal gestational age of less than 30 weeks were randomly divided into two groups. The treatment group included six pregnant women who had an intravascular port-system for the infusion of nutrients (amino acids and glucose in the umbilical vein of the fetus for 14 ± 3 days. The control group consisted of eight patients who received only traditional dynamic monitoring and delivery at the optimum time of pregnancy. Fetal status was assessed using ultrasound equipment Accuvix V20 (Medison, South Korea by examining indicators of biometry and Doppler study of blood flow in utero, umbilical arteries, middle cerebral artery, and ductus venosus with fetal vascular resistance index calculation - pulsatility index (PI. Criteria for blood flow disturbances in the vessels were considered PI values above normal values for their gestational age, which were defined as absence or reverse blood flow in a diastole in the umbilical artery.Results. In a comparative analysis of the two groups, the treatment led to a 44.7% increase in AC of the fetus (121.0 ± 11.5 mm and 219.3 ± 18.3 mm, respectively, p ˂ 0.001. In all cases, the profile of blood flow in the umbilical artery had a positive diastolic component. As a result, there was a 45.3% decrease in PI in the umbilical artery (2.14 ± 0.54 and 1.17 ± 0.15, respectively, p < 0.05. Average fetal weight in the study group was not significantly higher than the

  20. HEARING FUNCTION IN PREMATURE CHILDREN WITH INTRAUTERINE GROWTH RESTRICTION

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    I. V. Rakhmanova

    2012-01-01

    Full Text Available Initial audiological test was performed in 136 premature children with various gestational age born from single fetation. The children were divided into 2 groups: prematures with intrauterine growth restriction (IUGR and prematures with normal weight for their gestational age (normotrophy. The study showed that the rate of passing the initial audiological test using the method of DPOAE was lower in both ears in children with IUGR, than in children with normotrophy. The correlation between the results of initial audiological test and birth weight was found: the lower was weight, the higher was risk of absence of acoustic response registration on initial examination.

  1. Relationship between in utero sonographic evaluation and subcutaneous plicometry after birth in infants with intrauterine growth restriction: an exploratory study

    Directory of Open Access Journals (Sweden)

    Giannì Maria L

    2010-10-01

    Full Text Available Abstract Background Intrauterine growth restriction (IUGR is associated with several medical complications before and after delivery. The aim of this study was to evaluate the concordance between the fetal ultrasonographic measurement of subcutaneous tissue thicknesses and the skinfold thicknesses assessment in intrauterine growth restricted newborns. Methods We designed an exploratory study. Fetal ultrasonographic measurement of subcutaneous tissue thicknesses, according to Bernstein's and Galan's method, and neonatal skinfold thicknesses were evaluated in 13 intrauterine growth restricted newborns within 4 hours before delivery and on the first day of life, respectively. Concordance between fetal and neonatal measurements was assessed using the Lin's correlation coefficient and the Bland-Altman method. Results The data obtained by the measurements of neonatal skinfold thicknesses was significantly correlated with the prenatal measurements (Lin's coefficients, arm: 0.60; subscapular: 0.72; abdomen: 0.51. Bland-Altman analysis showed moderate agreement between the fetal ultrasonographic measurement of subcutaneous tissue thicknesses and the neonatal skinfold thicknesses assessment. Conclusions The present study provides preliminary evidence that fetal sonographic measurements may represent additional indices of intrauterine growth restriction.

  2. Maternal amino acid supplementation for intrauterine growth restriction

    Science.gov (United States)

    Brown, Laura D; Green, Alice S; Limesand, Sean W; Rozance, Paul J

    2011-01-01

    Maternal dietary protein supplementation to improve fetal growth has been considered as an option to prevent or treat intrauterine growth restriction. However, in contrast to balanced dietary supplementation, adverse perinatal outcomes in pregnant women who received high amounts of dietary protein supplementation have been observed. The responsible mechanisms for these adverse outcomes are unknown. This review will discuss relevant human and animal data to provide the background necessary for the development of explanatory hypotheses and ultimately for the development therapeutic interventions during pregnancy to improve fetal growth. Relevant aspects of fetal amino acid metabolism during normal pregnancy and those pregnancies affected by IUGR will be discussed. In addition, data from animal experiments which have attempted to determine mechanisms to explain the adverse responses identified in the human trials will be presented. Finally, we will suggest new avenues for investigation into how amino acid supplementation might be used safely to treat and/or prevent IUGR. PMID:21196387

  3. Cytosine methylation dysregulation in neonates following intrauterine growth restriction.

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    Francine Einstein

    2010-01-01

    Full Text Available Perturbations of the intrauterine environment can affect fetal development during critical periods of plasticity, and can increase susceptibility to a number of age-related diseases (e.g., type 2 diabetes mellitus; T2DM, manifesting as late as decades later. We hypothesized that this biological memory is mediated by permanent alterations of the epigenome in stem cell populations, and focused our studies specifically on DNA methylation in CD34+ hematopoietic stem and progenitor cells from cord blood from neonates with intrauterine growth restriction (IUGR and control subjects.Our epigenomic assays utilized a two-stage design involving genome-wide discovery followed by quantitative, single-locus validation. We found that changes in cytosine methylation occur in response to IUGR of moderate degree and involving a restricted number of loci. We also identify specific loci that are targeted for dysregulation of DNA methylation, in particular the hepatocyte nuclear factor 4alpha (HNF4A gene, a well-known diabetes candidate gene not previously associated with growth restriction in utero, and other loci encoding HNF4A-interacting proteins.Our results give insights into the potential contribution of epigenomic dysregulation in mediating the long-term consequences of IUGR, and demonstrate the value of this approach to studies of the fetal origin of adult disease.

  4. Cytosine Methylation Dysregulation in Neonates Following Intrauterine Growth Restriction

    Science.gov (United States)

    Bhagat, Tushar D.; Fazzari, Melissa J.; Verma, Amit; Barzilai, Nir; Greally, John M.

    2010-01-01

    Background Perturbations of the intrauterine environment can affect fetal development during critical periods of plasticity, and can increase susceptibility to a number of age-related diseases (e.g., type 2 diabetes mellitus; T2DM), manifesting as late as decades later. We hypothesized that this biological memory is mediated by permanent alterations of the epigenome in stem cell populations, and focused our studies specifically on DNA methylation in CD34+ hematopoietic stem and progenitor cells from cord blood from neonates with intrauterine growth restriction (IUGR) and control subjects. Methods and Findings Our epigenomic assays utilized a two-stage design involving genome-wide discovery followed by quantitative, single-locus validation. We found that changes in cytosine methylation occur in response to IUGR of moderate degree and involving a restricted number of loci. We also identify specific loci that are targeted for dysregulation of DNA methylation, in particular the hepatocyte nuclear factor 4α (HNF4A) gene, a well-known diabetes candidate gene not previously associated with growth restriction in utero, and other loci encoding HNF4A-interacting proteins. Conclusions Our results give insights into the potential contribution of epigenomic dysregulation in mediating the long-term consequences of IUGR, and demonstrate the value of this approach to studies of the fetal origin of adult disease. PMID:20126273

  5. Intrauterine growth restriction affects the preterm infant's hippocampus.

    Science.gov (United States)

    Lodygensky, Gregory A; Seghier, Mohammed L; Warfield, Simon K; Tolsa, Cristina Borradori; Sizonenko, Stephane; Lazeyras, François; Hüppi, Petra S

    2008-04-01

    The hippocampus is known to be vulnerable to hypoxia, stress, and undernutrition, all likely to be present in fetal intrauterine growth restriction (IUGR). The effect of IUGR in preterm infants on the hippocampus was studied using 3D magnetic resonance imaging at term-equivalent age Thirteen preterm infants born with IUGR after placental insufficiency were compared with 13 infants with normal intrauterine growth age matched for gestational age. The hippocampal structural differences were defined using voxel-based morphometry and manual segmentation. The specific neurobehavioral function was evaluated by the Assessment of Preterm Infants' Behavior at term and at 24 mo of corrected age by a Bayley Scales of Infant and Toddler Development. Voxel-based morphometry detected significant gray matter volume differences in the hippocampus between the two groups. This finding was confirmed by manual segmentation of the hippocampus with a reduction of hippocampal volume after IUGR. The hippocampal volume reduction was further associated with functional behavioral differences at term-equivalent age in all six subdomains of the Assessment of Preterm Infants' Behavior but not at 24 mo of corrected age. We conclude that hippocampal development in IUGR is altered and might result from a combination of maternal corticosteroid hormone exposure, hypoxemia, and micronutrient deficiency.

  6. Neonatal morbidity after induction vs expectant monitoring in intrauterine growth restriction at term: a subanalysis of the DIGITAT RCT

    NARCIS (Netherlands)

    Boers, Kim E.; van Wyk, Linda; van der Post, Joris A. M.; Kwee, Anneke; van Pampus, Maria G.; Spaanderdam, Marc E. A.; Duvekot, Johannes J.; Bremer, Henk A.; Delemarre, Friso M. C.; Bloemenkamp, Kitty W. M.; de Groot, Christianne J. M.; Willekes, Christine; Rijken, Monique; Roumen, Frans J. M. E.; Thornton, Jim G.; van Lith, Jan M. M.; Mol, Ben W. J.; le Cessie, Saskia; Scherjon, Sicco A.

    2012-01-01

    OBJECTIVE: The Disproportionate Intrauterine Growth Intervention Trial at Term (DIGITAT) compared induction of labor and expectant management in suspected intrauterine growth restriction (IUGR) at term. In this subanalysis, we report neonatal morbidity between the policies based on the Morbidity

  7. Early childhood neurodevelopment after intrauterine growth restriction: a systematic review.

    Science.gov (United States)

    Levine, Terri A; Grunau, Ruth E; McAuliffe, Fionnuala M; Pinnamaneni, RagaMallika; Foran, Adrienne; Alderdice, Fiona A

    2015-01-01

    Children who experienced intrauterine growth restriction (IUGR) may be at increased risk for adverse developmental outcomes in early childhood. The objective of this study was to carry out a systematic review of neurodevelopmental outcomes from 6 months to 3 years after IUGR. PubMed, Embase, PsycINFO, Maternity and Infant Care, and CINAHL databases were searched by using the search terms intrauterine, fetal, growth restriction, child development, neurodevelopment, early childhood, cognitive, motor, speech, language. Studies were eligible for inclusion if participants met specified criteria for growth restriction, follow-up was conducted within 6 months to 3 years, methods were adequately described, non-IUGR comparison groups were included, and full English text of the article was available. A specifically designed data extraction form was used. The methodological quality of included studies was assessed using well-documented quality-appraisal guidelines. Of 731 studies reviewed, 16 were included. Poorer neurodevelopmental outcomes after IUGR were described in 11. Ten found motor, 8 cognitive, and 7 language delays. Other delays included social development, attention, and adaptive behavior. Only 8 included abnormal Doppler parameters in their definitions of IUGR. Evidence suggests that children are at risk for poorer neurodevelopmental outcomes following IUGR from 6 months to 3 years of age. The heterogeneity of primary outcomes, assessment measures, adjustment for confounding variables, and definitions of IUGR limits synthesis and interpretation. Sample sizes in most studies were small, and some examined preterm IUGR children without including term IUGR or AGA comparison groups, limiting the value of extant studies. Copyright © 2015 by the American Academy of Pediatrics.

  8. MRI Differences Associated with Intrauterine Growth Restriction in Preterm Infants.

    Science.gov (United States)

    Bruno, Christie J; Bengani, Shreyans; Gomes, William A; Brewer, Mariana; Vega, Melissa; Xie, Xianhong; Kim, Mimi; Fuloria, Mamta

    2017-01-01

    Preterm infants are at risk for neurodevelopmental impairment. Intrauterine growth restriction (IUGR) further increases this risk. Brain imaging studies are often utilized at or near term-equivalent age to determine later prognosis. To evaluate the association between intrauterine growth and regional brain volume on MRI scans performed in preterm infants at or near term-equivalent age. This is a retrospective case-control study of 24 infants born at gestational age ≤30 weeks and cared for in a large, inner-city, academic neonatal intensive-care unit from 2012 to 2013. Each IUGR infant was matched with 1-2 appropriate for gestational age (AGA) infants who served as controls. Predischarge MRI scans routinely obtained at ≥36 weeks' adjusted age were analyzed for regional brain volumetric differences. We examined the association between IUGR and thalamic, basal ganglion, and cerebellar brain volumes in these preterm infants. Compared to AGA infants, IUGR infants had a smaller thalamus (7.88 vs. 5.87 mL, p = 0.001) and basal ganglion (8.87 vs. 6.92 mL, p = 0.002) volumes. There was no difference in cerebellar volumes between the two study groups. Linear regression analyses revealed similar trends in the associations between IUGR and brain volumes after adjusting for sex, gestational age at birth, and postconceptual age and weight at MRI. Thalamus and basal ganglion volumes are reduced in growth-restricted preterm infants. These differences may preferentially impact neurodevelopmental outcomes. Further research is needed to explore these relationships. © 2017 S. Karger AG, Basel.

  9. Intrauterine levonorgestrel delivery with frameless fibrous delivery system: review of clinical experience

    Directory of Open Access Journals (Sweden)

    Wildemeersch D

    2017-01-01

    Full Text Available Dirk Wildemeersch,1 Amaury Andrade,2 Norman D Goldstuck,3 Thomas Hasskamp,4 Geert Jackers5 1Gynecological Outpatient Clinic and IUD Training Center, Ghent, Belgium; 2Centro de Biologia da Reprodução, Universidade Federal Juiz de Fora, Juiz de Fora, Brazil; 3Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Hospital, Western Cape, South Africa; 4Klinik für Operativen Gynäkologie, GynMünster, Münster, Germany; 5Applied Controlled Release, Technology Park, Ghent (Zwijnaarde, Belgium Abstract: The concept of using a frameless intrauterine device (IUD instead of the conventional plastic framed IUD is not new. Frameless copper IUDs have been available since the late 1990s. They rely on an anchoring system to retain in the uterine cavity. The clinical experience with these IUDs suggests that frameless IUDs fit better as they are thin and, therefore, do not disturb or irritate the uterus. High tolerance and continuation rates have been achieved as complaints of pain are virtually nonexistent and the impact on menstrual blood loss is minimal. Conventional levonorgestrel-releasing intrauterine systems (LNG-IUSs are very popular as they significantly reduce menstrual bleeding and provide highly effective contraception. However, continuation of use remains problematic, particularly in young users. Total or partial expulsion and displacement of the LNG-IUS also occur too often due to spatial incompatibility within a small uterine cavity, as strong uterine contractions originate, attempting to get rid of the bothersome IUD/IUS. If not expelled, embedment ensues, often leading to chronic pain and early removal of the IUD/IUS. Several studies conducted recently have requested attention to the relationship between the LNG-IUS and the endometrial cavity. Some authors have proposed to measure the cavity width prior to inserting an IUD, as many uterine cavities are much smaller than the

  10. [Pathophysiological changes of umbilical vessels in intrauterine growth restriction].

    Science.gov (United States)

    Jakó, Mária; Surányi, Andrea; Kaiser, László; Domokos, Dóra; Gáspár, Róbert; Bártfai, György

    2014-12-14

    The prevalence of intrauterine growth restriction is 4-5000/100,000 births, and they give the majority of perinatal morbidity. The aim of the authors was to compare the pathomorphologic data and vasoreactivity of umbilical vessels and placenta of small for date newborns to that of the normal pregnancies. Samples of the umbilical cord and placenta were divided into case and control groups. Two 10 cm long segments were cut of the umbilical cord at placental insertion. Tissue bath experiment was performed on umbilical vessels and pathomorphologic data were collected according to the Royal College of Pathologists' protocol. After the development of basal tone, oxytocin and desmopressin did not enhance the vascular contraction, but the pathomorphological and ultrasonographic data were significantly different in the two groups. The results indicate that umbilical vessels might not have oxytocin or vasopressin receptors. The pathomorphologic and flowmetric differences could be the causes of small birth weight.

  11. The association between intrauterine inflammation and spontaneous vaginal delivery at term: a cross-sectional study.

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    Michiel L Houben

    Full Text Available BACKGROUND: Different factors contribute to the onset of labor at term. In animal models onset of labor is characterized by an inflammatory response. The role of intrauterine inflammation, although implicated in preterm birth, is not yet established in human term labor. We hypothesized that intrauterine inflammation at term is associated with spontaneous onset of labor. METHODS/RESULTS: In two large urban hospitals in the Netherlands, a cross-sectional study of spontaneous onset term vaginal deliveries and elective caesarean sections (CS, without signs of labor, was carried out. Placentas and amniotic fluid samples were collected during labor and/or at delivery. Histological signs of placenta inflammation were determined. Amniotic fluid proinflammatory cytokine concentrations were measured using ELISA. A total of 375 women were included. In term vaginal deliveries, more signs of intrauterine inflammation were found than in elective CS: the prevalence of chorioamnionitis was higher (18 vs 4%, p = 0.02 and amniotic fluid concentration of IL-6 was higher (3.1 vs 0.37 ng/mL, p<0.001. Similar results were obtained for IL-8 (10.93 vs 0.96 ng/mL, p<0.001 and percentage of detectable TNF-alpha (50 vs 4%, p<0.001. CONCLUSIONS: This large cross-sectional study shows that spontaneous term delivery is characterized by histopathological signs of placenta inflammation and increased amniotic fluid proinflammatory cytokines.

  12. Leptin administration affects growth and skeletal development in a rat intrauterine growth restriction model: preliminary study.

    Science.gov (United States)

    Bar-El Dadon, Shimrit; Shahar, Ron; Katalan, Vered; Monsonego-Ornan, Efrat; Reifen, Ram

    2011-09-01

    Skeletal abnormalities are one of the hallmarks of growth delay during gestation. The aim of this study was to determine changes induced by leptin in skeletal growth and development in a rat model of intrauterine growth retardation (IUGR) and to elucidate the possible underlying mechanisms. Intrauterine growth retardation was induced prepartum and the effects of leptin to mothers prenatally or to offspring postnatally were studied. Radii were harvested and tested mechanically and structurally. Tibias were evaluated for growth-plate morphometry. On day 40 postpartum, total bone length and mineral density and tibial growth-plate width and numbers of cells within its zones of offspring treated with leptin were significantly greater than in the control group. Postnatal leptin administration in an IUGR model improves the structural properties and elongation rate of bone. These findings could pave the way to preventing some phenotypic presentations of IUGR. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Intrauterine Cannabis Exposure Affects Fetal Growth Trajectories: The Generation R Study

    Science.gov (United States)

    El Marroun, Hanan; Tiemeier, Henning; Steegers, Eric A. P.; Jaddoe, Vincent W. V.; Hofman, Albert; Verhulst, Frank C.; van den Brink, Wim; Huizink, Anja C.

    2009-01-01

    Objective: Cannabis is the most commonly consumed illicit drug among pregnant women. Intrauterine exposure to cannabis may result in risks for the developing fetus. The importance of intrauterine growth on subsequent psychological and behavioral child development has been demonstrated. This study examined the relation between maternal cannabis use…

  14. Premature delivery due to intrauterine Candida infection that caused neonatal congenital cutaneous candidiasis: a case report.

    Science.gov (United States)

    Ito, Fumitake; Okubo, Tomoharu; Yasuo, Tadahiro; Mori, Taisuke; Iwasa, Koichi; Iwasaku, Kazuhiro; Kitawaki, Jo

    2013-01-01

    Congenital cutaneous candidiasis is a very rare disease with less than 100 cases published in the medical literature. Neonates having this disease present with systemic skin lesions caused by intrauterine Candida infections. We present a case of threatened premature delivery due to Candida chorioamnionitis, which caused both maternal postpartum endometritis and neonatal congenital cutaneous candidiasis. A 34-year-old woman who was admitted for fetal membrane bulging at 20 weeks of gestation underwent McDonald cervical cerclage. We diagnosed threatened premature delivery due to intrauterine infection; therefore, we terminated the gestation by cesarean section at 24 weeks of gestation. Fungi-like yeast was detected in infantile gastric juice. Histopathological findings of the placenta revealed that Candida albicans mycelium invaded the placenta, chorioamniotic membrane and umbilical cord. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

  15. Gene expression patterns of vascular endothelial growth factor (VEGF-A) in human placenta from pregnancies with intrauterine growth restriction.

    Science.gov (United States)

    Szentpéteri, Imre; Rab, Attila; Kornya, László; Kovács, Péter; Joó, József Gábor

    2013-07-01

    In this study, we describe changes in gene expression pattern of vascular endothelial growth factor (VEGF)-A in human placenta obtained from pregnancies with intrauterine growth restriction using placenta from normal pregnancies as control. We compared gene expression of VEGF-A in placental samples from Intrauterine growth restriction (IUGR) pregnancies versus placenta obtained from normal pregnancies. Among potential confounders, important clinical informations were also analyzed. In the IUGR group, the VEGF-A gene was overexpressed compared to the normal pregnancy group (Ln 2(α)β-actin: 1.32; Ln 2(α)GADPH: 1.56). There was no correlation between the degree of growth restriction and VEGF-A gene expression (Ln 2(α)(0-5)percentile: 0.58; Ln 2(α)(5-10)percentile: 0.64). Within the IUGR group, there was a trend toward a positive correlation between placental VEGF-A gene activity and gestational age at delivery (Ln 2(α) 37 weeks: 1.35). Our findings suggest that the increase in placental expression of the VEGF-A gene and the resultant stimulation of angiogenesis are a response to hypoxic environment developing in the placental tissue in IUGR. Thus, it appears to be a secondary event rather than a primary factor in the development of IUGR There is a trend toward a positive correlation between gestational age and placental VEGF-A gene activity.

  16. L-Citrulline Supplementation Enhances Fetal Growth and Protein Synthesis in Rats with Intrauterine Growth Restriction.

    Science.gov (United States)

    Bourdon, Aurélie; Parnet, Patricia; Nowak, Christel; Tran, Nhat-Thang; Winer, Norbert; Darmaun, Dominique

    2016-03-01

    Intrauterine growth restriction (IUGR) results from either maternal undernutrition or impaired placental blood flow, exposing offspring to increased perinatal mortality and a higher risk of metabolic syndrome and cardiovascular disease during adulthood. l-Citrulline is a precursor of l-arginine and nitric oxide (NO), which regulates placental blood flow. Moreover, l-citrulline stimulates protein synthesis in other models of undernutrition. The aim of the study was to determine whether l-citrulline supplementation would enhance fetal growth in a model of IUGR induced by maternal dietary protein restriction. Pregnant rats were fed either a control (20% protein) or a low-protein (LP; 4% protein) diet. LP dams were randomly allocated to drink tap water either as such or supplemented with l-citrulline (2 g · kg(-1) · d(-1)), an isonitrogenous amount of l-arginine, or nonessential l-amino acids (NEAAs). On day 21 of gestation, dams received a 2-h infusion of l-[1-(13)C]-valine until fetuses were extracted by cesarean delivery. Isotope enrichments were measured in free amino acids and fetal muscle, liver, and placenta protein by GC-mass spectrometry. Fetal weight was ∼29% lower in the LP group (3.82 ± 0.06 g) than in the control group (5.41 ± 0.10 g) (P growth in a model of IUGR, and the effect may be mediated by enhanced fetal muscle protein synthesis and/or increased NO production. © 2016 American Society for Nutrition.

  17. Volumetric MRI study of the intrauterine growth restriction fetal brain

    International Nuclear Information System (INIS)

    Polat, A.; Barlow, S.; Ber, R.; Achiron, R.; Katorza, E.

    2017-01-01

    Intrauterine growth restriction (IUGR) is a pathologic fetal condition known to affect the fetal brain regionally and associated with future neurodevelopmental abnormalities. This study employed MRI to assess in utero regional brain volume changes in IUGR fetuses compared to controls. Retrospectively, using MRI images of fetuses at 30-34 weeks gestational age, a total of 8 brain regions - supratentorial brain and cavity, cerebral hemispheres, temporal lobes and cerebellum - were measured for volume in 13 fetuses with IUGR due to placental insufficiency and in 21 controls. Volumes and their ratios were assessed for difference using regression models. Reliability was assessed by intraclass correlation coefficients (ICC) between two observers. In both groups, all structures increase in absolute volume during that gestation period, and the rate of cerebellar growth is higher compared to that of supratentorial structures. All structures' absolute volumes were significantly smaller for the IUGR group. Cerebellar to supratentorial ratios were found to be significantly smaller (P < 0.05) for IUGR compared to controls. No other significant ratio differences were found. ICC showed excellent agreement. The cerebellar to supratentorial volume ratio is affected in IUGR fetuses. Additional research is needed to assess this as a radiologic marker in relation to long-term outcome. (orig.)

  18. Volumetric MRI study of the intrauterine growth restriction fetal brain

    Energy Technology Data Exchange (ETDEWEB)

    Polat, A.; Barlow, S.; Ber, R.; Achiron, R.; Katorza, E. [Tel Aviv University, Sackler School of Medicine, Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, Tel Hashomer (Israel)

    2017-05-15

    Intrauterine growth restriction (IUGR) is a pathologic fetal condition known to affect the fetal brain regionally and associated with future neurodevelopmental abnormalities. This study employed MRI to assess in utero regional brain volume changes in IUGR fetuses compared to controls. Retrospectively, using MRI images of fetuses at 30-34 weeks gestational age, a total of 8 brain regions - supratentorial brain and cavity, cerebral hemispheres, temporal lobes and cerebellum - were measured for volume in 13 fetuses with IUGR due to placental insufficiency and in 21 controls. Volumes and their ratios were assessed for difference using regression models. Reliability was assessed by intraclass correlation coefficients (ICC) between two observers. In both groups, all structures increase in absolute volume during that gestation period, and the rate of cerebellar growth is higher compared to that of supratentorial structures. All structures' absolute volumes were significantly smaller for the IUGR group. Cerebellar to supratentorial ratios were found to be significantly smaller (P < 0.05) for IUGR compared to controls. No other significant ratio differences were found. ICC showed excellent agreement. The cerebellar to supratentorial volume ratio is affected in IUGR fetuses. Additional research is needed to assess this as a radiologic marker in relation to long-term outcome. (orig.)

  19. Isolated intrauterine growth restriction: a survey of Central Association of Obstetricians Gynecologists (CAOG) members

    NARCIS (Netherlands)

    Chauhan, Suneet P.; Dahlke, Joshua D.; Magann, Everett F.; Chang, Eugene; Gupta, Lata; Mol, Ben W.; Lewis, David F.

    2013-01-01

    The objective was to ascertain clinicians' opinions and current management with isolated (no concomitant morbidity) intrauterine growth restriction (IUGR). Members of the Central Association of Obstetricians and Gynecologists (CAOG) were surveyed. We considered consensus to be agreement among 90% of

  20. Abnormal endothelium-dependent microvascular dilator reactivity in pregnancies complicated by normotensive intrauterine growth restriction

    NARCIS (Netherlands)

    Koopmans, C.M.; Blaauw, Judith; van Pampus, Maria; Rakhorst, G.; Aarnoudse, J.G.

    OBJECTIVE: Normotensive intrauterine growth restriction and preeclampsia share a similar placenta pathophysiology, whereas maternal clinical manifestations differ. Clinical symptoms of preeclampsia are partly attributed to vascular endothelial dysfunction, but it is unclear whether this phenomenon

  1. Intrauterine growth restriction in pregnant women after kidney transplantation as a marker of preeclampsia.

    Science.gov (United States)

    Cyganek, Anna; Dabrowski, Filip Andrzej; Pietrzak, Bronislawa; Jabiry-Zieniewicz, Zoulikha; Grzechocinska, Barbara; Madej, Anna; Wielgos, Miroslaw

    2016-01-01

    Delayed motherhood is associated with an increasing number of comorbidities such as glomerulonephritis, systemic lupus erythematosus, and diabetic nephropathy. Women after renal transplant belong to the group of patients who require a highly individualized approach to treatment and diagnosis. The aim of the study was to validate the commonly used diagnostic criteria for preeclampsia which seem to be irrelevant in patients with chronic renal insufficiency. The course of pregnancy and delivery were retrospectively analyzed in 48 renal transplant patients. Two patients were excluded. Group I included 23 patients with eutrophic neonates, while Group II consisted of 23 patients with fetal hypotrophy (birth weight of women after kidney transplant. General criteria should be applied with special care in women with chronic kidney disease or in patients with systemic lupus erythematosus. As a predictive factor of neonatal morbidity, intrauterine growth restriction seems to be more valuable than typical markers of kidney function.

  2. Perinatal Changes of Cardiac Troponin-I in Normal and Intrauterine Growth-Restricted Pregnancies

    Directory of Open Access Journals (Sweden)

    Nicoletta Iacovidou

    2007-01-01

    Full Text Available Intrauterine growth restriction (IUGR implies fetal hypoxia, resulting in blood flow redistribution and sparing of vital organs (brain, heart. Serum cardiac Troponin-I (cTnI, a well-established marker of myocardial ischaemia, was measured in 40 mothers prior to delivery, the doubly clamped umbilical cords (representing fetal state, and their 20 IUGR and 20 appropriate-for-gestational-age (AGA neonates on day 1 and 4 postpartum. At all time points, no differences in cTnI levels were observed between the AGA and IUGR groups. Strong positive correlations were documented between maternal and fetal/neonatal values (r≥.498, P≤.025 in all cases in the AGA and r≥.615, P≤.009 in all cases in the IUGR group. These results may indicate (a normal heart function, due to heart sparing, in the IUGR group (b potential crossing of the placental barrier by cTnI in both groups

  3. Chromosomal aberrations as etiological factors of intrauterine growth retardation

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    Petrović Bojana

    2008-01-01

    Full Text Available Background/Aim. Intrauterine growth retardation (IUGR is a pathological condition of pregnancy characterised by birth weight below the 10th centile. A number of fetal, placental and maternal causes can lead to IUGR; although, in most cases no specific causes can be identified. The aim of this study was to determine the part of chromosomal abnormalities in IUGR etiology. Methods. Fetal blood karyotype taken by cordocentesis from 168 fetuses with diagnosed IUGR was analyzed. Results. Chromosomal rearrangements both numerical and structural were detected in 14 cases (12.2%. Two cases were triploid. Patau syndrome, Edwards syndrome and Down syndrome were found in two cases each. There was one case of trisomy 7 (47, XY, +7 and one case of trisomy 16 (47, XX, +16; one translocation, 46, XY, t (2; 14(q23; q32 and a deletion 46, XYdel (12 (p12 as well as two cases of sex chromosomes abnormalities, 45, X (Turner syndrome and 47, XYY. Conclusion. These findings suggest that a consistent number of symmetrical IUGR cases (about 12% can be associated with chromosomal rearrangements. Chromosomal aberrations that cause IUGR are heterogeneous, aberration of autosomes, mostly autosomal trisomies, being the most common.

  4. Impact of intrauterine growth restriction on preterm lung disease.

    Science.gov (United States)

    Sasi, Arun; Abraham, Vinita; Davies-Tuck, Miranda; Polglase, Graeme R; Jenkin, Graham; Miller, Suzanne L; Malhotra, Atul

    2015-12-01

    Intrauterine growth restriction (IUGR) is an important cause for prematurity and adversely influences prematurity-related morbidities. This study evaluates the impact of IUGR on respiratory outcomes in infants CLD), CLD or death, and need for home oxygen at discharge. Subgroup analysis by gestation-based stratification (CLD (45% vs. 17%, p = 0.0001), death (16% vs. 4.6%, p = 0.0001), CLD or death (46% vs. 21.5%, p = 0.0001), home oxygen rates (13.7% vs. 6.5%, p = 0.01) and duration of respiratory support was significantly higher in the IUGR group. IUGR emerged as the strongest predictor of CLD (adjusted OR, 95%CI: (8.4 [2, 35]) and CLD or death (12.7 [3, 54]) across all gestation. IUGR is a major risk factor for adverse short-term pulmonary outcomes as reflected by higher rates of CLD, CLD or death, and oxygen dependency at discharge in preterm infants. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  5. Neonatal cardiovascular system adaptation in babies with intrauterine growth retardation

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    I. N. Petrova

    2016-01-01

    Full Text Available Objective: to reveal the adaptive features of the cardiovascular system in newborn infants with intrauterine growth retardation (IUGR on the basis of a clinical instrumental study.Subjects and methods. A study group included 100 newborn infants with IUGR; a control group consisted of 40 babies with normal anthropometric measurements at birth. Medical history and clinical data and electrocardiographic and echocardiographic findings were analyzed.Results. All the examinees with IUGR had manifestations of cardiovascular system dysadaptation. There was a high rate of electrocardiographic changes, such as cardiac arrhythmias; low voltage; systolic overload of the right heart and left ventricle; signs of ventricular hypertrophy; and transient myocardial ischemia. The specific features of cardiac hemodynamics were decreased sizes of the left ventricle, lower parameters of its systolic function, and longer functioning of fetal communications.Conclusion. IUGR is associated with the development of cardiovascular system dysadaptation syndrome, which is due to prior perinatal hypoxia. The findings necessitate a follow-up of children by involving a cardiologist.

  6. Memory functions of children born with asymmetric intrauterine growth restriction.

    Science.gov (United States)

    Geva, Ronny; Eshel, Rina; Leitner, Yael; Fattal-Valevski, Aviva; Harel, Shaul

    2006-10-30

    Learning difficulties are frequently diagnosed in children born with intrauterine growth restriction (IUGR). Models of various animal species with IUGR were studied and demonstrated specific susceptibility and alterations of the hippocampal formation and its related neural structures. The main purpose was to study memory functions of children born with asymmetric IUGR in a large-scale cohort using a long-term prospective paradigm. One hundred and ten infants diagnosed with IUGR were followed-up from birth to 9 years of age. Their performance was compared with a group of 63 children with comparable gestational age and multiple socioeconomic factors. Memory functions (short-term, super- and long-term spans) for different stimuli types (verbal and visual) were evaluated using Visual Auditory Digit Span tasks (VADS), Rey Auditory Verbal Learning Test (Rey-AVLT), and Rey Osterrieth Complex Figure Test (ROCF). Children with IUGR had short-term memory difficulties that hindered both serial verbal processing system and simultaneous processing of high-load visuo-spatial stimuli. The difficulties were not related to prematurity, neonatal complications or growth catch-up, but were augmented by lower maternal education. Recognition skills and benefits from reiteration, typically affected by hippocampal dysfunction, were preserved in both groups. Memory profile of children born with IUGR is characterized primarily by a short-term memory deficit that does not necessarily comply with a typical hippocampal deficit, but rather may reflect an executive short-term memory deficit characteristic of anterior hippocampal-prefrontal network. Implications for cognitive intervention are discussed.

  7. KRN633, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, induces intrauterine growth restriction in mice.

    Science.gov (United States)

    Abe, Naomichi; Nakahara, Tsutomu; Morita, Akane; Wada, Yoshiko; Mori, Asami; Sakamoto, Kenji; Nagamitsu, Tohru; Ishii, Kunio

    2013-08-01

    We previously reported that treatment with KRN633, a vascular endothelial growth factor receptor tyrosine kinase inhibitor, during mid-pregnancy caused intrauterine growth restriction resulting from impairment of blood vessel growth in the labyrinthine zone of the placenta and fetal organs. However, the relative sensitivities of blood vessels in the placenta and fetal organs to vascular endothelial growth factor (VEGF) inhibitors have not been determined. In this study, we aimed to examine the effects of KRN633 on the vasculatures of organs in mother mice and their newborn pups by immunohistochemical analysis. Pregnant mice were treated daily with KRN633 (5 mg/kg) either from embryonic day 13.5 (E13.5) to E17.5 or from E13.5 to the day of delivery. The weights of the pups of KRN633-treated mice were lower than those of the pups of vehicle-treated mothers. However, no significant difference in body weight was observed between the vehicle- and KRN633-treated mice. The vascular development in the organs (the pancreas, kidney, and intestine) and intestinal lymphatic formation of the pups of KRN633-treated mothers was markedly impaired. In contrast, the KRN633 treatment showed no significant effect on the vascular beds in the organs, including the labyrinthine zone of the placenta, of the mother mice. These results suggest that blood vessels in fetal organs are likely to be more sensitive to reduced VEGF signaling than those in the mother. A partial loss of VEGF function during pregnancy could suppress vascular growth in the fetus without affecting the vasculature in the mother mouse, thereby increasing the risk of intrauterine growth restriction. © 2013 Wiley Periodicals, Inc.

  8. Heterogeneity of ventricular repolarization in newborns with intrauterine growth restriction.

    Science.gov (United States)

    Fouzas, Sotirios; Karatza, Ageliki A; Davlouros, Periklis A; Chrysis, Dionisios; Alexopoulos, Dimitrios; Mantagos, Stefanos; Dimitriou, Gabriel

    2014-12-01

    Intrauterine growth restriction (IUGR) is associated with structural and functional cardiac alterations but the electrophysiological consequences of these disturbances remain unknown. To explore the distribution of ventricular repolarization and its relation to myocardial mechanics in newborns with IUGR. STUDY DESIGN, SUBJECTS AND OUTCOME MEASUREMENTS: Conventional and tissue Doppler echocardiographic data, and electrocardiographic parameters used to describe the distribution of ventricular repolarization (dispersion of QT [QTd] and JT [JTd]), were obtained on the second (D2) and fifth (D5) postnatal day and compared between 25 IUGR newborns and 25 matched-for-gestational age controls. IUGR was associated with relative interventricular septum hypertrophy, increased left ventricular (LV) E/E' ratio and higher LV myocardial performance index (MPI). On both study days, the IUGR infants presented higher QTd and JTd compared to controls (QTd-D2: 66±20 ms vs. 36±12 ms, P<0.001; JTd-D2: 54±13 ms vs. 34±9 ms, P<0.001; QTd-D5: 61±14 ms vs. 27±12 ms, P<0.001; JTd-D5: 54±13 ms vs. 27±9 ms, P<0.001). The association between QTd and LV E/E' (D2: regression coefficient beta 0.747, R(2) 0.585; D5: beta 0.843, R(2) 0.646) and QTd and MPI (D2: beta 0.680, R(2) 0.576; D5: beta 0.698, R(2) 0.650) was also significant (P<0.001 for all analyses). Our findings suggest that IUGR is associated with electrophysiological remodeling of the neonatal heart, a process which is closely related to the underlying alterations in ventricular mechanics and might predispose to adverse electrophysiological events. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Intrauterine Growth Restriction Alters Mouse Intestinal Architecture during Development.

    Science.gov (United States)

    Fung, Camille M; White, Jessica R; Brown, Ashley S; Gong, Huiyu; Weitkamp, Jörn-Hendrik; Frey, Mark R; McElroy, Steven J

    2016-01-01

    Infants with intrauterine growth restriction (IUGR) are at increased risk for neonatal and lifelong morbidities affecting multiple organ systems including the intestinal tract. The underlying mechanisms for the risk to the intestine remain poorly understood. In this study, we tested the hypothesis that IUGR affects the development of goblet and Paneth cell lineages, thus compromising the innate immunity and barrier functions of the epithelium. Using a mouse model of maternal thromboxane A2-analog infusion to elicit maternal hypertension and resultant IUGR, we tested whether IUGR alters ileal maturation and specifically disrupts mucus-producing goblet and antimicrobial-secreting Paneth cell development. We measured body weights, ileal weights and ileal lengths from birth to postnatal day (P) 56. We also determined the abundance of goblet and Paneth cells and their mRNA products, localization of cellular tight junctions, cell proliferation, and apoptosis to interrogate cellular homeostasis. Comparison of the murine findings with human IUGR ileum allowed us to verify observed changes in the mouse were relevant to clinical IUGR. At P14 IUGR mice had decreased ileal lengths, fewer goblet and Paneth cells, reductions in Paneth cell specific mRNAs, and decreased cell proliferation. These findings positively correlated with severity of IUGR. Furthermore, the decrease in murine Paneth cells was also seen in human IUGR ileum. IUGR disrupts the normal trajectory of ileal development, particularly affecting the composition and secretory products of the epithelial surface of the intestine. We speculate that this abnormal intestinal development may constitute an inherent "first hit", rendering IUGR intestine susceptible to further injury, infection, or inflammation.

  10. Increased autophagy in placentas of intrauterine growth-restricted pregnancies.

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    Tai-Ho Hung

    Full Text Available Unexplained intrauterine growth restriction (IUGR may be a consequence of placental insufficiency; however, its etiology is not fully understood. We surmised that defective placentation in IUGR dysregulates cellular bioenergic homeostasis, leading to increased autophagy in the villous trophoblast. The aims of this work were (1 to compare the differences in autophagy, p53 expression, and apoptosis between placentas of women with normal or IUGR pregnancies; (2 to study the effects of hypoxia and the role of p53 in regulating trophoblast autophagy; and (3 to investigate the relationship between autophagy and apoptosis in hypoxic trophoblasts.Compared with normal pregnant women, women with IUGR had higher placental levels of autophagy-related proteins LC3B-II, beclin-1, and damage-regulated autophagy modulator (DRAM, with increased p53 and caspase-cleaved cytokeratin 18 (M30. Furthermore, cytotrophoblasts cultured under hypoxia (2% oxygen in the presence or absence of nutlin-3 (a p53 activity stimulator had higher levels of LC3B-II, DRAM, and M30 proteins and increased Bax mRNA expression compared with controls cultured under standard conditions. In contrast, administration of pifithrin-α (a p53 activity inhibitor during hypoxia resulted in protein levels that were similar to those of the control groups. Moreover, cytotrophoblasts transfected with LC3B, beclin-1, or DRAM siRNA had higher levels of M30 compared with the controls under hypoxia. However, transfection with Bcl-2 or Bax siRNA did not cause any significant change in the levels of LC3B-II in hypoxic cytotrophoblasts.Together, these results suggest that there is a crosstalk between autophagy and apoptosis in IUGR and that p53 plays a pivotal and complex role in regulating trophoblast cell turnover in response to hypoxic stress.

  11. Placental gene expression of the placental growth factor (PlGF) in intrauterine growth restriction.

    Science.gov (United States)

    Joó, József Gábor; Rigó, János; Börzsönyi, Balázs; Demendi, Csaba; Kornya, László

    2017-06-01

    We analyzed changes in gene expression of placental growth factor (PIGF) in human placental samples obtained postpartum from pregnancies with IUGR. During a twelve-month study period representing the calendar year of 2012 placental samples from 101 pregnancies with IUGR and from 140 normal pregnancies were obtained for analysis of a potential difference in PIGF gene expression. There was no significant difference in gene activity of the PIGF gene between the IUGR versus normal pregnancy groups (Ln2 α : 0.92; p intrauterine growth restriction PIGF expression does show a significant decrease indicating its potential role in the profound defect in angiogenesis in these cases.

  12. The hepatic transcriptome of young suckling and aging intrauterine growth restricted male rats.

    Science.gov (United States)

    Freije, William A; Thamotharan, Shanthie; Lee, Regina; Shin, Bo-Chul; Devaskar, Sherin U

    2015-04-01

    Intrauterine growth restriction leads to the development of adult onset obesity/metabolic syndrome, diabetes mellitus, cardiovascular disease, hypertension, stroke, dyslipidemia, and non-alcoholic fatty liver disease/steatohepatitis. Continued postnatal growth restriction has been shown to ameliorate many of these sequelae. To further our understanding of the mechanism of how intrauterine and early postnatal growth affects adult health we have employed Affymetrix microarray-based expression profiling to characterize hepatic gene expression of male offspring in a rat model of maternal nutrient restriction in early and late life. At day 21 of life (p21) combined intrauterine and postnatal calorie restriction treatment led to expression changes in circadian, metabolic, and insulin-like growth factor genes as part of a larger transcriptional response that encompasses 144 genes. Independent and controlled experiments at p21 confirm the early life circadian, metabolic, and growth factor perturbations. In contrast to the p21 transcriptional response, at day 450 of life (d450) only seven genes, largely uncharacterized, were differentially expressed. This lack of a transcriptional response identifies non-transcriptional mechanisms mediating the adult sequelae of intrauterine growth restriction. Independent experiments at d450 identify a circadian defect as well as validate expression changes to four of the genes identified by the microarray screen which have a novel association with growth restriction. Emerging from this rich dataset is a portrait of how the liver responds to growth restriction through circadian dysregulation, energy/substrate management, and growth factor modulation. © 2014 Wiley Periodicals, Inc.

  13. Diagnostic Criteria for Transient Myocardial Ischemia in Newborn Infants with Intrauterine Growth Retardation

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    Umida F. Nasirova, PhD

    2012-06-01

    Full Text Available Metabolic and hemodynamic disturbances in newborns with intrauterine growth retardation resulting from the transferred intrauterine hypoxia, lead to the development of transient myocardial ischemia. Study included 158 newborn infants with intrauterine growth retardation, 83% of which have the asymmetric and 17% - the symmetric form of IUGR, revealed differences in heart rate due to higher dispersion parameters of cardiac rhythm. It was determined that in infants with intrauterine growth retardation heart rate, respiratory rate accelerated and blood pressure increased in compare with the newborns in the control group. According to the ECG examination results, were revealed the signs of focal changes of ST-T, accompanied by inversion of the ST-T segment below the isoline, which accompanied with the positive and peaked T waves, considered as myocardial ischemia. In infants with intrauterine growth retardation, survived after perinatal damage of the central nervous system, the prolongation of the QRST interval was noted in compare with the control group newborns, which could be an indicator of conjunction of hypoxic and ischemic changes in the myocardium. Clinical manifestations of transient myocardial ischemia followed by pale skin, acrocyanosis, and perioral cyanosis against dullness of heart sounds. Obtained results deepened an understanding of posthypoxic myocardial dysfunction, which is characterized by cardiac rhythm and conductivity disturbances, as well as changes in ventricular complex, and causing the need for electrocardiographic screening in the neonatal period

  14. Optimizing the definition of intrauterine growth restriction: the multicenter prospective PORTO Study.

    LENUS (Irish Health Repository)

    Unterscheider, Julia

    2013-04-01

    The objective of the Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction (IUGR) (PORTO Study), a national prospective observational multicenter study, was to evaluate which sonographic findings were associated with perinatal morbidity and mortality in pregnancies affected by growth restriction, originally defined as estimated fetal weight (EFW) <10th centile.

  15. First trimester screening for intra-uterine growth restriction and early-onset pre-eclampsia

    NARCIS (Netherlands)

    Vandenberghe, G.; Mensink, I.; Twisk, J. W. R.; Blankenstein, M. A.; Heijboer, A. C.; van Vugt, J. M. G.

    2011-01-01

    To assess first trimester placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) as screening markers for early-onset pre-eclampsia (PE) and intra-uterine growth restriction (IUGR). PlGF concentration was retrospectively measured in first trimester serum specimens of 23

  16. First trimester screening for intra-uterine growth restriction and early-onset pre-eclampsia

    NARCIS (Netherlands)

    Vandenberghe, G.; Mensink, I.; Twisk, J.W.; Blankenstein, M.A.; Heijboer, A.C.; van Vugt, J.M.

    2011-01-01

    Objective: To assess first trimester placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) as screening markers for early-onset pre-eclampsia (PE) and intra-uterine growth restriction (IUGR). Methods: PlGF concentration was retrospectively measured in first trimester

  17. Non-invasive transabdominal uterine electromyography correlates with the strength of intrauterine pressure and is predictive of labor and delivery.

    Science.gov (United States)

    Maul, H; Maner, W L; Olson, G; Saade, G R; Garfield, R E

    2004-05-01

    The study was conducted to investigate whether the strength of uterine contractions monitored invasively by intrauterine pressure catheter could be determined from transabdominal electromyography (EMG) and to estimate whether EMG is a better predictor of true labor compared to tocodynamometry (TOCO). Uterine EMG was recorded from the abdominal surface in laboring patients simultaneously monitored with an intrauterine pressure catheter (n = 13) or TOCO (n = 24). Three to five contractions per patient and corresponding electrical bursts were randomly selected and analyzed (integral of intrauterine pressure; integral, frequency, amplitude of contraction curve on TOCO; burst energy for EMG). The Mann-Whitney test, Spearman correlation and receiver operator characteristics (ROC) analysis were used as appropriate (significance was assumed at a value of p TOCO parameters were different. In addition, burst energy levels were highly predictive of delivery within 48 h (AUC = 0.9531; p TOCO, transabdominal uterine EMG can be used reliably to predict labor and delivery.

  18. Language development in preschool children born after asymmetrical intrauterine growth retardation.

    Science.gov (United States)

    Simić Klarić, Andrea; Kolundžić, Zdravko; Galić, Slavka; Mejaški Bošnjak, Vlatka

    2012-03-01

    After intrauterine growth retardation, many minor neurodevelopmental disorders may occur, especially in the motor skills domain, language and speech development, and cognitive functions. The assessment of language development and impact of postnatal head growth in preschool children born with asymmetrical intrauterine growth retardation. Examinees were born at term with birth weight below the 10th percentile for gestational age, parity and gender. Mean age at the time of study was six years and four months. The control group was matched according to chronological and gestational age, gender and maternal education with mean age six years and five months. There were 50 children with intrauterine growth retardation and 50 controls, 28 girls and 22 boys in each group. For the assessment of language development Reynell Developmental Language Scale, the Naming test and Mottier test were performed. There were statistically significant differences (p language comprehension, total expressive language (vocabulary, structure, content), naming skills and non-words repetition. Statistically significant positive correlations were found between relative growth of the head [(Actual head circumference - head circumference at birth)/(Body weight - birth weight)] and language outcome. Children with neonatal complications had lower results (p language comprehension and total expressive language. Intrauterine growth retardation has a negative impact on language development which is evident in preschool years. Slow postnatal head growth is correlated with poorer language outcome. Neonatal complications were negatively correlated with language comprehension and total expressive language. Copyright © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  19. Intrauterine growth restriction and prematurity influence regulatory T cell development in newborns.

    Science.gov (United States)

    Mukhopadhyay, Dhriti; Weaver, Laura; Tobin, Richard; Henderson, Stephanie; Beeram, Madhava; Newell-Rogers, M Karen; Perger, Lena

    2014-05-01

    The aim of this study was to determine the relationship of birth weight and gestational age with regulatory T cells (Tregs) in cord blood of human newborns. Cord blood mononuclear cells (CBMCs) of 210 newborns were analyzed using flow cytometry to identify Tregs (CD3(+), CD4(+), CD25(high), FoxP3(high)) and measure FoxP3 mean fluorescence intensity (MFI). Suppressive index (SI) was calculated as FoxP3 MFI per Treg. Mode of delivery had no significant effect on Tregs at birth. Term babies with growth restriction had fewer Tregs than their appropriate weight counterparts but equivalent SI. Preterm babies had higher percentages of Tregs, but lower SI than term controls. SI steadily increased through gestation. Intrauterine growth restriction is correlated with fewer circulating Tregs and prematurity with decreased functionality of Tregs compared to term appropriate weight infants. This may have implications in diseases such as necrotizing enterocolitis that disproportionately affect premature and lower birth weight infants. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Intrauterine growth standards: a cross-sectional study in a population of Nigerian newborns

    Directory of Open Access Journals (Sweden)

    Olugbenga A. Mokuolu

    2012-09-01

    Full Text Available The aim of the study was to define an intrauterine growth curve for a population of Nigerian newborn babies. A cross-sectional observational study design was adopted. Weight, length and head circumference were all measured in consecutive singleton deliveries at the University of Ilorin Teaching Hospital over a 3-year period. Gestational age (GA of the babies was estimated from the last menstrual period or first trimester ultrasound. The estimates obtained were clinically validated using the Ballard score. Mean birth weights and percentiles of the weight, length and head circumferences for the respective GA were estimated using the SPSS 15 software package. A total of 5273 babies were recruited for the study with GA ranging from 25-44 weeks. Comparison of the mean birth weights of the various GA with the data from Denver, Colorado, showed that Nigerian babes tended to weigh less at the early GA, although these differences were not statistically significant. Between 26-36 weeks, the average weights of both sexes were similar; however, beyond this time point there was a consistent increase in the average weight of the males over the female babies. Growth curves for Nigerian newborn babies were generated and showed that the mean birth weight of Nigerian preterm babies was lighter than that of babies in Colorado. The impact of these differences on the classification of newborns will require further evaluation.

  1. Expression of von Willebrand factor and caldesmon in the placental tissues of pregnancies complicated with intrauterine growth restriction.

    Science.gov (United States)

    Göksever Çelik, Hale; Uhri, Mehmet; Yildirim, Gökhan

    2017-11-02

    The decreased placental perfusion is the underlying reason for intrauterine growth restriction that in turn leads to reduced placental perfusion and ischemia. However, there are several issues to be understood in the pathophysiology of intrauterine growth restriction. We aimed to study whether any compensatory response in placental vascular bed occur in pregnancies complicated with intrauterine growth restriction by the immunohistochemical staining of von Willebrand factor and caldesmon in placental tissues. A total of 103 pregnant women was enrolled in the study including 50 patients who were complicated with IUGR and 50 uncomplicated control patients. The study was designed in a prospective manner. All placentas were also stained with von Willebrand factor and caldesmon monoclonal kits. The immunohistochemical staining of von Willebrand factor and caldesmon expressions in placental tissues were different between normal and intrauterine growth restriction group. The percentages of 2+ and 3+ von Willebrand factor expression were higher in the intrauterine growth restriction group comparing with the normal group, although the difference was not statistically significant. The intensity of caldesmon expression was significantly lower in the intrauterine growth restriction group in comparison with the normal group (p intrauterine growth restriction which is a hypoxic condition. But newly formed vessels are immature and not strong enough. Our study is important to clarify the pathophysiology and placental compensatory responses in intrauterine growth restriction.

  2. Maternal health-related quality of life after induction of labor or expectant monitoring in pregnancy complicated by intrauterine growth retardation beyond 36 weeks

    NARCIS (Netherlands)

    Bijlenga, D.; Boers, K.E.; Birnie, E.; Mol, B.W.J.; Vijgen, S.C.M.; van der Post, J.A.M.; de Groot, C.J.; Rijnders, R.J.P.; Pernet, P.J.; Roumen, F.J.; Stigter, R.H.; Delemarre, F.M.C.; Bremer, H.A.; Porath, M.; Scherjon, S.A.; Bonsel, G.J.

    2011-01-01

    Pregnancies complicated by intrauterine growth retardation (IUGR) beyond 36 weeks of gestation are at increased risk of neonatal morbidity and mortality. Optimal treatment in IUGR at term is highly debated. Results from the multicenter DIGITAT (Disproportionate Intrauterine Growth Intervention Trial

  3. Growth hormone, insulin-like growth factor I and its binding proteins 1 and 3 in last trimester intrauterine growth retardation with increased pulsatility index in the umbilical artery

    DEFF Research Database (Denmark)

    Larsen, T; Main, K; Andersson, A M

    1996-01-01

    The interrelationships between maternal hormone levels and placental dysfunction in mothers bearing children with intrauterine growth retardation remain unclear. We have examined some endocrinological aspects of intrauterine growth retardation and, in particular, tested whether low levels of GH...

  4. Challenges in nourishing the intrauterine growth-restricted foetus - Lessons learned from studies in the intrauterine growth-restricted foetal sheep.

    Science.gov (United States)

    Hay, William W; Brown, Laura D; Rozance, Paul J; Wesolowski, Stephanie R; Limesand, Sean W

    2016-08-01

    Previous attempts to improve growth and development of the intrauterine growth-restricted (IUGR) foetus during pregnancy have not worked or caused harm. Our research identifies tissue-specific mechanisms underlying foetal growth restriction and then tests strategies to improve growth and ameliorate many of the metabolic problems before the infant is born. The goal of our studies is to reduce the impact of foetal growth restriction at critical stages of development on the lifelong complications of IUGR offspring. Defining specific mechanisms that cause growth restriction in the foetus might identify specific nutrients and hormones that could be given to the mother to improve foetal growth and reduce metabolic complications, using strategies first tested in our IUGR animal model. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  5. Changes in GH/IGF-1 axis in intrauterine growth retardation: consequences of fetal programming?

    Science.gov (United States)

    Setia, S; Sridhar, M G

    2009-11-01

    Fetal growth is a complex process that depends on the genotype and epigenotype of the fetus, maternal nutrition, the availability of nutrients and oxygen to the fetus, intrauterine insults, and a variety of growth factors and proteins of maternal and fetal/placental origin. In the fetus, growth hormone (GH) plays little or no role in regulating fetal growth, and insulin-like growth factors (IGFs) control growth directly independent of fetal GH secretion. Placental growth hormone (PGH) is the prime regulator of maternal serum IGF-1 during pregnancy. Total as well as free PGH and IGFs are significantly lower in pregnancies with intrauterine growth retardation (IUGR). The GH/IGF axis is significantly affected by intrauterine growth retardation and some of these alterations may lead to permanent pathological programming of the IGF axis. Alterations in the IGF axis may play a role in the future occurrence of insulin resistance and hypertension. In this review we focus on the regulation of fetal growth and the role of fetal programming in the late consequences of a poor fetal environment reflected in IUGR.

  6. The tissue and plasma concentration of polyols and sugars in sheep intrauterine growth retardation

    NARCIS (Netherlands)

    T.R.H. Regnault (Timothy); C. Teng (Cecilia); B. de Vrijer (Barbra); H.L. Galan (Henry); R.B. Wilkening (Randall); F.C. Battaglia (Frederick)

    2010-01-01

    textabstractIn an ovine model of placental insufficiency-induced intrauterine growth retardation (PI-IUGR), characterized by hypoxia, hypoglycemia and a significant reduction in fetal weight, we assessed alterations in fetal and placental polyols. Arterial maternal-fetal concentration differences of

  7. Enteral feeding of intrauterine growth restriction preterm infants: theoretical risks and practical implications

    Directory of Open Access Journals (Sweden)

    Valentina Bozzetti

    2017-06-01

    Full Text Available Intrauterine growth restriction (IUGR infants are thought to have impaired gut function after birth secondary to intrauterine redistribution of the blood flow, due to placental insufficiency, with a consequent reduction of gut perfusion. For this reason, infants complicated by IUGR have been considered at higher risk of feeding intolerance. Postnatal evaluation of splanchnic perfusion, through Doppler of the superior mesenteric artery, and of splanchnic oxygenation, through near infrared spectroscopy measurements, may be useful in evaluating the persistence (or not of the redistribution of blood flow occurred in utero.

  8. Biophysical profile in the treatment of intrauterine growth-restricted fetuses who weigh <1000 g.

    Science.gov (United States)

    Kaur, Satinder; Picconi, Jason L; Chadha, Rati; Kruger, Michael; Mari, Giancarlo

    2008-09-01

    The aim of this study was to determine the biophysical profile (BPP) usefulness in the prediction of cord pH, base excess, and guidance regarding the timing of delivery in preterm intrauterine growth-restricted (IUGR) fetuses. A BPP was performed daily in 48 IUGR fetuses and was considered abnormal when it was 2/10 on 1 single occasion or 4/10 on 2 consecutive occasions 2 hours apart. The median gestational age and fetal weight for the total population was 27.6 weeks and 632 g, respectively. In 13 fetuses with a BPP of 6, there were 3 deaths, and 7 fetuses were acidemic. In 27 fetuses with a BPP of 8, there were 3 deaths, and 12 fetuses were acidemic. BPP alone is not a reliable test in the treatment of preterm IUGR fetuses, because of high false-positive and -negative results. The common notion of a good BPP providing reassurance for at least 24 hours is not applicable in severely preterm IUGR fetuses who weigh <1000 g.

  9. Potential Utility of Melatonin in Preeclampsia, Intrauterine Fetal Growth Retardation, and Perinatal Asphyxia.

    Science.gov (United States)

    Marseglia, Lucia; D'Angelo, Gabriella; Manti, Sara; Reiter, Russel J; Gitto, Eloisa

    2016-08-01

    Reactive oxygen species play an important role in the pathogenesis of several diseases during gestation and the perinatal period. During pregnancy, increased oxygen demand augments the rate of production of free radicals. Oxidative stress is involved in pregnancy disorders including preeclampsia and intrauterine fetal growth retardation (IUGR). Moreover, increased levels of oxidative stress and reduced antioxidative capacities may contribute to the pathogenesis of perinatal asphyxia. Melatonin, an efficient antioxidant agent, diffuses through biological membranes easily and exerts pleiotropic actions on every cell and appears to be essential for successful gestation. This narrative review summarizes current knowledge concerning the role of melatonin in reducing complications during human pregnancy and in the perinatal period. Melatonin levels are altered in women with abnormally functioning placentae during preeclampsia and IUGR. Short-term melatonin therapy is highly effective and safe in reducing complications during pregnancy and in the perinatal period. Because melatonin has been shown to be safe for both mother and fetus, it could be an attractive therapy in pregnancy and is considered a promising neuroprotective agent in perinatal asphyxia. We believe that the use of melatonin treatment during the late fetal and early neonatal period might result in a wide range of health benefits, improved quality of life, and may help limit complications during the critical periods prior to, and shortly after, delivery. © The Author(s) 2015.

  10. Potential adverse effects of antenatal melatonin as a treatment for intrauterine growth restriction: findings in pregnant sheep.

    Science.gov (United States)

    González-Candia, Alejandro; Veliz, Marcelino; Araya, Claudio; Quezada, Sebastian; Ebensperger, Germán; Serón-Ferré, María; Reyes, Roberto V; Llanos, Aníbal J; Herrera, Emilio A

    2016-08-01

    Intrauterine growth restriction is a condition in which the fetus has a birthweight and/or length Intrauterine growth restriction can be associated with various causes, among which is low uteroplacental perfusion and chronic hypoxia during gestation. Often, intrauterine growth-restricted fetuses have increased oxidative stress; therefore, agents that decrease oxidative stress and increase utero, placental, and umbilical perfusion have been proposed as a beneficial therapeutic strategy. In this scenario, melatonin acts as an umbilical vasodilator and a potent antioxidant that has not been evaluated in pregnancies under chronic hypoxia that induce fetal growth restriction. However, this neurohormone has been proposed as a pharmacologic therapy for complicated pregnancies. The aim of this study was to determine the effects of prenatal administration of melatonin during the last trimester of pregnancy on the biometry of the growth-restricted lambs because of developmental hypoxia. Further, we aimed to determine melatonin and cortisol levels and oxidative stress markers in plasma of pregnant ewes during the treatment. High-altitude pregnant sheep received either vehicle (n = 5; 5 mL 1.4% ethanol) or melatonin (n = 7; 10 mg/kg(-1)day(-1) in 5 mL 1.4% ethanol) daily during the last one-third of gestation. Maternal plasma levels of melatonin, cortisol, antioxidant capacity, and oxidative stress were determined along treatment. At birth, neonates were examined, weighed, and measured (biparietal diameter, abdominal diameter, and crown-rump length). Antenatal treatment with melatonin markedly decreased neonatal biometry and weight at birth. Additionally, melatonin treatment increased the length of gestation by 7.5% and shifted the time of delivery. Furthermore, the prenatal treatment doubled plasma levels of melatonin and cortisol and significantly improved the antioxidant capacity of the pregnant ewes. Our findings indicate that antenatal melatonin induces further

  11. Postnatal Growth in a Cohort of Sardinian Intrauterine Growth-Restricted Infants

    Directory of Open Access Journals (Sweden)

    Maria Grazia Clemente

    2017-01-01

    Full Text Available Recent studies have shown that infants with intrauterine growth restriction (IUGR undergo catch-up growth during infancy. The aim of our study was to evaluate the postnatal growth in a cohort of IUGR infants born in a tertiary-level Obstetric University Hospital of Northern Sardinia. An observational retrospective study was conducted on 12 IUGR (group A and 12 control infants (group B by measuring the anthropometric parameters of weight (W, length (L and head circumference (HC from birth to the 3rd postnatal year. At birth, significant differences were found between group A and group B with regard to all the auxological parameters (W, mean 1846.6 versus 3170.8 g, p < 0.0001; HC, 30.1 versus 34.4 cm, p < 0.0001; L, mean 43.4 versus 49.4 cm, p < 0.0001. During the 1st year, 8 of 12 (70% IUGR infants exhibited a significant catch-up growth in the 3 anthropometric parameters and a regular growth until the 3rd year of follow-up. The majority but not all infants born with IUGR in our series showed significant postnatal catch-up growth essentially during the first 12 months of life. An improved knowledge of the causes of IUGR will help to develop measures for its prevention and individualized treatment.

  12. Insulin sensitivity and insulin secretion at birth in intrauterine growth retarded infants.

    Science.gov (United States)

    Setia, Sajita; Sridhar, M G; Bhat, Vishnu; Chaturvedula, Lata; Vinayagamoorti, R; John, Mathew

    2006-06-01

    To study insulin sensitivity, secretion and relation of insulin levels with birth weight and ponderal index in intrauterine growth retarded (IUGR) infants at birth. We studied 30 IUGR and 30 healthy newborns born at term by vaginal delivery in Jipmer, Pondicherry, India. Cord blood was collected at the time of delivery for measurement of plasma glucose and insulin. When compared with healthy newborns, IUGR newborns had lower plasma glucose levels (mean 2.3+/-0.98 versus 4.1+/-0.51 mmol/L, p<0.001); lower plasma insulin levels (mean 4.5+/-2.64 versus 11.03+/-1.68 microU/L, p<0.001); higher insulin sensitivity calculated using G/I ratio (mean 11.6+/-5.1 versus 6.7+/-0.31, p<0.001), HOMA IS (mean 5.5+/-6.0 versus 0.53+/-0.15, p<0.001), and QUICKI (mean 0.47+/-0.12 versus 0.34+/-0.02, p<0.001); and decreased pancreatic beta-cell function test measured as I/G (mean 0.10+/-0.037 versus 0.15+/-0.006, p<0.001). A positive correlation was identified between insulin levels and birth weight in both the healthy control group (r2 = 0.17, p = 0.024) and IUGR group (r2 = 0.13, p = 0.048). However correlation of insulin levels with ponderal index was much more confident in both healthy control (r2 = 0.90, p<0.001) and IUGR groups (r2 = 0.28, p = 0.003). Insulin status correlated both with birth weight and ponderal index more confidently in control group than in IUGR group. At birth, IUGR infants are hypoglycaemic, hypoinsulinaemic and display increased insulin sensitivity and decreased pancreatic beta-cell function. Insulin levels correlate with ponderal index much more confidently than with birth weight.

  13. [Placental gene activity of significant angiogenetic factors in the background of intrauterine growth restriction].

    Science.gov (United States)

    Kovács, Péter; Rab, Attila; Szentpéteri, Imre; Joó, József Gábor; Kornya, László

    2017-04-01

    Placental vascular endothelial growth factor A (VEGF-A) gene and endoglin gene are both overexpressed in placental samples obtained from pregnancies with intrauterine growth restriction compared to normal pregnancies. In the background of these changes a mechanism can be supposed, in which the increased endoglin activity in intrauterine growth restriction (IUGR) leads to impaired placental circulation through an antioangiogenetic effect. This results in the development of placental vascular dysfunction and chronic fetal hypoxia. It is chronic hypoxia that turns on VEGF-A as a compensatory mechanism to improve fetal vascular blood supply by promoting placental blood vessel formation. Although the maternal serum placental growth factor (PlGF) level is a potential predictor for both IUGR and praeeclampsia, placental PlGF gene activity may be less of an active in the regulation of placental circulation in IUGR pregnancies during the later stages of gestation. Orv. Hetil., 2017, 158(16), 612-617.

  14. Intrauterine growth restriction: impact on cardiovascular development and function throughout infancy.

    Science.gov (United States)

    Cohen, Emily; Wong, Flora Y; Horne, Rosemary S C; Yiallourou, Stephanie R

    2016-06-01

    Intrauterine growth restriction (IUGR) refers to the situation where a fetus does not grow according to its genetic growth potential. One of the main causes of IUGR is uteroplacental vascular insufficiency. Under these circumstances of chronic oxygen and nutrient deprivation, the growth-restricted fetus often displays typical circulatory changes, which in part represent adaptations to the suboptimal intrauterine environment. These fetal adaptations aim to preserve oxygen and nutrient supply to vital organs such as the brain, the heart, and the adrenals. These prenatal circulatory adaptations are thought to lead to an altered development of the cardiovascular system and "program" the fetus for life long cardiovascular morbidities. In this review, we discuss the alterations to cardiovascular structure, function, and control that have been observed in growth-restricted fetuses, neonates, and infants following uteroplacental vascular insufficiency. We also discuss the current knowledge on early life surveillance and interventions to prevent progression into chronic disease.

  15. Brain metabolite alterations in infants born preterm with intrauterine growth restriction: association with structural changes and neurodevelopmental outcome.

    Science.gov (United States)

    Simões, Rui V; Muñoz-Moreno, Emma; Cruz-Lemini, Mónica; Eixarch, Elisenda; Bargalló, Núria; Sanz-Cortés, Magdalena; Gratacós, Eduard

    2017-01-01

    Intrauterine growth restriction and premature birth represent 2 independent problems that may occur simultaneously and contribute to impaired neurodevelopment. The objective of the study was to assess changes in the frontal lobe metabolic profiles of 1 year old intrauterine growth restriction infants born prematurely and adequate-for-gestational-age controls, both premature and term adequate for gestational age and their association with brain structural and biophysical parameters and neurodevelopmental outcome at 2 years. A total of 26 prematurely born intrauterine growth restriction infants (birthweight intrauterine growth restriction infants had slightly smaller brain volumes and increased frontal lobe white matter mean diffusivity compared with both prematurely born but adequate for gestational age and term adequate for gestational age controls. Frontal lobe N-acetylaspartate levels were significantly lower in prematurely born intrauterine growth restriction than in prematurely born but adequate for gestational age infants but increased in prematurely born but adequate for gestational age compared with term adequate-for-gestational-age infants. The prematurely born intrauterine growth restriction group also showed slightly lower choline compounds, borderline decrements of estimated glutathione levels, and increased myoinositol to choline ratios, compared with prematurely born but adequate for gestational age controls. These specific metabolite changes were locally correlated to lower gray matter content and increased mean diffusivity and reduced white matter fraction and fractional anisotropy. Prematurely born intrauterine growth restriction infants also showed a tendency for poorer neurodevelopmental outcome at 2 years, associated with lower levels of frontal lobe N-acetylaspartate at 1 year within the preterm subset. Preterm intrauterine growth restriction infants showed altered brain metabolite profiles during a critical stage of brain maturation, which

  16. Left ventricular dimensions, systolic functions, and mass in term neonates with symmetric and asymmetric intrauterine growth restriction.

    Science.gov (United States)

    Cinar, Bahar; Sert, Ahmet; Gokmen, Zeynel; Aypar, Ebru; Aslan, Eyup; Odabas, Dursun

    2015-02-01

    Previous studies have demonstrated structural changes in the heart and cardiac dysfunction in foetuses with intrauterine growth restriction. There are no available data that evaluated left ventricular dimensions and mass in neonates with symmetric and asymmetric intrauterine growth restriction. Therefore, we aimed to evaluate left ventricular dimensions, systolic functions, and mass in neonates with symmetric and asymmetric intrauterine growth restriction. We also assessed associated maternal risk factors, and compared results with healthy appropriate for gestational age neonates. In all, 62 asymmetric intrauterine growth restriction neonates, 39 symmetric intrauterine growth restriction neonates, and 50 healthy appropriate for gestational age neonates were evaluated by transthoracic echocardiography. The asymmetric intrauterine growth restriction group had significantly lower left ventricular end-systolic and end-diastolic diameters and posterior wall diameter in systole and diastole than the control group. The symmetric intrauterine growth restriction group had significantly lower left ventricular end-diastolic diameter than the control group. All left ventricular dimensions were lower in the asymmetric intrauterine growth restriction neonates compared with symmetric intrauterine growth restriction neonates (p>0.05), but not statistically significant except left ventricular posterior wall diameter in diastole (3.08±0.83 mm versus 3.54 ±0.72 mm) (pintrauterine growth restriction groups had significantly lower relative posterior wall thickness (0.54±0.19 versus 0.48±0.13 versus 0.8±0.12), left ventricular mass (9.8±4.3 g versus 8.9±3.4 g versus 22.2±5.7 g), and left ventricular mass index (63.6±29.1 g/m2 versus 54.5±24.4 g/m2 versus 109±28.8 g/m2) when compared with the control group. Our study has demonstrated that although neonates with both symmetric and asymmetric intrauterine growth restriction had lower left ventricular dimensions, relative

  17. Motor and cortico-striatal-thalamic connectivity alterations in intrauterine growth restriction.

    Science.gov (United States)

    Eixarch, Elisenda; Muñoz-Moreno, Emma; Bargallo, Nuria; Batalle, Dafnis; Gratacos, Eduard

    2016-06-01

    Intrauterine growth restriction is associated with short- and long-term neurodevelopmental problems. Structural brain changes underlying these alterations have been described with the use of different magnetic resonance-based methods that include changes in whole structural brain networks. However, evaluation of specific brain circuits and its correlation with related functions has not been investigated in intrauterine growth restriction. In this study, we aimed to investigate differences in tractography-related metrics in cortico-striatal-thalamic and motor networks in intrauterine growth restricted children and whether these parameters were related with their specific function in order to explore its potential use as an imaging biomarker of altered neurodevelopment. We included a group of 24 intrauterine growth restriction subjects and 27 control subjects that were scanned at 1 year old; we acquired T1-weighted and 30 directions diffusion magnetic resonance images. Each subject brain was segmented in 93 regions with the use of anatomical automatic labeling atlas, and deterministic tractography was performed. Brain regions included in motor and cortico-striatal-thalamic networks were defined based in functional and anatomic criteria. Within the streamlines that resulted from the whole brain tractography, those belonging to each specific circuit were selected and tractography-related metrics that included number of streamlines, fractional anisotropy, and integrity were calculated for each network. We evaluated differences between both groups and further explored the correlation of these parameters with the results of socioemotional, cognitive, and motor scales from Bayley Scale at 2 years of age. Reduced fractional anisotropy (cortico-striatal-thalamic, 0.319 ± 0.018 vs 0.315 ± 0.015; P = .010; motor, 0.322 ± 0.019 vs 0.319 ± 0.020; P = .019) and integrity cortico-striatal-thalamic (0.407 ± 0.040 vs 0.399 ± 0.034; P = .018; motor, 0.417 ± 0.044 vs 0

  18. Influence of intrauterine and extrauterine growth on neurodevelopmental outcome of monozygotic twins

    Directory of Open Access Journals (Sweden)

    R.K. Reolon

    2008-08-01

    Full Text Available There have been indications that intrauterine and early extrauterine growth can influence childhood mental and motor function. The objective of the present study was to evaluate the influence of intrauterine growth restriction and early extrauterine head growth on the neurodevelopmental outcome of monozygotic twins. Thirty-six monozygous twin pairs were evaluated at the corrected age of 12 to 42 months. Intrauterine growth restriction was quantified using the fetal growth ratio. The effects of birth weight ratio, head circumference at birth and current head circumference on mental and motor outcomes were estimated using mixed-effect linear regression models. Separate estimates of the between (interpair and within (intrapair effects of each measure on development were thus obtained. Neurodevelopment was assessed with the Bayley Scales of Infant Development, 2nd edition, by a psychologist blind to the exposure. A standardized neurological examination was performed by a neuropediatrician who was unaware of the exposures under investigation. After adjustment, birth weight ratio and head circumference at birth were not associated with motor or mental outcomes. Current head circumference was associated with mental but not with motor outcomes. Only the intrapair twin effect was significant. An increase of 1 cm in current head circumference of one twin compared with the other was associated with 3.2 points higher in Mental Developmental Index (95%CI = 1.06-5.32; P < 0.03. Thus, no effect of intrauterine growth was found on cognition and only postnatal head growth was associated with cognition. This effect was not shared by the co-twin.

  19. Recurrent chronic histiocytic intervillositis with intrauterine growth restriction, osteopenia, and fractures.

    Science.gov (United States)

    Crawford, April; Moore, Lynette; Bennett, Gregory; Savarirayan, Ravi; Manton, Nicholas; Khong, Yee; Barnett, Christopher P; Haan, Eric

    2016-11-01

    Chronic histiocytic intervillositis (CHI) is characterized by the presence of histiocytes within the intervillous space of the placenta. The pathogenesis is unclear but available evidence supports an alloimmune mechanism on the basis of the presence in maternal blood of HLA antibodies directed against paternal HLA antigens. CHI has a high risk of recurrence and of abnormal perinatal outcomes. Little is known about the effects of CHI on the developing fetus, in particular on the growth and development of the skeleton. We have studied a woman whose third pregnancy was terminated after ultrasonography showed severe intrauterine growth restriction, raising the possibility of a lethal skeletal dysplasia. Postmortem radiographs showed multiple fractures and other signs of osteogenesis imperfecta (OI). However, bone histology was not typical of OI and no abnormalities were identified by sequencing OI genes. The subsequent pregnancy was also severely growth restricted and was terminated. The placenta showed chronic histiocytic intervillositis, which, on retrospective review, had also been present in her second and third pregnancies. Her fifth pregnancy was again associated with intrauterine growth restriction and CHI but resulted in a premature birth. CHI can be associated with radiographic features that mimic OI and should be considered when fetal fractures occur in the context of recurrent miscarriage, fetal death in utero, and intrauterine growth restriction. The correct diagnosis can be made by histopathology of the placenta, supported by bone histology and normal results of molecular studies for OI. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Essential nutrient supplementation prevents heritable metabolic disease in multigenerational intrauterine growth-restricted rats

    Science.gov (United States)

    Goodspeed, Danielle; Seferovic, Maxim D.; Holland, William; Mcknight, Robert A.; Summers, Scott A.; Branch, D. Ware; Lane, Robert H.; Aagaard, Kjersti M.

    2015-01-01

    Intrauterine growth restriction (IUGR) confers heritable alterations in DNA methylation, rendering risk of adult metabolic syndrome (MetS). Because CpG methylation is coupled to intake of essential nutrients along the one-carbon pathway, we reasoned that essential nutrient supplementation (ENS) may abrogate IUGR-conferred multigenerational MetS. Pregnant Sprague-Dawley rats underwent bilateral uterine artery ligation causing IUGR in F1. Among the F2 generation, IUGR lineage rats were underweight at birth (6.7 vs. 8.0 g, P 30% elevated, P 5-fold less central fat mass, normal hepatic glucose efflux, and >70% reduced circulating triglycerides and very-LDLs compared with IUGR control-fed F2 offspring (P intrauterine growth-restricted rats. PMID:25395450

  1. A computational model of the fetal circulation to quantify blood redistribution in intrauterine growth restriction.

    Directory of Open Access Journals (Sweden)

    Patricia Garcia-Canadilla

    2014-06-01

    Full Text Available Intrauterine growth restriction (IUGR due to placental insufficiency is associated with blood flow redistribution in order to maintain delivery of oxygenated blood to the brain. Given that, in the fetus the aortic isthmus (AoI is a key arterial connection between the cerebral and placental circulations, quantifying AoI blood flow has been proposed to assess this brain sparing effect in clinical practice. While numerous clinical studies have studied this parameter, fundamental understanding of its determinant factors and its quantitative relation with other aspects of haemodynamic remodeling has been limited. Computational models of the cardiovascular circulation have been proposed for exactly this purpose since they allow both for studying the contributions from isolated parameters as well as estimating properties that cannot be directly assessed from clinical measurements. Therefore, a computational model of the fetal circulation was developed, including the key elements related to fetal blood redistribution and using measured cardiac outflow profiles to allow personalization. The model was first calibrated using patient-specific Doppler data from a healthy fetus. Next, in order to understand the contributions of the main parameters determining blood redistribution, AoI and middle cerebral artery (MCA flow changes were studied by variation of cerebral and peripheral-placental resistances. Finally, to study how this affects an individual fetus, the model was fitted to three IUGR cases with different degrees of severity. In conclusion, the proposed computational model provides a good approximation to assess blood flow changes in the fetal circulation. The results support that while MCA flow is mainly determined by a fall in brain resistance, the AoI is influenced by a balance between increased peripheral-placental and decreased cerebral resistances. Personalizing the model allows for quantifying the balance between cerebral and peripheral

  2. Carboxyhemoglobin levels in umbilical cord blood of women with pre-eclampsia and intrauterine growth restriction.

    Science.gov (United States)

    Yusuf, Kamran; Kamaluddeen, Majeeda; Wilson, R Douglas; Akierman, Albert

    2012-11-01

    Pre-eclampsia (PE) and intrauterine growth restriction (IUGR) are associated with abnormal placentation. Heme oxygenase (HO) and carbon monoxide (CO) are involved in normal placental development and function and vasomotor control in the placenta. The objective of our study was to measure CO levels, as assessed by carboxyhemoglobin (COHb) levels in the umbilical cord arterial blood of women with PE, normotensive IUGR (<10th percentile for birth weight), and normotensive pregnancies with appropriate-for-gestational age (AGA) infants. We prospectively analyzed COHb levels in the umbilical arterial blood of women with PE, normotensive IUGR, and normotensive AGA pregnancies. Exclusion criteria included cigarette smoke exposure, hemolytic disorders, a positive direct anti-globulin test, chronic hypertension, fever, and any significant medical illness. COHb levels were measured using the ABL 725 blood gas analyzer. There were 41 women in the normotensive AGA group, 42 in the PE group, and 36 in the normotensive IUGR group. Maternal age, mode of delivery, gravidity, parity, and gender of the infants were similar in the three groups. Gestational age and birth weight were significantly higher in the normotensive AGA group compared with the other two groups. COHb levels were significantly lower in the PE group compared with the normotensive AGA group (0.38±0.06% vs. 0.77±0.11%, P<0.05). COHb levels, although lower in the normotensive IUGR group compared with the normotensive AGA group, did not reach statistical significance. Our data suggests the HO-CO system may have a role in the pathogenesis of PE. We also, for the first time, provide information on umbilical arterial COHb levels in normotensive IUGR pregnancies.

  3. Application of spectroscopy (1HMRS) to assess liver metabolite concentrations in rats with intrauterine growth restriction.

    Science.gov (United States)

    Wang, Tao; Chen, Pingyang; Bian, Dujun; Chen, Juncao

    2017-04-01

    Proton magnetic resonance spectroscopy ( 1 H-MRS) measurement of liver metabolism in intrauterine growth restriction rats has seldom been reported. This study investigated the application of 1 H-MRS in assessing liver metabolism in newborn pups that experienced intrauterine growth restriction. Intra-uterine growth restriction was established by feeding rats low-protein diets during pregnancy. Newborn pups received conventional magnetic resonance imaging and 1 H-MRS using a 3.0T whole body MR scanner at 3, 8 and 12 weeks post birth. The success rate of 1 H-MRS was 83.33%. Significantly lower body weight, BMI and body length at 3 weeks as well as significantly lower body weight, BMI and waist circumference at 8 and 12 weeks were observed in newborn pups of IUGR rats compared with pups of control rats. Significant differences in ACho/H 2 O, ACr/H 2 O, AGlx/H 2 O and ALipid/H 2 O at 3 and 8 weeks as well as significant differences in ACr/H 2 O, ALipid/H 2 O and AGlx/H 2 O at 12 weeks were observed between pups of control rats and pups of IUGR rats. 1 H-MRS allows noninvasive assessment of liver metabolism in the rat and demonstrated the poor liver development of rats that experienced IUGR.

  4. Placental pathology in early intrauterine growth restriction associated with maternal hypertension.

    Science.gov (United States)

    Veerbeek, J H W; Nikkels, P G J; Torrance, H L; Gravesteijn, J; Post Uiterweer, E D; Derks, J B; Koenen, S V; Visser, G H A; Van Rijn, B B; Franx, A

    2014-09-01

    To identify key pathological characteristics of placentas from pregnancies complicated by early intrauterine growth restriction, and to examine their relations with maternal hypertensive disease and umbilical artery Doppler waveform abnormalities. Single-center retrospective cohort study of singleton pregnancies with abnormal umbilical artery Doppler flow patterns resulting in a live birth intrauterine growth restriction with or without hypertensive disease and pathological characteristics were compared between these various conditions according to predefined scoring criteria. Among 164 placentas studied, we found high rates of characteristic histopathological features that were associated with intrauterine growth restriction, including infarction (>5% in 42%), chronic villitis (21%), chronic chorioamnionitis (36%), membrane necrosis (20%), elevated nucleated red blood cells (89%), increased syncytial knotting (93%), increased villous maturation (98%), fetal thrombosis (32%) and distal villous hypoplasia (35%). Chronic inflammation of fetal membranes and syncytial knotting were more common in women with concomitant hypertensive disease as compared to women with normotensive IUGR (p < 0.05). Placentas from women with umbilical artery AREDF were more likely to show increased numbers of nucleated red blood cells and distal villous hypoplasia (p < 0.05). Placentas of women with early IUGR show high rates of several histological aberrations. Further, concomitant maternal hypertension is associated with characteristic inflammatory changes and umbilical artery AREDF with signs of chronic hypoxia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Neuropsychological development in preschool children born with asymmetrical intrauterine growth restriction and impact of postnatal head growth.

    Science.gov (United States)

    Klaric, Andrea Simić; Galić, Slavka; Kolundzić, Zdravko; Bosnjak, Vlatka Mejaski

    2013-07-01

    Neuropsychological development and the impact of postnatal head growth were studied in preschool children with asymmetrical intrauterine growth restriction. Examinees born at term with a birth weight below the 10th percentile were matched to the control group according to chronological and gestational age, gender, and maternal education. Fifty children were in each group, with a mean age of 6 years, 4 months. The Touwen neurological examination, the Čuturić developmental test, an imitative hand positions test, and a visual attention test were performed. There were significant differences (Pmotor variables, the developmental quotient, and the imitative hand positions test. Fine motor skills had the most discriminative power. Relative growth of the head in relation to weight gain was positively correlated to neurocognitive outcome. Intrauterine growth-restricted children with a current head circumference ≤10th percentile had poorer outcomes. Conclusively, intrauterine growth restriction has a negative impact on neurocognitive development. Slow postnatal head growth is correlated with a poorer neuropsychological outcome.

  6. Novel role of NPY in neuroimmune interaction and lung growth after intrauterine growth restriction.

    Science.gov (United States)

    Thangaratnarajah, Chansutha; Dinger, Katharina; Vohlen, Christina; Klaudt, Christian; Nawabi, Jawed; Lopez Garcia, Eva; Kwapiszewska, Grazyna; Dobner, Julia; Nüsken, Kai D; van Koningsbruggen-Rietschel, Silke; von Hörsten, Stephan; Dötsch, Jörg; Alejandre Alcázar, Miguel A

    2017-09-01

    Individuals with intrauterine growth restriction (IUGR) are at risk for chronic lung disease. Using a rat model, we showed in our previous studies that altered lung structure is related to IL-6/STAT3 signaling. As neuropeptide Y (NPY), a coneurotransmitter of the sympathetic nervous system, regulates proliferation and immune response, we hypothesized that dysregulated NPY after IUGR is linked to IL-6, impaired myofibroblast function, and alveolar growth. IUGR was induced in rats by isocaloric low-protein diet; lungs were analyzed on embryonic day (E) 21, postnatal day (P) 3, P12, and P23. Finally, primary neonatal lung myofibroblasts (pnF) and murine embryonic fibroblasts (MEF) were used to assess proliferation, apoptosis, migration, and IL-6 expression. At E21, NPY and IL-6 expression was decreased, and AKT/PKC and STAT3/AMPKα signaling was reduced. Early reduction of NPY/IL-6 was associated with increased chord length in lungs after IUGR at P3, indicating reduced alveolar formation. At P23, however, IUGR rats exhibited a catch-up of body weight and alveolar growth coupled with more proliferating myofibroblasts. These structural findings after IUGR were linked to activated NPY/PKC, IL-6/AMPKα signaling. Complementary, IUGR-pnF showed increased survival, impaired migration, and reduced IL-6 compared with control-pnF (Co-pnF). In contrast, NPY induced proliferation, migration, and increased IL-6 synthesis in fibroblasts. Additionally, NPY -/- mice showed reduced IL-6 signaling and less proliferation of lung fibroblasts. Our study presents a novel role of NPY during alveolarization: NPY regulates 1 ) IL-6 and lung STAT3/AMPKα signaling, and 2 ) proliferation and migration of myofibroblasts. These new insights in pulmonary neuroimmune interaction offer potential strategies to enable lung growth. Copyright © 2017 the American Physiological Society.

  7. Evaluation of Feeding Torerance in Intrauterine Growth Restricted Preterm Infants

    NARCIS (Netherlands)

    Bozzetti, V.

    2016-01-01

    Intra Uterine Growth Restriction (IUGR) is an important and common problem in obstetrics. The purpose of the present thesis was to investigate: 1. Feeding issues in IUGR preterm infants; 2. Clinical and strumental parameters as predictors of feeding tolerance in IUGR preterm infants; 3. Splanchnic

  8. Intrauterine growth restriction programs an accelerated age-related increase in cardiovascular risk in male offspring

    Science.gov (United States)

    Dasinger, John Henry; Intapad, Suttira; Backstrom, Miles A.; Carter, Anthony J.

    2016-01-01

    Placental insufficiency programs an increase in blood pressure associated with a twofold increase in serum testosterone in male growth-restricted offspring at 4 mo of age. Population studies indicate that the inverse relationship between birth weight and blood pressure is amplified with age. Thus, we tested the hypothesis that intrauterine growth restriction programs an age-related increase in blood pressure in male offspring. Growth-restricted offspring retained a significantly higher blood pressure at 12 but not at 18 mo of age compared with age-matched controls. Blood pressure was significantly increased in control offspring at 18 mo of age relative to control counterparts at 12 mo; however, blood pressure was not increased in growth-restricted at 18 mo relative to growth-restricted counterparts at 12 mo. Serum testosterone levels were not elevated in growth-restricted offspring relative to control at 12 mo of age. Thus, male growth-restricted offspring no longer exhibited a positive association between blood pressure and testosterone at 12 mo of age. Unlike hypertension in male growth-restricted offspring at 4 mo of age, inhibition of the renin-angiotensin system with enalapril (250 mg/l for 2 wk) did not abolish the difference in blood pressure in growth-restricted offspring relative to control counterparts at 12 mo of age. Therefore, these data suggest that intrauterine growth restriction programs an accelerated age-related increase in blood pressure in growth-restricted offspring. Furthermore, this study suggests that the etiology of increased blood pressure in male growth-restricted offspring at 12 mo of age differs from that at 4 mo of age. PMID:27147668

  9. Soluble CD30 in normotensive pregnant women with isolated fetal intrauterine growth restriction: a comparison with preeclamptic women.

    Science.gov (United States)

    Laskowska, Marzena; Laskowska, Katarzyna; Oleszczuk, Jan

    2010-11-01

    This study investigated the serum concentration of soluble CD30 (sCD30) in pregnant women with isolated fetal intrauterine growth restriction, in pregnancies complicated by preeclampsia with and without accompanying intrauterine growth restriction, and in normotensive healthy pregnant controls. Lower serum concentrations of sCD30 were observed in the group of normotensive pregnant women with a growth-restricted fetus in comparison with the group of healthy pregnant controls, and also in comparison with both preeclamptic groups of pregnant women with and without fetal growth restriction. The concentration of sCD30 in maternal serum from preeclamptic women did not differ in comparison with values from healthy controls or pregnancies complicated by isolated fetal intrauterine growth restriction. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  10. Intrauterine Growth Restriction and the Fetal Programming of the Hedonic Response to Sweet Taste in Newborn Infants

    Directory of Open Access Journals (Sweden)

    Caroline Ayres

    2012-01-01

    Full Text Available Intrauterine growth restriction is associated with increased risk for adult metabolic syndrome and cardiovascular disease, which seems to be related to altered food preferences in these individuals later in life. In this study, we sought to understand whether intrauterine growth leads to fetal programming of the hedonic responses to sweet. Sixteen 1-day-old preterm infants received 24% sucrose solution or water and the taste reactivity was filmed and analyzed. Spearman correlation demonstrated a positive correlation between fetal growth and the hedonic response to the sweet solution in the first 15 seconds after the offer (r=0.864, P=0.001, without correlation when the solution given is water (r=0.314, P=0.455. In fact, the more intense the intrauterine growth restriction, the lower the frequency of the hedonic response observed. IUGR is strongly correlated with the hedonic response to a sweet solution in the first day of life in preterm infants. This is the first evidence in humans to demonstrate that the hedonic response to sweet taste is programmed very early during the fetal life by the degree of intrauterine growth. The altered hedonic response at birth and subsequent differential food preference may contribute to the increased risk of obesity and related disorders in adulthood in intrauterine growth-restricted individuals.

  11. Superimposition of postnatal calorie restriction protects the aging male intrauterine growth- restricted offspring from metabolic maladaptations.

    Science.gov (United States)

    Dai, Yun; Thamotharan, Shanthie; Garg, Meena; Shin, Bo-Chul; Devaskar, Sherin U

    2012-09-01

    Intrauterine growth restriction (IUGR) results in dysregulated glucose homeostasis and adiposity in the adult. We hypothesized that with aging, these perturbations will wane, and superimposition of postnatal growth restriction (PNGR) on IUGR [intrauterine and postnatal growth restriction (IPGR)] will reverse the residual IUGR phenotype. We therefore undertook hyperinsulinemic-euglycemic clamp, energy balance, and physical activity studies during fed, fasted, and refed states, in light and dark cycles, on postweaned chow diet-fed more than 17-month aging male IUGR, PNGR, and IPGR vs. control (CON) rat offspring. Hyperinsulinemic-euglycemic clamp revealed similar whole-body insulin sensitivity and physical activity in the nonobese IUGR vs. CON, despite reduced heat production and energy expenditure. Compared with CON and IUGR, IPGR mimicking PNGR was lean and growth restricted with increased physical activity, O(2) consumption (VO(2)), energy intake, and expenditure. Although insulin sensitivity was no different in IPGR and PNGR, skeletal muscle insulin-induced glucose uptake was enhanced. This presentation proved protective against the chronologically earlier (5.5 months) development of obesity and dysregulated energy homeostasis after 19 wk on a postweaned high-fat diet. This protective role of PNGR on the metabolic IUGR phenotype needs future fine tuning aimed at minimizing unintended consequences.

  12. Impaired Angiogenic Potential of Human Placental Mesenchymal Stromal Cells in Intrauterine Growth Restriction.

    Science.gov (United States)

    Mandò, Chiara; Razini, Paola; Novielli, Chiara; Anelli, Gaia Maria; Belicchi, Marzia; Erratico, Silvia; Banfi, Stefania; Meregalli, Mirella; Tavelli, Alessandro; Baccarin, Marco; Rolfo, Alessandro; Motta, Silvia; Torrente, Yvan; Cetin, Irene

    2016-04-01

    Human placental mesenchymal stromal cells (pMSCs) have never been investigated in intrauterine growth restriction (IUGR). We characterized cells isolated from placental membranes and the basal disc of six IUGR and five physiological placentas. Cell viability and proliferation were assessed every 7 days during a 6-week culture. Expression of hematopoietic, stem, endothelial, and mesenchymal markers was evaluated by flow cytometry. We characterized the multipotency of pMSCs and the expression of genes involved in mitochondrial content and function. Cell viability was high in all samples, and proliferation rate was lower in IUGR compared with control cells. All samples presented a starting heterogeneous population, shifting during culture toward homogeneity for mesenchymal markers and occurring earlier in IUGR than in controls. In vitro multipotency of IUGR-derived pMSCs was restricted because their capacity for adipocyte differentiation was increased, whereas their ability to differentiate toward endothelial cell lineage was decreased. Mitochondrial content and function were higher in IUGR pMSCs than controls, possibly indicating a shift from anaerobic to aerobic metabolism, with the loss of the metabolic characteristics that are typical of undifferentiated multipotent cells. This study demonstrates that the loss of endothelial differentiation potential and the increase of adipogenic ability are likely to play a significant role in the vicious cycle of abnormal placental development in intrauterine growth restriction (IUGR). This is the first observation of a potential role for placental mesenchymal stromal cells in intrauterine growth restriction, thus leading to new perspectives for the treatment of IUGR. ©AlphaMed Press.

  13. Placental mesenchymal dysplasia and intrauterine fetal growth restriction with doppler velocimetry alterations - a case report

    Directory of Open Access Journals (Sweden)

    Paula Vendruscolo Tozatti

    2014-06-01

    Full Text Available Placental mesenchymal dysplasia (PMD is a rare placental abnormality. We report a case of PMD associated with intrauterine growth restriction (IUGR, which was diagnosed by an ultrasound scan during the second trimester of pregnancy. A 36-year-old primiparous woman with signs of placental chorioangioma was referred to our hospital at the 23th gestational week. An ultrasonography revealed a small-for-gestational-age fetus with a large multicystic placenta. A serial Doppler sonographic assessment of umbilical and uterine artery blood flow showed a compromised fetus. A female, small-for-gestational-age baby was delivered by c-section at 28 weeks, and PMD was histopathologically confirmed.

  14. A new familial intrauterine growth retardation syndrome the "3-M syndrome".

    Science.gov (United States)

    Spranger, J; Opitz, J M; Nourmand, A

    1976-09-01

    Two pairs of siblings are described with proportionate dwarfism due to skeletal hypoplasia of prenatal onset. The head size was normal for age and disproportionately large for height. The patients had a characteristic face different from that seen in the Silver-Russell syndrome. The family data are in accordance with autosomal recessive inheritance. In spite of some similarities, the bulk of clinical and genetic evidence suggests that the described intrauterine growth retardation syndrome is different from the Silver-Russell syndrome and presents an apparently "new" entity which has been designated 3-M syndrome.

  15. Angiogenic factors for prediction of preeclampsia and intrauterine growth restriction onset in high-risk women: AngioPred study.

    Science.gov (United States)

    Raia-Barjat, Tiphaine; Prieux, Carole; Gris, Jean-Christophe; Chapelle, Céline; Laporte, Silvy; Chauleur, Céline

    2017-09-22

    The study aimed to compare the level of two angiogenic factors, soluble fms-like tyrosine kinase-1 (sFlt1) and soluble endoglin (sEng), for the prediction of preeclampsia and intrauterine growth restriction in high-risk pregnant women. A prospective multicenter cohort study of 200 pregnant patients was conducted between June 2008 and October 2010. sFlt1 and sEng were measured by enzyme-linked immunosorbent assay. Forty-five patients developed a placenta-mediated adverse pregnancy outcome. Plasma levels of sFlt1 and sEng were higher in patients who will experience a preeclampsia at 28, 32, and 36 weeks compared with patients with no complication. The same results were observed for intrauterine growth restriction. Plasma levels of sFlt1 and sEng were not significantly different for patients with preeclampsia compare to patients with intrauterine growth restriction. Patients with early pre-eclampsia (PE) had very high rates of angiogenic factors at 20, 24, and 28 weeks. Patients with late PE and early and late intrauterine growth retardation (IUGR) had high rates at 32 and 36 weeks. In high-risk women, angiogenic factors are disturbed before the onset of preeclampsia and this is true for intrauterine growth restriction.

  16. Fractal-dimension analysis detects cerebral changes in preterm infants with and without intrauterine growth restriction.

    Science.gov (United States)

    Esteban, Francisco J; Padilla, Nelly; Sanz-Cortés, Magdalena; de Miras, Juan Ruiz; Bargalló, Núria; Villoslada, Pablo; Gratacós, Eduard

    2010-12-01

    In the search for a useful parameter to detect and quantify subtle brain abnormalities in infants with intrauterine growth restriction (IUGR), we hypothesised that the analysis of the structural complexity of grey matter (GM) and white matter (WM) using the fractal dimension (FD), a measurement of the topological complexity of an object, could be established as a useful tool for quantitative studies of infant brain morphology. We studied a sample of 18 singleton IUGR premature infants, (12.72 months corrected age (CA), range: 12 months-14 months), 15 preterm infants matched one-to-one for gestational age (GA) at delivery (12.6 months; range: 12 months-14 months), and 15 neonates born at term (12.4 months; range: 11 months-14 months). The neurodevelopmental outcome was assessed in all subjects at 18 months CA according to the Bayley Scale for Infant and Toddler Development - Third edition (BSID-III). For MRI acquisition and processing, the infants were scanned at 12 months CA, in a TIM TRIO 3T scanner, sleeping naturally. Images were pre-processed using the SPM5 toolbox, the GM and WM segmented under the VBM5 toolbox, and the box-counting method was applied for FD calculation of normal and skeletonized segmented images. The results showed a significant decrease of the FD of the brain GM and WM in the IUGR group when compared to the preterm or at-term controls. We also identified a significant linear tendency of both GM and WM FD from IUGR to preterm and term groups. Finally, multiple linear analyses between the FD of the GM or WM and the neurodevelopmental scales showed a significant regression of the language and motor scales with the FD of the GM. In conclusion, a decreased FD of the GM and WM in IUGR infants could be a sensitive indicator for the investigation of structural brain abnormalities in the IUGR population at 12 months of age, which can also be related to functional disorders. Copyright © 2010 Elsevier Inc. All rights reserved.

  17. Reactive oxygen species are involved in lipopolysaccharide-induced intrauterine growth restriction and skeletal development retardation in mice.

    Science.gov (United States)

    Xu, De-Xiang; Chen, Yuan-Hua; Zhao, Lei; Wang, Hua; Wei, Wei

    2006-12-01

    Maternal infection is a cause of adverse developmental outcomes including embryonic resorption, intrauterine fetal death, and preterm labor. Lipopolysaccharide-induced developmental toxicity at early gestational stages has been well characterized. The purpose of the present study was to investigate the effects of maternal lipopolysaccharide exposure at late gestational stages on intrauterine fetal growth and skeletal development and to assess the potential role of reactive oxygen species in lipopolysaccharide-induced intrauterine fetal growth restriction and skeletal development retardation. The timed pregnant CD-1 mice were intraperitoneally injected with lipopolysaccharide (25 to 75 microg/kg per day) on gestational day 15 to 17. To investigate the role of reactive oxygen species on lipopolysaccharide-induced intrauterine fetal growth restriction and skeletal development retardation, the pregnant mice were injected with alpha-phenyl-N-t-butylnitrone (100 mg/kg, intraperitoneally) at 30 minutes before lipopolysaccharide (75 microg/kg per day, intraperitoneally), followed by an additional dose of alpha-phenyl-N-t-butylnitrone (50 mg/kg, intraperitoneally) at 3 hours after lipopolysaccharide. The number of live fetuses, dead fetuses, and resorption sites was counted on gestational day 18. Live fetuses in each litter were weighed. Crown-rump and tail lengths were examined and skeletal development was evaluated. Maternal lipopolysaccharide exposure significantly increased fetal mortality, reduced fetal weight and crown-rump and tail lengths of live fetuses, and retarded skeletal ossification in caudal vertebrae, anterior and posterior phalanges, and supraoccipital bone in a dose-dependent manner. Alpha-phenyl-N-t-butylnitrone, a free radical spin-trapping agent, almost completely blocked lipopolysaccharide-induced fetal death (63.2% in lipopolysaccharide group versus 6.5% in alpha-phenyl-N-t-butylnitrone + lipopolysaccharide group, P intrauterine growth restriction

  18. Proteome Differences in Placenta and Endometrium between Normal and Intrauterine Growth Restricted Pig Fetuses.

    Directory of Open Access Journals (Sweden)

    Fang Chen

    Full Text Available Uteroplacental tissue plays a key role in substance exchanges between maternal and fetal circulation, and, therefore, in the growth and development of fetuses. In this study, proteomics and western blotting were applied to investigate the changes of proteome in the placenta and endometrium of normal and intrauterine growth restriction (IUGR porcine fetuses during mid to late pregnancy (D60, 90, and 110 of gestation. Our results showed that proteins participating in cell structure, energy metabolism, stress response, cell turnover, as well as transport and metabolism of nutrients were differentially expressed in placenta and endometrium between normal and IUGR fetuses. Analysis of functions of these proteins suggests reductions in ATP production and nutrients transport, increases in oxidative stress and apoptosis, and impairment of cell metabolism in IUGR fetuses. Collectively, our findings aid in understanding of the mechanisms responsible for uteroplacental dysfunction in IUGR fetus, and are expected to provide new strategies to reduce fetal growth restriction in pigs and other mammals.

  19. Ultrasound evaluation of cortical brain development in fetuses with intrauterine growth restriction.

    Science.gov (United States)

    Businelli, Caterina; de Wit, Charlotte; Visser, Gerard H A; Pistorius, Lourens R

    2014-09-10

    Abstract Objective: We evaluated the ultrasound appearance of brain volume and cortical development in fetuses with early growth restriction and placental insufficiency. Methods: We examined a cohort of 20 fetuses with severe intrauterine growth restriction (IUGR) and evidence of placental insufficiency by three-dimensional (3D) ultrasound between 24 and 34 weeks. We graded cortical development and measured the supratentorial intracranial volume. The cortical grading and volume were compared to data obtained from a reference population of 28 adequate for gestational age (AGA) fetuses. Results: Ultrasound examinations were performed in 20 fetuses with IUGR. The biometry and brain volume were significantly reduced in IUGR fetuses. There was evidence of accelerated cortical development in IUGR fetuses. Conclusion: This study confirms that the smaller brain volume in IUGR fetuses, with normal or accelerated cortical maturation as previously depicted with postnatal MRI examination, can be demonstrated by prenatal 3D ultrasound.

  20. Maternal endothelial damage as a disorder shared by early preeclampsia, late preeclampsia and intrauterine growth restriction.

    Science.gov (United States)

    Kwiatkowski, Sebastian; Dołegowska, Barbara; Kwiatkowska, Ewa; Rzepka, Rafał; Marczuk, Natalia; Loj, Beata; Torbè, Andrzej

    2017-10-26

    Preeclampsia (PE) and intrauterine growth restriction (IUGR) are separate disease entities that have frequently been reported as sharing the same pathogenesis. In both of them, angiogenesis disorders and generalized endothelial damage with an accompanying inflammation are the dominant symptoms. In this study, we attempted to prove that both these processes demonstrate the same profile in early PE, late PE and IUGR patients, while the only difference is in the degree of exacerbation of the lesions. In 167 patients divided into four groups, three of those with early PE, late PE and IUGR and one control group, fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), high sensitive c-reactive protein (hsCRP) and fibronectin were determined. The behavior of these parameters in each of the groups was studied, and correlations between them were sought for. Higher concentrations of sFlt-1, hsCRP and fibronectin and a lower concentration of PlGF were found in the study groups compared to the control group. Significant correlations were observed between the factors concerned. The higher values of disordered angiogenesis markers, endothelial damage markers and inflammatory markers both in the PE and the intrauterine growth restriction (IUGR) groups suggest the existence of shared disorders in the development of these pathologies. The correlations between disordered angiogenesis markers and endothelial damage markers argue in favor of a mutual relationship between these two processes in the development of pathologies evolving as secondary to placental ischemia. The results obtained confirm that the lesion profiles are the same in both PE and IUGR patients, which can be utilized in developing common diagnostic criteria.

  1. Verbal Short-Term Memory Span in Children: Long-Term Modality Dependent Effects of Intrauterine Growth Restriction

    Science.gov (United States)

    Geva, R.; Eshel, R.; Leitner, Y.; Fattal-Valevski, A.; Harel, S.

    2008-01-01

    Background: Recent reports showed that children born with intrauterine growth restriction (IUGR) are at greater risk of experiencing verbal short-term memory span (STM) deficits that may impede their learning capacities at school. It is still unknown whether these deficits are modality dependent. Methods: This long-term, prospective design study…

  2. Readiness and Adjustments to School for Children with Intrauterine Growth Restriction (IUGR): An Extreme Test Case Paradigm

    Science.gov (United States)

    Geva, Ronny; Yosipof, Rina; Eshel, Rina; Leitner, Yael; Valevski, Aviva Fattal; Harel, Shaul

    2009-01-01

    This long-term, prospective study evaluated repeatedly school readiness and adjustment at kindergarten and first grade of children with extreme intrauterine growth restriction (IUGR; n = 20) in relation to controls (n = 19). Methods included individual testing of cognitive competence, self-perception, motivation, loneliness and academic…

  3. Increased lipolysis but diminished gene expression of lipases in subcutaneous adipose tissue of healthy young males with intrauterine growth retardation

    DEFF Research Database (Denmark)

    Højbjerre, Lise; Alibegovic, Amra C; Sonne, Mette P

    2011-01-01

    Intrauterine growth retardation (IUGR) is associated with a central fat distribution and risk of developing type 2 diabetes in adults when exposed to a sedentary Western lifestyle. Increased lipolysis is an early defect of metabolism in IUGR subjects, but the sites and molecular mechanisms involv...

  4. Skeletal muscle protein accretion rates and hindlimb growth are reduced in late gestation intrauterine growth-restricted fetal sheep.

    Science.gov (United States)

    Rozance, Paul J; Zastoupil, Laura; Wesolowski, Stephanie R; Goldstrohm, David A; Strahan, Brittany; Cree-Green, Melanie; Sheffield-Moore, Melinda; Meschia, Giacomo; Hay, William W; Wilkening, Randall B; Brown, Laura D

    2018-01-01

    Adults who were affected by intrauterine growth restriction (IUGR) suffer from reductions in muscle mass, which may contribute to insulin resistance and the development of diabetes. We demonstrate slower hindlimb linear growth and muscle protein synthesis rates that match the reduced hindlimb blood flow and oxygen consumption rates in IUGR fetal sheep. These adaptations resulted in hindlimb blood flow rates in IUGR that were similar to control fetuses on a weight-specific basis. Net hindlimb glucose uptake and lactate output rates were similar between groups, whereas amino acid uptake was significantly lower in IUGR fetal sheep. Among all fetuses, blood O 2 saturation and plasma glucose, insulin and insulin-like growth factor-1 were positively associated and norepinephrine was negatively associated with hindlimb weight. These results further our understanding of the metabolic and hormonal adaptations to reduced oxygen and nutrient supply with placental insufficiency that develop to slow hindlimb growth and muscle protein accretion. Reduced skeletal muscle mass in the fetus with intrauterine growth restriction (IUGR) persists into adulthood and may contribute to increased metabolic disease risk. To determine how placental insufficiency with reduced oxygen and nutrient supply to the fetus affects hindlimb blood flow, substrate uptake and protein accretion rates in skeletal muscle, late gestation control (CON) (n = 8) and IUGR (n = 13) fetal sheep were catheterized with aortic and femoral catheters and a flow transducer around the external iliac artery. Muscle protein kinetic rates were measured using isotopic tracers. Hindlimb weight, linear growth rate, muscle protein accretion rate and fractional synthetic rate were lower in IUGR compared to CON (P fetal norepinephrine and reduced IGF-1 and insulin. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

  5. Placental Expression Patterns of Galectin-1, Galectin-2, Galectin-3 and Galectin-13 in Cases of Intrauterine Growth Restriction (IUGR

    Directory of Open Access Journals (Sweden)

    Stefan Hutter

    2016-04-01

    Full Text Available Galectins (gal are members of the mammalian β-galactoside-binding proteins and recognize Galβ1-4GlcNAc and Galβ1-4GalNac (Thomsen-Friedenreich antigen (TF sequences of several cell surface oligosaccharides. In this study, gal-1, -2, -3 and -13 were investigated systematically in the trophoblast and decidua compartment of intrauterine growth restriction (IUGR placentas and normal third trimester control placentas and stratified by fetal gender and gestational age. Within this study, 29 third trimester placentas after delivery were analyzed. Fetal gender was equally divided within both groups, and immunohistochemical staining was analyzed according to fetal gender and gestational age. Double immune-fluorescence with trophoblast-specific markers was used to identify galectin-expressing cells at the feto-maternal interface in the decidua. Gal-3 was significantly downregulated only in the extravillous trophoblast of IUGR placentas. In contrast, expressions of gal-2 and gal-13 were downregulated in both villous and extravillous trophoblast cells of IUGR placentas. In addition, gal-2 and gal-13 showed a highly correlated expression scheme in the placenta. There are significant gender-specific expression patterns for single prototype galectins with downregulation of gal-2 and gal-13 of male gender placentas in cases of IUGR. Gal-3 as the chimera type galectin shows only little gender-specific differences in expression, which disappear in IUGR cases.

  6. Transferrin Sialylation in Smoking and Non-Smoking Pregnant Women with Intrauterine Growth Restriction.

    Science.gov (United States)

    Wrześniak, Marta; Kepinska, Marta; Bizoń, Anna; Milnerowicz-Nabzdyk, Ewa; Milnerowicz, Halina

    2015-01-01

    Transferrin (Tf) is a glycosylated protein responsible for transporting iron. Various sialylation levels of Tf are observed during physiological and pathological processes. We studied if the changes in iron stores as well as tobacco smoke may have an impact on foetal development and in consequence lead to intrauterine growth restriction (IUGR). In the third trimester of pregnancy, lower levels of 4-sialoTf isoform and higher levels of 5-sialoTf were observed in the serum of non-smoking women with IUGR in comparison to the control group. On the day of labour, level of 2-sialoTf was significantly lower and level of 3-sialo was Tf higher in the serum of non-smoking women. Level of 4-sialo was found lower in the serum of smoking women with IUGR than in the control group. The observed changes may suggest a connection between iron stores, transport of iron to the foetus and foetal development.

  7. Differential Effects of Intrauterine Growth Restriction on the Regional Neurochemical Profile of the Developing Rat Brain.

    Science.gov (United States)

    Maliszewski-Hall, Anne M; Alexander, Michelle; Tkáč, Ivan; Öz, Gülin; Rao, Raghavendra

    2017-01-01

    Intrauterine growth restricted (IUGR) infants are at increased risk for neurodevelopmental deficits that suggest the hippocampus and cerebral cortex may be particularly vulnerable. Evaluate regional neurochemical profiles in IUGR and normally grown (NG) 7-day old rat pups using in vivo 1 H magnetic resonance (MR) spectroscopy at 9.4 T. IUGR was induced via bilateral uterine artery ligation at gestational day 19 in pregnant Sprague-Dawley dams. MR spectra were obtained from the cerebral cortex, hippocampus and striatum at P7 in IUGR (N = 12) and NG (N = 13) rats. In the cortex, IUGR resulted in lower concentrations of phosphocreatine, glutathione, taurine, total choline, total creatine (P regions. Persistent neurochemical changes may lead to cortex-based long-term neurodevelopmental deficits in human IUGR infants.

  8. Nucleated red blood cells count in pregnancies with idiopathic intra-uterine growth restriction.

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    Fatemeh Davari-Tanha

    2014-06-01

    Full Text Available Elevated nucleated red blood cell (NRBC count is introduced as a potential marker of intra-uterine growth restriction (IUGR. To investigate the probable association regardless of any known underlying disease, we aimed to study disturbances in NRBC count in infants experiencing idiopathic IUGR.Twenty three infants regarded IUGR without any known cause were chosen to be compared to 48 normal neonates. Blood samples were collected instantly after birth and the same measurements were done in both groups.NRBC count/100 white blood cells was significantly higher in the IUGR group (P value < 0.001. pH measurements did not reveal any significant difference.Increased NRBC count in cases of idiopathic IUGR in absence of chronic hypoxia could strengthen its predictive value suggested in previous studies. It could help early IUGR detection and beneficial intervention.

  9. Maternal uterine artery VEGF gene therapy for treatment of intrauterine growth restriction.

    Science.gov (United States)

    David, Anna L

    2017-11-01

    Intrauterine growth restriction (IUGR) is a serious pregnancy complication affecting approximately 8% of all pregnancies. The aetiology is believed to be insufficient maternal uteroplacental perfusion which prevents adequate nutrient and oxygen availability for the fetus. There is no treatment that can improve uteroplacental perfusion and thereby increase fetal growth in the uterus. Maternal uterine artery gene therapy presents a promising treatment strategy for IUGR, with the use of adenoviral vectors encoding for proteins such as Vascular Endothelial Growth Factor (VEGF) demonstrating improvements in fetal growth and neonatal outcome in preclinical studies. Mechanistically, maternal VEGF gene therapy delivered to the uterine arteries increases uterine blood flow and enhances vascular relaxation short term, while reducing vascular contractility long term. It also leads to vascular remodeling with increased endothelial cell proliferation in the perivascular adventitia of uterine arteries. Safety assessments suggest no vector spread to the fetus and no adverse risk to the mother or fetus; a clinical trial is in development. This article assesses research into VEGF maternal uterine artery directed gene therapy for IUGR, investigating the use of transgenes and vectors, their route of administration in obstetrics, and the steps that will be needed to take this treatment modality into the clinic. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Early Onset Intrauterine Growth Restriction in a Mouse Model of Gestational Hypercholesterolemia and Atherosclerosis

    Science.gov (United States)

    Busso, Dolores; Mascareño, Lilian; Salas, Francisca; Berkowitz, Loni; Santander, Nicolás; Quiroz, Alonso; Amigo, Ludwig; Valdés, Gloria; Rigotti, Attilio

    2014-01-01

    The susceptibility to develop atherosclerosis is increased by intrauterine growth restriction and prenatal exposure to maternal hypercholesterolemia. Here, we studied whether mouse gestational hypercholesterolemia and atherosclerosis affected fetal development and growth at different stages of gestation. Female LDLR KO mice fed a proatherogenic, high cholesterol (HC) diet for 3 weeks before conception and during pregnancy exhibited a significant increase in non-HDL cholesterol and developed atherosclerosis. At embryonic days 12.5 (E12.5), E15.5, and E18.5, maternal gestational hypercholesterolemia and atherosclerosis were associated to a 22–24% reduction in male and female fetal weight without alterations in fetal number/litter or morphology nor placental weight or structure. Feeding the HC diet exclusively at the periconceptional period did not alter fetal growth, suggesting that maternal hypercholesterolemia affected fetal weight only after implantation. Vitamin E supplementation (1,000 UI of α-tocopherol/kg) of HC-fed females did not change the mean weight of E18.5 fetuses but reduced the percentage of fetuses exhibiting body weights below the 10th percentile of weight (HC: 90% vs. HC/VitE: 68%). In conclusion, our results showed that maternal gestational hypercholesterolemia and atherosclerosis in mice were associated to early onset fetal growth restriction and that dietary vitamin E supplementation had a beneficial impact on this condition. PMID:25295255

  11. Early metabolic defects in dexamethasone-exposed and undernourished intrauterine growth restricted rats.

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    Emmanuel Somm

    Full Text Available Poor fetal growth, also known as intrauterine growth restriction (IUGR, is a worldwide health concern. IUGR is commonly associated with both an increased risk in perinatal mortality and a higher prevalence of developing chronic metabolic diseases later in life. Obesity, type 2 diabetes or metabolic syndrome could result from noxious "metabolic programming." In order to better understand early alterations involved in metabolic programming, we modeled IUGR rat pups through either prenatal exposure to synthetic glucocorticoid (dams infused with dexamethasone 100 µg/kg/day, DEX or prenatal undernutrition (dams feeding restricted to 30% of ad libitum intake, UN. Physiological (glucose and insulin tolerance, morphometric (automated tissue image analysis and transcriptomic (quantitative PCR approaches were combined during early life of these IUGR pups with a special focus on their endocrine pancreas and adipose tissue development. In the absence of catch-up growth before weaning, DEX and UN IUGR pups both presented basal hyperglycaemia, decreased glucose tolerance, and pancreatic islet atrophy. Other early metabolic defects were model-specific: DEX pups presented decreased insulin sensitivity whereas UN pups exhibited lowered glucose-induced insulin secretion and more marked alterations in gene expression of pancreatic islet and adipose tissue development regulators. In conclusion, these results show that before any catch-up growth, IUGR rats present early physiologic, morphologic and transcriptomic defects, which can be considered as initial mechanistic basis of metabolic programming.

  12. Intraplacental gene therapy with Ad-IGF-1 corrects naturally occurring rabbit model of intrauterine growth restriction.

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    Keswani, Sundeep G; Balaji, Swathi; Katz, Anna B; King, Alice; Omar, Khaled; Habli, Mounira; Klanke, Charles; Crombleholme, Timothy M

    2015-03-01

    Intrauterine growth restriction (IUGR) due to placental insufficiency is a leading cause of perinatal complications for which there is no effective prenatal therapy. We have previously demonstrated that intraplacental injection of adenovirus-mediated insulin-like growth factor-1 (Ad-IGF-1) corrects fetal weight in a murine IUGR model induced by mesenteric uterine artery branch ligation. This study investigated the effect of intraplacental Ad-IGF-1 gene therapy in a rabbit model of naturally occurring IUGR (runt) due to placental insufficiency, which is similar to the human IUGR condition with onset in the early third trimester, brain sparing, and a reduction in liver weight. Laparotomy was performed on New Zealand White rabbits on day 21 of 30 days of gestation and litters were divided into five groups: Control (first position)+phosphate-buffered saline (PBS), control+Ad-IGF-1, runt (third position)+PBS, runt+Ad-IGF-1, and runt+Ad-LacZ. The effect of IGF-1 gene therapy on fetal, placental, liver, heart, lung, and musculoskeletal weights of the growth-restricted pups was examined. Protein expression after gene transfer was seen along the maternal-fetal placenta interface (n=12) 48 hr after gene therapy. There was minimal gene transfer detected in the pups or maternal organs. At term, compared with the normally grown first-position control, the runted third-position pups demonstrated significantly lower fetal, placental, liver, lung, and musculoskeletal weights. The fetal, liver, and musculoskeletal weights were restored to normal by intraplacental Ad-IGF-1 gene therapy (p<0.01), with no change in the placental weight. Intraplacental gene therapy is a novel strategy for the treatment of IUGR caused by placental insufficiency that takes advantage of an organ that will be discarded at birth. Development of nonviral IGF-1 gene delivery using placenta-specific promoters can potentially minimize toxicity to the mother and fetus and facilitate clinical translation of

  13. Maternal health-related quality of life after induction of labor or expectant monitoring in pregnancy complicated by intrauterine growth retardation beyond 36 weeks

    NARCIS (Netherlands)

    D. Bijlenga (Denise); K.E. Boers (Kim); E. Birnie (Erwin); B.W.J. Mol (Ben); S.C.M. Vijgen (Sylvia); J.A.M. van der Post (Joris); C.J.M. de Groot (Christianne); R.J.P. Rijnders (Robbert); P.J. Pernet (Paula); F.J.M.E. Roumen (Frans); R.H. Stigter (Rob); F.M.C. Delemarre (Friso); H.A. Bremer (Henk); M. Porath (Martina); S.A. Scherjon (Sico); G.J. Bonsel (Gouke)

    2011-01-01

    textabstractObjective: Pregnancies complicated by intrauterine growth retardation (IUGR) beyond 36 weeks of gestation are at increased risk of neonatal morbidity and mortality. Optimal treatment in IUGR at term is highly debated. Results from the multicenter DIGITAT (Disproportionate Intrauterine

  14. Reduced angiogenic factor expression in intrauterine fetal growth restriction using semiquantitative immunohistochemistry and digital image analysis.

    Science.gov (United States)

    Alahakoon, Thushari I; Zhang, Weiyi; Arbuckle, Susan; Zhang, Kewei; Lee, Vincent

    2018-05-01

    To localize, quantify and compare angiogenic factors, vascular endothelial growth factor (VEGF), placental growth factor (PlGF), as well as their receptors fms-like tyrosine kinase receptor (Flt-1) and kinase insert domain receptor (KDR) in the placentas of normal pregnancy and complications of preeclampsia (PE), intrauterine fetal growth restriction (IUGR) and PE + IUGR. In a prospective cross-sectional case-control study, 30 pregnant women between 24-40 weeks of gestation, were recruited into four clinical groups. Representative placental samples were stained for VEGF, PlGF, Flt-1 and KDR. Analysis was performed using semiquantitative methods and digital image analysis. The overall VEGF and Flt-1 were strongly expressed and did not show any conclusive difference in the expression between study groups. PlGF and KDR were significantly reduced in expression in the placentas from pregnancies complicated by IUGR compared with normal and preeclamptic pregnancies. The lack of PlGF and KDR may be a cause for the development of IUGR and may explain the loss of vasculature and villous architecture in IUGR. Automated digital image analysis software is a viable alternative method to the manual reading of placental immunohistochemical staining. © 2018 Japan Society of Obstetrics and Gynecology.

  15. Physiological alterations associated with intrauterine growth restriction in fetal pigs: Causes and insights for nutritional optimization.

    Science.gov (United States)

    Wang, Junjun; Feng, Cuiping; Liu, Ting; Shi, Meng; Wu, Guoyao; Bazer, Fuller W

    2017-09-01

    Intrauterine growth restriction (IUGR) remains a major problem in swine production since the associated low birth weight leads to high rates of pre-weaning morbidity and mortality plus permanent retardation of growth and development. Complex biological events-including genetics, epigenetics, maternal maturity, maternal nutrition, placenta efficiency, uterine capacity, and other environmental factors-can affect fetal growth and development during late gestation, as well as maturity of oocytes, duration of estrus, and both implantation and placentation of conceptuses in uteri of sows. Understanding the physiological changes related to initiation and progress of IUGR are, therefore, of great importance to formulate nutritional strategies that can mitigate IUGR in gilts and sows. Altering the nutritional status of sows prior to mating and during early-, mid-, and late-gestation may be effective at increasing the uniformity of oocytes and conceptuses, decreasing variation among conceptuses during elongation and implantation, and preventing increases in within-litter variation in fetal weights during late gestation. This review summarizes current progress on physiological alterations responsible for IUGR fetuses, as well as possible nutritional interventions to prevent the initiation and continuation of IUGR in gilts and sows. © 2017 Wiley Periodicals, Inc.

  16. Relationship between cord blood IGF-I, IGFBP-3 levels and intrauterine growth retardation (IUGR)

    International Nuclear Information System (INIS)

    Yu Suqing; Chu Kaiqiu; Chen Shengjie

    2008-01-01

    Objective: To study the cord blood insulin-like growth factor-I (IGF-I) and its binding protein-3 (IGFBP-3) levels in neonates with intrauterine growth retardation (IUGR). Methods: Cord serum IGF-I (with RIA) and IGFBP-3 (with IRMA) levels were measured in 22 neonates with IUGR and 64 neonates with appropriate gestational age (AGA). Results: Cord blood IGF-I and IGFBP-3 levels in IUGR neonates were significantly lower than those in AGA neonates (P<0.001). Among the 86 neonates studied in this article, 44 were born pre-term and 42 were born full term. From the data, we could see that the cord blood IGF-I and IGFBP-3 levels in pre-term neonates were significantly lower than those in full-term neonates (P also <0.001). IGF-I and IGFBP-3 levels were mutually positively correlated (P<0.01). Conclusion: Cord blood IGF-I and IGFBP-3 levels were useful indicator of neonates growth. (authors)

  17. Genome-wide placental DNA methylation analysis of severely growth-discordant monochorionic twins reveals novel epigenetic targets for intrauterine growth restriction.

    Science.gov (United States)

    Roifman, Maian; Choufani, Sanaa; Turinsky, Andrei L; Drewlo, Sascha; Keating, Sarah; Brudno, Michael; Kingdom, John; Weksberg, Rosanna

    2016-01-01

    Intrauterine growth restriction (IUGR), which refers to reduced fetal growth in the context of placental insufficiency, is etiologically heterogeneous. IUGR is associated not only with perinatal morbidity and mortality but also with adult-onset disorders, such as cardiovascular disease and diabetes, posing a major health burden. Placental epigenetic dysregulation has been proposed as one mechanism that causes IUGR; however, the spectrum of epigenetic pathophysiological mechanisms leading to IUGR remains to be elucidated. Monozygotic monochorionic twins are particularly affected by IUGR, in the setting of severe discordant growth. Because monozygotic twins have the same genotype at conception and a shared maternal environment, they provide an ideal model system for studying epigenetic dysregulation of the placenta. We compared genome-wide placental DNA methylation patterns of severely growth-discordant twins to identify novel candidate genes for IUGR. Snap-frozen placental samples for eight severely growth-discordant monozygotic monochorionic twin pairs were obtained at delivery from each twin. A high-resolution DNA methylation array platform was used to identify methylation differences between IUGR and normal twins. Our analysis revealed differentially methylated regions in the promoters of eight genes: DECR1, ZNF300, DNAJA4, CCL28, LEPR, HSPA1A/L, GSTO1, and GNE. The largest methylation differences between the two groups were in the promoters of DECR1 and ZNF300. The significance of these group differences was independently validated by bisulfite pyrosequencing, implicating aberrations in fatty acid beta oxidation and transcriptional regulation, respectively. Further analysis of the array data identified methylation changes most prominently affecting the Wnt and cadherin pathways in the IUGR cohort. Our results suggest that IUGR in monozygotic twins is associated with impairments in lipid metabolism and transcriptional regulation as well as cadherin and Wnt

  18. Influence of catch up growth on spatial learning and memory in a mouse model of intrauterine growth restriction.

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    Cristina Duran Fernandez-Feijoo

    Full Text Available Intrauterine growth restriction (IUGR and rapid postnatal weight gain or catch up growth (CUG increase the susceptibility to metabolic syndrome during adult life. Longitudinal studies have also revealed a high incidence of learning difficulties in children with IUGR. The aim of the present study was to investigate the effect of nutrition and CUG on learning memory in an IUGR animal model. We hypothesized that synaptic protein expression and transcription, an essential mechanism for memory consolidation, might be affected by intrauterine undernutrition.IUGR was induced by 50% maternal caloric undernutrition throughout late gestation. During the suckling period, dams were either fed ad libitum or food restricted. The pups were divided into: Normal prenatal diet-Normal postnatal diet (NN, Restricted prenatal diet- Normal postnatal diet + catch up growth (RN+, Normal prenatal diet-Restricted postnatal diet (NR and Restricted prenatal diet-Restricted postnatal diet (RR. At 4 weeks of age, memory was assessed via a water maze test. To evaluate synaptic function, 2 specific synaptic proteins (postsynaptic density-95 [PSD95], synaptophysin as well as insulin receptors (IR were tested by Western Blot and quantitative polymerase chain reaction (qPCR. Brain-derived neurotrophic factor and serum insulin levels were also studied.The RN+ group presented a learning curve similar to the NN animals. The RR animals without CUG showed learning disabilities. PSD95 was lower in the RR group than in the NN and RN+ mice. In contrast, synaptophysin was similar in all groups. IR showed an inverse expression pattern to that of the PSD95. In conclusion, perinatal nutrition plays an important role in learning. CUG after a period of prenatal malnutrition seems to improve learning skills. The functional alterations observed might be related to lower PSD95 activity and a possible dysfunction in the hormone regulation of synaptic plasticity.

  19. Maternal protein restriction induces alterations in insulin signaling and ATP sensitive potassium channel protein in hypothalami of intrauterine growth restriction fetal rats.

    Science.gov (United States)

    Liu, Xiaomei; Qi, Ying; Gao, Hong; Jiao, Yisheng; Gu, Hui; Miao, Jianing; Yuan, Zhengwei

    2013-01-01

    It is well recognized that intrauterine growth restriction leads to the development of insulin resistance and type 2 diabetes mellitus in adulthood. To investigate the mechanisms behind this "metabolic imprinting" phenomenon, we examined the impact of maternal undernutrition on insulin signaling pathway and the ATP sensitive potassium channel expression in the hypothalamus of intrauterine growth restriction fetus. Intrauterine growth restriction rat model was developed through maternal low protein diet. The expression and activated levels of insulin signaling molecules and K(ATP) protein in the hypothalami which were dissected at 20 days of gestation, were analyzed by western blot and real time PCR. The tyrosine phosphorylation levels of the insulin receptor substrate 2 and phosphatidylinositol 3'-kinase p85α in the hypothalami of intrauterine growth restriction fetus were markedly reduced. There was also a downregulation of the hypothalamic ATP sensitive potassium channel subunit, sulfonylurea receptor 1, which conveys the insulin signaling. Moreover, the abundances of gluconeogenesis enzymes were increased in the intrauterine growth restriction livers, though no correlation was observed between sulfonylurea receptor 1 and gluconeogenesis enzymes. Our data suggested that aberrant intrauterine milieu impaired insulin signaling in the hypothalamus, and these alterations early in life might contribute to the predisposition of the intrauterine growth restriction fetus toward the adult metabolic disorders.

  20. Cardiac remodelling in a baboon model of intrauterine growth restriction mimics accelerated ageing.

    Science.gov (United States)

    Kuo, Anderson H; Li, Cun; Li, Jinqi; Huber, Hillary F; Nathanielsz, Peter W; Clarke, Geoffrey D

    2017-02-15

    Rodent models of intrauterine growth restriction (IUGR) successfully identify mechanisms that can lead to short-term and long-term detrimental cardiomyopathies but differences between rodent and human cardiac physiology and placental-fetal development indicate a need for models in precocial species for translation to human development. We developed a baboon model for IUGR studies using a moderate 30% global calorie restriction of pregnant mothers and used cardiac magnetic resonance imaging to evaluate offspring heart function in early adulthood. Impaired diastolic and systolic cardiac function was observed in IUGR offspring with differences between male and female subjects, compared to their respective controls. Aspects of cardiac impairment found in the IUGR offspring were similar to those found in normal controls in a geriatric cohort. Understanding early cardiac biomarkers of IUGR using non-invasive imaging in this susceptible population, especially taking into account sexual dimorphisms, will aid recognition of the clinical presentation, development of biomarkers suitable for use in humans and management of treatment strategies. Extensive rodent studies have shown that reduced perinatal nutrition programmes chronic cardiovascular disease. To enable translation to humans, we developed baboon offspring cohorts from mothers fed ad libitum (control) or 70% of the control ad libitum diet in pregnancy and lactation, which were growth restricted at birth. We hypothesized that intrauterine growth restriction (IUGR) offspring hearts would show impaired function and a premature ageing phenotype. We studied IUGR baboons (8 male, 8 female, 5.7 years), control offspring (8 male, 8 female, 5.6 years - human equivalent approximately 25 years), and normal elderly (OLD) baboons (6 male, 6 female, mean 15.9 years). Left ventricular (LV) morphology and systolic and diastolic function were evaluated with cardiac MRI and normalized to body surface area. Two-way ANOVA by group

  1. Vascular dysfunction in women with a history of preeclampsia and intrauterine growth restriction: insights into future vascular risk.

    Science.gov (United States)

    Yinon, Yoav; Kingdom, John C P; Odutayo, Ayodele; Moineddin, Rahim; Drewlo, Sascha; Lai, Vesta; Cherney, David Z I; Hladunewich, Michelle A

    2010-11-02

    Women with a history of placental disease are at increased risk for the future development of vascular disease. It is unknown whether preexisting endothelial dysfunction underlies both the predisposition to placental disease and the later development of vascular disease. The aim of this study was to assess vascular function in postpartum women and to determine whether differences emerged depending on the presentation of placental disease. Women with a history of early-onset preeclampsia (n=15), late-onset preeclampsia (n=9), intrauterine growth restriction without preeclampsia (n=9), and prior normal pregnancy (n=16) were studied 6 to 24 months postpartum. Flow-mediated vasodilatation and flow-independent (glyceryl trinitrate-induced) vasodilatation were studied through the use of high-resolution vascular ultrasound examination of the brachial artery. Arterial stiffness was assessed by pulse-wave analysis (augmentation index). Laboratory assessment included circulating angiogenic factors (vascular endothelial growth factor, soluble fms-like tyrosine kinase 1, placental growth factor, and soluble endoglin). Flow-mediated vasodilatation was significantly reduced in women with previous early-onset preeclampsia and intrauterine growth restriction compared with women with previous late-onset preeclampsia and control subjects (3.2±2.7% and 2.1±1.2% versus 7.9±3.8% and 9.1±3.5%, respectively; Pwomen with previous early-onset preeclampsia and intrauterine growth restriction, but not among late preeclamptic women and control subjects (P=0.0105). Circulating angiogenic factors were similar in all groups. Only women with a history of early-onset preeclampsia or intrauterine growth restriction without preeclampsia exhibit impaired vascular function, which might explain their predisposition to placental disease and their higher risk of future vascular disease.

  2. Genome-wide DNA methylation analysis in jejunum of Sus scrofa with intrauterine growth restriction.

    Science.gov (United States)

    Hu, Yue; Hu, Liang; Gong, Desheng; Lu, Hanlin; Xuan, Yue; Wang, Ru; Wu, De; Chen, Daiwen; Zhang, Keying; Gao, Fei; Che, Lianqiang

    2018-02-01

    Intrauterine growth restriction (IUGR) may elicit a series of postnatal body developmental and metabolic diseases due to their impaired growth and development in the mammalian embryo/fetus during pregnancy. In the present study, we hypothesized that IUGR may lead to abnormally regulated DNA methylation in the intestine, causing intestinal dysfunctions. We applied reduced representation bisulfite sequencing (RRBS) technology to study the jejunum tissues from four newborn IUGR piglets and their normal body weight (NBW) littermates. The results revealed extensively regional DNA methylation changes between IUGR/NBW pairs from different gilts, affecting dozens of genes. Hiseq-based bisulfite sequencing PCR (Hiseq-BSP) was used for validations of 19 genes with epigenetic abnormality, confirming three genes (AIFM1, MTMR1, and TWIST2) in extra samples. Furthermore, integrated analysis of these 19 genes with proteome data indicated that there were three main genes (BCAP31, IRAK1, and AIFM1) interacting with important immunity- or metabolism-related proteins, which could explain the potential intestinal dysfunctions of IUGR piglets. We conclude that IUGR can lead to disparate DNA methylation in the intestine and these changes may affect several important biological processes such as cell apoptosis, cell differentiation, and immunity, which provides more clues linking IUGR and its long-term complications.

  3. Developmental Programming in Response to Intrauterine Growth Restriction Impairs Myoblast Function and Skeletal Muscle Metabolism

    Science.gov (United States)

    Yates, D. T.; Macko, A. R.; Nearing, M.; Chen, X.; Rhoads, R. P.; Limesand, S. W.

    2012-01-01

    Fetal adaptations to placental insufficiency alter postnatal metabolic homeostasis in skeletal muscle by reducing glucose oxidation rates, impairing insulin action, and lowering the proportion of oxidative fibers. In animal models of intrauterine growth restriction (IUGR), skeletal muscle fibers have less myonuclei at birth. This means that myoblasts, the sole source for myonuclei accumulation in fibers, are compromised. Fetal hypoglycemia and hypoxemia are complications that result from placental insufficiency. Hypoxemia elevates circulating catecholamines, and chronic hypercatecholaminemia has been shown to reduce fetal muscle development and growth. We have found evidence for adaptations in adrenergic receptor expression profiles in myoblasts and skeletal muscle of IUGR sheep fetuses with placental insufficiency. The relationship of β-adrenergic receptors shifts in IUGR fetuses because Adrβ2 expression levels decline and Adrβ1 expression levels are unaffected in myofibers and increased in myoblasts. This adaptive response would suppress insulin signaling, myoblast incorporation, fiber hypertrophy, and glucose oxidation. Furthermore, this β-adrenergic receptor expression profile persists for at least the first month in IUGR lambs and lowers their fatty acid mobilization. Developmental programming of skeletal muscle adrenergic receptors partially explains metabolic and endocrine differences in IUGR offspring, and the impact on metabolism may result in differential nutrient utilization. PMID:22900186

  4. Developmental Programming in Response to Intrauterine Growth Restriction Impairs Myoblast Function and Skeletal Muscle Metabolism

    Directory of Open Access Journals (Sweden)

    D. T. Yates

    2012-01-01

    Full Text Available Fetal adaptations to placental insufficiency alter postnatal metabolic homeostasis in skeletal muscle by reducing glucose oxidation rates, impairing insulin action, and lowering the proportion of oxidative fibers. In animal models of intrauterine growth restriction (IUGR, skeletal muscle fibers have less myonuclei at birth. This means that myoblasts, the sole source for myonuclei accumulation in fibers, are compromised. Fetal hypoglycemia and hypoxemia are complications that result from placental insufficiency. Hypoxemia elevates circulating catecholamines, and chronic hypercatecholaminemia has been shown to reduce fetal muscle development and growth. We have found evidence for adaptations in adrenergic receptor expression profiles in myoblasts and skeletal muscle of IUGR sheep fetuses with placental insufficiency. The relationship of β-adrenergic receptors shifts in IUGR fetuses because Adrβ2 expression levels decline and Adrβ1 expression levels are unaffected in myofibers and increased in myoblasts. This adaptive response would suppress insulin signaling, myoblast incorporation, fiber hypertrophy, and glucose oxidation. Furthermore, this β-adrenergic receptor expression profile persists for at least the first month in IUGR lambs and lowers their fatty acid mobilization. Developmental programming of skeletal muscle adrenergic receptors partially explains metabolic and endocrine differences in IUGR offspring, and the impact on metabolism may result in differential nutrient utilization.

  5. Intra-uterine Growth Restriction Downregulates the Hepatic Toll Like Receptor-4 Expression and Function

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    Ozlem Equils

    2005-01-01

    Full Text Available Maternal starvation is a significant cause of intrauterine growth restriction (IUGR in the world and increases the risk of infection in the neonate. We examined the effect of maternal starvation on Toll like receptor (TLR4 expression in hepatic, splenic and intestinal tissues obtained from the adult IUGR offspring of prenatal calorie restricted rats. The hepatic TLR4 protein concentration was undetectable in the IUGR rats that had restricted milk intake during the suckling period (SM/SP; n = 4, p < 0.05 as compared to the normal growth controls (CM/CP; n=4, and access to ad lib milk intake during the sucking period partially corrected the hepatic TLR4 expression (SM/CP; n = 4. IUGR had no effect on the splenic (n = 4 or intestinal (n = 4 TLR4 mRNA levels. In the liver, IUGR led to a 20% increase in baseline tumor necrosis factor (TNF-α mRNA expression ( p < 0.03 and a 70% increase in interleukin-1β (IL-1β mRNA expression ( p < 0.008 as compared to the control rats (CM/CP; n = 7. LPS-induced hepatic TNF-α release was significantly higher in SM/SP as compared to CM/CP. We propose that IUGR dysregulates TLR4 expression and function in the offspring, which may help explain the increased risk of Gram-negative sepsis and inflammatory diseases in this population.

  6. Thoracic and abdominal aortas stiffen through unique extracellular matrix changes in intrauterine growth restricted fetal sheep.

    Science.gov (United States)

    Dodson, R Blair; Rozance, Paul J; Petrash, Carson C; Hunter, Kendall S; Ferguson, Virginia L

    2014-02-01

    Intrauterine growth restriction (IUGR) is a fetal complication of pregnancy epidemiologically linked to cardiovascular disease in the newborn later in life. However, the mechanism is poorly understood with very little research on the vascular structure and function during development in healthy and IUGR neonates. Previously, we found vascular remodeling and increased stiffness in the carotid and umbilical arteries, but here we examine the remodeling and biomechanics in the larger vessels more proximal to the heart. To study this question, thoracic and abdominal aortas were collected from a sheep model of placental insufficiency IUGR (PI-IUGR) due to exposure to elevated ambient temperatures. Aortas from control (n = 12) and PI-IUGR fetuses (n = 10) were analyzed for functional biomechanics and structural remodeling. PI-IUGR aortas had a significant increase in stiffness (P fetal vascular remodeling in PI-IUGR may set the stage for possible altered growth and development and help to explain the pathophysiology of adult cardiovascular disease in previously IUGR individuals.

  7. Endoplasmic reticulum stress disrupts placental morphogenesis: implications for human intrauterine growth restriction.

    Science.gov (United States)

    Yung, Hong Wa; Hemberger, Myriam; Watson, Erica D; Senner, Claire E; Jones, Carolyn P; Kaufman, Randal J; Charnock-Jones, D Stephen; Burton, Graham J

    2012-12-01

    We recently reported the first evidence of placental endoplasmic reticulum (ER) stress in the pathophysiology of human intrauterine growth restriction. Here, we used a mouse model to investigate potential underlying mechanisms. Eif2s1(tm1RjK) mice, in which Ser51 of eukaryotic initiation factor 2 subunit alpha (eIF2α) is mutated, display a 30% increase in basal translation. In Eif2s1(tm1RjK) placentas, we observed increased ER stress and anomalous accumulation of glycoproteins in the endocrine junctional zone (Jz), but not in the labyrinthine zone where physiological exchange occurs. Placental and fetal weights were reduced by 15% (97 mg to 82 mg, p growth factor for placental development; indeed, activity in the Pdk1-Akt-mTOR pathways was decreased in Eif2s1(tm1RjK) placentas, indicating loss of Igf2 signalling. Furthermore, we observed premature differentiation of trophoblast progenitors at E9.5 in mutant placentas, consistent with the in vitro results and with the disproportionate development of the labyrinth and Jz seen in placentas at E18.5. Similar disproportion has been reported in the Igf2-null mouse. These results demonstrate that ER stress adversely affects placental development, and that modulation of post-translational processing, and hence bioactivity, of secreted growth factors contributes to this effect. Placental dysmorphogenesis potentially affects fetal growth through reduced exchange capacity. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  8. Impact of intrauterine growth retardation and body proportionality on fetal and neonatal outcome.

    Science.gov (United States)

    Kramer, M S; Olivier, M; McLean, F H; Willis, D M; Usher, R H

    1990-11-01

    Previous prognostic studies of infants with intrauterine growth retardation (IUGR) have not adequately considered the heterogeneity of IUGR in terms of cause, severity, and body proportionality and have been prone to misclassification of IUGR because of errors in estimation of gestational age. Based on a cohort of 8719 infants with early-ultrasound-validated gestational ages and indexes of body proportionality standardized for birth weight, the consequences of severity and cause-specific IUGR and proportionality for fetal and neonatal morbidity and mortality were assessed. With progressive severity of IUGR, there were significant (all P less than .001) linear trends for increasing risks of stillbirth, fetal distress (abnormal electronic fetal heart tracings)O during parturition, neonatal hypoglycemia (minimum plasma glucose less than 40 mg/dL), hypocalcemia (minimum Ca less than 7 mg/dL), polycythemia (maximum capillary hemoglobin greater than or equal to 21 g/dL), severe depression at birth (manual ventilation greater than 3 minutes), 1-minute and 5-minute Apgar scores less than or equal to 6, 1-minute Apgar score less than or equal to 3, and in-hospital death. These trends persisted for the more common outcomes even after restriction to term (37 to 42 weeks) births. There was no convincing evidence that outcome among infants with a given degree of growth retardation varied as a function of cause of that growth retardation. Among infants with IUGR, increased length-for-weight had significant crude associations with hypoglycemia and polycythemia, but these associations disappeared after adjustment for severity of growth retardation and gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Inflammatory Markers in the Second Trimester Prior to Clinical Onset of Preeclampsia, Intrauterine Growth Restriction, and Spontaneous Preterm Birth

    DEFF Research Database (Denmark)

    Haedersdal, Sofie; Salvig, Jannie Dalby; Aabye, Martine

    2013-01-01

    Low-grade inflammation has been associated with pregnancy complications including preeclampsia (PE), intrauterine growth restriction (IUGR), and spontaneous preterm birth (SPB). In an unmatched, nested case-control study, we assessed the possible predictive association of maternal C-reactive prot......Low-grade inflammation has been associated with pregnancy complications including preeclampsia (PE), intrauterine growth restriction (IUGR), and spontaneous preterm birth (SPB). In an unmatched, nested case-control study, we assessed the possible predictive association of maternal C...... to normotensive healthy pregnant controls (n = 127). We found no statistically significant difference in CRP, IP-10, or suPAR in second trimester plasma samples from pregnant women with later PE, IUGR, and SPB when compared to normotensive healthy controls. Second trimester plasma samples of CRP, IP-10, and su...

  10. INTRAUTERINE GROWTH RETARDATION AND ITS IMPACT ON CHILDREN'S HEALTH IN LATER LIFE. THE POSSIBILITY OF NUTRITIONAL SUPPORT

    Directory of Open Access Journals (Sweden)

    T. V. Belousova

    2015-01-01

    Full Text Available The sources of development, homeostasis and metabolism habits, long-term effects on the health of infants delivered with intrauterine growth retardation are considered. Principals and aspects of nutrition choice for these particular infants as well as some controversial aspects on this topic are discussed. Research data represents nutrition of newborns and up to 3 months infants, including those with the IGR and moderate postnatal inanition, fed with goat milk based formula, containing pre- and probiotics. 

  11. Transplacental Nutrient Transport Mechanisms of Intrauterine Growth Restriction in Rodent Models and Humans

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    Elke Winterhager

    2017-11-01

    Full Text Available Although the causes of intrauterine growth restriction (IUGR have been intensively investigated, important information is still lacking about the role of the placenta as a link from adverse maternal environment to adverse pregnancy outcomes of IUGR and preterm birth. IUGR is associated with an increased risk of cardiovascular, metabolic, and neurological diseases later in life. Determination of the most important pathways that regulate transplacental transport systems is necessary for identifying marker genes as diagnostic tools and for developing drugs that target the molecular pathways. Besides oxygen, the main nutrients required for appropriate fetal development and growth are glucose, amino acids, and fatty acids. Dysfunction in transplacental transport is caused by impairments in both placental morphology and blood flow, as well as by factors such as alterations in the expression of insulin-like growth factors and changes in the mTOR signaling pathway leading to a change in nutrient transport. Animal models are important tools for systematically studying such complex events. Debate centers on whether the rodent placenta is an appropriate tool for investigating the alterations in the human placenta that result in IUGR. This review provides an overview of the alterations in expression and activity of nutrient transporters and alterations in signaling associated with IUGR and compares these findings in rodents and humans. In general, the data obtained by studies of the various types of rodent and human nutrient transporters are similar. However, direct comparison is complicated by the fact that the results of such studies are controversial even within the same species, making the interpretation of the results challenging. This difficulty could be due to the absence of guidelines of the experimental design and, especially in humans, the use of trophoblast cell culture studies instead of clinical trials. Nonetheless, developing new therapy

  12. Transplacental Nutrient Transport Mechanisms of Intrauterine Growth Restriction in Rodent Models and Humans.

    Science.gov (United States)

    Winterhager, Elke; Gellhaus, Alexandra

    2017-01-01

    Although the causes of intrauterine growth restriction (IUGR) have been intensively investigated, important information is still lacking about the role of the placenta as a link from adverse maternal environment to adverse pregnancy outcomes of IUGR and preterm birth. IUGR is associated with an increased risk of cardiovascular, metabolic, and neurological diseases later in life. Determination of the most important pathways that regulate transplacental transport systems is necessary for identifying marker genes as diagnostic tools and for developing drugs that target the molecular pathways. Besides oxygen, the main nutrients required for appropriate fetal development and growth are glucose, amino acids, and fatty acids. Dysfunction in transplacental transport is caused by impairments in both placental morphology and blood flow, as well as by factors such as alterations in the expression of insulin-like growth factors and changes in the mTOR signaling pathway leading to a change in nutrient transport. Animal models are important tools for systematically studying such complex events. Debate centers on whether the rodent placenta is an appropriate tool for investigating the alterations in the human placenta that result in IUGR. This review provides an overview of the alterations in expression and activity of nutrient transporters and alterations in signaling associated with IUGR and compares these findings in rodents and humans. In general, the data obtained by studies of the various types of rodent and human nutrient transporters are similar. However, direct comparison is complicated by the fact that the results of such studies are controversial even within the same species, making the interpretation of the results challenging. This difficulty could be due to the absence of guidelines of the experimental design and, especially in humans, the use of trophoblast cell culture studies instead of clinical trials. Nonetheless, developing new therapy concepts for IUGR will

  13. Global health indicators and maternal health futures: The case of Intrauterine Growth Restriction.

    Science.gov (United States)

    Erikson, Susan L

    2015-01-01

    Public health indicators generally operate in the world as credible, apolitical and authoritative. But indicators are less stable than they appear. Clinical critiques of Intrauterine Growth Restriction (IUGR) criteria have been forthcoming for decades. This article, though, takes up the measuring and calculation gradients of IUGR in the ultrasound machine itself, including the software algorithms that identify IUGR. One hospital where research was conducted incorrectly predicted pathological birth outcomes 14 of 14 times. We are at a historical moment when the global use of prenatal diagnostic ultrasound for the express purpose of assessing IUGR is set to escalate. Medical imaging device corporations like Siemens, Toshiba, General Electric and Phillips are quite literally banking on it, and new forms of ultrasound technology and diagnostic software are increasingly available on smartphones, tablets and laptops. Clinical guidelines for IUGR--assumed to be authoritative and evidence-based--are evolving right along with the installation throughout the world of the technology capable of diagnosing it. Maternal malnutrition remains the single strongest predictive factor for IUGR, regardless of the technological investments currently amassing to identify the indicator, which is cause for a reassessment of priority spending and investment.

  14. Altered resting-state whole-brain functional networks of neonates with intrauterine growth restriction.

    Science.gov (United States)

    Batalle, Dafnis; Muñoz-Moreno, Emma; Tornador, Cristian; Bargallo, Nuria; Deco, Gustavo; Eixarch, Elisenda; Gratacos, Eduard

    2016-04-01

    The feasibility to use functional MRI (fMRI) during natural sleep to assess low-frequency basal brain activity fluctuations in human neonates has been demonstrated, although its potential to characterise pathologies of prenatal origin has not yet been exploited. In the present study, we used intrauterine growth restriction (IUGR) as a model of altered neurodevelopment due to prenatal condition to show the suitability of brain networks to characterise functional brain organisation at neonatal age. Particularly, we analysed resting-state fMRI signal of 20 neonates with IUGR and 13 controls, obtaining whole-brain functional networks based on correlations of blood oxygen level-dependent (BOLD) signal in 90 grey matter regions of an anatomical atlas (AAL). Characterisation of the networks obtained with graph theoretical features showed increased network infrastructure and raw efficiencies but reduced efficiency after normalisation, demonstrating hyper-connected but sub-optimally organised IUGR functional brain networks. Significant association of network features with neurobehavioral scores was also found. Further assessment of spatiotemporal dynamics displayed alterations into features associated to frontal, cingulate and lingual cortices. These findings show the capacity of functional brain networks to characterise brain reorganisation from an early age, and their potential to develop biomarkers of altered neurodevelopment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. HEMODYNAMIC DOPPLER PARAMETERS IN THE FETUS FETOPLACENTAL UNIT WITH INTRAUTERINE GROWTH RESTRICTIONWITHIN PREGNANCY INDUCED HYPERTENSION

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    Snezana Stamenovic

    2005-04-01

    Full Text Available Based on the spectral analysis of Doppler velocity waveform in uteroplacental and fetoplacental circulation, a Doppler parameters diagnostic efficiency was examined in fetus prenatal detection with intrauterine growth restriction (IUGR within Pregnancy Induced Hypertension (PIH and their respiratory menace.A prospective analysis was performed in 141 third-trimester pregnancies. The control group included 65 normal pregnancies and the expeimental group included 76 high-risk pregnancies, which was divided into three sub-groups, namely, 31 with IUGR within PIH, 24 with PIH only and 21 with IUGR only. The uterine artery was examined in uteroplacental circulation and umbilical artery was examined in fetoplacental circulation. Perinatal outcome and birth weight were recorded in each case.Uteroplacental circulation analysis showed statistically higer values of Pourcelot resistance index Ri in uterine artery in IUGR within PIH pregnancies. Statistically higher pulsatility index in umbilical artery was recorded in IUGR pregnancies compared to the control group and PIH subgroup. Higher values of pulsatility index were particulary noticed in IUGR within PIH subgroup. Doppler parameters in uteroplacental and fetoplacental circulation showed a significant negative correlation in relation to Apgar score of the newborn.In combination with biophysical profile and CTG, Doppler parameters diagnostic efficiency is increased on the evaluation of the fetus respiratory menace with IUGR and PIH.

  16. Refeeding syndrome in very-low-birth-weight intrauterine growth-restricted neonates.

    Science.gov (United States)

    Ross, J R; Finch, C; Ebeling, M; Taylor, S N

    2013-09-01

    Determine the incidence of refeeding syndrome, defined by the presence of hypophosphatemia in very-low-birth-weight (VLBW) infants with intrauterine growth restriction (IUGR) compared with those without IUGR. In this retrospective cohort study, VLBW infants admitted over a 10-year period (271 IUGR and 1982 non-IUGR) were evaluated for specific electrolyte abnormalities in the first postnatal week. IUGR infants were significantly more likely to have hypophosphatemia (41% vs 8.9%, relative risk (95% confidence interval: 7.25 (5.45, 9.65)) and severe hypophosphatemia (11.4% vs 1%, 12.06 (6.82, 21.33)) in the first postnatal week. The incidence of hypophosphatemia was significantly associated with the presence of maternal preeclampsia in all VLBW infants (odds ratio (OR): 2.58 (1.96, 3.40)) when controlling for birth weight and gestational age. Refeeding syndrome occurs in VLBW infants with IUGR and born to mothers with preeclampsia. Close monitoring of electrolytes, especially phosphorus, is warranted in this population.

  17. Intrauterine Growth Restriction Impairs Small Intestinal Mucosal Immunity in Neonatal Piglets

    Science.gov (United States)

    Dong, Li; Zhong, Xiang; Ahmad, Hussain; Li, Wei; Wang, Yuanxiao; Zhang, Lili

    2014-01-01

    Intrauterine growth restriction (IUGR) is a very common problem in both piglet and human neonate populations. We hypothesized that IUGR neonates have impaired intestinal mucosal immunity from birth. Using neonatal piglets as IUGR models, immune organ weights, the weight and length of the small intestine (SI), intestinal morphology, intraepithelial immune cell numbers, levels of cytokines and immunoglobulins, and the relative gene expression of cytokines in the SI were investigated. IUGR neonatal piglets were observed to have lower absolute immune organ weight and SI length, decreased relative weights of the thymus, spleen, mesenteric lymph node, and thinner but longer SIs. Damaged and jagged villi, shorter microvilli, presence of autophagosomes, swelled mitochondria, and decreased villus surface areas were also found in the SIs of IUGR neonatal piglets. We also found a smaller number of epithelial goblet cells and lymphocytes in the SIs of IUGR neonates. In addition, we detected reduced levels of the cytokines TNF-α and IFN-γ and decreased gene expression of cytokines in IUGR neonates. In conclusion, IUGR was shown to impair the mucosal immunity of the SI in neonatal piglets, and the ileum was the major site of impairment. PMID:24710659

  18. Blocked, delayed, or obstructed: What causes poor white matter development in intrauterine growth restricted infants?

    Science.gov (United States)

    Tolcos, Mary; Petratos, Steven; Hirst, Jonathan J; Wong, Flora; Spencer, Sarah J; Azhan, Aminath; Emery, Ben; Walker, David W

    2017-07-01

    Poor white matter development in intrauterine growth restricted (IUGR) babies remains a major, untreated problem in neonatology. New therapies, guided by an understanding of the mechanisms that underlie normal and abnormal oligodendrocyte development and myelin formation, are required. Much of our knowledge of the mechanisms that underlie impaired myelination come from studies in adult demyelinating disease, preterm brain injury, or experimental models of hypoxia-ischemia. However, relatively less is known for IUGR which is surprising because IUGR is a leading cause of perinatal mortality and morbidity, second only to premature birth. IUGR is also a significant risk factor for the later development of cerebral palsy, and is a greater risk compared to some of the more traditionally researched antecedents - asphyxia and inflammation. Recent evidence suggests that the white matter injury and reduced myelination in the brains of some preterm babies is due to impaired maturation of oligodendrocytes thereby resulting in the reduced capacity to synthesize myelin. Therefore, it is not surprising that the hypomyelination observable in the central nervous system of IUGR infants has similarly lead to investigations identifying a delay or blockade in the progress of maturation of oligodendrocytes in these infants. This review will discuss current ideas thought to account for the poor myelination often present in the neonate's brain following IUGR, and discuss novel interventions that are promising as treatments that promote oligodendrocyte maturation, and thereby repair the myelination deficits that otherwise persist into infancy and childhood and lead to neurodevelopmental abnormalities. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Sex and intrauterine growth restriction modify brain neurotransmitters profile of newborn piglets.

    Science.gov (United States)

    Vázquez-Gómez, M; Valent, D; García-Contreras, C; Arroyo, L; Óvilo, C; Isabel, B; Bassols, A; González-Bulnes, A

    2016-12-01

    The current study aimed to determine, using a swine model of intrauterine growth restriction (IUGR), whether short- and long-term neurological deficiencies and interactive dysfunctions of Low Birth-Weight (LBW) offspring might be related to altered pattern of neurotransmitters. Hence, we compared the quantities of different neurotransmitters (catecholamines and indoleamines), which were determined by HPLC, at brain structures related to the limbic system (hippocampus and amygdala) in 14 LBW and 10 Normal Body-Weight (NBW) newborn piglets. The results showed, firstly, significant effects of sex on the NBW newborns, with females having higher dopamine (DA) concentrations than males. The IUGR processes affected DA metabolism, with LBW piglets having lower concentrations of noradrenaline at the hippocampus and higher concentrations of the DA metabolites, homovanillic acid (HVA), at both the hippocampus and the amygdala than NBW neonates. The effects of IUGR were modulated by sex; there were no significant differences between LBW and NBW females, but LBW males had higher HVA concentration at the amygdala and higher concentration of 5-hydroxyindoleacetic acid, the serotonin metabolite, at the hippocampus than NBW males. In conclusion, the present study shows that IUGR is mainly related to changes, modulated by sex, in the concentrations of catecholamine neurotransmitters, which are related to adaptation to physical activity and to essential cognitive functions such as learning, memory, reward-motivated behavior and stress. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

  20. Maternal Serum Endocan Concentration in Pregnancies Complicated by Intrauterine Growth Restriction.

    Science.gov (United States)

    Szpera-Gozdziewicz, Agata; Kosicka, Katarzyna; Gozdziewicz, Tomasz; Krzyscin, Mariola; Wirstlein, Przemyslaw; Siemiatkowska, Anna; Glowka, Franciszek; Wender-Ozegowska, Ewa; Breborowicz, Grzegorz H

    2018-01-01

    Endocan plays a role in the development of vascular tissue in health and disease and is an indicator of endothelial cells activation and angiogenesis. Therefore, this study aimed to investigate the relationship between maternal endocan serum level and intrauterine growth restriction (IUGR) as well as ultrasound Doppler flow measurements indicating placental insufficiency. This study included a group of women with IUGR (n = 37) and a group of healthy pregnant women (controls, n = 37). The endocan serum concentrations were assessed using commercially available enzyme-linked immunosorbent assay kit. Every woman underwent an ultrasound examination with Doppler flow measurements of the uterine arteries, umbilical vessels, and fetal middle cerebral artery. We used the cerebroplacental ratio (CPR) to determine placental insufficiency. We found significant differences in median (interquartile) endocan serum level (pg/mL) between study and control groups (464 [374-532] vs 339 [189-496], respectively; P < .001). The endocan serum level correlated neither with umbilical cord blood gases nor with Apgar score. Ultrasound Doppler findings revealed significant differences in middle cerebral artery pulsatility index (PI), umbilical artery PI, CPR, as well as mean uterine arteries PI between IUGR group and controls. In the study group, we found significant correlations between the serum endocan and CPR ( R = 0.56, P < .001) as well as between serum endocan and mean uterine arteries PI ( R = 0.46, P = .006). Endocan is likely involved in the pathogenesis of IUGR in pregnant women and possibly is a useful marker of endothelial dysfunction in these cases.

  1. Intrauterine growth restriction is a direct consequence of localized maternal uropathogenic Escherichia coli cystitis.

    Directory of Open Access Journals (Sweden)

    Michael Bolton

    Full Text Available Despite the continually increasing rates of adverse perinatal outcomes across the globe, the molecular mechanisms that underlie adverse perinatal outcomes are not completely understood. Clinical studies report that 10% of pregnant women will experience a urinary tract infection (UTI and there is an association of UTIs with adverse perinatal outcomes. We introduced bacterial cystitis into successfully outbred female mice at gestational day 14 to follow pregnancy outcomes and immunological responses to determine the mechanisms that underlie UTI-mediated adverse outcomes. Outbred fetuses from mothers experiencing localized cystitis displayed intrauterine growth restriction (20-80% as early as 48 hours post-infection and throughout the remainder of normal gestation. Robust infiltration of cellular innate immune effectors was observed in the uteroplacental tissue following introduction of UTI despite absence of viable bacteria. The magnitude of serum proinflammatory cytokines is elevated in the maternal serum during UTI. This study demonstrates that a localized infection can dramatically impact the immunological status as well as the function of non-infected distal organs and tissues. This model can be used as a platform to determine the mechanism(s by which proinflammatory changes occur between non-contiguous genitourinary organs.

  2. Intrauterine Growth Restriction Is a Direct Consequence of Localized Maternal Uropathogenic Escherichia coli Cystitis

    Science.gov (United States)

    Bolton, Michael; Horvath, Dennis J.; Li, Birong; Cortado, Hanna; Newsom, David; White, Peter; Partida-Sanchez, Santiago; Justice, Sheryl S.

    2012-01-01

    Despite the continually increasing rates of adverse perinatal outcomes across the globe, the molecular mechanisms that underlie adverse perinatal outcomes are not completely understood. Clinical studies report that 10% of pregnant women will experience a urinary tract infection (UTI) and there is an association of UTIs with adverse perinatal outcomes. We introduced bacterial cystitis into successfully outbred female mice at gestational day 14 to follow pregnancy outcomes and immunological responses to determine the mechanisms that underlie UTI-mediated adverse outcomes. Outbred fetuses from mothers experiencing localized cystitis displayed intrauterine growth restriction (20–80%) as early as 48 hours post-infection and throughout the remainder of normal gestation. Robust infiltration of cellular innate immune effectors was observed in the uteroplacental tissue following introduction of UTI despite absence of viable bacteria. The magnitude of serum proinflammatory cytokines is elevated in the maternal serum during UTI. This study demonstrates that a localized infection can dramatically impact the immunological status as well as the function of non-infected distal organs and tissues. This model can be used as a platform to determine the mechanism(s) by which proinflammatory changes occur between non-contiguous genitourinary organs PMID:22470490

  3. Early Environmental Enrichment Enhances Abnormal Brain Connectivity in a Rabbit Model of Intrauterine Growth Restriction.

    Science.gov (United States)

    Illa, Miriam; Brito, Verónica; Pla, Laura; Eixarch, Elisenda; Arbat-Plana, Ariadna; Batallé, Dafnis; Muñoz-Moreno, Emma; Crispi, Fatima; Udina, Esther; Figueras, Francesc; Ginés, Silvia; Gratacós, Eduard

    2017-10-12

    The structural correspondence of neurodevelopmental impairments related to intrauterine growth restriction (IUGR) that persists later in life remains elusive. Moreover, early postnatal stimulation strategies have been proposed to mitigate these effects. Long-term brain connectivity abnormalities in an IUGR rabbit model and the effects of early postnatal environmental enrichment (EE) were explored. IUGR was surgically induced in one horn, whereas the contralateral one produced the controls. Postnatally, a subgroup of IUGR animals was housed in an enriched environment. Functional assessment was performed at the neonatal and long-term periods. At the long-term period, structural brain connectivity was evaluated by means of diffusion-weighted brain magnetic resonance imaging and by histological assessment focused on the hippocampus. IUGR animals displayed poorer functional results and presented altered whole-brain networks and decreased median fractional anisotropy in the hippocampus. Reduced density of dendritic spines and perineuronal nets from hippocampal neurons were also observed. Of note, IUGR animals exposed to enriched environment presented an improvement in terms of both function and structure. IUGR is associated with altered brain connectivity at the global and cellular level. A strategy based on early EE has the potential to restore the neurodevelopmental consequences of IUGR. © 2017 S. Karger AG, Basel.

  4. Intrauterine Growth Restriction Increases TNFα and Activates the Unfolded Protein Response in Male Rat Pups

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    Emily S. Riddle

    2014-01-01

    Full Text Available Intrauterine growth restriction (IUGR programs adult disease, including obesity and insulin resistance. Our group previously demonstrated that IUGR dysregulates adipose deposition in male, but not female, weanling rats. Dysregulated adipose deposition is often accompanied by the release of proinflammatory signaling molecules, such as tumor necrosis factor alpha (TNFα. TNFα contributes to adipocyte inflammation and impaired insulin signaling. TNFα has also been implicated in the activation of the unfolded protein response (UPR, which impairs insulin signaling. We hypothesized that, in male rat pups, IUGR would increase TNFα, TNFR1, and components of the UPR (Hspa5, ATF6, p-eIF2α, and Ddit3 prior to the onset of obesity. We further hypothesized that impaired glucose tolerance would occur after the onset of adipose dysfunction in male IUGR rats. To test this hypothesis, we used a well-characterized rat model of uteroplacental insufficiency-induced IUGR. Our primary findings are that, in male rats, IUGR (1 increased circulating and adipose TNFα, (2 increased mRNA levels of UPR components as well as p-eIF2a, and (3 impaired glucose tolerance after observed TNFα increased and after UPR activation. We speculate that programmed dysregulation of TNFα and UPR contributed to the development of glucose intolerance in male IUGR rats.

  5. Gender-specific heart rate dynamics in severe intrauterine growth-restricted fetuses.

    Science.gov (United States)

    Gonçalves, Hernâni; Bernardes, João; Ayres-de-Campos, Diogo

    2013-06-01

    Management of intrauterine growth restriction (IUGR) remains a major issue in perinatology. The objective of this paper was the assessment of gender-specific fetal heart rate (FHR) dynamics as a diagnostic tool in severe IUGR. FHR was analyzed in the antepartum period in 15 severe IUGR fetuses and 18 controls, matched for gestational age, in relation to fetal gender. Linear and entropy methods, such as mean FHR (mFHR), low (LF), high (HF) and movement frequency (MF), approximate, sample and multiscale entropy. Sensitivities and specificities were estimated using Fisher linear discriminant analysis and the leave-one-out method. Overall, IUGR fetuses presented significantly lower mFHR and entropy compared with controls. However, gender-specific analysis showed that significantly lower mFHR was only evident in IUGR males and lower entropy in IUGR females. In addition, lower LF/(MF+HF) was patent in IUGR females compared with controls, but not in males. Rather high sensitivities and specificities were achieved in the detection of the FHR recordings related with IUGR male fetuses, when gender-specific analysis was performed at gestational ages less than 34 weeks. Severe IUGR fetuses present gender-specific linear and entropy FHR changes, compared with controls, characterized by a significantly lower entropy and sympathetic-vagal balance in females than in males. These findings need to be considered in order to achieve better diagnostic results. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Preeclampsia with and without intrauterine growth restriction-Two pathogenetically different entities?

    Science.gov (United States)

    Milosevic-Stevanovic, Jelena; Krstic, Miljan; Radovic-Janosevic, Dragana; Stefanovic, Milan; Antic, Vladimir; Djordjevic, Ivana

    2016-11-01

    The objective of this study is to determine the differences in histopathological features of basal decidua and placenta in cases of preeclampsia with or without fetal intrauterine growth restriction (IUGR). A prospective case-control study included a study group consisting of 30 pregnant women with preeclampsia completed by cesarean section (CS), in 19 of whom preeclampsia was associated with IUGR, and in 11 it was not. The control group consisted of 20 healthy pregnant women delivered by elective CS. Placentas and samples of placental bed obtained during CS were histopathologically (HP) analyzed after hematoxylin-eosin staining and immunohistochemical labeling of Cytokeratin 7 (CK7) trophoblastic cells in decidua. Regarding the HP changes in the spiral arteries in preeclampsia, the most frequent features were inadequate transformation of spiral arteries with poor trophoblastic invasion (70.0%) and fibrinoid necrosis of the media (66.7%), and rarely acute atherosis (33.3%) and thrombosis (30.0%). Villous hypermaturity was more frequently found in placentas of patients with preeclampsia with IUGR (p preeclampsia with and without IUGR regarding some of HP alterations of placental bed. Alterations of the placental bed in terms of decidual vasculopathy are more the characteristics of the preeclampsia itself than IUGR, while changes in placental villi primarily follow the presence of IUGR, which could indicate that preeclampsia with and without IUGR are two pathogenetically different entities.

  7. Increased insulin sensitivity in intrauterine growth retarded newborns--do thyroid hormones play a role?

    Science.gov (United States)

    Setia, Sajita; Sridhar, M G; Koner, B C; Bobby, Zachariah; Bhat, Vishnu; Chaturvedula, Lata

    2007-02-01

    Thyroid hormones are necessary for normal brain development. We studied thyroid hormone profile and insulin sensitivity in intrauterine growth retarded (IUGR) newborns to find correlation between insulin sensitivity and thyroid status in IUGR newborns. Fifty IUGR and fifty healthy control infants were studied at birth. Cord blood was collected for determination of T(3), T(4), TSH, glucose and insulin levels. IUGR newborns had significantly lower insulin, mean+/-S.D., 5.25+/-2.81 vs. 11.02+/-1.85microU/ml, but significantly higher insulin sensitivity measured as glucose to insulin ratio (G/I), 9.80+/-2.91 vs. 6.93+/-1.08 compared to healthy newborns. TSH was also significantly higher 6.0+/-2.70 vs. 2.99+/-1.05microU/ml with significantly lower T(4), 8.65+/-1.95 vs. 9.77+/-2.18microg/dl, but similar T(3) levels, 100.8+/-24.36 vs. 101.45+/-23.45ng/dl. On stepwise linear regression analysis in IUGR infants, insulin sensitivity was found to have a significant negative association with T(4) and significant positive association with TSH. Thyroid hormones may play a role in increased insulin sensitivity at birth in IUGR.

  8. Cord Blood Ischemia-Modified Albumin Levels in Normal and Intrauterine Growth Restricted Pregnancies

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    Nicoletta Iacovidou

    2008-01-01

    Full Text Available Ischemia-modified albumin (IMA is a sensitive biomarker of cardiac ischemia. Intrauterine growth restriction (IUGR may imply fetal hypoxia, resulting in blood flow centralization in favour of vital organs (brain, heart, adrenals—‘‘brain sparing effect’’. Based on the latter, we hypothesized that cord blood IMA levels should not differ between IUGR and appropriate-for-gestational-age (AGA full-term pregnancies. IMA was measured in blood samples from doubly-clamped umbilical cords of 110 AGA and 57 asymmetric IUGR pregnancies. No significant differences in IMA levels were documented between AGA and IUGR groups. IMA levels were elevated in cases of elective cesarean section (P = .035, and offspring of multigravidas (P = .021. In conclusion, ‘‘brain sparing effect’’ is possibly responsible for the lack of differences in cord blood IMA levels at term, between IUGR and AGA groups. Furthermore, higher oxidative stress could account for the elevated IMA levels in cases of elective cesarean section, and offspring of multigravidas.

  9. Epigenetics of hypoxic pulmonary arterial hypertension following intrauterine growth retardation rat: epigenetics in PAH following IUGR

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    Xu Xue-Feng

    2013-02-01

    Full Text Available Abstract Background Accumulating evidence reveals that intrauterine growth retardation (IUGR can cause varying degrees of pulmonary arterial hypertension (PAH later in life. Moreover, epigenetics plays an important role in the fetal origin of adult disease. The goal of this study was to investigate the role of epigenetics in the development of PAH following IUGR. Methods The IUGR rats were established by maternal undernutrition during pregnancy. Pulmonary vascular endothelial cells (PVEC were isolated from the rat lungs by magnetic-activated cell sorting (MACS. We investigated epigenetic regulation of the endothelin-1 (ET-1 gene in PVEC of 1-day and 6-week IUGR rats, and response of IUGR rats to hypoxia. Results The maternal nutrient restriction increased the histone acetylation and hypoxia inducible factor-1α (HIF-1α binding levels in the ET-1 gene promoter of PVEC in IUGR newborn rats, and continued up to 6 weeks after birth. These epigenetic changes could result in an IUGR rat being highly sensitive to hypoxia later in life, causing more significant PAH or pulmonary vascular remodeling. Conclusions These findings suggest that epigenetics is closely associated with the development of hypoxic PAH following IUGR, further providing a new insight for improved prevention and treatment of IUGR-related PAH.

  10. Features of newborns with intrauterine growth restriction (according to the data of perinatal center of the Saratov region

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    Chernenkov Yu.V.

    2017-03-01

    Full Text Available Objective: to identify risk factors that adversely affect the development of fetus and child small for gestational age; to assess the incidence of the intrauterine development of fetus and newborn; to analyze the health indicators of these children. Material and Methods. Cases of 226 children (6.6% with diagnosed intrauterine growth restriction of the fetus were examined, including 134 of prematurity (59%. Results. The most common risk factors for the intrauterine development of the fetus were: violation of the utero-placental circulation — 196 cases, the uterine scar — 78 women, urinary tract infection — 94. Extragenital pathology was found in all women, the threat of termination of pregnancy in 109 cases, medical history of abortions in 106 women and 83 anaemia in women. Birth asphyxia was observed in 102 children (45%, prematurity in 71 cases (31.4%. Asphyxia of severe degree accounted 1 (0.5% premature and 1 (0.45% full-term baby. Asphyxia of moderate severity (4-6 points accounted 70 (30.9% preterm and 31 (13.7% full-term infants. The most common form of the intrauterine development of the fetus asymmetrical revealed 178 cases (79.1%. Conclusion: Perinatal factors such as medical abortion, urinary tract infection, extragenital pathology are preventable. The predominant form of the intrauterine development of the fetus is asymmetric form, symmetric and dysplastic revealed to a greater degree in premature infants. Children with low weight for gestational age should be adequately provided with the necessary nutrients, fortifiers, vitamins and in the process of rehabilitation — cerebropro-tective therapy.

  11. Intrauterine growth and intelligence within sibling pairs: findings from the Mater-University study of pregnancy and its outcomes.

    Science.gov (United States)

    Lawlor, Debbie A; Bor, William; O'Callaghan, Michael J; Williams, Gail M; Najman, Jake M

    2005-04-01

    To examine the association between intrauterine growth and intelligence. Population based birth cohort study of sibling pairs born within a maximum of three years of each other. Mater-University women and children's hospital, Brisbane, Australia. 235 (470 children) sibling pairs. Among one randomly selected sibling from each pair verbal comprehension at age 5, general intelligence at age 14, and reading ability at age 14 increased linearly with increasing gestational age and sex standardised birth weight z scores. With adjustment for maternal age, race, and smoking during pregnancy, birth order, family income, and parental education the associations with verbal comprehension at age 5 and general intelligence at age 14 remained, whereas the association with reading ability at age 14 was attenuated to the null. Within sibling pairs, differences in intrauterine growth were positively associated with differences in verbal comprehension at age 5 (test score difference per one unit difference in birth weight z score = 1.52 (0.11 to 3.26)) and general intelligence at age 14 (1.09 (0.01 to 2.18)), but not with reading ability at age 14. Socioeconomic position or other fixed maternal characteristics do not seem to explain the positive association between intrauterine growth and childhood intelligence.

  12. Study of foetal heart rate patterns in pregnancy with intra-uterine growth restriction during antepartum period

    International Nuclear Information System (INIS)

    Fardiazar, Z.; Abassalizade, F.

    2013-01-01

    Objectives: To evaluate foetal heart rate pattern during antepartum period in pregnancies suffering from intra-uterine growth restriction. Methods: The case control study was conducted at the Alzahra Hospital, Tabriz, Iran from April 2008 to April 2011. It comprised 100 pregnancies with intra-uterine growth restriction and 92 normal pregnancies. The foetal heart rate pattern including basal heart rate, beat-to-beat variation, non-stress test (NST) result and acceleration and deceleration patterns of the heart rate were determined in both groups during the antepartum period. Findings were compared between the two groups and their relation with pregnancy-foetal outcomes was specified in the case group. SPSS 15 was used for statistical analysis. Results: There was no statistically significant difference between the foetus mean basal heart rate in the two groups (p <0.960). Frequency of cases with non-reactive non-stress test in the Cases was significantly higher than Controls (p <0.005). The difference in heart rate acceleration was also not statistically significant (p <0.618). Frequency of cases with low birth weight and caesarian was non-significantly but borderline higher among the Cases (p <0.081 and 0.060, respectively). Conclusion: Abnormal foetal heart rate pattern is more common in pregnancies marked by intra-uterine growth restriction and is directly associated with worse pregnancy/foetal outcomes. (author)

  13. [Customized and non-customized French intrauterine growth curves. II - Comparison with existing curves and benefits of customization].

    Science.gov (United States)

    Ego, A; Prunet, C; Blondel, B; Kaminski, M; Goffinet, F; Zeitlin, J

    2016-02-01

    Our aim is to compare the new French EPOPé intrauterine growth curves, developed to address the guidelines 2013 of the French College of Obstetricians and Gynecologists, with reference curves currently used in France, and to evaluate the consequences of their adjustment for fetal sex and maternal characteristics. Eight intrauterine and birthweight curves, used in France were compared to the EPOPé curves using data from the French Perinatal Survey 2010. The influence of adjustment on the rate of SGA births and the characteristics of these births was analysed. Due to their birthweight values and distribution, the selected intrauterine curves are less suitable for births in France than the new curves. Birthweight curves led to low rates of SGA births from 4.3 to 8.5% compared to 10.0% with the EPOPé curves. The adjustment for maternal and fetal characteristics avoids the over-representation of girls among SGA births, and reclassifies 4% of births. Among births reclassified as SGA, the frequency of medical and obstetrical risk factors for growth restriction, smoking (≥10 cigarettes/day), and neonatal transfer is higher than among non-SGA births (P<0.01). The EPOPé curves are more suitable for French births than currently used curves, and their adjustment improves the identification of mothers and babies at risk of growth restriction and poor perinatal outcomes. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  14. Effect of insulin-like growth factor-I during the early postnatal period in intrauterine growth-restricted rats.

    Science.gov (United States)

    Ikeda, Naho; Shoji, Hiromichi; Suganuma, Hiroki; Ohkawa, Natsuki; Kantake, Masato; Murano, Yayoi; Sakuraya, Koji; Shimizu, Toshiaki

    2016-05-01

    Insulin-like growth factor-I (IGF-I) is essential for perinatal growth and development; low serum IGF-I has been observed during intrauterine growth restriction (IUGR). We investigated the effects of recombinant human (rh) IGF-I in IUGR rats during the early postnatal period. Intrauterine growth restriction was induced by bilateral uterine artery ligation in pregnant rats. IUGR pups were divided into two groups injected daily with rhIGF-I (2 mg/kg; IUGR/IGF-I, n = 16) or saline (IUGR/physiologic saline solution (PSS), n = 16) from postnatal day (PND) 7 to 13. Maternal sham-operated pups injected with saline were used as controls (control, n = 16). Serum IGF-I and IGF binding proteins (IGFBP) 3 and 5 were measured on PND25. The expression of Igf-i, IGF-I receptor (Igf-ir), Igfbp3, and 5 mRNA in the liver and brain was measured using real-time polymerase chain reaction on PND25. Immunohistochemical staining of the liver for IGF expression was performed. Mean bodyweight on PND3 and PND25 in the IUGR pups (IUGR/IGF-I and IUGR/PSS) was significantly lower than that of the control pups. Serum IGF-I and hepatic Igf-ir mRNA in the IUGR pups were significantly lower than those in the control pups. In the IUGR/IGF-I group, hepatic Igfbp3 mRNA and liver immunohistochemical staining were increased. In the IUGR/PSS and control pups, there were no significant differences between these two groups in serum IGFBP3 and IGFBP5, hepatic Igf-i and Igfbp-5 mRNA, or brain Igf mRNA. No benefits on body and brain weight gain but an effective increase in hepatic IGFBP-3 was observed after treatment with 2 mg/kg rhIGF-I during the early postnatal period. © 2015 Japan Pediatric Society.

  15. Synergistic effects of pyrrolizidine alkaloids and lipopolysaccharide on preterm delivery and intrauterine fetal death in mice.

    Science.gov (United States)

    Guo, Yu; Ma, Zhenguo; Kou, Hao; Sun, Rongze; Yang, Hanxiao; Smith, Charles Vincent; Zheng, Jiang; Wang, Hui

    2013-08-29

    Preterm birth is the leading cause of death for newborn infants, and lipopolysaccharide (LPS) is commonly used to induce preterm delivery in experimental animals. Pyrrolizidine alkaloids (PAs) are widespread and occur in foods, herbs, and other plants. This study was to investigate the synergistic effects of LPS and two representative PAs, retrorsine (RTS) and monocrotaline (MCT), on preterm delivery and fetal death. Pregnant Kunming mice were divided into seven groups: control, RTS, MCT, LPS, RTS+LPS and two MCT+LPS groups. Animals in PAs and PAs+LPS groups were dosed intragastrically with RTS (10mg/kg) or MCT (20 mg/kg or 60 mg/kg) from gestational day (GD) 9 to GD16; mice given LPS were injected intraperitoneally with 150 μg/kg on GD15.5. Latencies to delivery, numbers of pups live and dead at birth were recorded, and livers of live neonates were collected. The incidence of LPS-induced preterm birth was enhanced in dams pretreated with MCT, and combination of PAs and LPS increased fetal mortality from PAs. The enhancement of LPS-induced preterm delivery and fetal demise in animals exposed chronically to PAs and other substances found in foods and beverages consumed widely by humans merits further focused investigation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  16. Sildenafil citrate treatment enhances amino acid availability in the conceptus and fetal growth in an ovine model of intrauterine growth restriction.

    Science.gov (United States)

    Satterfield, M Carey; Bazer, Fuller W; Spencer, Thomas E; Wu, Guoyao

    2010-02-01

    Adequate placental blood flow is essential for the optimal delivery of nutrients from mother to fetus for conceptus growth. Restricted fetal development results from pathophysiological and environmental factors that alter utero-placental blood flow, placental function, and, therefore, nutrient availability in the fetus. To test this hypothesis, 0, 75, or 150 mg/d sildenafil citrate (Viagra) was administered subcutaneously from d 28 to 115 of gestation to either nutrient-restricted [50% of NRC requirements) or adequately-fed ewes (100% of NRC requirements). On d 115, maternal, fetal, and placental tissues and fluids were collected. Concentrations of total amino acids and polyamines in uterine venous and arterial sera, amniotic and allantoic fluids, and fetal umbilical venous serum were lower (P < 0.05) in nutrient-restricted ewes than in adequately fed ewes, as were the ratios of total amino acids in fetal umbilical venous serum to uterine arterial serum. Sildenafil citrate dose-dependently increased (P < 0.05) total amino acids and polyamines in amniotic fluid, allantoic fluid, and fetal serum without affecting values in maternal serum. Fetal weight was lower (P < 0.05) in nutrient-restricted ewes on d 115. Sildenafil citrate treatment dose-dependently increased (P < 0.05) fetal weight in both nutrient-restricted and adequately fed ewes. This study supports the hypothesis that long-term sildenafil citrate treatment enhances fetal growth, at least in part, by increasing the availability of amino acids in the conceptus. These findings may lead to the clinical use of sildenafil citrate in human pregnancies suspected to be at risk for intrauterine fetal growth retardation.

  17. Intrauterine growth restriction is associated with structural alterations in human umbilical cord and decreased nitric oxide-induced relaxation of umbilical vein.

    Science.gov (United States)

    Peyter, A-C; Delhaes, F; Baud, D; Vial, Y; Diaceri, G; Menétrey, S; Hohlfeld, P; Tolsa, J-F

    2014-11-01

    Intrauterine growth restriction (IUGR) affects ∼8% of all pregnancies and is associated with major perinatal mortality and morbidity, and with an increased risk to develop cardiovascular diseases in adulthood. Despite identification of several risk factors, the mechanisms implicated in the development of IUGR remain poorly understood. In case of placental insufficiency, reduced delivery of oxygen and/or nutrients to the fetus could be associated with alterations in the umbilical circulation, contributing further to the impairment of maternal-fetal exchanges. We compared the structural and functional properties of umbilical cords from growth-restricted and appropriate for gestational age (AGA) term newborns, with particular attention to the umbilical vein (UV). Human umbilical cords were collected at delivery. Morphological changes were investigated by histomorphometry, and UV's reactivity by pharmacological studies. Growth-restricted newborns displayed significantly lower growth parameters, placental weight and umbilical cord diameter than AGA controls. Total cross-section and smooth muscle areas were significantly smaller in UV of growth-restricted neonates than in controls. Maximal vasoconstriction achieved in isolated UV was lower in growth-restricted boys than in controls, whereas nitric oxide-induced relaxation was significantly reduced in UV of growth-restricted girls compared to controls. IUGR is associated with structural alterations of the UV in both genders, and with a decreased nitric oxide-induced relaxation in UV of newborn girls, whereas boys display impaired vasoconstriction. Further investigations will allow to better understand the regulation of umbilical circulation in growth-restricted neonates, which could contribute to devise potential novel therapeutic strategies to prevent or limit the development of IUGR. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Nutritional and Hormonal Status of Premature Infants Born with Intrauterine Growth Restriction at the Term Corrected Age.

    Science.gov (United States)

    Belyaeva, I A; Namazova-Baranova, L S; Bombardirova, E P; Okuneva, M V

    Inadequate nutrition supply during the period of intrauterine growth and the first year of life leads to persistent metabolic changes and provokes development of various diseases. Тo compare physical development, body composition, and hormonal status (insulin, insulin-like growth factor-1 (IGF-1), somatotropic hormone (STH), C-Peptide, cortisol) indices in premature infants born with intrauterine growth restriction (IUGR) at the term corrected age with the same indices in mature infants with IUGR and premature infants with weight appropriate for their gestational age (GA). А crossover study of anthropometric measures, body composition and growth hormones changes assessment was carried out. It included 140 premature infants with weight appropriate for their GA, 58 premature infants with IUGR and 64 mature infants with IUGR. Anthropometric measures were assessed with Fenton and Anthro growth charts (WHO, 2009); body composition was studied with the air plethysmography method (РЕA POD, LMi, USA). Level of hormones in blood serum was assessed with biochemical methods. It is found that anthropometric measures in premature infants with weight appropriate for their GA and premature infants with IUGR at the term corrected age did not have any significant differences while premature infants with IUGR tended to have lower weight. Studying body composition we found that both groups of premature infants had slightly higher level of fat mass in comparison with mature infants. High concentration of insulin, cortisol, IGF-1, and C-peptide was found in premature and mature infants with IUGR. Instead, lower levels of STH was found in infants with IUGR. Formula fed premature infants (comparing to breastfed ones) had higher levels of fat mass, insulin, IGF-1, and C-peptide. Mature infants with IUGR did not tend to have the correlation between levels of fat mass, insulin, IGF-1, C-peptide, and type of feeding. Not only insufficient intrauterine growth but also nutrition pattern

  19. The Intrauterine Growth Restriction Phenotype: Fetal Adaptations and Potential Implications for Later Life Insulin Resistance and Diabetes

    Science.gov (United States)

    Thorn, Stephanie R.; Rozance, Paul J.; Brown, Laura D.; Hay, William W.

    2011-01-01

    The intrauterine growth restricted (IUGR) fetus develops unique metabolic adaptations in response to exposure to reduced nutrient supply. These adaptations provide survival value for the fetus by enhancing the capacity of the fetus to take up and use nutrients, thereby reducing the need for nutrient supply. Each organ and tissue in the fetus adapts differently, with the brain showing the greatest capacity for maintaining nutrient supply and growth. Such adaptations, if persistent, also have the potential in later life to promote nutrient uptake and storage, which directly lead to complications of obesity, insulin resistance, reduced insulin production, and type 2 diabetes. PMID:21710398

  20. First-trimester ADAM12 and PAPP-A as markers for intrauterine fetal growth restriction through their roles in the insulin-like growth factor system.

    Science.gov (United States)

    Cowans, Nicholas J; Spencer, Kevin

    2007-03-01

    PAPP-A is a marker used as part of the most effective method of screening for chromosomal anomalies in the first trimester. ADAM12 is a recently discovered pregnancy associated member of the ADAM (a multidomain glycoprotein metalloprotease) family. Recently, ADAM12 has been shown as a potential marker for early screening for chromosomal anomalies. Both PAPP-A and ADAM12 have been identified as proteases to insulin-like growth factor binding proteins. In this role, they may have a regulatory function in controlling the amount of free bioactive insulin-like growth factor (IGF). We therefore wish to examine if the levels of either of these proteases are related to various growth related adverse pregnancy outcomes. PAPP-A and ADAM12 were measured in a subset of samples collected at 11 to 14 weeks as part of an OSCAR clinic screening for chromosomal anomalies. Follow-up of pregnancies screened between September 1999 and August 2003 identified 1705 pregnancies with an outcome of intrauterine fetal demise on or after 24 weeks, preterm delivery at 24-34 weeks or 35-36 weeks, very low birthweight (4.5 kg), and birth weight below the 3rd or 5th or 10th centile for gestation. A series of 414 normal outcome pregnancies constituted the control group. Marker levels were adjusted for gestation and maternal weight and the log MoM of the markers were compared using t-test of unequal variance between the control group and the various adverse outcome groups. ADAM12 and PAPP-A concentrations were reduced in low for gestational age birth weights and in all births with weights below 2.5 kg. There was a linear relationship between the severity of the IUGR and the decrease in PAPP-A and ADAM12. In the larger babies, only ADAM12 was found to be significantly increased in babies above the 90th centile of weight for gestation. The results of our study are compatible with the proposed role of ADAM12 and PAPP-A in promoting growth and development by breaking down IGF binding proteins and

  1. Long-term reorganization of structural brain networks in a rabbit model of intrauterine growth restriction.

    Science.gov (United States)

    Batalle, Dafnis; Muñoz-Moreno, Emma; Arbat-Plana, Ariadna; Illa, Miriam; Figueras, Francesc; Eixarch, Elisenda; Gratacos, Eduard

    2014-10-15

    Characterization of brain changes produced by intrauterine growth restriction (IUGR) is among the main challenges of modern fetal medicine and pediatrics. This condition affects 5-10% of all pregnancies and is associated with a wide range of neurodevelopmental disorders. Better understanding of the brain reorganization produced by IUGR opens a window of opportunity to find potential imaging biomarkers in order to identify the infants with a high risk of having neurodevelopmental problems and apply therapies to improve their outcomes. Structural brain networks obtained from diffusion magnetic resonance imaging (MRI) is a promising tool to study brain reorganization and to be used as a biomarker of neurodevelopmental alterations. In the present study this technique is applied to a rabbit animal model of IUGR, which presents some advantages including a controlled environment and the possibility to obtain high quality MRI with long acquisition times. Using a Q-Ball diffusion model, and a previously published rabbit brain MRI atlas, structural brain networks of 15 IUGR and 14 control rabbits at 70 days of age (equivalent to pre-adolescence human age) were obtained. The analysis of graph theory features showed a decreased network infrastructure (degree and binary global efficiency) associated with IUGR condition and a set of generalized fractional anisotropy (GFA) weighted measures associated with abnormal neurobehavior. Interestingly, when assessing the brain network organization independently of network infrastructure by means of normalized networks, IUGR showed increased global and local efficiencies. We hypothesize that this effect could reflect a compensatory response to reduced infrastructure in IUGR. These results present new evidence on the long-term persistence of the brain reorganization produced by IUGR that could underlie behavioral and developmental alterations previously described. The described changes in network organization have the potential to be used

  2. Intrauterine Growth Restriction Alters the Postnatal Development of the Rat Cerebellum.

    Science.gov (United States)

    McDougall, Annie R A; Wiradjaja, Vanny; Azhan, Aminath; Li, Anqi; Hale, Nadia; Wlodek, Mary E; Hooper, Stuart B; Wallace, Megan J; Tolcos, Mary

    2017-01-01

    Intrauterine growth restriction (IUGR) is a major cause of antenatal brain injury. We aimed to characterize cerebellar deficits following IUGR and to investigate the potential underlying cellular and molecular mechanisms. At embryonic day 18, pregnant rats underwent either sham surgery (controls; n = 23) or bilateral uterine vessel ligation to restrict blood flow to fetuses (IUGR; n = 20). Offspring were collected at postnatal day 2 (P2), P7, and P35. Body weights were reduced at P2, P7, and P35 in IUGR offspring (p < 0.05) compared with controls. At P7, the width of the external granule layer (EGL) was 30% greater in IUGR than control rats (p < 0.05); there was no difference in the width of the proliferative zone or in the density of Ki67-positive cells in the EGL. Bergmann glia were disorganized at P7 and P35 in IUGR pups, and by P35, there was a 10% decrease in Bergmann glial fiber density (p < 0.05) compared with controls. At P7, trophoblast antigen-2 (Trop2) mRNA and protein levels in the cerebellum were decreased by 88 and 40%, respectively, and astrotactin 1 mRNA levels were increased by 20% in the IUGR rats (p < 0.05) compared with controls; there was no difference in ASTN1 protein. The expressions of other factors known to regulate cerebellar development (astrotactin 2, brain-derived neurotrophic factor, erb-b2 receptor tyrosine kinase 4, neuregulin 1, sonic hedgehog and somatostatin) were not different between IUGR and control rats at P7 or P35. These data suggest that damage to the migratory scaffold (Bergmann glial fibers) and alterations in the genes that influence migration (Trop2 and Astn1) may underlie the deficits in postnatal cerebellar development following IUGR. © 2017 S. Karger AG, Basel.

  3. Cardiovascular function in women with recurrent miscarriage, pre-eclampsia and/or intrauterine growth restriction.

    Science.gov (United States)

    Mahendru, Amita A; Everett, Thomas R; McEniery, Carmel M; Wilkinson, Ian B; Lees, Christoph C

    2013-03-01

    To investigate prepregnancy cardiovascular function and risk factors in women with previous pregnancy complications. Thirty-four women with previous normal pregnancy (controls), 26 with unexplained recurrent miscarriage (RM) and 14 with pre-eclampsia (PE) and/or intrauterine growth restriction (IUGR), planning to conceive were recruited. Brachial and central blood pressures (BP), cardiac output (CO), peripheral vascular resistance (PVR), aortic stiffness, blood biochemistry and platelet aggregation were assessed. Women with previous PE/IUGR had higher brachial diastolic BP (78 ± 9 vs 71 ± 7 mmHg; p = 0.03), central systolic BP (107 ± 10 vs 99 ± 8 mmHg; p = 0.03), mean arterial pressure (92 ± 10 vs 84 ± 8 mmHg; p = 0.01) and PVR (1499 ± 300 vs 1250 ± 220 dynes.s(-1) cm(-5); p = 0.005), than the controls. No differences were observed in either cardiovascular function or blood biochemistry in women with unexplained RM compared with the controls. Women with previous PE/IUGR though not with RM had a stronger family history of cardiovascular disease (CVD) than controls. Women with previous PE and/or IUGR had higher BP and PVR compared with controls, which may predispose them to CVD later in life. However, in the absence of underlying vascular pathology, women with unexplained RM did not have abnormal cardiovascular function. Prepregnancy period provides an opportunity to identify cardiovascular risks in relation to previous obstetric history.

  4. Developmental programming: impact of excess prenatal testosterone on intrauterine fetal endocrine milieu and growth in sheep.

    Science.gov (United States)

    Veiga-Lopez, Almudena; Steckler, Teresa L; Abbott, David H; Welch, Kathleen B; MohanKumar, Puliyur S; Phillips, David J; Refsal, Kent; Padmanabhan, Vasantha

    2011-01-01

    Prenatal testosterone excess in sheep leads to reproductive and metabolic disruptions that mimic those seen in women with polycystic ovary syndrome. Comparison of prenatal testosterone-treated sheep with prenatal dihydrotestosterone-treated sheep suggests facilitation of defects by androgenic as well as androgen-independent effects of testosterone. We hypothesized that the disruptive impact of prenatal testosterone on adult pathology may partially depend on its conversion to estrogen and consequent changes in maternal and fetal endocrine environments. Pregnant Suffolk sheep were administered either cottonseed oil (control) or testosterone propionate in cottonseed oil (100 mg, i.m. twice weekly), from Day 30 to Day 90 of gestation (term is ~147 d). Maternal (uterine) and fetal (umbilical) arterial samples were collected at Days 64-66, 87-90, and 139-140 (range; referred to as D65, D90, and D140, respectively) of gestation. Concentrations of gonadal and metabolic hormones, as well as differentiation factors, were measured using liquid chromatography/mass spectrometer, radioimmunoassay, or ELISA. Findings indicate that testosterone treatment produced maternal and fetal testosterone levels comparable to adult males and D65 control male fetuses, respectively. Testosterone treatment increased fetal estradiol and estrone levels during the treatment period in both sexes, supportive of placental aromatization of testosterone. These steroidal changes were followed by a reduction in maternal estradiol levels at term, a reduction in activin A availability, and induction of intrauterine growth restriction in D140 female fetuses. Overall, our findings provide the first direct evidence in support of the potential for both androgenic as well as estrogenic contribution in the development of adult reproductive and metabolic pathology in prenatal testosterone-treated sheep.

  5. Lactobacillus rhamnosus GG suspected infection in a newborn with intrauterine growth restriction.

    Science.gov (United States)

    Sadowska-Krawczenko, I; Paprzycka, M; Korbal, P; Wiatrzyk, A; Krysztopa-Grzybowska, K; Polak, M; Czajka, U; Lutyńska, A

    2014-12-01

    A disseminated Lactobacillus rhamnosus GG ATCC 53103 infection was suspected in a 6 day-old newborn with intrauterine growth restriction (IUGR) symptoms, treated empirically with antibiotics and given L. rhamnosus GG with the aim of preventing antibiotic-associated gastrointestinal complications. The level of C-reactive protein on day 5 compared with day 2 was increased in spite of negative urine and cerebrospinal fluid cultures. The blood sampled on day 6 was found to be positive for lactobacilli, and the isolate was pre-identified as L. rhamnosus or Lactobacillus casei on day 11. The strain identity was then verified as L. rhamnosus GG through PCR and 16S rRNA sequencing. Genotyping with the rep-PCR and AFLP methods confirmed the 100% genetic similarity for both the strain isolated from patient blood and the probiotic product. The newborn became touch-sensitive, cried a lot, had worsening laboratory test results, and increased inflammation parameters, but no fever was observed. After a further 9 days of antibiotic therapy, blood cultures became negative, and laboratory tests improved on day 25. The patient was discharged from the hospital after 27 days. IUGR with a possible link to L. rhamnosus GG bacteraemia might be a new potential risk group, beside patients with organ failure, immunocompromised status and dysfunctional gut barrier mechanisms, for which safe use of probiotics needs careful attention. Universally accepted or improved guidelines for the safer administration of probiotics in risk groups are urgently needed. This report should not discourage the use of probiotics, but should highlight the need for their careful use in IUGR patients.

  6. Intrauterine growth retardation in Iowa communities with herbicide-contaminated drinking water supplies

    Science.gov (United States)

    Munger, R.; Isacson, P.; Hu, S.; Burns, T.; Hanson, J.; Lynch, C.F.; Cherryholmes, K.; Van Dorpe, P.; Hausler, W.J.

    1997-01-01

    In a statewide survey of 856 Iowa municipal drinking water supplies in 1986-1987 the Rathbun rural water system was found to contain elevated levels of triazine herbicides. Rates of low birth weight, prematurity, and intrauterine growth retardation (IUGR) in live singleton births during the period 1984-1990 by women living in 13 communities served by the Rathbun water system were compared to other communities of similar size in the same Iowa counties. The Rathbun communities had a greater risk of IUGR than southern Iowa communities with other surface sources of drinking water (relative risk = 1.8; 95% CI = 1.3, 2.7). Multiple linear regression analyses revealed that levels of the herbicides atrazine, metolachlor, and cyanazine were each significant predictors of community IUGR rates in southern Iowa after controlling for several potentially confounding factors including maternal smoking and socioeconomic variables. The association with IUGR was strongest for atrazine, but all three herbicides were intercorrelated and the independent contributions of each to IUGR risk could not be determined. We conclude that communities in southern Iowa with drinking water supplies contaminated with herbicides have elevated rates of IUGR compared to neighboring communities with different water supplies. Because of the limitations of the ecologic design of this study, including aggregate rather than individual measures of exposure and limited ability to control for confounding factors related to source of drinking water and risk of IUGR, a strong causal relationship between any specific water contaminant and risk of IUGR cannot yet be inferred. The association between the water supplied to the Rathbun communities and the increased risk of IUGR should be considered a preliminary finding that needs to be verified by more detailed epidemiologic studies.

  7. Electrographic imaging of recognition memory in 34-38 week gestation intrauterine growth restricted newborns.

    Science.gov (United States)

    Black, Linda S; deRegnier, Raye-Ann; Long, Jeffrey; Georgieff, Michael K; Nelson, Charles A

    2004-11-01

    Electrophysiological imaging of recognition memory using event-related potentials (ERPs) in intrauterine growth-restricted (IUGR) newborns allows assessment of recognition memory before the onset of multiple confounding variables. Animal models that reproduce the physiologic components associated with IUGR have demonstrated adverse effects on the hippocampus, a structure that is essential to normal memory processing. Previous electrophysiologic studies have demonstrated shortened auditory-evoked potential (AEP) and visual-evoked potential (VEP) latencies in IUGR infants suggesting accelerated neural maturation in response to the adverse in-utero environment. The hypothesis of the current study was that newborns with IUGR and head-sparing would demonstrate altered auditory recognition memory when compared to controls and that the configuration of the alteration would evidence advanced maturation but still be different from that of typically grown newborns. Twelve IUGR newborns born at 34-38 weeks gestation with head-sparing and 16 age-matched control newborns were tested with both a speech/nonspeech paradigm to assess auditory sensory processing and a novel (stranger's voice) and familiar (mother's voice) paradigm to assess recognition memory. In the recognition memory experiment, a three-way interaction of condition, lead, and group was identified for the lateral leads T4, CM3, and CM4 with the response to the mother being of much greater area in the IUGR cohort than in the controls. This ERP configuration has previously been reported for the midline leads in term newborns. The findings indicate that IUGR newborns with head-sparing have electrophysiologic evidence of accelerated maturation of cognitive processing suggesting an atypical process of maturation that may not support typical cognitive development.

  8. Metabolomics reveals metabolic alterations by intrauterine growth restriction in the fetal rabbit brain.

    Directory of Open Access Journals (Sweden)

    Erwin van Vliet

    Full Text Available Intrauterine Growth Restriction (IUGR due to placental insufficiency occurs in 5-10% of pregnancies and is a major risk factor for abnormal neurodevelopment. The perinatal diagnosis of IUGR related abnormal neurodevelopment represents a major challenge in fetal medicine. The development of clinical biomarkers is considered a promising approach, but requires the identification of biochemical/molecular alterations by IUGR in the fetal brain. This targeted metabolomics study in a rabbit IUGR model aimed to obtain mechanistic insight into the effects of IUGR on the fetal brain and identify metabolite candidates for biomarker development.At gestation day 25, IUGR was induced in two New Zealand rabbits by 40-50% uteroplacental vessel ligation in one horn and the contralateral horn was used as control. At day 30, fetuses were delivered by Cesarian section, weighed and brains collected for metabolomics analysis. Results showed that IUGR fetuses had a significantly lower birth and brain weight compared to controls. Metabolomics analysis using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS and database matching identified 78 metabolites. Comparison of metabolite intensities using a t-test demonstrated that 18 metabolites were significantly different between control and IUGR brain tissue, including neurotransmitters/peptides, amino acids, fatty acids, energy metabolism intermediates and oxidative stress metabolites. Principle component and hierarchical cluster analysis showed cluster formations that clearly separated control from IUGR brain tissue samples, revealing the potential to develop predictive biomarkers. Moreover birth weight and metabolite intensity correlations indicated that the extent of alterations was dependent on the severity of IUGR.IUGR leads to metabolic alterations in the fetal rabbit brain, involving neuronal viability, energy metabolism, amino acid levels, fatty acid profiles and oxidative stress

  9. Humanin (HN and glucose transporter 8 (GLUT8 in pregnancies complicated by intrauterine growth restriction.

    Directory of Open Access Journals (Sweden)

    Carla Janzen

    Full Text Available Intrauterine growth restriction (IUGR results from a lack of nutrients transferred to the developing fetus, particularly oxygen and glucose. Increased expression of the cytoprotective mitochondrial peptide, humanin (HN, and the glucose transporter 8, GLUT8, has been reported under conditions of hypoxic stress. However, the presence and cellular localization of HN and GLUT8 in IUGR-related placental pathology remain unexplored. Thus, we undertook this study to investigate placental expression of HN and GLUT8 in IUGR-affected versus normal pregnancies.We found 1 increased HN expression in human IUGR-affected pregnancies on the maternal aspect of the placenta (extravillous trophoblastic (EVT cytoplasm compared to control (i.e. appropriate for gestational age pregnancies, and a concomitant increase in GLUT8 expression in the same compartment, 2 HN and GLUT8 showed a protein-protein interaction by co-immunoprecipitation, 3 elevated HN and GLUT8 levels in vitro under simulated hypoxia in human EVT cells, HTR8/SVneo, and 4 increased HN expression but attenuated GLUT8 expression in vitro under serum deprivation in HTR8/SVneo cells.There was elevated HN expression with cytoplasmic localization to EVTs on the maternal aspect of the human placenta affected by IUGR, also associated with increased GLUT8 expression. We found that while hypoxia increased both HN and GLUT8, serum deprivation increased HN expression alone. Also, a protein-protein interaction between HN and GLUT8 suggests that their interaction may fulfill a biologic role that requires interdependency. Future investigations delineating molecular interactions between these proteins are required to fully uncover their role in IUGR-affected pregnancies.

  10. Detection of expressional changes induced by intrauterine growth restriction in the developing rat pancreas.

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    Zhang, Lin; Chen, Wei; Dai, Yuee; Zhu, Ziyang; Liu, Qianqi

    2016-07-01

    Intrauterine growth retardation (IUGR) is a disorder that can result in permanent changes in the physiology and metabolism of the newborn, which increased the risk of disease in adulthood. Evidence supports IUGR as a risk factor for the development of diabetes mellitus, which could reflect changes in pancreas developmental pathways. We sought to characterize the IUGR-induced alterations of the complex pathways of pancreas development in a rat model of IUGR. We analyzed the pancreases of Sprague Dawley rats after inducing IUGR by feeding a maternal low calorie diet from gestational day 1 until term. IUGR altered the pancreatic structure, islet areas, and islet quantities and resulted in abnormal morphological changes during pancreatic development, as determined by HE staining and light microscopy. We identified multiple differentially expressed genes in the pancreas by RT-PCR. The genes of the insulin/FoxO1/Pdx1/MafA signaling pathway were first expressed at embryonic day 14 (E14). The expressions of insulin and MafA increased as the fetus grew while the expressions of FoxO1 and Pdx1 decreased. Compared with the control rats, the expressions of FoxO1, Pdx1, and MafA were lower in the IUGR rats, whereas insulin levels showed no change. Microarray profiling, in combination with quantitative real-time PCR, uncovered a subset of microRNAs that changed in their degree of expression throughout pancreatic development. In conclusion, our data support the hypothesis that IUGR influences the development of the rat pancreas. We also identified new pathways that appear to be programmed by IUGR. © 2016 by the Society for Experimental Biology and Medicine.

  11. Factor VIII levels and the risk of pre-eclampsia, HELLP syndrome, pregnancy related hypertension and severe intrauterine growth retardation.

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    Witsenburg, C P J; Rosendaal, F R; Middeldorp, J M; Van der Meer, F J M; Scherjon, S A

    2005-01-01

    Recently, acquired as well as genetic prothrombotic factors are associated with thrombotic events. These factors have also been related to conditions of uteroplacental insufficiency such as pre-eclampsia, HELLP syndrome and severe intrauterine growth restriction (IUGR). The aim of this study was to determine whether elevated factor VIII levels are associated with uteroplacental insufficiency, in particular pre-eclampsia, HELLP syndrome or pregnancy-induced hypertension and intrauterine growth retardation. Plasma samples of 75 women with a history of pregnancy complicated by pre-eclampsia, HELLP syndrome, pregnancy induced hypertension or intrauterine growth restriction were tested for factor VIII:C (FVIII:C) levels at a minimum of 10 weeks post-partum. Laboratory results were compared to factor VIII:C levels found in a healthy control group of 272 women. Mean factor VIII:C levels were similar at 123 IU/dl in both the patient group and the controls. In a logistic regression model, after adjusting for age and blood group, no effect of factor VIII:C levels on the risk of pregnancy complications was observed, with the exception of IUGR with (OR 2.9, CI 1.0-8.7) or without hypertension (OR 2.0, CI 0.7-6.4). If the elevated level of factor VIII would be the sole factor responsible for the increased risk observed, one would expect to find an effect of blood group on risk as well (blood group being an important determinant of FVIII:C). While no such effect could be shown a causal relationship between elevated levels of factor VIII and conditions of uteroplacental insufficiency such as pre-eclampsia, HELLP syndrome, pregnancy-induced hypertension and IUGR is not very likely.

  12. Associations between neural injury markers of intrauterine growth-restricted infants and neurodevelopment at 2 years of age.

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    Mazarico, E; Llurba, E; Cabero, L; Sánchez, O; Valls, A; Martín-Ancel, A; Cardenas, D; Gómez Roig, M D

    2018-04-18

    The aim of this study was to evaluate the relationships between brain injury biomarkers in intrauterine growth-restricted (IUGR) infants (S100B and neuron-specific enolase (NSE)) and neurodevelopment at 2 years of age. This prospective case-control study was a cooperative effort among Spanish Maternal and Child Health Network (Retic SAMID) hospitals. At inclusion, biometry for estimated fetal weight and feto-placental Doppler variables were measured for each infant. Maternal venous blood and fetal umbilical arterial blood samples were collected at the time of delivery and neural injury markers S100B and NSE concentrations were measured. Neurodevelopment was evaluated at 2 years of age using the Bayley Scales of Infant and Toddler Development, third edition (Bayley-III). Fifty six pregnancies were included. Thirty-one infants were classified as IUGR and 25 as non-IUGR. Neurodevelopmental evaluation at 2 years of age indicated that there were no between-group differences for any of the tests. For all patients in both groups, we found statistically significant inverse relationships between the concentrations of NSE in the cord blood and the results of the cognitive test (r = -271, p = .042), fine motor subtest (r = -280, p = .036), and social-emotional test (r = -349, p = .015). We also found statistically significant differences between the concentrations of S100B in the cord blood and the results of the cognitive test (r = -306, p = .022) and expressive communication subtest (r = -304, p = .023). For the IUGR group, we found a significant inverse relationship between the concentrations of S100B in the maternal serum and the results of adaptive behavior test (p < .05). In the non-IUGR group, we found statistically significant inverse relationships between the concentration of NSE in the cord blood and the results of the fine motor subtest (r = -446, p = .025) and social-emotional test (r = -489, p = .021

  13. Identification of placental nutrient transporters associated with intrauterine growth restriction and pre-eclampsia.

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    Huang, Xiao; Anderle, Pascale; Hostettler, Lu; Baumann, Marc U; Surbek, Daniel V; Ontsouka, Edgar C; Albrecht, Christiane

    2018-03-02

    Gestational disorders such as intrauterine growth restriction (IUGR) and pre-eclampsia (PE) are main causes of poor perinatal outcomes worldwide. Both diseases are related with impaired materno-fetal nutrient transfer, but the crucial transport mechanisms underlying IUGR and PE are not fully elucidated. In this study, we aimed to identify membrane transporters highly associated with transplacental nutrient deficiencies in IUGR/PE. In silico analyses on the identification of differentially expressed nutrient transporters were conducted using seven eligible microarray datasets (from Gene Expression Omnibus), encompassing control and IUGR/PE placental samples. Thereby 46 out of 434 genes were identified as potentially interesting targets. They are involved in the fetal provision with amino acids, carbohydrates, lipids, vitamins and microelements. Targets of interest were clustered into a substrate-specific interaction network by using Search Tool for the Retrieval of Interacting Genes. The subsequent wet-lab validation was performed using quantitative RT-PCR on placentas from clinically well-characterized IUGR/PE patients (IUGR, n = 8; PE, n = 5; PE+IUGR, n = 10) and controls (term, n = 13; preterm, n = 7), followed by 2D-hierarchical heatmap generation. Statistical evaluation using Kruskal-Wallis tests was then applied to detect significantly different expression patterns, while scatter plot analysis indicated which transporters were predominantly influenced by IUGR or PE, or equally affected by both diseases. Identified by both methods, three overlapping targets, SLC7A7, SLC38A5 (amino acid transporters), and ABCA1 (cholesterol transporter), were further investigated at the protein level by western blotting. Protein analyses in total placental tissue lysates and membrane fractions isolated from disease and control placentas indicated an altered functional activity of those three nutrient transporters in IUGR/PE. Combining bioinformatic analysis

  14. Early functional and morphological brain disturbances in late-onset intrauterine growth restriction.

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    Starčević, Mirta; Predojević, Maja; Butorac, Dražan; Tumbri, Jasna; Konjevoda, Paško; Kadić, Aida Salihagić

    2016-02-01

    To determine whether the brain disturbances develop in late-onset intrauterine growth restriction (IUGR) before blood flow redistribution towards the fetal brain (detected by Doppler measurements in the middle cerebral artery and umbilical artery). Further, to evaluate predictive values of Doppler arterial indices and umbilical cord blood gases and pH for early functional and/or morphological brain disturbances in late-onset IUGR. This cohort study included 60 singleton term pregnancies with placental insufficiency caused late-onset IUGR (IUGR occurring after 34 gestational weeks). Umbilical artery resistance index (URI), middle cerebral artery resistance index (CRI), and cerebroumbilical (C/U) ratio (CRI/URI) were monitored once weekly. Umbilical blood cord samples (arterial and venous) were collected for the analysis of pO2, pCO2 and pH. Morphological neurological outcome was evaluated by cranial ultrasound (cUS), whereas functional neurological outcome by Amiel-Tison Neurological Assessment at Term (ATNAT). 50 fetuses had C/U ratio>1, and 10 had C/U ratio≤1; among these 10 fetuses, 9 had abnormal neonatal cUS findings and all 10 had non-optimal ATNAT. However, the total number of abnormal neurological findings was much higher. 32 neonates had abnormal cUS (53.37%), and 42 (70.00%) had non-optimal ATNAT. Furthermore, Doppler indices had higher predictive validity for early brain disturbances than umbilical cord blood gases and pH. C/U ratio had the highest predictive validity with threshold for adverse neurological outcome at value 1.13 (ROC analysis), i.e., 1.18 (party machine learning algorithm). Adverse neurological outcome at average values of C/U ratios>1 confirmed that early functional and/or structural brain disturbances in late-onset IUGR develop even before activation of fetal cardiovascular compensatory mechanisms, i.e., before Doppler signs of blood flow redistribution between the fetal brain and the placenta. Copyright © 2015 Elsevier Ireland Ltd

  15. CORRELATION OF CEREBROPLACENTAL RATIO WITH PERINATAL OUTCOME IN INTRAUTERINE GROWTH RESTRICTION

    Directory of Open Access Journals (Sweden)

    Sajala Vimalraj

    2016-07-01

    Full Text Available BACKGROUND Doppler velocimetry is a non-invasive method of measuring changes in blood flow. (1,2,3 Randomised Control Trials (RCTs have shown that using Doppler indices in the management of Intrauterine Growth Restriction (IUGR cases leads to a significant reduction in perinatal mortality rate. Deterioration of various Doppler indices precedes abnormal Biophysical Profile (BPP by 1-2 weeks. (1,2,3,4 Umbilical artery indices only reflect the placental status. Fetal response to this increasing placental insufficiency can be deduced from studying the Cerebroplacental Ratio {CPR}, which gives us an idea of the fetal response to the placental status and is potentially more advantageous in predicting fetal outcome. OBJECTIVES To compare CPR in predicting fetal outcome with UA and MCA indices. MATERIALS AND METHODS Prospective cohort study of cases of IUGR - January 2013 to December 2013. 180 cases of clinically diagnosed IUGR were selected. Obstetric USG and Doppler was performed. The S/D ratio, RI, PR values were obtained and CPR calculated. All cases were managed as per the protocol then in place using U/A SD ratios for determining the timing & mode of termination RESULTS Of 180 cases of IUGR were selected most women were primigravidae, 20-34 years, and from low socio-economic status. (3 25 women (13.8% had oligohydramnios (AFI <5. Of these women, 24 had an abnormal CPR, 1 normal CPR. 47% with abnormal CPR had caesarean for fetal distress. Birth weight was <1.5 kg in 14.4% of patients all of whom were in the abnormal CPR group. 7.5% had an Apgar <7; all these babies were in the abnormal CPR group. 43.9% of babies from the abnormal CPR group needed resuscitation. 79% of the abnormal CPR group babies needed NICU admission. CONCLUSION Utilization of only UA and MCA indices may cause unnecessary early intervention in some cases. (1,5 CPR can help triage pregnancies in need of termination while prolonging those which are relatively stable so as to gain

  16. Doppler changes as the earliest parameter in fetal surveillance to detect fetal compromise in intrauterine growth-restricted fetuses

    Directory of Open Access Journals (Sweden)

    Bansal Saloni

    2016-01-01

    Full Text Available Introduction. It is estimated that 3-10% of infants are growth restricted. Growth disturbances may have long-term issues. Doppler allows insight into the fetal response to intrauterine stress. Objective. The aim of this study was to detect fetal compromise in intrauterine growth-restricted (IUGR fetuses by means of biophysical profile (BPP vis-а-vis Doppler velocimetry studies of the fetal umbilical artery, and to find out which of the two is a better and earlier predictor of fetal compromise. Methods. A prospective study was conducted on a total of 50 singleton pregnancies with IUGR between 28 and 42 weeks of gestation. Study patients were managed expectantly with nonstress testing and amniotic fluid assessment, BPP and Doppler velocimetry studies of the fetal umbilical artery. Results. Fetal outcome was poor in 5/50 (10% of the fetuses, defined as presence of all of the following: poor Apgar test score, neonatal intensive care unit stay, necrotizing enterocolitis, and low birth weight. Of the four with abnormal BPP, 50% had poor fetal outcomes. Out of 46 with normal BPP, 6.5% had poor fetal outcomes. Conclusion. Inference drawn from the study is that the Doppler technology provides us the opportunity for repetitive noninvasive hemodynamic monitoring in IUGR pregnancies.

  17. Developmental Programming of Cardiovascular Disease Following Intrauterine Growth Restriction: Findings Utilising A Rat Model of Maternal Protein Restriction

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    Zohdi, Vladislava; Lim, Kyungjoon; Pearson, James T.; Black, M. Jane

    2014-01-01

    Over recent years, studies have demonstrated links between risk of cardiovascular disease in adulthood and adverse events that occurred very early in life during fetal development. The concept that there are embryonic and fetal adaptive responses to a sub-optimal intrauterine environment often brought about by poor maternal diet that result in permanent adverse consequences to life-long health is consistent with the definition of “programming”. The purpose of this review is to provide an overview of the current knowledge of the effects of intrauterine growth restriction (IUGR) on long-term cardiac structure and function, with particular emphasis on the effects of maternal protein restriction. Much of our recent knowledge has been derived from animal models. We review the current literature of one of the most commonly used models of IUGR (maternal protein restriction in rats), in relation to birth weight and postnatal growth, blood pressure and cardiac structure and function. In doing so, we highlight the complexity of developmental programming, with regards to timing, degree of severity of the insult, genotype and the subsequent postnatal phenotype. PMID:25551250

  18. Intrauterine growth restriction and placental gene expression in severe preeclampsia, comparing early-onset and late-onset forms.

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    Nevalainen, Jaana; Skarp, Sini; Savolainen, Eeva-Riitta; Ryynänen, Markku; Järvenpää, Jouko

    2017-10-26

    To evaluate placental gene expression in severe early- or late-onset preeclampsia with intrauterine growth restriction compared to controls. Chorionic villus sampling was conducted after cesarean section from the placentas of five women with early- or late-onset severe preeclampsia and five controls for each preeclampsia group. Microarray analysis was performed to identify gene expression differences between the groups. Pathway analysis showed over-representation of gene ontology (GO) biological process terms related to inflammatory and immune response pathways, platelet development, vascular development, female pregnancy and reproduction in early-onset preeclampsia. Pathways related to immunity, complement and coagulation cascade were overrepresented in the hypergeometric test for the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Ten genes (ABI3BP, C7, HLA-G, IL2RB, KRBOX1, LRRC15, METTL7B, MPP5, RFLNB and SLC20A) had a ≥±1 fold expression difference in severe early-onset preeclampsia group compared to early controls. There were 362 genes that had a ≥±1 fold expression difference in severe early-onset preeclampsia group compared to late-onset preeclampsia group including ABI3BP, C7, HLA-G and IL2RB. There are significant differences in placental gene expression between severe early- and late-onset preeclampsia when both are associated with intrauterine growth restriction. ABI3BP, C7, HLA-G and IL2RB might contribute to the development of early form of severe preeclampsia.

  19. IVF culture medium affects human intrauterine growth as early as the second trimester of pregnancy.

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    Nelissen, Ewka C M; Van Montfoort, Aafke P A; Smits, Luc J M; Menheere, Paul P C A; Evers, Johannes L H; Coonen, Edith; Derhaag, Josien G; Peeters, Louis L; Coumans, Audrey B; Dumoulin, John C M

    2013-08-01

    When does a difference in human intrauterine growth of singletons conceived after IVF and embryo culture in two different culture media appear? Differences in fetal development after culture of embryos in one of two IVF media were apparent as early as the second trimester of pregnancy. Abnormal fetal growth patterns are a major risk factor for the development of chronic diseases in adult life. Previously, we have shown that the medium used for culturing embryos during the first few days after fertilization significantly affects the birthweight of the resulting human singletons. The exact onset of this growth difference was unknown. In this retrospective cohort study, all 294 singleton live births after fresh embryo transfer in the period July 2003 to December 2006 were included. These embryos originated from IVF treatments that were part of a previously described clinical trial. Embryos were allocated to culture in either Vitrolife or Cook commercially available sequential culture media. We analysed ultrasound examinations at 8 (n = 290), 12 (n = 83) and 20 weeks' (n = 206) gestation and used first-trimester serum markers [pregnancy-associated plasma protein-A (PAPP-A) and free β-hCG]. Differences between study groups were tested by the Student's t-test, χ(2) test or Fisher's exact test, and linear multivariable regression analysis to adjust for possible confounders (for example, parity, gestational age at the time of ultrasound and fetal gender). A total of 294 singleton pregnancies (Vitrolife group nVL = 168, Cook group: nC = 126) from 294 couples were included. At 8 weeks' gestation, there was no difference between crown-rump length-based and ovum retrieval-based gestational age (ΔGA) (nVL = 163, nC = 122, adjusted mean difference, -0.04 days, P = 0.84). A total of 83 women underwent first-trimester screening at 12 weeks' gestation (nVL = 45, nC = 38). ΔGA, nuchal translucency (multiples of median, MoM) and PAPP-A (MoM) did not differ between the study

  20. Molecular pathways reflecting poor intrauterine growth are found in Wharton's jelly-derived mesenchymal stem cells.

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    Sukarieh, Rami; Joseph, Roy; Leow, Shi Chi; Li, Ying; Löffler, Mona; Aris, Izzuddin M; Tan, Jun Hao; Teh, Ai Ling; Chen, Li; Holbrook, Joanna D; Ng, Kai Lyn; Lee, Yung Seng; Chong, Yap Seng; Summers, Scott A; Gluckman, Peter D; Stünkel, Walter

    2014-10-10

    Are molecular pathways reflecting the biology of small for gestational age (SGA) neonates preserved in umbilical cord-derived mesenchymal stem cells (MSCs)? MSCs from SGA newborns were found to express an altered EGR-1-dependent gene network involved in the regulation of cell proliferation and oxidative stress. Individuals with suboptimal intrauterine development are at greater risk of metabolic diseases such as type II diabetes, obesity and cardiovascular disease. Umbilical cords (n = 283) from the GUSTO (growing up in Singapore towards healthy outcomes) birth cohort study, and primary MSC isolates established from SGA and matched control cases (n = 6 per group), were subjected to gene expression analysis and candidate genes were studied for functional validation. Umbilical cord specimens were derived from babies born at the National University Hospital (NUH) in Singapore. Local ethical approval was obtained. MSC isolates were established in Wharton's jelly and molecular analysis was conducted by gene expression microarrays and RT-PCR. Cells from SGA and control groups were compared in the presence and absence of insulin and candidate gene function was studied via siRNA-mediated gene knockdown and over-expression experiments in MSCs. Using repeated measure ANOVAs, proliferation rates of MSCs isolated from SGA neonates were found to be significantly increased (P < 0.01). In the absence of insulin, EGR-1 levels were found to be significantly reduced in the group of SGA-derived MSCs, whereas EGR-1 expression was found to be up-regulated in the same group in the presence of insulin (P < 0.01). EGR-1 was found to induce expression of COX-2 in the SGA group (P < 0.01) and both, EGR-1 and COX-2 stimulated glucose uptake in MSCs (P < 0.01). EGR-1 and COX-2 levels were associated in whole umbilical cords (n = 283, P < 0.01) and EGR-1 positively correlated with abdominal circumference and birthweight (n = 91, P < 0.01 and n = 91, P < 0.01). Cell models may not entirely

  1. Intrauterine Growth Restriction Programs the Hypothalamus of Adult Male Rats: Integrated Analysis of Proteomic and Metabolomic Data.

    Science.gov (United States)

    Pedroso, Amanda P; Souza, Adriana P; Dornellas, Ana P S; Oyama, Lila M; Nascimento, Cláudia M O; Santos, Gianni M S; Rosa, José C; Bertolla, Ricardo P; Klawitter, Jelena; Christians, Uwe; Tashima, Alexandre K; Ribeiro, Eliane B

    2017-04-07

    Programming of hypothalamic functions regulating energy homeostasis may play a role in intrauterine growth restriction (IUGR)-induced adulthood obesity. The present study investigated the effects of IUGR on the hypothalamus proteome and metabolome of adult rats submitted to 50% protein-energy restriction throughout pregnancy. Proteomic and metabolomic analyzes were performed by data independent acquisition mass spectrometry and multiple reaction monitoring, respectively. At age 4 months, the restricted rats showed elevated adiposity, increased leptin and signs of insulin resistance. 1356 proteins were identified and 348 quantified while 127 metabolites were quantified. The restricted hypothalamus showed down-regulation of 36 proteins and 5 metabolites and up-regulation of 21 proteins and 9 metabolites. Integrated pathway analysis of the proteomics and metabolomics data indicated impairment of hypothalamic glucose metabolism, increased flux through the hexosamine pathway, deregulation of TCA cycle and the respiratory chain, and alterations in glutathione metabolism. The data suggest IUGR modulation of energy metabolism and redox homeostasis in the hypothalamus of male adult rats. The present results indicated deleterious consequences of IUGR on hypothalamic pathways involved in pivotal physiological functions. These results provide guidance for future mechanistic studies assessing the role of intrauterine malnutrition in the development of metabolic diseases later in life.

  2. Myeloperoxidase in the plasma and placenta of normal pregnant women and women with pregnancies complicated by preeclampsia and intrauterine growth restriction.

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    Hung, T-H; Chen, S-F; Lo, L-M; Li, M-J; Yeh, Y-L; Hsieh, T-T

    2012-04-01

    Myeloperoxidase (MPO) is a heme protein produced and released by activated neutrophils and monocytes, and increased MPO is considered important in the pathophysiology of cardiovascular diseases (CVD). Accumulating evidence suggests that preeclampsia (PE), idiopathic intrauterine growth restriction (IUGR), and CVD share many similar metabolic disturbances, including an enhanced systemic inflammatory response and endothelial dysfunction. We hypothesized that MPO plays an important role in the development of PE and IUGR. Plasma samples were collected mid-gestation and at delivery from women with normal pregnancies (n = 40) and those who subsequently developed PE (n = 20), IUGR (n = 11) or both (PE + IUGR, n = 8). Placental samples were obtained immediately after delivery from 22 women with normal pregnancies, 19 women with PE, 14 women with IUGR, and 14 women with PE + IUGR. The MPO concentrations were measured using ELISA. Women with PE + IUGR had significantly higher plasma MPO before delivery than normal pregnant women. There was no difference in plasma levels at mid-gestation or the placental concentrations between women with normal pregnancies and those who developed PE, IUGR, or PE + IUGR. Using explants prepared from the placentas of 8 women with normal pregnancies and 8 women with PE, we found no difference in the levels of MPO in the tissue homogenates and culture media between these two groups of women. Together, these results indicate that increased maternal circulating MPO in women with PE + IUGR is likely a result of enhanced systemic inflammation caused by the established disease rather than a primary pathophysiological factor. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Intrauterine growth restriction decreases pulmonary alveolar and vessel growth and causes pulmonary artery endothelial cell dysfunction in vitro in fetal sheep

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    Seedorf, Gregory J.; Brown, Alicia; Roe, Gates; O'Meara, Meghan C.; Gien, Jason; Tang, Jen-Ruey; Abman, Steven H.

    2011-01-01

    Intrauterine growth restriction (IUGR) increases the risk for bronchopulmonary dysplasia (BPD). Abnormal lung structure has been noted in animal models of IUGR, but whether IUGR adversely impacts fetal pulmonary vascular development and pulmonary artery endothelial cell (PAEC) function is unknown. We hypothesized that IUGR would decrease fetal pulmonary alveolarization, vascular growth, and in vitro PAEC function. Studies were performed in an established model of severe placental insufficiency and IUGR induced by exposing pregnant sheep to elevated temperatures. Alveolarization, quantified by radial alveolar counts, was decreased 20% (P growth by 68% (P growth was reduced in IUGR PAECs by 29% at baseline (P growth and PAEC dysfunction in vitro. This may contribute to the increased risk for adverse respiratory outcomes and BPD in infants with IUGR. PMID:21873446

  4. A Common Profile of Disordered Angiogenic Factor Production and the Exacerbation of Inflammation in Early Preeclampsia, Late Preeclampsia, and Intrauterine Growth Restriction.

    Science.gov (United States)

    Kwiatkowski, Sebastian; Dołęgowska, Barbara; Kwiatkowska, Ewa; Rzepka, Rafał; Torbè, Andrzej; Bednarek-Jędrzejek, Magdalena

    2016-01-01

    Preeclampsia and intrauterine growth restriction are two separate disease entities that, according to numerous reports, share the same pathogenesis. In both, angiogenesis disorders and generalized inflammation are the dominant symptoms. In this study, we hypothesized that both diseases demonstrate the same profile in early preeclampsia, late preeclampsia, and intrauterine growth restriction patients, with the only difference being the degree of exacerbation of lesions. One hundred sixty-seven patients were enrolled in the study and divided into four groups: early preeclampsia, late preeclampsia, and intrauterine growth restriction groups, and one control group. Concentrations of the angiogenesis and inflammatory markers soluble fms-like tyrosine kinase receptor 1, placental growth factor, high-sensitivity C-reactive protein, and interleukin-6 were determined, and the behavior of these markers and correlations among them were studied. Higher concentrations of soluble fms-like tyrosine kinase receptor 1, high-sensitivity C-reactive protein, and interleukin-6 and a lower concentration of placental growth factor were observed in the study groups compared with the control group. No differences in concentrations of the studied markers were found among the study groups but significant correlations were observed. The higher values for the angiogenesis and inflammatory markers both in preeclampsia patients and patients with intrauterine growth restriction of placental origin compared with the control group suggest the existence of the same underlying disorders in the development of these pathologies. The observed mutual correlations for disordered angiogenesis and inflammatory markers are suggestive of a mutual relationship between these processes in the development of pathologies evolving secondary to placental ischemia. The same lesion profile was observed for both preeclampsia and 'placental' intrauterine growth restriction patients, which could be used in developing

  5. Use of uterine artery Doppler ultrasonography to predict pre-eclampsia and intrauterine growth restriction: a systematic review and bivariable meta-analysis

    NARCIS (Netherlands)

    Cnossen, Jeltsje S.; Morris, Rachel K.; ter Riet, Gerben; Mol, Ben W. J.; van der Post, Joris A. M.; Coomarasamy, Arri; Zwinderman, Aeilko H.; Robson, Stephen C.; Bindels, Patrick J. E.; Kleijnen, Jos; Khan, Khalid S.

    2008-01-01

    BACKGROUND: Alterations in waveforms in the uterine artery are associated with the development of pre-eclampsia and intrauterine growth restriction. We investigated the predictive accuracy of all uterine artery Doppler indices for both conditions in the first and second trimesters. METHODS: We

  6. Differences in the association between maternal serum homocysteine and ADMA levels in women with pregnancies complicated by preeclampsia and/or intrauterine growth restriction.

    Science.gov (United States)

    Laskowska, Marzena; Laskowska, Katarzyna; Oleszczuk, Jan

    2013-01-01

    The aim of our study was to investigate the association between homocysteine and asymmetric dimethylarginine in preeclamptic women with and without intrauterine growth restriction compared with normal healthy uncomplicated pregnancies and normotensive pregnancies complicated by idiopathic isolated intrauterine fetal growth restriction. The maternal serum homocysteine and asymmetric dimethylarginine concentrations were determined using a sandwich enzyme-linked immunosorbent assays. A statistically significant positive correlation of maternal serum homocysteine levels with the serum asymmetric dimethylarginine levels was observed in healthy normotensive uncomplicated pregnant women from the control group and in preeclamptic patients with appropriate-for-gestational-age fetuses (R = 0.380079, p-value = 0.002311* and R = 0.455797, p-value = 0.004030* for the control and the P groups, respectively). However, this correlation was not significant in women with pregnancy complicated by intrauterine growth restriction, both isolated and in the course of severe preeclampsia. These findings provide support for the hypothesis that elevated levels of asymmetric dimethylarginine in pregnancy complicated by preeclampsia are associated with elevated homocysteine levels. But our results also demonstrate that in pregnancies complicated by intrauterine growth restriction, this mechanism is important, although not the only one.

  7. Is blood pressure increased 19 years after intrauterine growth restriction and preterm birth? A prospective follow-up study in the Netherlands

    NARCIS (Netherlands)

    Keijzer-Veen, M.G.; Finken, M.J.J.; Nauta, J.; Dekker, F.W.; Hille, E.T.M.; Frölich, M.; Wit, J.M.; Heijden, A.J. van der

    2005-01-01

    Objective. To determine whether intrauterine growth restriction (IUGR) is a predisposing factor for high blood pressure (BP) in 19-year-olds who were born (very) preterm. Methods. A prospective follow-up study was conducted at age 19 in individuals who born preterm in the Netherlands in 1983.

  8. Glucocorticoid programming of intrauterine development.

    Science.gov (United States)

    Fowden, A L; Valenzuela, O A; Vaughan, O R; Jellyman, J K; Forhead, A J

    2016-07-01

    Glucocorticoids (GCs) are important environmental and maturational signals during intrauterine development. Toward term, the maturational rise in fetal glucocorticoid receptor concentrations decreases fetal growth and induces differentiation of key tissues essential for neonatal survival. When cortisol levels rise earlier in gestation as a result of suboptimal conditions for fetal growth, the switch from tissue accretion to differentiation is initiated prematurely, which alters the phenotype that develops from the genotype inherited at conception. Although this improves the chances of survival should delivery occur, it also has functional consequences for the offspring long after birth. Glucocorticoids are, therefore, also programming signals that permanently alter tissue structure and function during intrauterine development to optimize offspring fitness. However, if the postnatal environmental conditions differ from those signaled in utero, the phenotypical outcome of early-life glucocorticoid receptor overexposure may become maladaptive and lead to physiological dysfunction in the adult. This review focuses on the role of GCs in developmental programming, primarily in farm species. It examines the factors influencing GC bioavailability in utero and the effects that GCs have on the development of fetal tissues and organ systems, both at term and earlier in gestation. It also discusses the windows of susceptibility to GC overexposure in early life together with the molecular mechanisms and long-term consequences of GC programming with particular emphasis on the cardiovascular, metabolic, and endocrine phenotype of the offspring. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Intrauterine Growth Retardation Increases the Susceptibility of Pigs to High-Fat Diet-Induced Mitochondrial Dysfunction in Skeletal Muscle

    Science.gov (United States)

    Liu, Jingbo; Chen, Daiwen; Yao, Ying; Yu, Bing; Mao, Xiangbing; He, Jun; Huang, Zhiqing; Zheng, Ping

    2012-01-01

    It has been recognized that there is a relationship between prenatal growth restriction and the development of metabolic-related diseases in later life, a process involved in mitochondrial dysfunction. In addition, intrauterine growth retardation (IUGR) increases the susceptibility of offspring to high-fat (HF) diet-induced metabolic syndrome. Recent findings suggested that HF feeding decreased mitochondrial oxidative capacity and impaired mitochondrial function in skeletal muscle. Therefore, we hypothesized that the long-term consequences of IUGR on mitochondrial biogenesis and function make the offspring more susceptible to HF diet-induced mitochondrial dysfunction. Normal birth weight (NBW), and IUGR pigs were allotted to control or HF diet in a completely randomized design, individually. After 4 weeks of feeding, growth performance and molecular pathways related to mitochondrial function were determined. The results showed that IUGR decreased growth performance and plasma insulin concentrations. In offspring fed a HF diet, IUGR was associated with enhanced plasma leptin levels, increased concentrations of triglyceride and malondialdehyde (MDA), and reduced glycogen and ATP contents in skeletal muscle. High fat diet-fed IUGR offspring exhibited decreased activities of lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G6PD). These alterations in metabolic traits of IUGR pigs were accompanied by impaired mitochondrial respiration function, reduced mitochondrial DNA (mtDNA) contents, and down-regulated mRNA expression levels of genes responsible for mitochondrial biogenesis and function. In conclusion, our results suggest that IUGR make the offspring more susceptible to HF diet-induced mitochondrial dysfunction. PMID:22523560

  10. Tyrosine phosphorylation of Kv1.5 is upregulated in intrauterine growth retardation rats with exaggerated pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    L.C. Fu

    2017-09-01

    Full Text Available Intrauterine growth retardation (IUGR is associated with the development of adult-onset diseases, including pulmonary hypertension. However, the underlying mechanism of the early nutritional insult that results in pulmonary vascular dysfunction later in life is not fully understood. Here, we investigated the role of tyrosine phosphorylation of voltage-gated potassium channel 1.5 (Kv1.5 in this prenatal event that results in exaggerated adult vascular dysfunction. A rat model of chronic hypoxia (2 weeks of hypoxia at 12 weeks old following IUGR was used to investigate the physiological and structural effect of intrauterine malnutrition on the pulmonary artery by evaluating pulmonary artery systolic pressure and vascular diameter in male rats. Kv1.5 expression and tyrosine phosphorylation in pulmonary artery smooth muscle cells (PASMCs were determined. We found that IUGR increased mean pulmonary artery pressure and resulted in thicker pulmonary artery smooth muscle layer in 14-week-old rats after 2 weeks of hypoxia, while no difference was observed in normoxia groups. In the PASMCs of IUGR-hypoxia rats, Kv1.5 mRNA and protein expression decreased while that of tyrosine-phosphorylated Kv1.5 significantly increased. These results demonstrate that IUGR leads to exaggerated chronic hypoxia pulmonary arterial hypertension (CH-PAH in association with decreased Kv1.5 expression in PASMCs. This phenomenon may be mediated by increased tyrosine phosphorylation of Kv1.5 in PASMCs and it provides new insight into the prevention and treatment of IUGR-related CH-PAH.

  11. The effects of sildenafil citrate on feto-placental development and haemodynamics in a rabbit model of intrauterine growth restriction.

    Science.gov (United States)

    López-Tello, Jorge; Arias-Álvarez, María; Jiménez-Martínez, Maria-Ángeles; Barbero-Fernández, Alicia; García-García, Rosa María; Rodríguez, María; Lorenzo, Pedro L; Torres-Rovira, Laura; Astiz, Susana; González-Bulnes, Antonio; Rebollar, Pilar G

    2017-06-01

    The present study evaluated the effectiveness of sildenafil citrate (SC) to improve placental and fetal growth in a diet-induced rabbit model of intrauterine growth restriction (IUGR). Pregnant rabbits were fed either ad libitum (Group C) or restricted to 50% of dietary requirements (Group R) or restricted and treated with SC (Group SC). The treatment with SC improved placental development by increasing vascularity and vessel hypertrophy in the decidua. The assessment of feto-placental haemodynamics showed higher resistance and pulsatility indices at the middle cerebral artery (MCA) in fetuses treated with SC when compared with Group R, which had increased systolic peak and time-averaged mean velocities at the MCA. Furthermore, fetuses in the SC group had significantly higher biparietal and thoracic diameters and longer crown-rump lengths than fetuses in Group R. Hence, the SC group had a reduced IUGR rate and a higher kit size at birth compared with Group R. In conclusion, SC may provide potential benefits in pregnancies with placental insufficiency and IUGR, partially counteracting the negative effects of food restriction on placental development and fetal growth. However, the present study also found evidence of a possible blood overflow in the brain that warrants further investigation.

  12. N-Acetylcysteine, a glutathione precursor, reverts vascular dysfunction and endothelial epigenetic programming in intrauterine growth restricted guinea pigs.

    Science.gov (United States)

    Herrera, Emilio A; Cifuentes-Zúñiga, Francisca; Figueroa, Esteban; Villanueva, Cristian; Hernández, Cherie; Alegría, René; Arroyo-Jousse, Viviana; Peñaloza, Estefania; Farías, Marcelo; Uauy, Ricardo; Casanello, Paola; Krause, Bernardo J

    2017-02-15

    Intrauterine growth restriction (IUGR) is associated with vascular dysfunction, oxidative stress and signs of endothelial epigenetic programming of the umbilical vessels. There is no evidence that this epigenetic programming is occurring on systemic fetal arteries. In IUGR guinea pigs we studied the functional and epigenetic programming of endothelial nitric oxide synthase (eNOS) (Nos3 gene) in umbilical and systemic fetal arteries, addressing the role of oxidative stress in this process by maternal treatment with N-acetylcysteine (NAC) during the second half of gestation. The present study suggests that IUGR endothelial cells have common molecular markers of programming in umbilical and systemic arteries. Notably, maternal treatment with NAC restores fetal growth by increasing placental efficiency and reverting the functional and epigenetic programming of eNOS in arterial endothelium in IUGR guinea pigs. In humans, intrauterine growth restriction (IUGR) is associated with vascular dysfunction, oxidative stress and signs of endothelial programming in umbilical vessels. We aimed to determine the effects of maternal antioxidant treatment with N-acetylcysteine (NAC) on fetal endothelial function and endothelial nitric oxide synthase (eNOS) programming in IUGR guinea pigs. IUGR was induced by implanting ameroid constrictors on uterine arteries of pregnant guinea pigs at mid gestation, half of the sows receiving NAC in the drinking water (from day 34 until term). Fetal biometry and placental vascular resistance were followed by ultrasound throughout gestation. At term, umbilical arteries and fetal aortae were isolated to assess endothelial function by wire-myography. Primary cultures of endothelial cells (ECs) from fetal aorta, femoral and umbilical arteries were used to determine eNOS mRNA levels by quantitative PCR and analyse DNA methylation in the Nos3 promoter by pyrosequencing. Doppler ultrasound measurements showed that NAC reduced placental vascular resistance

  13. Intrauterine growth retardation and consequences for endocrine and cardiovascular diseases in adult life

    DEFF Research Database (Denmark)

    Jensen, Rikke Bodin Beck; Chellakooty, Marla; Vielwerth, Signe

    2003-01-01

    Low birth weight has been associated with an increased incidence of ischaemic heart disease (IHD) and type 2 diabetes. Endocrine regulation of fetal growth by growth hormone (GH) and insulin-like growth factor (IGF)-I is complex. Placental GH is detectable in maternal serum from the 8th to the 12...... postnatal growth, insulin resistance and consequently the risk of cardiovascular disease. Thus IGF-I may serve as a link between fetal growth and adult-onset disease.......Low birth weight has been associated with an increased incidence of ischaemic heart disease (IHD) and type 2 diabetes. Endocrine regulation of fetal growth by growth hormone (GH) and insulin-like growth factor (IGF)-I is complex. Placental GH is detectable in maternal serum from the 8th to the 12th...

  14. Apolipoprotein E Genotype in Very Preterm Neonates with Intrauterine Growth Restriction: An Analysis of the German Neonatal Network Cohort

    Directory of Open Access Journals (Sweden)

    Stephen Norda

    2017-01-01

    Full Text Available Aim. Cord blood of intrauterine growth restricted (IUGR neonates displays lipid changes towards atherosclerotic profiles. Apolipoprotein E (ApoE and its isoforms (e2, e3, and e4 are involved in the regulation of lipid metabolism. Specifically, ApoE e4 has been associated with atherosclerotic diseases, while e2 has a favorable effect. We therefore hypothesized that ApoE e4 haplotype is frequently observed in IUGR neonates and contributes to impaired fetal growth and the association of IUGR with cardiovascular and metabolic diseases later in life. Methods. A cohort of 4885 preterm infants (≥22+0 and 10th birth weight percentile. Analysis of the single nucleotides rs429358 and rs7412, identifying the ApoE genotype, was carried out using TaqMan® SNP genotyping assays. The proportional odds model was used to assess data. Results. No association was found between genotype and birth weight percentiles in each of the subgroups. Conclusion. ApoE genotype and low birth weight depict two distinct risk factors for cardiovascular disease without being directly associated.

  15. Apolipoprotein E Genotype in Very Preterm Neonates with Intrauterine Growth Restriction: An Analysis of the German Neonatal Network Cohort.

    Science.gov (United States)

    Norda, Stephen; Rausch, Tanja K; Orlikowsky, Thorsten; Hütten, Matthias; Schulz, Sören; Göpel, Wolfgang; Pecks, Ulrich

    2017-01-01

    Aim. Cord blood of intrauterine growth restricted (IUGR) neonates displays lipid changes towards atherosclerotic profiles. Apolipoprotein E (ApoE) and its isoforms (e2, e3, and e4) are involved in the regulation of lipid metabolism. Specifically, ApoE e4 has been associated with atherosclerotic diseases, while e2 has a favorable effect. We therefore hypothesized that ApoE e4 haplotype is frequently observed in IUGR neonates and contributes to impaired fetal growth and the association of IUGR with cardiovascular and metabolic diseases later in life. Methods. A cohort of 4885 preterm infants (≥22+0 and 10th birth weight percentile. Analysis of the single nucleotides rs429358 and rs7412, identifying the ApoE genotype, was carried out using TaqMan® SNP genotyping assays. The proportional odds model was used to assess data. Results. No association was found between genotype and birth weight percentiles in each of the subgroups. Conclusion. ApoE genotype and low birth weight depict two distinct risk factors for cardiovascular disease without being directly associated.

  16. Verbal short-term memory span in children: long-term modality dependent effects of intrauterine growth restriction.

    Science.gov (United States)

    Geva, R; Eshel, R; Leitner, Y; Fattal-Valevski, A; Harel, S

    2008-12-01

    Recent reports showed that children born with intrauterine growth restriction (IUGR) are at greater risk of experiencing verbal short-term memory span (STM) deficits that may impede their learning capacities at school. It is still unknown whether these deficits are modality dependent. This long-term, prospective design study examined modality-dependent verbal STM functions in children who were diagnosed at birth with IUGR (n = 138) and a control group (n = 64). Their STM skills were evaluated individually at 9 years of age with four conditions of the Visual-Aural Digit Span Test (VADS; Koppitz, 1981): auditory-oral, auditory-written, visuospatial-oral and visuospatial-written. Cognitive competence was evaluated with the short form of the Wechsler Intelligence Scales for Children--revised (WISC-R95; Wechsler, 1998). We found IUGR-related specific auditory-oral STM deficits (p long-term relationship between prenatal aberrant head growth and auditory verbal STM deficits by the end of the first decade of life. Empirical, clinical and educational implications are presented.

  17. Temporal proteomic analysis reveals defects in small-intestinal development of porcine fetuses with intrauterine growth restriction.

    Science.gov (United States)

    Wang, Xiaoqiu; Lin, Gang; Liu, Chuang; Feng, Cuiping; Zhou, Huaijun; Wang, Taiji; Li, Defa; Wu, Guoyao; Wang, Junjun

    2014-07-01

    The fetus/neonate with intrauterine growth restriction (IUGR) has a high perinatal mortality and morbidity rate, as well as reduced efficiency for nutrients utilization. Our previous studies showed alterations of intestinal proteome in IUGR piglets both at birth and during the nursing period. Considering the potential long-term impacts of fetal programming and substantial increases in amounts of amniotic fluid nutrients from mid-gestation in pigs, the present study involved IUGR porcine fetuses from days 60 to 110 of gestation (mid to late gestation). We identified 59 differentially expressed proteins in the fetal small intestine that are related to intestinal growth, development and reprogramming. Our results further indicated increased abundances of proteins and enzymes associated with oxidative stress, apoptosis and protein degradation, as well as decreased abundances of proteins that are required for maintenance of cell structure and motility, absorption and transport of nutrients, energy metabolism, and protein synthesis in the fetal gut. Moreover, IUGR from middle to late gestation was associated with reduced expression of intestinal proteins that participate in regulation of gene expression and signal transduction. Collectively, these findings provide the first evidence for altered proteomes in the small intestine of IUGR fetuses, thereby predisposing the gut to metabolic defects during gestation and neonatal periods. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Alterations in expression of imprinted genes from the H19/IGF2 loci in a multigenerational model of intrauterine growth restriction (IUGR).

    Science.gov (United States)

    Gonzalez-Rodriguez, Pablo; Cantu, Jessica; O'Neil, Derek; Seferovic, Maxim D; Goodspeed, Danielle M; Suter, Melissa A; Aagaard, Kjersti M

    2016-05-01

    The H19/IGF2 imprinted loci have attracted recent attention because of their role in cellular differentiation and proliferation, heritable gene regulation, and in utero or early postnatal growth and development. Expression from the imprinted H19/IGF2 locus involves a complex interplay of 3 means of epigenetic regulation: proper establishment of DNA methylation, promoter occupancy of CTCF, and expression of microRNA-675. We have demonstrated previously in a multigenerational rat model of intrauterine growth restriction the epigenetic heritability of adult metabolic syndrome in a F2 generation. We have further demonstrated abrogation of the F2 adult metabolic syndrome phenotype with essential nutrient supplementation of intermediates along the 1-carbon pathway and shown that alterations in the metabolome precede the adult onset of metabolic syndrome. The upstream molecular and epigenomic mediators underlying these observations, however, have yet to be elucidated fully. In the current study, we sought to characterize the impact of the intrauterine growth-restricted lineage and essential nutrient supplementation on both levels and molecular mediators of H19 and IGF2 gene expression in the F2 generation. F2 intrauterine growth-restricted and sham lineages were obtained by exposing P1 (grandmaternal) pregnant dams to bilateral uterine artery ligation or sham surgery at gestational day 19.5. F1 pups were allocated to the essential nutrient supplemented or control diet at postnatal day 21, and bred at 6-7 weeks of age. Hepatic tissues from the resultant F2 offspring at birth and at weaning (day 21) were obtained. Bisulfite modification and sequencing was employed for methylation analysis. H19 and IGF2 expression was measured by quantitative polymerase chain reaction. Promoter occupancy was quantified by the use of chromatin immunoprecipitation, or ChIP, against CTCF insulator proteins. Growth-restricted F2 on control diet demonstrated significant down-regulation in H19

  19. Frizzled-4 Variations Associated with Retinopathy and Intrauterine Growth Retardation: A Potential Marker for Prematurity and Retinopathy.

    Science.gov (United States)

    Dailey, Wendy A; Gryc, Wojciech; Garg, Pooja G; Drenser, Kimberly A

    2015-09-01

    To present the association between mutations affecting the Wnt-signaling receptor protein (FZD4), inherited vitreoretinopathies, and retinopathy of prematurity (ROP). Retrospective analysis of prospective samples at a tertiary referral center. Patients referred to our practice for management of a variety of pediatric vitreoretinopathies were offered participation in an ophthalmic biobank (421 participants with vitreoretinopathies were included in this study). Full-term healthy infants (n = 98) were recruited to the study as controls. Patients with various vitreoretinopathies were prospectively enrolled in an ophthalmic biobank, approved by the Human Investigation Committee at William Beaumont Hospital. Retrospective genetic analysis of the FZD4 gene was performed (Sanger sequencing). Participants with a diagnosis of familial exudative vitreoretinopathy (FEVR), Norrie disease, Coats' disease, bilateral persistent fetal vasculature, and ROP were reviewed for the presence of a FZD4 variant. Data retrieval included status of retinopathy (including staging when possible), gestational age (GA), birth weight (BW) (when available), and family and birth histories. The association of FZD4 variants with the presence of vitreoretinopathy. The sequence variation p.[P33S(;)P168S] is the most prevalent FZD4 variant and is statistically significant for ROP and FEVR (P = 4.6E-04 and P = 2.4E-03, respectively) compared with full-term newborns (P = 1.7E-01). In addition, infants expressing the sequence variation tended to have significantly lower BWs for respective GA (P = 0.04). This suggests that the FZD4 p.[P33S(;)P168S] variant may be a risk factor for retinopathy and restricted intrauterine growth. Testing for FZD4 gene mutations is useful in patients with suspected FEVR and ROP. The relatively high prevalence of the p.[P33S(;)P168S] variant in ROP and intrauterine growth restriction suggests that it also may be a marker for increased risk of developing ROP and preterm birth

  20. Intrauterine growth retardation increases the susceptibility of pigs to high-fat diet-induced mitochondrial dysfunction in skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Jingbo Liu

    Full Text Available It has been recognized that there is a relationship between prenatal growth restriction and the development of metabolic-related diseases in later life, a process involved in mitochondrial dysfunction. In addition, intrauterine growth retardation (IUGR increases the susceptibility of offspring to high-fat (HF diet-induced metabolic syndrome. Recent findings suggested that HF feeding decreased mitochondrial oxidative capacity and impaired mitochondrial function in skeletal muscle. Therefore, we hypothesized that the long-term consequences of IUGR on mitochondrial biogenesis and function make the offspring more susceptible to HF diet-induced mitochondrial dysfunction. Normal birth weight (NBW, and IUGR pigs were allotted to control or HF diet in a completely randomized design, individually. After 4 weeks of feeding, growth performance and molecular pathways related to mitochondrial function were determined. The results showed that IUGR decreased growth performance and plasma insulin concentrations. In offspring fed a HF diet, IUGR was associated with enhanced plasma leptin levels, increased concentrations of triglyceride and malondialdehyde (MDA, and reduced glycogen and ATP contents in skeletal muscle. High fat diet-fed IUGR offspring exhibited decreased activities of lactate dehydrogenase (LDH and glucose-6-phosphate dehydrogenase (G6PD. These alterations in metabolic traits of IUGR pigs were accompanied by impaired mitochondrial respiration function, reduced mitochondrial DNA (mtDNA contents, and down-regulated mRNA expression levels of genes responsible for mitochondrial biogenesis and function. In conclusion, our results suggest that IUGR make the offspring more susceptible to HF diet-induced mitochondrial dysfunction.

  1. Identification of messenger RNA of fetoplacental source in maternal plasma of women with normal pregnancies and pregnancies with intrauterine growth restriction.

    Science.gov (United States)

    Ayala Ramírez, Paola; García Robles, Reggie; Rojas, Juan Diego; Bermúdez, Martha; Bernal, Jaime

    2012-07-01

    to quantify placenta-specific RNA in plasma of women carrying foetuses with intrauterine growth restriction and pregnant women with normal pregnancies. 8 pregnant women with foetuses with intrauterine growth restriction were studied as well as 18 women with uncomplicated pregnancies in the third pregnancy trimester. Total free RNA was quantified in maternal plasma by spectrophotometry and the gene expression of hPL (Human Placental Lactogen) at the messenger RNA level through technical Real Time-Chain Reaction Polymerase. plasma RNA of fetoplacental origin was successfully detected in 100% of pregnant women. There were no statistically significant differences between the values of total RNA extracted from plasma (p= 0.5975) nor in the messenger RNA expression of hPL gene (p= 0.5785) between cases and controls. messenger RNA of fetoplacental origin can be detected in maternal plasma during pregnancy.

  2. Report of a consultants meeting on causes and consequences of intrauterine growth retardation (IUGR) in populations from developing countries

    International Nuclear Information System (INIS)

    2003-01-01

    The International Atomic Energy Agency (IAEA) at its Headquarters in Vienna convened a consultants meeting from 9-13 December, 2002, to provide the Agency current insights into the application of nuclear and isotopic techniques as tool to support studies aimed at assessing the causes of Intrauterine Growth Retardation (IUGR). The consultants were: Dr. B. Caballero, Dr. D. Labadarios, Dr. G. Carroli, Dr. L.S. Bakketeig and Dr. P.T.V Nair. Representatives from the World Health Organization (WHO), Dr. G. Glugston and Dr. S. Khanum, were present as observers during the initial part of the meeting. Given the Consultants' areas of expertise and the topics covered in the discussions, the scope of the Meeting was modified to 'The application of isotopic and nuclear techniques to address the problem of intrauterine growth retardation (IUGR) in populations from developing countries'. The objectives of the meeting were to: (i) Evaluate the overall scope of a new co-ordinated research project (CRP) and suggest options for specific areas of research within that scope; (ii) Examine the applicability of nuclear and isotope based techniques in researches related to practical approaches for monitoring maternal weight and weight gain during pregnancy (e.g. body composition and energy balance assessment); (iii) Establish harmonised methods and criteria for appropriate weight gain and foetal growth charts for pregnant women in developing countries; (iv) Suggest approaches to assess the effectiveness of nutrition interventions aimed at reducing IUGR and its consequences. This meeting benefited from the broad areas of experience of scientists from both developed and developing countries. Their expertise in the use of isotopes and nuclear techniques, and in studies on human nutrition, epidemiology, IUGR, Low birth weight and undernutrition provided the advocacy and approaches to fellow in the application of nuclear and isotopic techniques as part of maternal malnutrition and IUGR studies

  3. Metabolomic profile of umbilical cord blood plasma from early and late intrauterine growth restricted (IUGR neonates with and without signs of brain vasodilation.

    Directory of Open Access Journals (Sweden)

    Magdalena Sanz-Cortés

    Full Text Available OBJECTIVES: To characterize via NMR spectroscopy the full spectrum of metabolic changes in umbilical vein blood plasma of newborns diagnosed with different clinical forms of intrauterine growth restriction (IUGR. METHODS: 23 early IUGR cases and matched 23 adequate-for-gestational-age (AGA controls and 56 late IUGR cases with 56 matched AGAs were included in this study. Early IUGR was defined as a birth weight 35 weeks. This group was subdivided in 18 vasodilated (VD and 38 non-VD late IUGR fetuses. All AGA patients had a birth weight >10(th centile. (1H nuclear magnetic resonance (NMR metabolomics of the blood samples collected from the umbilical vein at delivery was obtained. Multivariate statistical analysis identified several metabolites that allowed the discrimination between the different IUGR subgroups, and their comparative levels were quantified from the NMR data. RESULTS: The NMR-based analysis showed increased unsaturated lipids and VLDL levels in both early and late IUGR samples, decreased glucose and increased acetone levels in early IUGR. Non-significant trends for decreased glucose and increased acetone levels were present in late IUGR, which followed a severity gradient when the VD and non-VD subgroups were considered. Regarding amino acids and derivatives, early IUGR showed significantly increased glutamine and creatine levels, whereas the amounts of phenylalanine and tyrosine were decreased in early and late-VD IUGR samples. Valine and leucine were decreased in late IUGR samples. Choline levels were decreased in all clinical subforms of IUGR. CONCLUSIONS: IUGR is not associated with a unique metabolic profile, but important changes are present in different clinical subsets used in research and clinical practice. These results may help in characterizing comprehensively specific alterations underlying different IUGR subsets.

  4. Enoxaparin for the prevention of preeclampsia and intrauterine growth restriction in women with a prior history - an open-label randomised trial (the EPPI trial): study protocol.

    Science.gov (United States)

    Groom, K M; McCowan, L M; Stone, P R; Chamley, L C; McLintock, C

    2016-11-22

    Preeclampsia and intrauterine fetal growth restriction (IUGR) are two of the most common causes of maternal and perinatal morbidity and mortality. Current methods of predicting those at most risk of these conditions remain relatively poor, and in clinical practice past obstetric history remains the most commonly used tool. Aspirin and, in women at risk of preeclampsia only, calcium have been demonstrated to have a modest effect on risk reduction. Several observational studies and randomised trials suggest that low molecular weight heparin (LMWH) therapy may confer some benefit. This is a multicentre open label randomised controlled trial to determine the effect of the LMWH, enoxaparin, on the prevention of recurrence of preeclampsia and/or IUGR in women at high risk due to their past obstetric history in addition to standard high risk care for all participants. A singleton pregnancy >6 +0 and 12 weeks having; (1) preeclampsia delivered women are randomly assigned to 'standard high risk care' or 'standard high risk care' plus enoxaparin 40 mg from recruitment until 36 +0 weeks or delivery, whichever occurs sooner. Standard high risk care includes the use of aspirin 100 mg daily and calcium 1000-1500 mg daily (unless only had previous SGA with no preeclampsia). The primary outcome is preeclampsia and/or SGA restricted composite primary outcome. The inclusion of standard use of aspirin (and calcium) for all participants will help to ensure that any differences observed in outcome are likely to be related to enoxaparin use. These data will make a significant contribution to future meta-analyses and systematic reviews on the use of LMWH for the prevention of placental mediated conditions. ACTRN12609000699268 Australian New Zealand Clinical Trials Registry. Date registered 13/Aug/2009 (prospective registration).

  5. Comparison of two models of intrauterine growth restriction for early catch-up growth and later development of glucose intolerance and obesity in rats.

    Science.gov (United States)

    Shahkhalili, Yasaman; Moulin, Julie; Zbinden, Irene; Aprikian, Olivier; Macé, Katherine

    2010-01-01

    Two models of intrauterine growth restriction, maternal food restriction (FR), and dexamethasone (DEX) exposure were compared for early postnatal catch-up growth and later development of glucose intolerance and obesity in Sprague-Dawley rats. Mated dams were randomly divided into three groups at 10 days gestational age. Group FR was food restricted (50% of nongestating rats) during the last 11 days of gestation; Group DEX received DEX injections during the last week of gestation, and Group CON, the control group, had no intervention. Birth weight, catch-up growth, body weight, and food intake were measured in male offspring for 22 wk. Body composition, blood glucose, and plasma insulin in response to a glucose load were assessed at 8, 16, and 22 wk. Pups from both FR and DEX dams had similarly lower birth weights than CON (22% and 25%, P growth, which occurred during the suckling period, was much more rapid in FR than DEX offspring (6 vs. 25 days, 95% CI). Postweaning, there were no significant differences between groups in food intake, body weight, body fat, and plasma insulin, but baseline plasma glucose at 22 wk and 2-h glucose area-under-the-curve at 8 and 22 wk were greater only in FR vs. CON offspring (P restriction is a more sensitive model than DEX exposure for studies aimed at investigating the link between low birth weight, early postnatal catch-up growth, and later development of glucose intolerance.

  6. Fetal Adrenal Demedullation Lowers Circulating Norepinephrine and Attenuates Growth Restriction but not Reduction of Endocrine Cell Mass in an Ovine Model of Intrauterine Growth Restriction

    Directory of Open Access Journals (Sweden)

    Melissa A. Davis

    2015-01-01

    Full Text Available Placental insufficiency is associated with fetal hypoglycemia, hypoxemia, and elevated plasma norepinephrine (NE that become increasingly pronounced throughout the third trimester and contribute to intrauterine growth restriction (IUGR. This study evaluated the effect of fetal adrenal demedullation (AD on growth and pancreatic endocrine cell mass. Placental insufficiency-induced IUGR was created by exposing pregnant ewes to elevated ambient temperatures during mid-gestation. Treatment groups consisted of control and IUGR fetuses with either surgical sham or AD at 98 days gestational age (dGA; term = 147 dGA, a time-point that precedes IUGR. Samples were collected at 134 dGA. IUGR-sham fetuses were hypoxemic, hypoglycemic, and hypoinsulinemic, and values were similar in IUGR-AD fetuses. Plasma NE concentrations were ~5-fold greater in IUGR-sham compared to control-sham, control-AD, and IUGR-AD fetuses. IUGR-sham and IUGR-AD fetuses weighed less than controls. Compared to IUGR-sham fetuses, IUGR-AD fetuses weighed more and asymmetrical organ growth was absent. Pancreatic β-cell mass and α-cell mass were lower in both IUGR-sham and IUGR-AD fetuses compared to controls, however, pancreatic endocrine cell mass relative to fetal mass was lower in IUGR-AD fetuses. These findings indicate that NE, independently of hypoxemia, hypoglycemia and hypoinsulinemia, influence growth and asymmetry of growth but not pancreatic endocrine cell mass in IUGR fetuses.

  7. Fetal Adrenal Demedullation Lowers Circulating Norepinephrine and Attenuates Growth Restriction but not Reduction of Endocrine Cell Mass in an Ovine Model of Intrauterine Growth Restriction

    Science.gov (United States)

    Davis, Melissa A.; Macko, Antoni R.; Steyn, Leah V.; Anderson, Miranda J.; Limesand, Sean W.

    2015-01-01

    Placental insufficiency is associated with fetal hypoglycemia, hypoxemia, and elevated plasma norepinephrine (NE) that become increasingly pronounced throughout the third trimester and contribute to intrauterine growth restriction (IUGR). This study evaluated the effect of fetal adrenal demedullation (AD) on growth and pancreatic endocrine cell mass. Placental insufficiency-induced IUGR was created by exposing pregnant ewes to elevated ambient temperatures during mid-gestation. Treatment groups consisted of control and IUGR fetuses with either surgical sham or AD at 98 days gestational age (dGA; term = 147 dGA), a time-point that precedes IUGR. Samples were collected at 134 dGA. IUGR-sham fetuses were hypoxemic, hypoglycemic, and hypoinsulinemic, and values were similar in IUGR-AD fetuses. Plasma NE concentrations were ~5-fold greater in IUGR-sham compared to control-sham, control-AD, and IUGR-AD fetuses. IUGR-sham and IUGR-AD fetuses weighed less than controls. Compared to IUGR-sham fetuses, IUGR-AD fetuses weighed more and asymmetrical organ growth was absent. Pancreatic β-cell mass and α-cell mass were lower in both IUGR-sham and IUGR-AD fetuses compared to controls, however, pancreatic endocrine cell mass relative to fetal mass was lower in IUGR-AD fetuses. These findings indicate that NE, independently of hypoxemia, hypoglycemia and hypoinsulinemia, influence growth and asymmetry of growth but not pancreatic endocrine cell mass in IUGR fetuses. PMID:25584967

  8. Differential Receptor for Advanced Glycation End Products Expression in Preeclamptic, Intrauterine Growth Restricted, and Gestational Diabetic Placentas.

    Science.gov (United States)

    Alexander, Kristen L; Mejia, Camilo A; Jordan, Clinton; Nelson, Michael B; Howell, Brian M; Jones, Cameron M; Reynolds, Paul R; Arroyo, Juan A

    2016-02-01

    Receptor for advanced glycation end products (RAGE) is a receptor implicated in the modulation of inflammation. Inflammation has been associated with pregnancy pathologies including preeclampsia (PE), intrauterine growth restriction (IUGR), and gestational diabetes mellitus (GDM). Our objective was to examine placental RAGE expression in PE, IUGR, and GDM complications. Human placental tissues were obtained for RAGE determination using Q-PCR, immunohistochemistry, and Western blot. Invasive trophoblast cells were cultured and treated with AGES for RAGE activation studies. Compared to control placenta, we observed: (i) decreased RAGE gene expression during GDM, (ii) increased RAGE protein in the PE placenta, and (iii) decreased RAGE protein in the IUGR placenta. In trophoblast cells exposed AGEs, we observed: (i) decreased trophoblast invasion, (ii) increased c-Jun N-terminal kinases (JNK) and Extracellular signal-regulated kinases (ERK), and (iii) increased TNF-α and IL-1β secretion. We conclude that placental RAGE is activated during PE and that RAGE-mediated inflammation in the trophoblast involves increased pro-inflammatory cytokine secretion. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Dietary Tributyrin Supplementation Attenuates Insulin Resistance and Abnormal Lipid Metabolism in Suckling Piglets with Intrauterine Growth Retardation

    Science.gov (United States)

    He, Jintian; Dong, Li; Xu, Wen; Bai, Kaiwen; Lu, Changhui; Wu, Yanan; Huang, Qiang; Zhang, Lili; Wang, Tian

    2015-01-01

    Intrauterine growth retardation (IUGR) is associated with insulin resistance and lipid disorder. Tributyrin (TB), a pro-drug of butyrate, can attenuate dysfunctions in body metabolism. In this study, we investigated the effects of TB supplementation on insulin resistance and lipid metabolism in neonatal piglets with IUGR. Eight neonatal piglets with normal birth weight (NBW) and 16 neonatal piglets with IUGR were selected, weaned on the 7th day, and fed basic milk diets (NBW and IUGR groups) or basic milk diets supplemented with 0.1% tributyrin (IT group, IUGR piglets) until day 21 (n = 8). Relative parameters for lipid metabolism and mRNA expression were measured. Piglets with IUGR showed higher (P insulin in the serum, higher (P insulin, HOMA-IR, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in the serum, and the concentrations of TG and NEFA in the liver, and increased (P insulin signal transduction pathway and hepatic lipogenic pathway (including transcription factors and nuclear factors) was significantly (P insulin resistance and abnormal lipid metabolism in IUGR piglets by increasing enzyme activities and upregulating mRNA expression, leading to an early improvement in the metabolic efficiency of IUGR piglets. PMID:26317832

  10. [Examination of placental three-dimensional power Doppler indices and perinatal outcome in pregnancies complicated by intrauterine growth restriction].

    Science.gov (United States)

    Molnár, András; Surányi, Andrea; Jakó, Mária; Nyári, Tibor; Németh, Gábor

    2017-07-01

    Development of intrauterine growth restriction (IUGR) can be traced back to maternal or fetal factors, but in many cases we find placental factors (reduced placental circulation) in the background. Our aim was to examine whether the reduced placental bloodperfusion and vascularity show any correlation with cesarean section frequency and the clinical outcome in IUGR pregnancies. The aim of the present study was also to use a properly calibrated and reproducible method for evaluating placental blood flow, that can later be incorporated into the routine examination. 254 women were recruited in our prospective case-control study. The 3 dimensional power Doppler (3DPD) ultrasound indices; vascularisation index (VI), flow index (FI) and vascularization flow index (VFI) were measured on each participant. Median VI was 3.7% (interquartile range [IQR] 3.2%-4.2%) in the IUGR group and 10.1% (IQR 8.6%-10.9%) in the control group (p = 0.001). Median FI value was 40.0 (IQR 39.7-42.5) in the IUGR group and 45.1 (IQR 44.1-53.1) in the control group (p = 0.012). Median VFI was 2.2 (IQR 2.1-2.4) in the IUGR group and 4.8 (IQR 4.4-5.3) in the control. The 3DPD indices may be useful for examining changes in circulation in IUGR pregnancies to characterize the underlying pathology. Orv Hetil. 2017; 158(26): 1008-1013.

  11. The effects of sildenafil citrate (Viagra) on uterine blood flow and well being in the intrauterine growth-restricted fetus.

    Science.gov (United States)

    Miller, Suzanne L; Loose, Jan M; Jenkin, Graham; Wallace, Euan M

    2009-01-01

    This study examined whether the type-5 phosphodiesterase inhibitor sildenafil citrate (Viagra; Pfizer, New York, NY) could increase uterine blood flow in intrauterine growth restriction (IUGR), thereby improving fetal oxygenation and well being. In fetal sheep, we induced IUGR at 105-110 days (0.7 gestation) using single umbilical artery ligation (SUAL). In SUAL and control animals, we measured uterine blood flow (UBF) and blood gases before and after sildenafil administration. SUAL fetuses were hypoxemic compared with controls. Following sildenafil, UBF was significantly decreased in both SUAL and control ewes for approximately 40 minutes. In response to sildenafil, pO(2) was decreased in SUAL and control fetuses and both groups displayed significant hypotension and tachycardia. At postmortem SUAL fetal body weight was significantly reduced by 23% compared with controls. Sildenafil does not improve UBF or fetal well being in SUAL-induced IUGR pregnancies and should be used with caution in IUGR and healthy pregnancies because of its detrimental effects on uteroplacental perfusion and on the fetus.

  12. Pregnancy-associated plasma protein A gene polymorphism in pregnant women with preeclampsia and intrauterine growth restriction

    Directory of Open Access Journals (Sweden)

    Sultan Ozkan

    2015-10-01

    Full Text Available Preeclampsia (PE and intrauterine growth restriction (IUGR are still among the most commonly researched titles in perinatology. To shed light on their etiology, new prevention and treatment strategies are the major targets of studies. In this study, we aimed to investigate the relation between gene polymorphism of one of the products of trophoblasts, pregnancy-associated plasma protein A (PAPP-A and PE/IUGR.A total of 147 women (IUGR, n = 61; PE, n = 47; IUGR + PE, n = 37; eclampsia, n = 2 were compared with 103 controls with respect to the sequencing of exon 14 of the PAPP-A gene to detect (rs7020782 polymorphism. Genotypes “AA” and “CC” were given in the event of A or C allele homozygosity and “AC” in A and C allele heterozygosity. Our findings revealed that the rate of AA, CC homozygotes, and AC heterozygotes did not differ between groups. Moreover, there was no difference in the distribution of PAPP-A genotypes among the patients with IUGR, PE, IUGR + PE, or eclampsia. Finally, birth weight, rate of the presence of proteinuria, and total protein excretion on 24-hour urine were similar in the subgroups of AA, AC, and CC genotypes in the study group. Our study demonstrated no association between PAPP-A gene rs7020782 polymorphism and PE/IUGR.

  13. Kidney gene expression analysis in a rat model of intrauterine growth restriction reveals massive alterations of coagulation genes.

    Science.gov (United States)

    Buffat, Christophe; Boubred, Farid; Mondon, Françoise; Chelbi, Sonia T; Feuerstein, Jean-Marc; Lelièvre-Pégorier, Martine; Vaiman, Daniel; Simeoni, Umberto

    2007-11-01

    In this study, low birth weight was induced in rats by feeding the dams with a low-protein diet during pregnancy. Kidneys from the fetuses at the end of gestation were collected and showed a reduction in overall and relative weight, in parallel with other tissues (heart and liver). This reduction was associated with a reduction in nephrons number. To better understand the molecular basis of this observation, a transcriptome analysis contrasting kidneys from control and protein-deprived rats was performed, using a platform based upon long isothermic oligonucleotides, strengthening the robustness of the results. We could identify over 1800 transcripts modified more than twice (772 induced and 1040 repressed). Genes of either category were automatically classified according to functional criteria, making it possible to bring to light a large cluster of genes involved in coagulation and complement cascades. The promoters of the most induced and most repressed genes were contrasted for their composition in putative transcription factor binding sites, suggesting an overrepresentation of the AP1R binding site, together with the transcription induction of factors actually binding to this site in the set of induced genes. The induction of coagulation cascades in the kidney of low-birth-weight rats provides a putative rationale for explaining thrombo-endothelial disorders also observed in intrauterine growth-restricted human newborns. These alterations in the kidneys have been reported as a probable cause for cardiovascular diseases in the adult.

  14. The Long-Term Effects of Prematurity and Intrauterine Growth Restriction on Cardiovascular, Renal, and Metabolic Function

    Directory of Open Access Journals (Sweden)

    Patricia Y. L. Chan

    2010-01-01

    Full Text Available Objective. To determine relative influences of intrauterine growth restriction (IUGR and preterm birth on risks of cardiovascular, renal, or metabolic dysfunction in adolescent children. Study Design. Retrospective cohort study. 71 periadolescent children were classified into four groups: premature small for gestational age (SGA, premature appropriate for gestational age (AGA, term SGA, and term AGA. Outcome Measures. Systolic blood pressure (SBP, augmentation index (Al, glomerular filtration rate (GFR following protein load; plasma glucose and serum insulin levels. Results. SGA had higher SBP (average 4.6 mmHg and lower GFR following protein load (average 28.5 mL/min/1.73 m2 than AGA. There was no effect of prematurity on SBP (P=.4 or GFR (P=.9. Both prematurity and SGA were associated with higher AI (average 9.7% and higher serum insulin levels 2 hr after glucose load (average 15.5 mIU/L than all other groups. Conclusion. IUGR is a more significant risk factor than preterm birth for later systolic hypertension and renal dysfunction. Among children born preterm, those who are also SGA are at increased risk of arterial stiffness and metabolic dysfunction.

  15. Effects of intrauterine growth restriction on sleep and the cardiovascular system: The use of melatonin as a potential therapy?

    Science.gov (United States)

    Yiallourou, Stephanie R; Wallace, Euan M; Miller, Suzanne L; Horne, Rosemary S C

    2016-04-01

    Intrauterine growth restriction (IUGR) complicates 5-10% of pregnancies and is associated with increased risk of preterm birth, mortality and neurodevelopmental delay. The development of sleep and cardiovascular control are closely coupled and IUGR is known to alter this development. In the long-term, IUGR is associated with altered sleep and an increased risk of hypertension in adulthood. Melatonin plays an important role in the sleep-wake cycle. Experimental animal studies have shown that melatonin therapy has neuroprotective and cardioprotective effects in the IUGR fetus. Consequently, clinical trials are currently underway to assess the short and long term effects of antenatal melatonin therapy in IUGR pregnancies. Given melatonin's role in sleep regulation, this hormone could affect the developing infants' sleep-wake cycle and cardiovascular function after birth. In this review, we will 1) examine the role of melatonin as a therapy for IUGR pregnancies and the potential implications on sleep and the cardiovascular system; 2) examine the development of sleep-wake cycle in fetal and neonatal life; 3) discuss the development of cardiovascular control during sleep; 4) discuss the effect of IUGR on sleep and the cardiovascular system and 5) discuss the future implications of melatonin therapy in IUGR pregnancies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Ouabain rescues rat nephrogenesis during intrauterine growth restriction by regulating the complement and coagulation cascades and calcium signaling pathway.

    Science.gov (United States)

    Chen, L; Yue, J; Han, X; Li, J; Hu, Y

    2016-02-01

    Intrauterine growth restriction (IUGR) is associated with a reduction in the numbers of nephrons in neonates, which increases the risk of hypertension. Our previous study showed that ouabain protects the development of the embryonic kidney during IUGR. To explore this molecular mechanism, IUGR rats were induced by protein and calorie restriction throughout pregnancy, and ouabain was delivered using a mini osmotic pump. RNA sequencing technology was used to identify the differentially expressed genes (DEGs) of the embryonic kidneys. DEGs were submitted to the Database for Annotation and Visualization and Integrated Discovery, and gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted. Maternal malnutrition significantly reduced fetal weight, but ouabain treatment had no significant effect on body weight. A total of 322 (177 upregulated and 145 downregulated) DEGs were detected between control and the IUGR group. Meanwhile, 318 DEGs were found to be differentially expressed (180 increased and 138 decreased) between the IUGR group and the ouabain-treated group. KEGG pathway analysis indicated that maternal undernutrition mainly disrupts the complement and coagulation cascades and the calcium signaling pathway, which could be protected by ouabain treatment. Taken together, these two biological pathways may play an important role in nephrogenesis, indicating potential novel therapeutic targets against the unfavorable effects of IUGR.

  17. Pregnancy-associated plasma protein A gene polymorphism in pregnant women with preeclampsia and intrauterine growth restriction.

    Science.gov (United States)

    Ozkan, Sultan; Sanhal, Cem Yasar; Yeniel, Ozgur; Arslan Ates, Esra; Ergenoglu, Mete; Bınbır, Birol; Onay, Huseyin; Ozkınay, Ferda; Sagol, Sermet

    2015-10-01

    Preeclampsia (PE) and intrauterine growth restriction (IUGR) are still among the most commonly researched titles in perinatology. To shed light on their etiology, new prevention and treatment strategies are the major targets of studies. In this study, we aimed to investigate the relation between gene polymorphism of one of the products of trophoblasts, pregnancy-associated plasma protein A (PAPP-A) and PE/IUGR.A total of 147 women (IUGR, n = 61; PE, n = 47; IUGR + PE, n = 37; eclampsia, n = 2) were compared with 103 controls with respect to the sequencing of exon 14 of the PAPP-A gene to detect (rs7020782) polymorphism. Genotypes "AA" and "CC" were given in the event of A or C allele homozygosity and "AC" in A and C allele heterozygosity. Our findings revealed that the rate of AA, CC homozygotes, and AC heterozygotes did not differ between groups. Moreover, there was no difference in the distribution of PAPP-A genotypes among the patients with IUGR, PE, IUGR + PE, or eclampsia. Finally, birth weight, rate of the presence of proteinuria, and total protein excretion on 24-hour urine were similar in the subgroups of AA, AC, and CC genotypes in the study group. Our study demonstrated no association between PAPP-A gene rs7020782 polymorphism and PE/IUGR. Copyright © 2015. Published by Elsevier Taiwan.

  18. The role of thromboxane A(2) in the pathogenesis of intrauterine growth restriction associated with maternal smoking in pregnancy.

    LENUS (Irish Health Repository)

    Lynch, Caoimhe M

    2012-02-01

    BACKGROUND: To examine the effect of maternal smoking in pregnancy on the production of two eicosanoids, thromboxane A(2) and prostacyclin I2, and their role in the pathogenesis of intrauterine growth restriction. METHODS: Prospective case control study enrolled smoking and non-smoking women at <\\/=14 weeks gestation. Maternal urine samples were obtained at <\\/=14, 28 and 36 weeks. High performance liquid chromatography tandem mass spectrometry (LC-MS-MS) was used to quantify 11-dehydrothromboxane B(2) (TX-M) and 2,3 dinor-6-ketoprostaglandin F1alpha (PG-M), stable urinary metabolites of thromboxane A(2) and prostacyclin I2. Confirmation of the smoking status was performed by quantitation of urinary nicotine metabolites. Data was analysed using SPSS and Stata((R)). RESULTS: Thirty five were enrolled in the smoking group and 32 in the non-smoking group. Smoking resulted higher levels of TX-M at <\\/=14, 28 and 36 weeks gestation. There was no difference in PG-M at any gestational time point between the two groups. The median customised birthweight centile in the smoking group was 17.0 (0-78) compared to 55.5 (4-100) in the non-smoking group (P<0.001). A causal relationship between elevated TX-M and IUGR could not be established. CONCLUSIONS: Maternal smoking in pregnancy is associated with altered eicosanoid production in favour of the vasoconstrictor thromboxane A(2) which occurs early in the first trimester.

  19. Differential effects of intrauterine growth restriction on brain structure and development in preterm infants: a magnetic resonance imaging study.

    Science.gov (United States)

    Padilla, Nelly; Falcón, Carles; Sanz-Cortés, Magdalena; Figueras, Francesc; Bargallo, Núria; Crispi, Fátima; Eixarch, Elisenda; Arranz, Angela; Botet, Francesc; Gratacós, Eduard

    2011-03-25

    Previous evidence suggests that preterm newborns with intrauterine growth restriction (IUGR) have specific neurostructural and neurodevelopmental anomalies, but it is unknown whether these effects persist in early childhood. We studied a sample of 18 preterm IUGR, 15 preterm AGA - born between 26 and 34 weeks of gestational age (GA) - and 15 healthy born-term infants. Infants were scanned at 12 months corrected age (CA), in a 3T scanner, without sedation. Analyses were made by automated lobar volumetry and voxel-based morphometry (VBM). The neurodevelopmental outcome was assessed in all subjects at 18 months CA with the Bayley Scale for Infant and Toddler Development, third edition. IUGR infants had reduced relative volumes for the insular and temporal lobes. According to VBM, IUGR infants had bilateral reduced gray matter (GM) in the temporal, parietal, frontal, and insular regions compared with the other groups. IUGR infants had increased white matter (WM) in temporal regions compared to the AGA group and in frontal, parietal, occipital, and insular regions compared to the term group. They also showed decreased WM in the cerebellum and a non-significant trend in the hippocampus compared to term infants. IUGR infants had reduced neurodevelopmental scores, which were positively correlated with GM in various regions. These data suggest that the IUGR induces a distinct brain pattern of structural changes that persist at 1 year of life and are associated with specific developmental difficulties. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Effect of Folic Acid Supplementation on Renal Phenotype and Epigenotype in Early Weanling Intrauterine Growth Retarded Rats

    Directory of Open Access Journals (Sweden)

    Xiaori He

    2015-07-01

    Full Text Available Background/Aims: The objective of this study was to examine the responses of p53 promoter methylation involved in kidney structure and function of early weaning intrauterine growth retarded (IUGR rats to dietary folic acid supplementation. Method: Sprague-Dawley rats were fed isocaloric diets containing either 21% protein diet (normal feed or 10% protein diet throughout pregnancy and normal feed during lactation. After weaning, Offspring were then fed onto normal feed and normal feed supplemented with 5 mg folic acid/kg feed for a month, this produced 4 dietary groups (maternal diet/ weanling diet: Con, Folic, IUGR and IUGR+Folic. Renal function, renal structure, p53 promoter methylation and protein expression of offspring rats were measured at postnatal 2 months and 3 months. Results: Glomerular volume, blood urea nitrogen, 24 hours urine protein were significantly elevated in IUGR rats compared with Con rats but were decreased by dietary folic acid supplementation. p53 protein expression in IUGR rats were significantly higher than that in Con rats, and p53 promoter methylation status in IUGR rats was reduced significantly compared with Con rats. However, the changes in p53 gene expression and DNA methylation status of IUGR rats were reversed by dietary folic acid supplementation. Conclusions: Our study showed for the first time that folic acid supplementation during early period of life could reverse the abnormality in renal p53 methylation status and protein expression, glomerular volume and renal function of IUGR rats offspring.

  1. Placental alterations in structure and function in intra-uterine growth-retarded horses.

    Science.gov (United States)

    Robles, M; Peugnet, P M; Valentino, S A; Dubois, C; Dahirel, M; Aubrière, M-C; Reigner, F; Serteyn, D; Wimel, L; Couturier-Tarrade, A; Chavatte-Palmer, P

    2018-05-01

    Following embryo transfer (ET), the size and breed of the recipient mare can affect fetal development and subsequent post natal growth rate and insulin sensitivity in foals. To investigate placental adaptation in pregnancies where increased or restricted fetal growth was induced through ET between Pony, Saddlebred and Draught horses. In vivo experiment. Control Pony (P, n = 21) and Saddlebred (S, n = 28) pregnancies were obtained by artificial insemination. Increased pregnancies were obtained by transferring Pony (P-D, n = 6) and Saddlebred (S-D, n = 8) embryos into Draught mares. Restricted pregnancies were obtained by transferring Saddlebred embryos into Pony mares (S-P, n = 6). Placental weight and surface were recorded and samples collected for stereology and analysis of expression of genes involved in placental growth, vascularisation and nutrient transport. Data were analysed by linear model. S-P foals were growth retarded when compared with controls despite increased gestational length. Placental weight was reduced but placental surface density and volume fraction were increased. Placental expression of genes involved in growth and development and nutrient transfer was strongly reduced. In contrast, placental size and weight were increased in enhanced growth P-D and S-D foals. The trophoblastic surface density and the allantoic vessels surface density were decreased in P-D and S-D, respectively, both with very few modifications in gene expression. Control embryos were produced by artificial insemination whereas experimental embryos were produced by ET. Placental structure and gene expression are modified after ET into a smaller or larger breed than that of the embryo. These adaptations contribute to the observed phenotype of foal growth restriction or enhanced growth at birth. © 2017 EVJ Ltd.

  2. Successful Intrauterine Pregnancy following salpingostomy; Case ...

    African Journals Online (AJOL)

    by salpingostomy, after which she had spontaneous abortion of the associated intrauterine pregnancy. Result: Initial marital disharmony, followed by an uneventful intrauterine pregnancy carried to term with caesarean delivery of a live female baby. Conclusion: In well-selected cases, conservative tubal surgeries should be ...

  3. School-age effects of the newborn individualized developmental care and assessment program for preterm infants with intrauterine growth restriction: preliminary findings.

    Science.gov (United States)

    McAnulty, Gloria; Duffy, Frank H; Kosta, Sandra; Weisenfeld, Neil I; Warfield, Simon K; Butler, Samantha C; Alidoost, Moona; Bernstein, Jane Holmes; Robertson, Richard; Zurakowski, David; Als, Heidelise

    2013-02-19

    The experience in the newborn intensive care nursery results in premature infants' neurobehavioral and neurophysiological dysfunction and poorer brain structure. Preterms with severe intrauterine growth restriction are doubly jeopardized given their compromised brains. The Newborn Individualized Developmental Care and Assessment Program improved outcome at early school-age for preterms with appropriate intrauterine growth. It also showed effectiveness to nine months for preterms with intrauterine growth restriction. The current study tested effectiveness into school-age for preterms with intrauterine growth restriction regarding executive function (EF), electrophysiology (EEG) and neurostructure (MRI). Twenty-three 9-year-old former growth-restricted preterms, randomized at birth to standard care (14 controls) or to the Newborn Individualized Developmental Care and Assessment Program (9 experimentals) were assessed with standardized measures of cognition, achievement, executive function, electroencephalography, and magnetic resonance imaging. The participating children were comparable to those lost to follow-up, and the controls to the experimentals, in terms of newborn background health and demographics. All outcome measures were corrected for mother's intelligence. Analysis techniques included two-group analysis of variance and stepwise discriminate analysis for the outcome measures, Wilks' lambda and jackknifed classification to ascertain two-group classification success per and across domains; canonical correlation analysis to explore relationships among neuropsychological, electrophysiological and neurostructural domains at school-age, and from the newborn period to school-age. Controls and experimentals were comparable in age at testing, anthropometric and health parameters, and in cognitive and achievement scores. Experimentals scored better in executive function, spectral coherence, and cerebellar volumes. Furthermore, executive function, spectral coherence

  4. Psychomotor and intellectual development of children born with intrauterine growth retardation (IUGR).

    Science.gov (United States)

    Puga, B; Ferrández Longás, A; García Romero, R; Mayayo, E; Labarta, J I

    2004-03-01

    The possible impact of IUGR on the intellectual outcome of children born with IUGR gives special relevance to this condition. In order to determine the psychomotor and intellectual development of such children, we analyzed the evolution of 60 children through appropriate tests, along the years, and the possible influence of two factors, the socio-economic status of the family, and whether or not there was catch-up growth. Our results show a negative impact of IUGR on the intellectual outcome of these children, independent of catch-up growth, although those with catch-up growth showed better evolution. The socio-economic status plays a limited role only at older age. Those children followed longitudinally for 1 year did not show any amelioration of their IQ.

  5. Intrauterine Growth Restriction, Head Size at Birth, and Outcome in Very Preterm Infants.

    Science.gov (United States)

    Guellec, Isabelle; Marret, Stephane; Baud, Olivier; Cambonie, Gilles; Lapillonne, Alexandre; Roze, Jean-Christophe; Fresson, Jeanne; Flamant, Cyril; Charkaluk, Marie-Laure; Arnaud, Catherine; Ancel, Pierre-Yves

    2015-11-01

    To determine whether small head circumference (HC) or birth weight (BW) or both are associated with neonatal and long-term neurologic outcome in very preterm infants. All 2442 live births from the 1997 Epipage study between 26 and 32 weeks of gestational age in 9 regions of France were analyzed. A total of 1395 were tested at age 5 years for cognitive performance and 1315 with school performance reports at age 8 years. Symmetric growth restriction (SGR) was defined by HC and BW growth restriction by at least 1 of HC and BW growth restriction: head growth restriction (HGR) and weight growth restriction (WGR). Appropriate for gestational age was defined by both BW and HC >20th percentile. Compared with appropriate for gestational age, SGR was significantly associated with neonatal mortality (aOR 2.99, 95% CI 1.78-5.03), moderate and severe cognitive deficiency (aOR 1.65, 95% CI 1.01-2.71 and aOR 2.61, 95% CI 1.46-4.68, respectively), and poor school performance (aOR 1.79; 95% CI 1.13-2.83). HGR was significantly associated with severe cognitive deficiency (aOR 2.07, 95% CI 1.15-3.74). WGR was not significantly associated with cognitive or school performance despite higher rates of neonatal morbidity. SGR in preterm infants was associated with neonatal mortality and impaired cognitive and school performance. The outcome of asymmetric growth restriction differed according to HC. HGR was associated with impaired cognitive function; WGR was not. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Volumetric analysis of the normal infant brain and in intrauterine growth retardation

    DEFF Research Database (Denmark)

    Toft, P B; Leth, H; Ring, P B

    1995-01-01

    and the volumes were determined by encircling each structure of interest on every slice. Segmentation into grey matter, white matter and CSF was done by semi-automatic discriminant analysis. Growth charts for the cerebrum, cerebellum, corpora striata, thalami, ventricles, and grey and white matter are provided...... for infants with appropriate birth weight. The striatal (P = 0.02) and thalamic (P matter to white matter (G/W-ratio) increased (P = 0.01). In the neonatal patients, brain volumes were independently associated...... growth retardation reduces grey matter volume more than white matter....

  7. Effect of two models of intrauterine growth restriction on alveolarization in rat lungs: morphometric and gene expression analysis.

    Directory of Open Access Journals (Sweden)

    Elodie Zana-Taieb

    Full Text Available Intrauterine growth restriction (IUGR in preterm infants increases the risk of bronchopulmonary dysplasia, characterized by arrested alveolarization. We evaluated the impact of two different rat models (nitric oxide synthase inhibition or protein deprivation of IUGR on alveolarization, before, during, and at the end of this postnatal process. We studied IUGR rat pups of dams fed either a low protein (LPD or a normal diet throughout gestation and pups of dams treated by continuous infusion of Nω-nitro-L-arginine methyl ester (L-NAME or its diluent on the last four days of gestation. Morphometric parameters, alveolar surface (Svap, mean linear intercept (MLI and radial alveolar count (RAC and transcriptomic analysis were determined with special focus on genes involved in alveolarization. IUGR pups regained normal weight at day 21 in the two treated groups. In the LPD group, Svap, MLI and RAC were not different from those of controls at day 4, but were significantly decreased at day 21, indicating alveolarization arrest. In the L-NAME group, Svap and RAC were significantly decreased and MLI was increased at day 4 with complete correction at day 21. In the L-NAME model, several factors involved in alveolarization, VEGF, VEGF-R1 and -R2, MMP14, MMP16, FGFR3 and 4, FGF18 and 7, were significantly decreased at day 4 and/or day 10, while the various factors studied were not modified in the LPD group. These results demonstrate that only maternal protein deprivation leads to sustained impairment of alveolarization in rat pups, whereas L-NAME impairs lung development before alveolarization. Known growth factors involved in lung development do not seem to be involved in LPD-induced alveolarization disorders, raising the question of a possible programming of altered alveolarization.

  8. Intrauterine growth retarded progeny of pregnant sows fed high protein:low carbohydrate diet is related to metabolic energy deficit.

    Directory of Open Access Journals (Sweden)

    Cornelia C Metges

    Full Text Available High and low protein diets fed to pregnant adolescent sows led to intrauterine growth retardation (IUGR. To explore underlying mechanisms, sow plasma metabolite and hormone concentrations were analyzed during different pregnancy stages and correlated with litter weight (LW at birth, sow body weight and back fat thickness. Sows were fed diets with low (6.5%, LP, adequate (12.1%, AP, and high (30%, HP protein levels, made isoenergetic by adjusted carbohydrate content. At -5, 24, 66, and 108 days post coitum (dpc fasted blood was collected. At 92 dpc, diurnal metabolic profiles were determined. Fasted serum urea and plasma glucagon were higher due to the HP diet. High density lipoprotein cholesterol (HDLC, %HDLC and cortisol were reduced in HP compared with AP sows. Lowest concentrations were observed for serum urea and protein, plasma insulin-like growth factor-I, low density lipoprotein cholesterol, and progesterone in LP compared with AP and HP sows. Fasted plasma glucose, insulin and leptin concentrations were unchanged. Diurnal metabolic profiles showed lower glucose in HP sows whereas non-esterified fatty acids (NEFA concentrations were higher in HP compared with AP and LP sows. In HP and LP sows, urea concentrations were 300% and 60% of AP sows, respectively. Plasma total cholesterol was higher in LP than in AP and HP sows. In AP sows, LW correlated positively with insulin and insulin/glucose and negatively with glucagon/insulin at 66 dpc, whereas in HP sows LW associated positively with NEFA. In conclusion, IUGR in sows fed high protein:low carbohydrate diet was probably due to glucose and energy deficit whereas in sows with low protein:high carbohydrate diet it was possibly a response to a deficit of indispensable amino acids which impaired lipoprotein metabolism and favored maternal lipid disposal.

  9. Placental Underperfusion in a Rat Model of Intrauterine Growth Restriction Induced by a Reduced Plasma Volume Expansion.

    Directory of Open Access Journals (Sweden)

    Karine Bibeau

    Full Text Available Lower maternal plasma volume expansion was found in idiopathic intrauterine growth restriction (IUGR but the link remains to be elucidated. An animal model of IUGR was developed by giving a low-sodium diet to rats over the last week of gestation. This treatment prevents full expansion of maternal circulating volume and the increase in uterine artery diameter, leading to reduced placental weight compared to normal gestation. We aimed to verify whether this is associated with reduced remodeling of uteroplacental circulation and placental hypoxia. Dams were divided into two groups: IUGR group and normal-fed controls. Blood velocity waveforms in the main uterine artery were obtained by Doppler sonography on days 14, 18 and 21 of pregnancy. On day 22 (term = 23 days, rats were sacrificed and placentas and uterine radial arteries were collected. Diameter and myogenic response of uterine arteries supplying placentas were determined while expression of hypoxia-modulated genes (HIF-1α, VEGFA and VEGFR2, apoptotic enzyme (Caspase -3 and -9 and glycogen cells clusters were measured in control and IUGR term-placentas. In the IUGR group, impaired blood velocity in the main uterine artery along with increased resistance index was observed without alteration in umbilical artery blood velocity. Radial uterine artery diameter was reduced while myogenic response was increased. IUGR placentas displayed increased expression of hypoxia markers without change in the caspases and increased glycogen cells in the junctional zone. The present data suggest that reduced placental and fetal growth in our IUGR model may be mediated, in part, through reduced maternal uteroplacental blood flow and increased placental hypoxia.

  10. Intrauterine growth retardation and consequences for endocrine and cardiovascular diseases in adult life

    DEFF Research Database (Denmark)

    Jensen, Rikke Bodin Beck; Chellakooty, Marla; Vielwerth, Signe

    2003-01-01

    to 40 weeks of gestation, but IGF-I levels are four to five times lower than those in the maternal circulation. Thus IGF-I levels in fetal as well as in maternal circulation are thought to regulate fetal growth. Circulating levels of IGF-I are thought to be genetically controlled and several IGF-I gene......Low birth weight has been associated with an increased incidence of ischaemic heart disease (IHD) and type 2 diabetes. Endocrine regulation of fetal growth by growth hormone (GH) and insulin-like growth factor (IGF)-I is complex. Placental GH is detectable in maternal serum from the 8th to the 12th...... gestational week, and rises gradually during pregnancy where it replaces pituitary GH in the maternal circulation. The rise in placental GH may explain the pregnancy-induced rise in maternal serum IGF-I levels. In the fetal compartment, IGF-I levels increase significantly in normally growing fetuses from 18...

  11. Serial hemodynamic measurement in normal pregnancy, preeclampsia, and intrauterine growth restriction

    NARCIS (Netherlands)

    Rang, Saskia; van Montfrans, Gert A.; Wolf, Hans

    2008-01-01

    OBJECTIVE: The study hypothesis was that hemodynamic measurements in conjunction with uterine artery Doppler could enable selection of women at risk for the development of preeclampsia or fetal growth restriction. STUDY DESIGN: Systolic (SBP) and diastolic blood pressure, heart rate (RR), cardiac

  12. Expanding Access to a New, More Affordable Levonorgestrel Intrauterine System in Kenya: Service Delivery Costs Compared With Other Contraceptive Methods and Perspectives of Key Opinion Leaders.

    Science.gov (United States)

    Rademacher, Kate H; Solomon, Marsden; Brett, Tracey; Bratt, John H; Pascual, Claire; Njunguru, Jesse; Steiner, Markus J

    2016-08-11

    The levonorgestrel intrauterine system (LNG IUS) is one of the most effective forms of contraception and offers important non-contraceptive health benefits. However, it is not widely available in developing countries, largely due to the high price of existing products. Medicines360 plans to introduce its new, more affordable LNG IUS in Kenya. The public-sector transfer price will vary by volume between US$12 to US$16 per unit; for an order of 100,000 units, the public-sector transfer price will be approximately US$15 per unit. We calculated the direct service delivery cost per couple-years of protection (CYP) of various family planning methods. The model includes the costs of contraceptive commodities, consumable supplies, instruments per client visit, and direct labor for counseling, insertion, removal, and resupply, if required. The model does not include costs of demand creation or training. We conducted interviews with key opinion leaders in Kenya to identify considerations for scale-up of a new LNG IUS, including strategies to overcome barriers that have contributed to low uptake of the copper intrauterine device. The direct service delivery cost of Medicines360's LNG IUS per CYP compares favorably with other contraceptive methods commonly procured for public-sector distribution in Kenya. The cost is slightly lower than that of the 3-month contraceptive injectable, which is currently the most popular method in Kenya. Almost all key opinion leaders agreed that introducing a more affordable LNG IUS could increase demand and uptake of the method. They thought that women seeking the product's non-contraceptive health benefits would be a key market segment, and most agreed that the reduced menstrual bleeding associated with the method would likely be viewed as an advantage. The key opinion leaders indicated that myths and misconceptions among providers and clients about IUDs must be addressed, and that demand creation and provider training should be prioritized

  13. Fetal window of vulnerability to airborne polycyclic aromatic hydrocarbons on proportional intrauterine growth restriction.

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    Hyunok Choi

    Full Text Available Although the entire duration of fetal development is generally considered a highly susceptible period, it is of public health interest to determine a narrower window of heightened vulnerability to polycyclic aromatic hydrocarbons (PAHs in humans. We posited that exposure to PAHs during the first trimester impairs fetal growth more severely than a similar level of exposure during the subsequent trimesters.In a group of healthy, non-smoking pregnant women with no known risks of adverse birth outcomes, personal exposure to eight airborne PAHs was monitored once during the second trimester for the entire cohort (n = 344, and once each trimester within a subset (n = 77. Both air monitoring and self-reported PAH exposure data were used in order to statistically estimate PAH exposure during the entire gestational period for each individual newborn.One natural-log unit increase in prenatal exposure to the eight summed PAHs during the first trimester was associated with the largest decrement in the Fetal Growth Ratio (FGR (-3%, 95% Confidence Interval (CI, -5 to -0%, birthweight (-105 g, 95% CI, -188 to -22 g, and birth length (-0.78 cm, 95% CI, -1.30 to -0.26 cm, compared to the unit effects of PAHs during the subsequent trimesters, after accounting for confounders. Furthermore, a unit exposure during the first trimester was associated with the largest elevation in Cephalization Index (head to weight ratio (3 μm/g, 95% CI, 1 to 5 μm/g. PAH exposure was not associated with evidence of asymmetric growth restriction in this cohort.PAH exposure appears to exert the greatest adverse effect on fetal growth during the first trimester. The present data support the need for the protection of pregnant women and the embryo/fetus, particularly during the earliest stage of pregnancy.

  14. A Maternal High-Energy Diet Promotes Intestinal Development and Intrauterine Growth of Offspring

    Science.gov (United States)

    Liu, Peilin; Che, Long; Yang, Zhenguo; Feng, Bin; Che, Lianqiang; Xu, Shengyu; Lin, Yan; Fang, Zhengfeng; Li, Jian; Wu, De

    2016-01-01

    It has been suggested that maternal nutrition during gestation is involved in an offspring’s intestinal development. The aim of this study was therefore to evaluate the effects of maternal energy on the growth and small intestine development of offspring. After mating, twenty gilts (Large White (LW) breeding, body weight (BW) at 135.54 ± 0.66 kg) were randomly allocated to two dietary treatments: a control diet (CON) group and a high-energy diet (HED) group, respectively. The nutrient levels of the CON were referred to meet the nutrient recommendations by the National Research Council (NRC, 2012), while the HED was designed by adding an amount of soybean oil that was 4.6% of the total diet weight to the CON. The dietary treatments were introduced from day 1 of gestation to farrowing. At day 90 of gestation, day 1 post-birth, and day 28 post-birth, the weights of fetuses and piglets, intestinal morphology, enzyme activities, and gene and protein expressions of intestinal growth factors were determined. The results indicated that the maternal HED markedly increased the BW, small intestinal weight, and villus height of fetuses and piglets. Moreover, the activities of lactase in fetal intestine, sucrase in piglet intestine were markedly increased by the maternal HED. In addition, the maternal HED tended to increase the protein expression of insulin-like growth factor 1 receptor (IGF-1R) in fetal intestine, associated with significantly increased the gene expression of IGF-1R. In conclusion, increasing energy intake could promote fetal growth and birth weight, with greater intestinal morphology and enzyme activities. PMID:27164130

  15. Paternal body mass index (BMI is associated with offspring intrauterine growth in a gender dependent manner.

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    You-Peng Chen

    Full Text Available BACKGROUND: Environmental alternations leading to fetal programming of cardiovascular diseases in later life have been attributed to maternal factors. However, animal studies showed that paternal obesity may program cardio-metabolic diseases in the offspring. In the current study we tested the hypothesis that paternal BMI may be associated with fetal growth. METHODS AND RESULTS: We analyzed the relationship between paternal body mass index (BMI and birth weight, ultrasound parameters describing the newborn's body shape as well as parameters describing the newborns endocrine system such as cortisol, aldosterone, renin activity and fetal glycated serum protein in a birth cohort of 899 father/mother/child triplets. Since fetal programming is an offspring sex specific process, male and female offspring were analyzed separately. Multivariable regression analyses considering maternal BMI, paternal and maternal age, hypertension during pregnancy, maternal total glycated serum protein, parity and either gestational age (for birth weight or time of ultrasound investigation (for ultrasound parameters as confounding showed that paternal BMI is associated with growth of the male but not female offspring. Paternal BMI correlated with birth parameters of male offspring only: birth weight; biparietal diameter, head circumference; abdominal diameter, abdominal circumference; and pectoral diameter. Cortisol was likewise significantly correlated with paternal BMI in male newborns only. CONCLUSIONS: Paternal BMI affects growth of the male but not female offspring. Paternal BMI may thus represent a risk factor for cardiovascular diseases of male offspring in later life. It remains to be demonstrated whether this is linked to an offspring sex specific paternal programming of cortisol secretion.

  16. Effects of intrauterine growth restriction during late pregnancy on the cell apoptosis and related gene expression in ovine fetal liver.

    Science.gov (United States)

    Liu, Yingchun; Ma, Chi; Li, Hui; Li, Lingyao; Gao, Feng; Ao, Changjin

    2017-03-01

    This study investigated the effect of intrauterine growth restriction (IUGR) during late pregnancy on the cell apoptosis and related gene expression in ovine fetal liver. Eighteen time-mated Mongolian ewes with singleton fetuses were allocated to three groups at d 90 of pregnancy: Restricted Group 1 (RG1, 0.18 MJ ME kg BW -0.75  d -1 , n = 6), Restricted Group 2 (RG2, 0.33 MJ ME kg BW -0.75  d -1 , n = 6) and a Control Group (CG, ad libitum, 0.67 MJ ME kg BW -0.75  d -1 , n = 6). Fetuses were recovered at slaughter on d 140. Fetal liver weight, DNA content and protein/DNA ratio, proliferation index, cytochrome c, activities of Caspase-3, 8, and 9 were examined, along with relative expression of genes related to apoptosis. Fetuses in both restricted groups exhibited decreased BW, hepatic weight, DNA content, and protein/DNA ratio when compared to CG (P restricted groups (P  0.05). Hepatic expression of gene related to apoptosis showed reduced protein 21 (P21), B-cell lymphoma 2 (Bcl-2) and apoptosis antigen 1 ligand (FasL) expression in RG1 and RG2 (P < 0.05). In contrast, the increased hepatic expression of protein 53 (P53), Bcl-2 associated X protein (Bax) and apoptosis antigen 1 (Fas) in both IUGR fetuses were found (P < 0.05). These results indicate that the fetal hepatocyte proliferation were arrested in G1 cell cycle, and the fetal hepatocyte apoptosis was sensitive to the IUGR resulted from maternal undernutrition. The cell apoptosis in IUGR fetal liver were the potential mechanisms for its retarded proliferation and impaired development. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Differential vulnerability of gray matter and white matter to intrauterine growth restriction in preterm infants at 12 months corrected age.

    Science.gov (United States)

    Padilla, Nelly; Junqué, Carme; Figueras, Francesc; Sanz-Cortes, Magdalena; Bargalló, Núria; Arranz, Angela; Donaire, Antonio; Figueras, Josep; Gratacos, Eduard

    2014-01-30

    Intrauterine growth restriction (IUGR) is associated with a high risk of abnormal neurodevelopment. Underlying neuroanatomical substrates are partially documented. We hypothesized that at 12 months preterm infants would evidence specific white-matter microstructure alterations and gray-matter differences induced by severe IUGR. Twenty preterm infants with IUGR (26-34 weeks of gestation) were compared with 20 term-born infants and 20 appropriate for gestational age preterm infants of similar gestational age. Preterm groups showed no evidence of brain abnormalities. At 12 months, infants were scanned sleeping naturally. Gray-matter volumes were studied with voxel-based morphometry. White-matter microstructure was examined using tract-based spatial statistics. The relationship between diffusivity indices in white matter, gray matter volumes, and perinatal data was also investigated. Gray-matter decrements attributable to IUGR comprised amygdala, basal ganglia, thalamus and insula bilaterally, left occipital and parietal lobes, and right perirolandic area. Gray-matter volumes positively correlated with birth weight exclusively. Preterm infants had reduced FA in the corpus callosum, and increased FA in the anterior corona radiata. Additionally, IUGR infants had increased FA in the forceps minor, internal and external capsules, uncinate and fronto-occipital white matter tracts. Increased axial diffusivity was observed in several white matter tracts. Fractional anisotropy positively correlated with birth weight and gestational age at birth. These data suggest that IUGR differentially affects gray and white matter development preferentially affecting gray matter. At 12 months IUGR is associated with a specific set of structural gray-matter decrements. White matter follows an unusual developmental pattern, and is apparently affected by IUGR and prematurity combined. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Placental Expressions of CDKN1C and KCNQ1OT1 in Monozygotic Twins with Selective Intrauterine Growth Restriction.

    Science.gov (United States)

    Gou, Chenyu; Liu, Xiangzhen; Shi, Xiaomei; Chai, Hanjing; He, Zhi-Ming; Huang, Xuan; Fang, Qun

    2017-10-01

    CDKN1C and KCNQ1OT1 are imprinted genes that might be potential regulators of placental development. This study investigated placental expressions of CDKN1C and KCNQ1OT1 in monozygotic twins with and without selective intrauterine growth restriction (sIUGR). Seventeen sIUGR and fifteen normal monozygotic(MZ) twin pairs were examined. Placental mRNA expressions of CDKN1C and KCNQ1OT1 were detected by real-time fluorescent quantitative PCR. CDKN1C protein expression was detected by immunohistochemical assay and Western-blotting. In the sIUGR group, smaller fetuses had a smaller share of the placenta, and CDKN1C protein expression was significantly increased while KCNQ1OT1 mRNA expression was significantly decreased. The CDKN1C/KCNQ1OT1 mRNA ratio was lower in the larger fetus than in the smaller fetus (p < .05). In the control group, CDKN1C protein expression showed no difference between larger and smaller fetuses, while KCNQ1OT1 mRNA expression was significantly lower in the larger fetus, and the CDKN1C/KCNQ1OT1 mRNA ratio was higher in the larger fetus than in the smaller fetus (p < .05). Our findings showed that pathogenesis of sIUGR may be related to the co-effect of the up-regulated protein expression of CDKN1C and down-regulated mRNA expression of KCNQ1OT1 in the placenta.

  19. In Vivo Detection of Perinatal Brain Metabolite Changes in a Rabbit Model of Intrauterine Growth Restriction (IUGR.

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    Rui V Simões

    Full Text Available Intrauterine growth restriction (IUGR is a risk factor for abnormal neurodevelopment. We studied a rabbit model of IUGR by magnetic resonance imaging (MRI and spectroscopy (MRS, to assess in vivo brain structural and metabolic consequences, and identify potential metabolic biomarkers for clinical translation.IUGR was induced in 3 pregnant rabbits at gestational day 25, by 40-50% uteroplacental vessel ligation in one horn; the contralateral horn was used as control. Fetuses were delivered at day 30 and weighted. A total of 6 controls and 5 IUGR pups underwent T2-w MRI and localized proton MRS within the first 8 hours of life, at 7T. Changes in brain tissue volumes and respective contributions to each MRS voxel were estimated by semi-automated registration of MRI images with a digital atlas of the rabbit brain. MRS data were used for: (i absolute metabolite quantifications, using linear fitting; (ii local temperature estimations, based on the water chemical shift; and (iii classification, using spectral pattern analysis.Lower birth weight was associated with (i smaller brain sizes, (ii slightly lower brain temperatures, and (iii differential metabolite profile changes in specific regions of the brain parenchyma. Specifically, we found estimated lower levels of aspartate and N-acetylaspartate (NAA in the cerebral cortex and hippocampus (suggesting neuronal impairment, and higher glycine levels in the striatum (possible marker of brain injury. Our results also suggest that the metabolic changes in cortical regions are more prevalent than those detected in hippocampus and striatum.IUGR was associated with brain metabolic changes in vivo, which correlate well with the neurostructural changes and neurodevelopment problems described in IUGR. Metabolic parameters could constitute non invasive biomarkers for the diagnosis and abnormal neurodevelopment of perinatal origin.

  20. Quantitative Shear-Wave Elastography of the Liver in Preterm Neonates with Intra-Uterine Growth Restriction.

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    Marianne Alison

    Full Text Available The feasibility and reproducibility of liver stiffness measurements using Supersonic Shear-wave Imaging (SSI in preterm neonate have not been reported. Our aim was to determine if liver stiffness differs between intra-uterine growth restriction (IUGR and appropriate for gestational age (AGA preterm infants with/without cholestasis. We measured liver stiffness (in kPa in 45 AGA and 18 IUGR preterm infants, and assessed reproducibility in 26 preterms using Intraclass Correlation Coefficients (ICC and Bland-Altman tests. Liver stiffness values were compared between AGA and IUGR with and without cholestasis and correlated with birth weight. Measurements showed high reproducibility (ICC = 0.94-0.98 for intra-operator, 0.86 for inter-operator with good agreement (95% limits: -1.24 to 1.24 kPa. During the first postnatal week, liver stiffness was higher in IUGR (7.50 ±1.53 kPa than in AGA infants (5.11 ±0.80 kPa, p<0.001. After day 8, liver stiffness remained unchanged in AGA but increased progressively in IUGR infants (15.57 ±6.49 kPa after day 21. Liver stiffness was higher in IUGR neonates with cholestasis (19.35 ± 9.80 kPa than without cholestasis (7.72 ± 1.27 kPa, p<0.001. In conclusion, quantitative liver SSI in preterms is feasible and reproducible. IUGR preterms who will develop cholestasis present high liver stiffness even at birth, before biological cholestasis occurs.

  1. Comparison of blood lead levels of mothers and cord blood in intrauterine growth retarded neonates and normal term neonates

    International Nuclear Information System (INIS)

    Iranpour, R.; Besharati, Amir A.; Nasseri, F.; Hashemipour, M.; Kelishadi, R.; Balali-Mood, M.

    2007-01-01

    Objective was to compare the blood lead levels of mothers and cord blood in intrauterine growth retarded (IUGR) neonates and normal term neonates. From April 2005, we carried out a cross-sectional, prospective study in Isfahan University of Medical Sciences, Isfahan, Iran. Blood lead levels were measured in the umbilical cord and maternal venous blood samples in the 32 mother-infant pairs with IUGR full term neonates and 34 mother-infant pairs with normal full term neonates. Blood-lead levels were analyzed by atomic absorption spectrometry. The mean lead concentration in neonates of IUGR and normal groups was not significantly different (107.47+- 16.75 versus 113.08+-19.08 ug/L, p=0.2). The mean lead concentration in mothers of IUGR group was lower than normal groups, but this difference was not significant (124.56+-19.71 versus 135.26+-26.91 ug/L, p=0.07). Maternal lead levels were strongly related with related with cord blood in both IUGR and normal groups (r=0.8, p 100ug/L by the centers for disease control; however, this was not statistically different between the groups. Our results indicate that the mean lead level was not higher in IUGR neonates, and the whole blood lead was not related to the birth weight. In addition, maternal and cord blood lead levels were strongly correlated, and there were remarkable lead burdens on both the mothers and their neonates in this industrial area. (author)

  2. Islet inflammation, hemosiderosis, and fibrosis in intrauterine growth-restricted and high fat-fed Sprague-Dawley rats.

    Science.gov (United States)

    Delghingaro-Augusto, Viviane; Madad, Leili; Chandra, Arin; Simeonovic, Charmaine J; Dahlstrom, Jane E; Nolan, Christopher J

    2014-05-01

    Prenatal and postnatal factors such as intrauterine growth restriction (IUGR) and high-fat (HF) diet contribute to type 2 diabetes. Our aim was to determine whether IUGR and HF diets interact in type 2 diabetes pathogenesis, with particular attention focused on pancreatic islet morphology including assessment for inflammation. A surgical model of IUGR (bilateral uterine artery ligation) in Sprague-Dawley rats with sham controls was used. Pups were fed either HF or chow diets after weaning. Serial measures of body weight and glucose tolerance were performed. At 25 weeks of age, rat pancreases were harvested for histologic assessment. The birth weight of IUGR pups was 13% lower than that of sham pups. HF diet caused excess weight gain, dyslipidemia, hyperinsulinemia, and mild glucose intolerance, however, this was not aggravated further by IUGR. Markedly abnormal islet morphology was evident in 0 of 6 sham-chow, 5 of 8 sham-HF, 4 of 8 IUGR-chow, and 8 of 9 IUGR-HF rats (chi-square, P = 0.007). Abnormal islets were characterized by larger size, irregular shape, inflammation with CD68-positive cells, marked fibrosis, and hemosiderosis. β-Cell mass was not altered by IUGR. In conclusion, HF and IUGR independently contribute to islet injury characterized by inflammation, hemosiderosis, and fibrosis. This suggests that both HF and IUGR can induce islet injury via converging pathways. The potential pathogenic or permissive role of iron in this process of islet inflammation warrants further investigation. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  3. Developmental Programming: Impact of Excess Prenatal Testosterone on Intrauterine Fetal Endocrine Milieu and Growth in Sheep1

    Science.gov (United States)

    Veiga-Lopez, Almudena; Steckler, Teresa L.; Abbott, David H.; Welch, Kathleen B.; MohanKumar, Puliyur S.; Phillips, David J.; Refsal, Kent; Padmanabhan, Vasantha

    2010-01-01

    Prenatal testosterone excess in sheep leads to reproductive and metabolic disruptions that mimic those seen in women with polycystic ovary syndrome. Comparison of prenatal testosterone-treated sheep with prenatal dihydrotestosterone-treated sheep suggests facilitation of defects by androgenic as well as androgen-independent effects of testosterone. We hypothesized that the disruptive impact of prenatal testosterone on adult pathology may partially depend on its conversion to estrogen and consequent changes in maternal and fetal endocrine environments. Pregnant Suffolk sheep were administered either cottonseed oil (control) or testosterone propionate in cottonseed oil (100 mg, i.m. twice weekly), from Day 30 to Day 90 of gestation (term is ∼147 d). Maternal (uterine) and fetal (umbilical) arterial samples were collected at Days 64–66, 87–90, and 139–140 (range; referred to as D65, D90, and D140, respectively) of gestation. Concentrations of gonadal and metabolic hormones, as well as differentiation factors, were measured using liquid chromatography/mass spectrometer, radioimmunoassay, or ELISA. Findings indicate that testosterone treatment produced maternal and fetal testosterone levels comparable to adult males and D65 control male fetuses, respectively. Testosterone treatment increased fetal estradiol and estrone levels during the treatment period in both sexes, supportive of placental aromatization of testosterone. These steroidal changes were followed by a reduction in maternal estradiol levels at term, a reduction in activin A availability, and induction of intrauterine growth restriction in D140 female fetuses. Overall, our findings provide the first direct evidence in support of the potential for both androgenic as well as estrogenic contribution in the development of adult reproductive and metabolic pathology in prenatal testosterone-treated sheep. PMID:20739662

  4. Caspase dependent and independent mechanisms of apoptosis across gestation in a sheep model of placental insufficiency and intrauterine growth restriction.

    Science.gov (United States)

    Monson, Troy; Wright, Tanner; Galan, Henry L; Reynolds, Paul R; Arroyo, Juan A

    2017-05-01

    Increased placental apoptosis is a hallmark of intrauterine growth restricted (IUGR). Several molecules have been shown to be involved in the control of apoptosis during this disease. Our objective was to determine the expression of Bcl2, Bax, phospho XIAP, AIF, caspase 3 and 9, and telomerase activity across gestation in an ovine hyperthermia-induced model of IUGR. Pregnant sheep were placed in hyperthermic (HT) conditions to induce IUGR along with age-matched controls. Placental tissues were collected at 55 (early), 95 (mid-gestation) and 130 (near-term) days of gestational age (dGA) to determine the expression of apoptotic molecules during the development of IUGR. Compared to the control placenta, IGUR pregnancies showed: significantly reduced placental Bcl2 in early gestation (55 dGA) with a significant increase observed at mid gestation (95 dGA); decreased placental pXIAP at both mid and near term gestational days (95 and 130 dGA); placental AIF increased only at 55 dGA (early gestation); active caspase 3 increased at both mid and near term gestational days (95 and 130 dGA); caspase 9 only increased at mid gestation (95 dGA) and decreased Telomerase activity near term. Placental apoptosis, mediated in part by the apoptosis related molecule, participates in the development of IUGR. Findings from this study suggest a caspase-independent apoptotic pathway during early gestation and caspase-dependent apoptosis at mid and near term gestation. The data also implicate decreased activation of XIAP as a plausible factor involved in the control of placental apoptosis during IUGR.

  5. Hypoxia-activated genes from early placenta are elevated in Preeclampsia, but not in Intra-Uterine Growth Retardation

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    Danan Jean-Louis

    2005-08-01

    Full Text Available Abstract Background As a first step to explore the possible relationships existing between the effects of low oxygen pressure in the first trimester placenta and placental pathologies developing from mid-gestation, two subtracted libraries totaling 2304 cDNA clones were constructed. For achieving this, two reciprocal suppressive/subtractive hybridization procedures (SSH were applied to early (11 weeks human placental villi after incubation either in normoxic or in hypoxic conditions. The clones from both libraries (1440 hypoxia-specific and 864 normoxia-specific were spotted on nylon macroarrays. Complex cDNAs probes prepared from placental villi (either from early pregnancy, after hypoxic or normoxic culture conditions, or near term for controls or pathological placentas were hybridized to the membranes. Results Three hundred and fifty nine clones presenting a hybridization signal above the background were sequenced and shown to correspond to 276 different genes. Nine of these genes are mitochondrial, while 267 are nuclear. Specific expression profiles characteristic of preeclampsia (PE could be identified, as well as profiles specific of intra-uterine growth retardation (IUGR. Focusing on the chromosomal distribution of the fraction of genes that responded in at least one hybridization experiment, we could observe a highly significant chromosomal clustering of 54 genes into 8 chromosomal regions, four of which containing imprinted genes. Comparative mapping data indicate that these imprinted clusters are maintained in synteny in mice, and apparently in cattle and pigs, suggesting that the maintenance of such syntenies is requested for achieving a normal placental physiology in eutherian mammals. Conclusion We could demonstrate that genes induced in PE were also genes highly expressed under hypoxic conditions (P = 5.10-5, which was not the case for isolated IUGR. Highly expressed placental genes may be in syntenies conserved interspecifically

  6. Postnatal growth velocity modulates alterations of proteins involved in metabolism and neuronal plasticity in neonatal hypothalamus in rats born with intrauterine growth restriction.

    Science.gov (United States)

    Alexandre-Gouabau, Marie-Cécile F; Bailly, Emilie; Moyon, Thomas L; Grit, Isabelle C; Coupé, Bérengère; Le Drean, Gwenola; Rogniaux, Hélène J; Parnet, Patricia

    2012-02-01

    Intrauterine growth restriction (IUGR) due to maternal protein restriction is associated in rats with an alteration in hypothalamic centers involved in feeding behaviour. In order to gain insight into the mechanism of perinatal maternal undernutrition in the brain, we used proteomics approach to identify hypothalamic proteins that are altered in their expression following protein restriction in utero. We used an animal model in which restriction of the protein intake of pregnant rats (8% vs. 20%) produces IUGR pups which were randomized to a nursing regimen leading to either rapid or slow catch-up growth. We identified several proteins which allowed, by multivariate analysis, a very good discrimination of the three groups according to their perinatal nutrition. These proteins were related to energy-sensing pathways (Eno 1, E(2)PDH, Acot 1 and Fabp5), redox status (Bcs 1L, PrdX3 and 14-3-3 protein) or amino acid pathway (Acy1) as well as neurodevelopment (DRPs, MAP2, Snca). In addition, the differential expressions of several key proteins suggested possible shunts towards ketone-body metabolism and lipid oxidation, providing the energy and carbon skeletons necessary to lipogenesis. Our results show that maternal protein deprivation during pregnancy only (IUGR with rapid catch-up growth) or pregnancy and lactation (IUGR with slow postnatal growth) modulates numerous metabolic pathways resulting in alterations of hypothalamic energy supply. As several of these pathways are involved in signalling, it remains to be determined whether hypothalamic proteome adaptation of IUGR rats in response to different postnatal growth rates could also interfere with cerebral plasticity or neuronal maturation. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. [Intra-uterine growth restriction impact on maternal serum concentration of PlGF (placental growth factor): A case control study].

    Science.gov (United States)

    Margossian, A; Boisson-Gaudin, C; Subtil, F; Rudigoz, R-C; Dubernard, G; Allias, F; Huissoud, C

    2016-01-01

    Placental growth factor (PlGF) is a pro-angiogenic factor mainly assessed in preeclampsia in which its blood concentration is decreased. The aim of this study was to dose the blood concentration of PlGF in women with fetal intra-uterine growth restriction (IUGR) without associated preeclampsia at the time of diagnosis. Case/control study: IUGR was defined by a fetal biometry with abnormal uterine and/or umbilical doppler (n=23). This group was compared to a control group of fetuses (n=25) matched for gestational age at blood sampling for the dosage of maternal seric PlGF. Women with preeclampsia were not included. The plasma PlGF concentration was 11pg/mL (IQR [11-42,8]) in the IUGR group vs 287pg/mL [135-439] in the control group (P<0.001) and this difference was available after adjustment for gestational age at the time of blood sampling (P<0.001). PlGF sensitivity and specificity for discrimination were respectively 87% (CI 95% [66-97]) and 88% (CI 95% [69-97]). Maternal serum PlGF concentrations were very low in IUGR group compared with those of the control group. Copyright © 2015. Published by Elsevier SAS.

  8. Enamel defect of primary dentition in SGA children in relation to onset time of intrauterine growth disturbance

    Directory of Open Access Journals (Sweden)

    Willyanti Soewondo Sjarif

    2013-06-01

    Full Text Available Background: Prenatal disturbances disturb the development of organs resulting in small for gestational age (SGA babies and also causes enamel defects in primary teeth. There are disturbances occur in the beginning of pregnancy causing symmetrical SGA, and asymmetrical type of SGA, where the disturbances occur late in pregnancy. Purpose: This research was to determined differences in severity of enamel defect of primary dentition in small for gestational age children based on the time of intrauterine growth restriction. Methods: This was a clinical epidemiological cohort study. The Ponderal index was used to determine SGA type. The subjects were 129 SGA children aged 9-42 months, 82 with asymmetrical SGA and 47 with symmetrical SGA. Two hundred normal birth weight children were the control group. Intra-oral examinations to determine enamel defect used the FDI modification of the Developmental Defect of Enamel score at 3 months intervals. Statistical t-tests were used to test the difference in severity of enamel defect, and chisquare to find out the difference of Relative Risk Ratio (RRR. Results: The results showed that the enamel defect scores of symmetrical SGA were significantly higher than those with asymmetrical SGA. RRR for severe defect was also significantly higher in symmetrical type for anterior and canines. Conclusion: The study suggested that the severity of enamel defect for infants with symmetrical SGA was higher than those with asymmetrical SGA, indicating that the severity of the defect occurs in the beginning of pregnancy is more severe than in the late pregnancy.Latar belakang: Adanya gangguan prenatal mengganggu perkembangan organ, mengakibatkan terjadinya bayi lahir dengan kecil masa kehamilan (KMK dan defek email pada gigi sulung. Terdapat 2 tipe KMK yaitu tipe simetri; gangguan terjadi pada awal kehamilan; dimana lingkar kepala, berat dan panjang lahir lebih rendah dari normal. Tipe asimetri dimana gangguan terjadi saat

  9. The extent of intrauterine growth restriction determines the severity of cerebral injury and neurobehavioural deficits in rodents.

    Science.gov (United States)

    Ruff, Crystal A; Faulkner, Stuart D; Rumajogee, Prakasham; Beldick, Stephanie; Foltz, Warren; Corrigan, Jennifer; Basilious, Alfred; Jiang, Shangjun; Thiyagalingam, Shanojan; Yager, Jerome Y; Fehlings, Michael G

    2017-01-01

    Cerebral Palsy (CP) is the most common physical pediatric neurodevelopmental disorder and spastic diplegic injury is its most frequent subtype. CP results in substantial neuromotor and cognitive impairments that have significant socioeconomic impact. Despite this, its underlying pathophysiological mechanisms and etiology remain incompletely understood. Furthermore, there is a need for clinically relevant injury models, which a) reflect the heterogeneity of the condition and b) can be used to evaluate new translational therapies. To address these key knowledge gaps, we characterized a chronic placental insufficiency (PI) model, using bilateral uterine artery ligation (BUAL) of dams. This injury model results in intrauterine growth restriction (IUGR) in pups, and animals recapitulate the human phenotype both in terms of neurobehavioural and anatomical deficits. Effects of BUAL were studied using luxol fast blue (LFB)/hematoxylin & eosin (H&E) staining, immunohistochemistry, quantitative Magnetic Resonance Imaging (MRI), and Catwalk neurobehavioural tests. Neuroanatomical analysis revealed regional ventricular enlargement and corpus callosum thinning in IUGR animals, which was correlated with the extent of growth restriction. Olig2 staining revealed reductions in oligodendrocyte density in white and grey matter structures, including the corpus callosum, optic chiasm, and nucleus accumbens. The caudate nucleus, along with other brain structures such as the optic chiasm, internal capsule, septofimbrial and lateral septal nuclei, exhibited reduced size in animals with IUGR. The size of the pretectal nucleus was reduced only in moderately injured animals. MAG/NF200 staining demonstrated reduced myelination and axonal counts in the corpus callosum of IUGR animals. NeuN staining revealed changes in neuronal density in the hippocampus and in the thickness of hippocampal CA2 and CA3 regions. Diffusion weighted imaging (DWI) revealed regional white and grey matter changes at 3

  10. The extent of intrauterine growth restriction determines the severity of cerebral injury and neurobehavioural deficits in rodents.

    Directory of Open Access Journals (Sweden)

    Crystal A Ruff

    Full Text Available Cerebral Palsy (CP is the most common physical pediatric neurodevelopmental disorder and spastic diplegic injury is its most frequent subtype. CP results in substantial neuromotor and cognitive impairments that have significant socioeconomic impact. Despite this, its underlying pathophysiological mechanisms and etiology remain incompletely understood. Furthermore, there is a need for clinically relevant injury models, which a reflect the heterogeneity of the condition and b can be used to evaluate new translational therapies. To address these key knowledge gaps, we characterized a chronic placental insufficiency (PI model, using bilateral uterine artery ligation (BUAL of dams. This injury model results in intrauterine growth restriction (IUGR in pups, and animals recapitulate the human phenotype both in terms of neurobehavioural and anatomical deficits.Effects of BUAL were studied using luxol fast blue (LFB/hematoxylin & eosin (H&E staining, immunohistochemistry, quantitative Magnetic Resonance Imaging (MRI, and Catwalk neurobehavioural tests.Neuroanatomical analysis revealed regional ventricular enlargement and corpus callosum thinning in IUGR animals, which was correlated with the extent of growth restriction. Olig2 staining revealed reductions in oligodendrocyte density in white and grey matter structures, including the corpus callosum, optic chiasm, and nucleus accumbens. The caudate nucleus, along with other brain structures such as the optic chiasm, internal capsule, septofimbrial and lateral septal nuclei, exhibited reduced size in animals with IUGR. The size of the pretectal nucleus was reduced only in moderately injured animals. MAG/NF200 staining demonstrated reduced myelination and axonal counts in the corpus callosum of IUGR animals. NeuN staining revealed changes in neuronal density in the hippocampus and in the thickness of hippocampal CA2 and CA3 regions. Diffusion weighted imaging (DWI revealed regional white and grey matter

  11. Intrauterine growth-restricted sheep fetuses exhibit smaller hindlimb muscle fibers and lower proportions of insulin-sensitive Type I fibers near term.

    Science.gov (United States)

    Yates, Dustin T; Cadaret, Caitlin N; Beede, Kristin A; Riley, Hannah E; Macko, Antoni R; Anderson, Miranda J; Camacho, Leticia E; Limesand, Sean W

    2016-06-01

    Intrauterine growth restriction (IUGR) reduces muscle mass and insulin sensitivity in offspring. Insulin sensitivity varies among muscle fiber types, with Type I fibers being most sensitive. Differences in fiber-type ratios are associated with insulin resistance in adults, and thus we hypothesized that near-term IUGR sheep fetuses exhibit reduced size and proportions of Type I fibers. Placental insufficiency-induced IUGR fetuses were ∼54% smaller (P fetal muscles develop smaller fibers and have proportionally fewer Type I fibers, which is indicative of developmental adaptations that may help explain the link between IUGR and adulthood insulin resistance. Copyright © 2016 the American Physiological Society.

  12. Effects of medium-chain triglycerides on intestinal morphology and energy metabolism of intrauterine growth retarded weanling piglets.

    Science.gov (United States)

    Zhang, Li-Li; Zhang, Hao; Li, Yue; Wang, Tian

    2017-06-01

    It has been shown that there is a relationship between intrauterine growth retardation (IUGR) and postnatal intestinal damage involved in energy deficits. Therefore, the present study was conducted to investigate the effect of medium-chain triglycerides (MCT) on the intestinal morphology, intestinal function and energy metabolism of piglets with IUGR. At weaning (21 ± 1.1 d of age), 24 IUGR piglets and 24 normal birth weight (NBW) piglets were selected according to their birth weights (BW) (IUGR: 0.95 ± 0.04 kg BW; NBW: 1.58 ± 0.04 kg BW) and their weights at the time of weaning (IUGR: 5.26 ± 0.15 kg BW; NBW: 6.98 ± 0.19 kg BW). The piglets were fed a diet of either long-chain triglycerides (LCT) (containing 5% LCT) or MCT (containing 1% LCT and 4% MCT) for 28 d. Then, the piglets' intestinal morphology, biochemical parameters and mRNA abundance related to intestinal damage and energy metabolism were determined. IUGR was found to impair intestinal morphology, with evidence of decreased villus height and increased crypt depth; however, these negative effects of IUGR were ameliorated by MCT treatment. IUGR piglets showed compromised intestinal digestion and absorption functions when compared with NBW piglets. However, feeding MCT increased the maltase activity in the jejunum and alleviated IUGR-induced reductions in plasma d-xylose concentrations and jejunal sucrase activity. IUGR decreased the efficiency of the piglets' intestinal energy metabolism; however, piglets fed an MCT diet exhibited increased adenosine triphosphate (ATP) concentrations and ATP synthase F1 complex beta polypeptide expression, as well as decreased adenosine monophosphate-activated kinase alpha 1 expression in the jejunum of piglets. In addition, up-regulation of the piglets' citrate synthase and succinate dehydrogenase levels was found to occur following MCT treatment at both the activity and the transcriptional levels of the jejunum. Therefore, it can be postulated that

  13. A hierarchical analysis of transcriptome alterations in intrauterine growth restriction (IUGR) reveals common pathophysiological pathways in mammals.

    Science.gov (United States)

    Buffat, C; Mondon, F; Rigourd, V; Boubred, F; Bessières, B; Fayol, L; Feuerstein, J-M; Gamerre, M; Jammes, H; Rebourcet, R; Miralles, F; Courbières, B; Basire, A; Dignat-Georges, F; Carbonne, B; Simeoni, U; Vaiman, D

    2007-11-01

    Intra-uterine growth restriction (IUGR) is a frequent disease, affecting up to 10% of human pregnancies and responsible for increased perinatal morbidity and mortality. Moreover, low birth weight is an important cause of the metabolic syndrome in the adult. Protein depletion during the gestation of rat females has been widely used as a model for human IUGR. By transcriptome analysis of control and protein-deprived rat placentas, we were able to identify 2543 transcripts modified more than 2.5 fold (1347 induced and 1196 repressed). Automatic functional classification enabled us to identify clusters of induced genes affecting chromosome structure, transcription, intracellular transport, protein modifications and apoptosis. In particular, we suggest the existence of a complex balance regulating apoptosis. Among repressed genes, we noted several groups of genes involved in immunity, signalling and degradation of noxious chemicals. These observations suggest that IUGR placentas have a decreased resistance to external aggression. The promoters of the most induced and most repressed genes were contrasted for their composition in putative transcription factor binding sites. There was an over-representation of Zn finger (ZNF) proteins and Pdx1 (pancreatic and duodenal homeobox protein 1) putative binding sites. Consistently, Pdx1 and a high proportion of ZNF genes were induced at the transcriptional level. A similar analysis of ZNF promoters showed an increased presence of putative binding sites for the Tata box binding protein (Tbp). Consistently again, we showed that the Tbp and TBP-associated factors (Tafs) were up-regulated in IUGR placentas. Also, samples of human IUGR and control placentas showed that human orthologous ZNFs and PDX1 were transcriptionally induced, especially in non-vascular IUGR. Immunohistochemistry revealed increased expression of PDX1 in IUGR human placentas. In conclusion, our approach permitted the proposition of hypotheses on a hierarchy of

  14. Intrauterine growth restriction

    Science.gov (United States)

    ... a baby while in the mother's womb during pregnancy. Causes Many different things can lead to IUGR. An unborn baby may not get enough oxygen and nutrition from the placenta during pregnancy because of: High altitudes Multiple pregnancy, such as ...

  15. Neurodevelopment in preterm infants with and without placenta-related intrauterine growth restriction and its relation to perinatal and postnatal factors.

    Science.gov (United States)

    Candel-Pau, Júlia; Perapoch López, Josep; Castillo Salinas, Félix; Sánchez Garcia, Olga; Pérez Hoyos, Santiago; Llurba Olivé, Elisa

    2016-01-01

    Intrauterine-growth restriction is associated with impaired neurodevelopment. However, studies on early childhood neurodevelopment of premature infants with placenta-related intrauterine-growth restriction (IUGR) are scarce and heterogeneous. We aimed to analyze the impact of placenta-related IUGR on preschool age neurodevelopment in preterm infants, and to ascertain which prenatal and postnatal factors influence neurodevelopment in these infants. Prospective cohorts study: 48 placenta-related IUGR premature infants and 25 matched non-IUGR premature infants (mean gestational age: 31.4 and 31.6 weeks, respectively). Preschool neurodevelopment assessment with cognitive Bayley Scales III and with ASQ-III surveys (age interval: 34.07-42.50 months). Inter-cohort result comparison. Analysis of perinatal and environmental factors associated with impaired neurodevelopment in both cohorts. No statistically significant neurodevelopment differences were observed at preschool age between both preterm cohorts. Multivariate analysis of perinatal and environmental factors showed daycare, breastfeeding, higher parental educational level, and absence of severe neonatal morbidity to be associated with a lower risk of altered neurodevelopment at preschool age. Placenta-related IUGR does not have a significant impact on preschool neurodevelopment in our preterm patients. Instead, post-natal positive environmental factors such as parental educational level, breastfeeding, and daycare attendance make a difference towards an improvement in neurodevelopment in these infants.

  16. Reduced telomere length is not associated with early signs of vascular aging in young men born after intrauterine growth restriction: a paradox?

    DEFF Research Database (Denmark)

    Laganovic, M.; Bendix, L.; Rubelj, I.

    2014-01-01

    Objective: The mechanisms that increase cardiovascular risk in individuals born small for gestational age (SGA) are not well understood. Telomere shortening has been suggested to be a predictor of disease onset. Our aim was to determine whether impaired intrauterine growth is associated with earl...... of cardiovascular risk in SGA participants. Follow-up of this cohort will clarify hypothesis and validate telomere dynamics as indicators of future health risks.......Objective: The mechanisms that increase cardiovascular risk in individuals born small for gestational age (SGA) are not well understood. Telomere shortening has been suggested to be a predictor of disease onset. Our aim was to determine whether impaired intrauterine growth is associated with early......IMT, and a trend to increased SBP and heart rate in comparison to the AGA group. Interestingly, SGA men exhibited a 42% longer LTL than the AGA group. LTL was inversely associated with age, BMI, BP and birth parameters. In multiple regression analysis, BMI was the key determinant of SBP and cIMT. Conclusion: Young...

  17. Prenatal Mechanistic Target of Rapamycin Complex 1 (m TORC1) Inhibition by Rapamycin Treatment of Pregnant Mice Causes Intrauterine Growth Restriction and Alters Postnatal Cardiac Growth, Morphology, and Function.

    Science.gov (United States)

    Hennig, Maria; Fiedler, Saskia; Jux, Christian; Thierfelder, Ludwig; Drenckhahn, Jörg-Detlef

    2017-08-04

    Fetal growth impacts cardiovascular health throughout postnatal life in humans. Various animal models of intrauterine growth restriction exhibit reduced heart size at birth, which negatively influences cardiac function in adulthood. The mechanistic target of rapamycin complex 1 (mTORC1) integrates nutrient and growth factor availability with cell growth, thereby regulating organ size. This study aimed at elucidating a possible involvement of mTORC1 in intrauterine growth restriction and prenatal heart growth. We inhibited mTORC1 in fetal mice by rapamycin treatment of pregnant dams in late gestation. Prenatal rapamycin treatment reduces mTORC1 activity in various organs at birth, which is fully restored by postnatal day 3. Rapamycin-treated neonates exhibit a 16% reduction in body weight compared with vehicle-treated controls. Heart weight decreases by 35%, resulting in a significantly reduced heart weight/body weight ratio, smaller left ventricular dimensions, and reduced cardiac output in rapamycin- versus vehicle-treated mice at birth. Although proliferation rates in neonatal rapamycin-treated hearts are unaffected, cardiomyocyte size is reduced, and apoptosis increased compared with vehicle-treated neonates. Rapamycin-treated mice exhibit postnatal catch-up growth, but body weight and left ventricular mass remain reduced in adulthood. Prenatal mTORC1 inhibition causes a reduction in cardiomyocyte number in adult hearts compared with controls, which is partially compensated for by an increased cardiomyocyte volume, resulting in normal cardiac function without maladaptive left ventricular remodeling. Prenatal rapamycin treatment of pregnant dams represents a new mouse model of intrauterine growth restriction and identifies an important role of mTORC1 in perinatal cardiac growth. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  18. Prevention of early postnatal hyperalimentation protects against activation of transforming growth factor-β/bone morphogenetic protein and interleukin-6 signaling in rat lungs after intrauterine growth restriction.

    Science.gov (United States)

    Alcázar, Miguel Angel Alejandre; Dinger, Katharina; Rother, Eva; Östreicher, Iris; Vohlen, Christina; Plank, Christian; Dötsch, Jörg

    2014-12-01

    Intrauterine growth restriction (IUGR) is intimately linked with postnatal catch-up growth, leading to impaired lung structure and function. However, the impact of catch-up growth induced by early postnatal hyperalimentation (HA) on the lung has not been addressed to date. The aim of this study was to investigate whether prevention of HA subsequent to IUGR protects the lung from 1) deregulation of the transforming growth factor-β(TGF-β)/bone morphogenetic protein (BMP) pathway, 2) activation of interleukin (IL)-6 signaling, and 3) profibrotic processes. IUGR was induced in Wistar rats by isocaloric protein restriction during gestation by feeding a control (Co) or a low-protein diet with 17% or 8% casein, respectively. On postnatal day 1 (P1), litters from both groups were randomly reduced to 6 pups per dam to induce HA or adjusted to 10 pups and fed with standard diet: Co, Co with HA (Co-HA), IUGR, and IUGR with HA (IUGR-HA). Birth weights in rats after IUGR were lower than in Co rats (P < 0.05). HA during lactation led to accelerated body weight gain from P1 to P23 (Co vs. Co-HA, IUGR vs. IUGR-HA; P < 0.05). At P70, prevention of HA after IUGR protected against the following: 1) activation of both TGF-β [phosphorylated SMAD (pSMAD) 2; plasminogen activator inhibitor 1 (Pai1)] and BMP signaling [pSMAD1; inhibitor of differentiation (Id1)] compared with Co (P < 0.05) and Co or IUGR (P < 0.05) rats, respectively; 2) greater mRNA expression of interleukin (Il) 6 and Il13 (P < 0.05) as well as activation of signal transducer and activator of transcription 3 (STAT3) signaling (P < 0.05) after IUGR-HA; and 3) greater gene expression of collagen Iα1 and osteopontin (P < 0.05) and increased deposition of bronchial subepithelial connective tissue in IUGR-HA compared with Co and IUGR rats. Moreover, HA had a significant additive effect (P < 0.05) on the increased enhanced pause (indicator of airway resistance) in the IUGR group (P < 0.05) at P70. This study demonstrates

  19. Structural and functional development of small intestine in intrauterine growth retarded porcine offspring born to gilts fed diets with differing protein ratios throughout pregnancy

    DEFF Research Database (Denmark)

    Mickiewicz, M; Zabielski, R; Grenier, B

    2012-01-01

    Protein level in the maternal diet plays a crucial role in fetal programming during pregnancy. Low or high protein level increases the risk of intrauterine growth retardation (IUGR). The aim of this study was to investigate the structural and functional development of the small intestine in piglets...... and active caspase 3 in mid-jejunum epithelium of HP and LP non-IUGR neonates were significantly lower as compared to C non-IUGRs whilst in IUGRs the respective expressions were as high as in C non-IUGRs. The postnatal dynamics of brush border enzyme activities and vacuolated enterocytes disappearance showed...... significant drop in enterocyte maturation in IUGR as compared to non-IUGR neonates. In conclusion, both HP and LP diets led to retarded development of non-IUGR piglets. In IUGR piglets both HP and LP diets resulted in delayed catch-up growth, without adaptive changes in brush border digestive enzymes....

  20. Relationship of maternal mean platelet volume with fetal Doppler parameters and neonatal complications in pregnancies with and without intrauterine growth restriction.

    Science.gov (United States)

    Ureyen, Isin; Ozyuncu, Ozgur; Sahin-Uysal, Nihal; Kara, Ozgur; Basaran, Derman; Turgal, Mert; Deren, Ozgur

    2017-02-01

    In this study, we investigated the relationship of mean platelet volume (MPV) with the presence and the severity of intrauterine growth restriction (IUGR) and with neonatal complications. The pregnancies with and without IUGR, that were followed-up in our hospital between 2003 and 2009 were analyzed retrospectively. Pregnancies which resulted in birth of a newborn with a birthweight less than 10th percentile for the gestational age were selected for IUGR group. IUGR cases were divided into three groups according to the Doppler parameters. There was no significant difference between the MPV values in the groups. There was no association between MPV and Doppler parameters that can be used in predicting the severity of IUGR. There was no significant relation between MPV and the perinatal complications such as intracranial hemorrhage (ICH), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), the development of sepsis, postpartum exitus (PPEX) and intrauterine exitus (IUEX). Higher MPV values were associated with hospitalization in the neonatal intensive care unit (NICU) and respiratory distress syndrome (RDS) in the IUGR group. Analysis of MPV is a simple and readily available laboratory test. Prospective researches employing standard measurement technics are required to clarify the relationship between MPV and IUGR.

  1. Local Delivery of Growth Factors Using Coated Suture Material

    Directory of Open Access Journals (Sweden)

    T. F. Fuchs

    2012-01-01

    Full Text Available The optimization of healing processes in a wide range of tissues represents a central point for surgical research. One approach is to stimulate healing processes with growth factors. These substances have a short half-life and therefore it seems useful to administer these substances locally rather than systemically. One possible method of local delivery is to incorporate growth factors into a bioabsorbable poly (D, L-lactide suspension (PDLLA and coat suture material. The aim of the present study was to establish a procedure for the local delivery of growth factors using coated suture material. Sutures coated with growth factors were tested in an animal model. Anastomoses of the colon were created in a rat model using monofilament sutures. These were either untreated or coated with PDLLA coating alone or coated with PDLLA incorporating insulin—like growth factor-I (IGF-I. The anastomoses were subjected to biomechanical, histological, and immunohistochemical examination. After 3 days the treated groups showed a significantly greater capacity to withstand biomechanical stress than the control groups. This finding was supported by the results of the histomorphometric. The results of the study indicate that it is possible to deliver bioactive growth factors locally using PDLLA coated suture material. Healing processes can thus be stimulated locally without subjecting the whole organism to potentially damaging high systemic doses.

  2. Effectiveness and cost-effectiveness of routine third trimester ultrasound screening for intrauterine growth restriction : study protocol of a nationwide stepped wedge cluster-randomized trial in The Netherlands (The IRIS Study)

    NARCIS (Netherlands)

    Henrichs, Jens; Verfaille, Viki; Viester, Laura; Westerneng, Myrte; Molewijk, Bert; Franx, Arie; van der Horst, Henriette; Bosmans, Judith E; de Jonge, Ank; Jellema, Petra

    2016-01-01

    BACKGROUND: Intrauterine growth retardation (IUGR) is a major risk factor for perinatal mortality and morbidity. Thus, there is a compelling need to introduce sensitive measures to detect IUGR fetuses. Routine third trimester ultrasonography is increasingly used to detect IUGR. However, we lack

  3. Effectiveness and cost-effectiveness of routine third trimester ultrasound screening for intrauterine growth restriction : Study protocol of a nationwide stepped wedge cluster-randomized trial in The Netherlands (The IRIS Study)

    NARCIS (Netherlands)

    Henrichs, Jens; Verfaille, Viki; Viester, Laura; Westerneng, Myrte; Molewijk, Bert; Franx, Arie; van der Horst, Henriette; Bosmans, Judith E.; de Jonge, Ank; Jellema, Petra; van Baar, Anneloes L.; Bais, Joke; Bonsel, Gouke J.; van Dillen, Jeroen; van Duijnhoven, Noortje T L; Grobman, William A.; Groen, Henk; Hukkelhoven, Chantal W P M; Klomp, Trudy; Kok, Marjolein; de Kroon, Marlou L.; Kruijt, Maya; Kwee, Anneke; Ledda, Sabina; Lafeber, Harry N.; van Lith, Jan M.; Mol, Ben Willem; Nieuwenhuijze, Marianne; Oei, Guid; Oudejans, Cees; Marieke Paarlberg, K.; Pajkrt, Eva; Papageorghiou, Aris T.; Reddy, Uma M.; De Reu, Paul A O M; Rijnders, Marlies; de Roon-Immerzeel, Alieke; Scheele, Connie; Scherjon, Sicco A.; Snijders, Rosalinde; Spaanderman, Marc E.; Teunissen, Pim W.; Torij, Hanneke W.; Vrijkotte, Tanja G.; Twisk, Jos; Zeeman, Kristel C.; Zhang, Jun; {collab} The IRIS Study Group, The IRIS Study Group

    2016-01-01

    Background Intrauterine growth retardation (IUGR) is a major risk factor for perinatal mortality and morbidity. Thus, there is a compelling need to introduce sensitive measures to detect IUGR fetuses. Routine third trimester ultrasonography is increasingly used to detect IUGR. However, we lack

  4. Intrauterine growth-restricted piglets have similar gastric emptying rates but lower rectal temperatures and altered blood values when compared with normal-weight piglets at birth

    DEFF Research Database (Denmark)

    Williams, Charlotte Amdi; Klarlund, M. V.; Pedersen, Janni Hales

    2016-01-01

    Intrauterine growth-restricted (IUGR) piglets have lower survival rates and are more likely to have empty stomachs 24 h after birth than normal piglets. Although hypoglycemia may result from low colostrum intake per se, it is not known if slow gastric emptying may be an additional risk factor...... that the gastric emptying rate and blood glucose would be lower in IUGR piglets. We investigated gastric emptying rates in normal and IUGR piglets and blood glucose and rectal temperatures at birth and after 15, 30, 60, and 120 min. In addition, blood parameters relevant for metabolism were studied. Forty......-eight piglets (24 normal and 24 IUGR) were classified at birth as either normal or IUGR on the basis of head morphology. Piglets were removed from the sow at birth before suckling, and birth weight was recorded. Pooled porcine colostrum was tube-fed to all piglets at 12 mL/kg BW as soon as possible after birth...

  5. Expression of Myostatin in Intrauterine Growth Restriction and Preeclampsia Complicated Pregnancies and Alterations to Cytokine Production by First-Trimester Placental Explants Following Myostatin Treatment.

    Science.gov (United States)

    Peiris, Hassendrini N; Georgiou, Harry; Lappas, Martha; Kaitu'u-Lino, Tu'uhevaha; Salomón, Carlos; Vaswani, Kanchan; Rice, Gregory E; Mitchell, Murray D

    2015-10-01

    Preeclampsia (PE) and intrauterine growth restriction (IUGR) are major obstetric health problems. Higher levels of T-helper (Th) 1 (proinflammatory) cytokines have been observed in pregnancies complicated with PE and IUGR; this is in contrast to the predominant Th2 (anti-inflammatory) cytokine environment found in uncomplicated pregnancies. Myostatin is best known as a negative regulator of muscle development and reportedly has a role in fat deposition, glucose metabolism, and cytokine modulation (outside the placenta). Myostatin concentrations in plasma and protein expression in placental tissue are significantly higher in women with PE. Expression of myostatin in IUGR and PE-IUGR and the effect of this protein on the cytokine production from the placenta is unknown. In the current study, significant differences were identified in the expression of myostatin in pregnancies complicated with IUGR, PE, and PE with IUGR. Furthermore, cytokine production by first-trimester placental tissues was altered following myostatin treatment. © The Author(s) 2015.

  6. Is willingness to exercise programmed in utero? Reviewing sedentary behavior and the benefits of physical activity in intrauterine growth restricted individuals.

    Science.gov (United States)

    Bischoff, Adrianne Rahde; Cunha, Fábio da Silva; Dalle Molle, Roberta; Maróstica, Paulo José Cauduro; Silveira, Patrícia Pelufo

    2018-02-22

    The literature suggests that a fetus will adapt to surrounding adversities by optimizing its use of energy to improve survival, ultimately leading to the programming of the individual's energy intake and expenditure. While recent reviews focused on the fetal programming of energy intake and food preferences, there is also some evidence that fetal adversity is associated with diminished physical activity levels. Therefore, we aimed to review (a) the evidence for an association between being born with intrauterine growth restriction and sedentarism over the life-course and (b) the potential benefits of physical activity over cardiometabolic risk factors for this population. PubMed, Scielo, Scopus and Embase. Most clinical studies that used objective measures found no association between intrauterine growth restriction and physical activity levels, while most studies that used self-reported questionnaires revealed such relationships, particularly leisure time physical activity. Experimental studies support the existence of fetal programming of physical activity, and show that exposure to exercise during IUGR individuals' life improves metabolic outcomes but less effect was seen on muscle architecture or function. Alterations in muscle strength and metabolism, as well as altered aerobic performance, may predispose IUGR individuals to be spontaneously less physically active, suggesting that this population may be an important target for preventive interventions. Although very heterogeneous, the different studies allow us to infer that physical activity may have beneficial effects especially for individuals that are more vulnerable to metabolic modifications such as those with IUGR. Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  7. Study of the evolution of the placenta and fetal pancreas in the pathophysiology of growth retardation intrauterine due to restricted maternal diet

    Directory of Open Access Journals (Sweden)

    Marilza Vieira Cunha Rudge

    1999-03-01

    Full Text Available CONTEXT: Intrauterine growth retard (IUGR continues to be a significant perinatology problem at the end of this century. The nature of the etiologic agent, the time when the attack occurred during pregnancy and its duration affect the type of IUGR. OBJECTIVE: To study the evolution of fetal pancreas and placenta between the 18th and 21st day of pregnancy in rats submitted to maternal protein-calorie restriction. DESIGN: Randomized controlled trial on laboratory animal. SAMPLE: Forty-one normoglycemic pregnant Wistar rats. INTERVENTION: Rats were divided into six experimental groups according to their access to food and date of cesarean section (18th or 21st day: control with free access to food; diet restricted to 25% introduced on 1st day of pregnancy; and diet restricted to 25% after the 3rd day of pregnancy. MAIN MEASUREMENTS: Newborn weight, placenta weight, histopathological study (morphological histochemistry RESULTS: Maternal protein-calorie malnutrition caused intrauterine growth retard (IUGR after the 18th day of pregnancy. Dietary restriction did not interfere with the morphology of the fetal pancreas and the immunohistochemical study of the placenta showed that glycogen stores were decreased between the 18th and 21st day in the control group and in a diet restricted to 25% from the first day of pregnancy. Dietary restriction after the 3rd day of pregnancy led to low placental glycogen concentrations on the 18th day and disappearance on the 21st day. CONCLUSION: The pathophysiology of IUGR due to maternal protein-calorie restriction in rats is related to lower placental weight and low placental glycogen stores.

  8. Maternal glucocorticoid elevation and associated blood metabonome changes might be involved in metabolic programming of intrauterine growth retardation in rats exposed to caffeine prenatally

    International Nuclear Information System (INIS)

    Kou, Hao; Liu, Yansong; Liang, Gai; Huang, Jing; Hu, Jieqiong; Yan, You-e; Li, Xiaojun; Yu, Hong; He, Xiaohua; Zhang, Baifang; Zhang, Yuanzhen; Feng, Jianghua; Wang, Hui

    2014-01-01

    Our previous studies demonstrated that prenatal caffeine exposure causes intrauterine growth retardation (IUGR), fetuses are over-exposed to high levels of maternal glucocorticoids (GC), and intrauterine metabolic programming and associated metabonome alteration that may be GC-mediated. However, whether maternal metabonomes would be altered and relevant metabolite variations might mediate the development of IUGR remained unknown. In the present studies, we examined the dose- and time-effects of caffeine on maternal metabonome, and tried to clarify the potential roles of maternal GCs and metabonome changes in the metabolic programming of caffeine-induced IUGR. Pregnant rats were treated with caffeine (0, 20, 60 or 180 mg/kg · d) from gestational days (GD) 11 to 20, or 180 mg/kg · d caffeine from GD9. Metabonomes of maternal plasma on GD20 in the dose–effect study and on GD11, 14 and 17 in the time–course study were analyzed by 1 H nuclear magnetic resonance spectroscopy, respectively. Caffeine administration reduced maternal weight gains and elevated both maternal and fetal corticosterone (CORT) levels. A negative correlation between maternal/fetal CORT levels and fetal bodyweight was observed. The maternal metabonome alterations included attenuated metabolism of carbohydrates, enhanced lipolysis and protein breakdown, and amino acid accumulation, suggesting GC-associated metabolic effects. GC-associated metabolite variations (α/β-glucoses, high density lipoprotein-cholesterol, β-hydroxybutyrate) were observed early following caffeine administration. In conclusion, prenatal caffeine exposure induced maternal GC elevation and metabonome alteration, and maternal GC and relevant discriminatory metabolites might be involved in the metabolic programming of caffeine-induced IUGR. - Highlights: • Prenatal caffeine exposure elevated maternal blood glucocorticoid levels. • Prenatal caffeine exposure altered maternal blood metabonomes. • Maternal metabonome

  9. Maternal glucocorticoid elevation and associated blood metabonome changes might be involved in metabolic programming of intrauterine growth retardation in rats exposed to caffeine prenatally

    Energy Technology Data Exchange (ETDEWEB)

    Kou, Hao; Liu, Yansong; Liang, Gai; Huang, Jing; Hu, Jieqiong; Yan, You-e; Li, Xiaojun [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Yu, Hong; He, Xiaohua; Zhang, Baifang [Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan 430071 (China); Zhang, Yuanzhen [Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan 430071 (China); Center for Reproductive Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Feng, Jianghua, E-mail: jianghua.feng@xmu.edu.cn [Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen 361005 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan 430071 (China)

    2014-03-01

    Our previous studies demonstrated that prenatal caffeine exposure causes intrauterine growth retardation (IUGR), fetuses are over-exposed to high levels of maternal glucocorticoids (GC), and intrauterine metabolic programming and associated metabonome alteration that may be GC-mediated. However, whether maternal metabonomes would be altered and relevant metabolite variations might mediate the development of IUGR remained unknown. In the present studies, we examined the dose- and time-effects of caffeine on maternal metabonome, and tried to clarify the potential roles of maternal GCs and metabonome changes in the metabolic programming of caffeine-induced IUGR. Pregnant rats were treated with caffeine (0, 20, 60 or 180 mg/kg · d) from gestational days (GD) 11 to 20, or 180 mg/kg · d caffeine from GD9. Metabonomes of maternal plasma on GD20 in the dose–effect study and on GD11, 14 and 17 in the time–course study were analyzed by {sup 1}H nuclear magnetic resonance spectroscopy, respectively. Caffeine administration reduced maternal weight gains and elevated both maternal and fetal corticosterone (CORT) levels. A negative correlation between maternal/fetal CORT levels and fetal bodyweight was observed. The maternal metabonome alterations included attenuated metabolism of carbohydrates, enhanced lipolysis and protein breakdown, and amino acid accumulation, suggesting GC-associated metabolic effects. GC-associated metabolite variations (α/β-glucoses, high density lipoprotein-cholesterol, β-hydroxybutyrate) were observed early following caffeine administration. In conclusion, prenatal caffeine exposure induced maternal GC elevation and metabonome alteration, and maternal GC and relevant discriminatory metabolites might be involved in the metabolic programming of caffeine-induced IUGR. - Highlights: • Prenatal caffeine exposure elevated maternal blood glucocorticoid levels. • Prenatal caffeine exposure altered maternal blood metabonomes. • Maternal

  10. Maternal glucocorticoid elevation and associated blood metabonome changes might be involved in metabolic programming of intrauterine growth retardation in rats exposed to caffeine prenatally.

    Science.gov (United States)

    Kou, Hao; Liu, Yansong; Liang, Gai; Huang, Jing; Hu, Jieqiong; Yan, You-e; Li, Xiaojun; Yu, Hong; He, Xiaohua; Zhang, Baifang; Zhang, Yuanzhen; Feng, Jianghua; Wang, Hui

    2014-03-01

    Our previous studies demonstrated that prenatal caffeine exposure causes intrauterine growth retardation (IUGR), fetuses are over-exposed to high levels of maternal glucocorticoids (GC), and intrauterine metabolic programming and associated metabonome alteration that may be GC-mediated. However, whether maternal metabonomes would be altered and relevant metabolite variations might mediate the development of IUGR remained unknown. In the present studies, we examined the dose- and time-effects of caffeine on maternal metabonome, and tried to clarify the potential roles of maternal GCs and metabonome changes in the metabolic programming of caffeine-induced IUGR. Pregnant rats were treated with caffeine (0, 20, 60 or 180 mg/kg·d) from gestational days (GD) 11 to 20, or 180 mg/kg·d caffeine from GD9. Metabonomes of maternal plasma on GD20 in the dose-effect study and on GD11, 14 and 17 in the time-course study were analyzed by ¹H nuclear magnetic resonance spectroscopy, respectively. Caffeine administration reduced maternal weight gains and elevated both maternal and fetal corticosterone (CORT) levels. A negative correlation between maternal/fetal CORT levels and fetal bodyweight was observed. The maternal metabonome alterations included attenuated metabolism of carbohydrates, enhanced lipolysis and protein breakdown, and amino acid accumulation, suggesting GC-associated metabolic effects. GC-associated metabolite variations (α/β-glucoses, high density lipoprotein-cholesterol, β-hydroxybutyrate) were observed early following caffeine administration. In conclusion, prenatal caffeine exposure induced maternal GC elevation and metabonome alteration, and maternal GC and relevant discriminatory metabolites might be involved in the metabolic programming of caffeine-induced IUGR. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Global Liver Proteome Analysis Using iTRAQ Reveals AMPK-mTOR-Autophagy Signaling Is Altered by Intrauterine Growth Restriction in Newborn Piglets.

    Science.gov (United States)

    Long, Baisheng; Yin, Cong; Fan, Qiwen; Yan, Guokai; Wang, Zhichang; Li, Xiuzhi; Chen, Changqing; Yang, Xingya; Liu, Lu; Zheng, Zilong; Shi, Min; Yan, Xianghua

    2016-04-01

    Intrauterine growth restriction (IUGR) impairs fetal growth and development, perturbs nutrient metabolism, and increases the risk of developing diseases in postnatal life. However, the underlying mechanisms by which IUGR affects fetal liver development and metabolism remain incompletely understood. Here, we applied a high-throughput proteomics approach and biochemical analysis to investigate the impact of IUGR on the liver of newborn piglets. As a result, we identified 78 differentially expressed proteins in the three biological replicates, including 31 significantly up-regulated proteins and 47 significantly down-regulated proteins. Among them, a majority of differentially expressed proteins were related to nutrient metabolism and mitochondrial function. Additionally, many significantly down-regulated proteins participated in the mTOR signaling pathway and the phagosome maturation signaling pathway. Further analysis suggested that glucose concentration and hepatic glycogen storage were both reduced in IUGR newborn piglets, which may contribute to AMPK activation and mTORC1 inhibition. However, AMPK activation and mTORC1 inhibition failed to induce autophagy in the liver of IUGR neonatal pigs. A possible reason is that PP2Ac, a potential candidate in autophagy regulation, is significantly down-regulated in the liver of IUGR newborn piglets. These findings may provide implications for preventing and treating IUGR in human beings and domestic animals.

  12. Fatty acid profile of maternal and fetal erythrocytes and placental expression of fatty acid transport proteins in normal and intrauterine growth restriction pregnancies.

    Science.gov (United States)

    Assumpção, Renata P; Mucci, Daniela B; Fonseca, Fernanda C P; Marcondes, Henrique; Sardinha, Fátima L C; Citelli, Marta; Tavares do Carmo, Maria G

    2017-10-01

    Long-chain polyunsaturated fatty acids (LC-PUFA), mainly docosahexaenoic (DHA) and arachidonic acids (AA), are critical for adequate fetal growth and development. We investigated mRNA expression of proteins involved in hydrolysis, uptake and/or transport of fatty acids in placenta of fifteen full term normal pregnancies and eleven pregnancies complicated by intrauterine growth restriction (IUGR) with normal umbilical blood flows. The mRNA expression of LPL, FATPs (-1, -2 and -4) and FABPs (-1 and -3) was increased in IUGR placentas, however, tissue profile of LC-PUFA was not different between groups. Erythrocytes from both mothers and fetuses of the IUGR group showed lower concentrations of AA and DHA and inferior DHA/ALA ratio compared to normal pregnancies (P < 0.05). We hypothesize that reduced circulating levels of AA and DHA could up-regulate mRNA expression of placental fatty acids transporters, as a compensatory mechanism, however this failed to sustain normal LC-PUFA supply to the fetus in IUGR. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. How does tobacco smoke influence the morphometry of the fetus and the umbilical cord?-Research on pregnant women with intrauterine growth restriction exposed to tobacco smoke.

    Science.gov (United States)

    Milnerowicz-Nabzdyk, Ewa; Bizoń, Anna

    2015-12-01

    Proper structure of the umbilical cord is important for the fetal development. We evaluated effects of toxic factors from tobacco smoke on fetal and umbilical cord morphometry. 109 women in weeks 29-40 of pregnancy (31 smokers with intrauterine growth restriction (IUGR); 28 non-smoking women with IUGR; 50 healthy pregnancies) were included. In smokers with IUGR, cotinine, cadmium and lead concentrations were significantly higher than in controls (mean 55.23ng/l; 1.52ng/ml; 14.85ng/ml vs 1.07; 0.34; 9.42) and inverse correlation between lead concentration and uncoiled umbilical cord was significant (r=-0.80). In smokers with IUGR, area of Wharton's jelly was increased compared to nonsmokers and controls. Inverse correlations occurred between cotinine and cadmium concentration and fetal percentile in smokers (r=-0.87; r=-0.87) and non-smokers (r=-0.47; r=-0.78) with IUGR. Exposure to tobacco smoke measured by cotinine, cadmium and lead concentration has an impact on fetal growth and umbilical cord morphometry and correlates with intensity of IUGR. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Intra-uterine hematoma in pregnancy

    DEFF Research Database (Denmark)

    Glavind, K; Nøhr, S; Nielsen, P H

    1991-01-01

    In 60 patients with a live fetus and an intra-uterine hematoma (IUH) proven by ultrasonic scanning the outcome of pregnancy was spontaneous abortion in 12% and premature delivery in 10%. No correlation between the outcome of the pregnancy and the maximum size of the hematoma or the week...

  15. Down-Regulation of Placental Transport of Amino Acids Precedes the Development of Intrauterine Growth Restriction in Maternal Nutrient Restricted Baboons.

    Science.gov (United States)

    Pantham, Priyadarshini; Rosario, Fredrick J; Weintraub, Susan T; Nathanielsz, Peter W; Powell, Theresa L; Li, Cun; Jansson, Thomas

    2016-11-01

    Intrauterine growth restriction (IUGR) is an important risk factor for perinatal complications and adult disease. IUGR is associated with down-regulation of placental amino acid transporter expression and activity at birth. It is unknown whether these changes are a cause or a consequence of human IUGR. We hypothesized that placental amino acid transport capacity is reduced prior to onset of reduced fetal growth in baboons with maternal nutrient restriction (MNR). Pregnant baboons were fed either a control (n = 8) or MNR diet (70% of control diet, n = 9) from Gestational Day 30. At Gestational Day 120 (0.65 of gestation), fetuses and placentas were collected. Microvillous (MVM) and basal (BM) plasma membrane vesicles were isolated. System A and system L transport activity was determined in MVM, and leucine transporter activity was assessed in BM using radiolabeled substrates. MVM amino acid transporter isoform expression (SNAT1, SNAT2, and SNAT4 and LAT1 and LAT2) was measured using Western blots. LAT1 and LAT2 expression were also determined in BM. Maternal and fetal plasma amino acids concentrations were determined using mass spectrometry. Fetal and placental weights were unaffected by MNR. MVM system A activity was decreased by 37% in MNR baboon placentas (P = 0.03); however MVM system A amino acid transporter protein expression was unchanged. MVM system L activity and BM leucine transporter activity were not altered by MNR. Fetal plasma concentrations of essential amino acids isoleucine and leucine were reduced, while citrulline increased (P growth trajectory. The reduction in plasma leucine and isoleucine in MNR fetuses may be caused by reduced activity of MVM system A, which is strongly coupled with system L essential amino acid uptake. Our findings indicate that reduced placental amino acid transport may be a cause rather than a consequence of IUGR due to inadequate maternal nutrition. © 2016 by the Society for the Study of Reproduction, Inc.

  16. Survival Rate without Brain Abnormalities on Postnatal Ultrasonography among Monochorionic Twins after Fetoscopic Laser Photocoagulation for Selective Intrauterine Growth Restriction with Concomitant Oligohydramnios.

    Science.gov (United States)

    Ishii, Keisuke; Wada, Seiji; Takano, Mayumi; Nakata, Masahiko; Murakoshi, Takeshi; Sago, Haruhiko

    2018-02-20

    We aimed to clarify the survival rate without brain abnormalities (BA) after fetoscopic laser photoco-agulation (FLP) for monochorionic diamniotic twin gestations (MCDA) with selective intrauterine growth restriction (sIUGR) accompanied by abnormal umbilical artery (UA) Doppler waveforms and isolated oligohydramnios in the sIUGR twin. This retrospective study included 52 cases that underwent FLP. The main outcome was survival rate without BA of the twins at age 28 days. BA was defined as severe intraventricular hemorrhage and periventricular leukomalacia on postnatal ultrasonography. Median gestational age at FLP was 20 (16-24) weeks. Ten cases were classified as type III based on Doppler for the UA. For all cases, including 20 cases of anterior placenta, FLP was completed without major intraoperative complications. Amnioinfusion was required in 49 cases for better fetoscopic visualization. Fetal loss occurred in 29 sIUGR twins and two larger twins, whereas one larger twin experienced neonatal death. Survival rates without BA were 44% (n = 23) for sIUGR twins and 94% (n = 49) for the larger twins. FLP for MCDA with sIUGR presenting with oligohydramnios in the sIUGR twin might be considered a prenatal treatment option. © 2018 S. Karger AG, Basel.

  17. Decreased activation of placental mTOR family members is associated with the induction of intrauterine growth restriction by secondhand smoke in the mouse.

    Science.gov (United States)

    Mejia, Camilo; Lewis, Josh; Jordan, Clinton; Mejia, Juan; Ogden, Connor; Monson, Troy; Winden, Duane; Watson, Marc; Reynolds, Paul R; Arroyo, Juan A

    2017-02-01

    Cigarette smoke is known to be a risk for the development of intrauterine growth restriction (IUGR). Our objective was to assess the effects of secondhand smoke (SHS) during pregnancy and to what extent it regulates the activation of mTOR family members and murine trophoblast invasion. Mice were treated to SHS for 4 days. Placental and fetal weights were recorded at the time of necropsy. Immunohistochemistry was used to determine the level of placental trophoblast invasion. Western blots were utilized to assess the activation of caspase 3, XIAP, mTOR, p70 and 4EBP1 in treated and control placental lysates. As compared to controls, treated animals showed: (1) decreased placental (1.4-fold) and fetal (2.3-fold) weights (p smoke extract (CSE). Similar to primary smoking, SHS may induce IUGR via decreased activation of the mTOR family of proteins in the placenta. Increased activation of the placental XIAP protein could be a survival mechanism for abnormal trophoblast cells during SHS exposure. Further, CSE reduced trophoblast invasion, suggesting a direct causative effect of smoke on susceptible trophoblast cells involved in IUGR progression. These results provide important insight into the physiological consequences of SHS exposure and smoke-mediated placental disease.

  18. Low Birth Weight due to Intrauterine Growth Restriction and/or Preterm Birth: Effects on Nephron Number and Long-Term Renal Health

    Science.gov (United States)

    Zohdi, Vladislava; Sutherland, Megan R.; Lim, Kyungjoon; Gubhaju, Lina; Zimanyi, Monika A.; Black, M. Jane

    2012-01-01

    Epidemiological studies have clearly demonstrated a strong association between low birth weight and long-term renal disease. A potential mediator of this long-term risk is a reduction in nephron endowment in the low birth weight infant at the beginning of life. Importantly, nephrons are only formed early in life; during normal gestation, nephrogenesis is complete by about 32–36 weeks, with no new nephrons formed after this time during the lifetime of the individual. Hence, given that a loss of a critical number of nephrons is the hallmark of renal disease, an increased severity and acceleration of renal disease is likely when the number of nephrons is already reduced prior to disease onset. Low birth weight can result from intrauterine growth restriction (IUGR) or preterm birth; a high proportion of babies born prematurely also exhibit IUGR. In this paper, we describe how IUGR and preterm birth adversely impact on nephrogenesis and how a subsequent reduced nephron endowment at the beginning of life may lead to long-term risk of renal disease, but not necessarily hypertension. PMID:22970368

  19. Clinical and Metabolic Response to Selenium Supplementation in Pregnant Women at Risk for Intrauterine Growth Restriction: Randomized, Double-Blind, Placebo-Controlled Trial.

    Science.gov (United States)

    Mesdaghinia, Elaheh; Rahavi, Azam; Bahmani, Fereshteh; Sharifi, Nasrin; Asemi, Zatollah

    2017-07-01

    Data on the effects of selenium supplementation on clinical signs and metabolic profiles in women at risk for intrauterine growth restriction (IUGR) are scarce. This study was designed to assess the effects of selenium supplementation on clinical signs and metabolic status in pregnant women at risk for IUGR. This randomized double-blind placebo-controlled clinical trial was performed among 60 women at risk for IUGR according to abnormal uterine artery Doppler waveform. Participants were randomly assigned to intake either 100 μg selenium supplements as tablet (n = 30) or placebo (n = 30) for 10 weeks between 17 and 27 weeks of gestation. After 10 weeks of selenium administration, a higher percentage of women in the selenium group had pulsatility index (PI) of women at risk for IUGR resulted in improved PI, TAC, GSH, hs-CRP, and markers of insulin metabolism and HDL-C levels, but it did not affect MDA, NO, FPG, and other lipid profiles.Clinical trial registration number http://www.irct.ir : IRCT201601045623N64.

  20. [Obstructive Sleep Apnea Syndrom during pregnancy: prevalence of main symptoms and relationship with Pregnancy Induced-Hypertension and Intra-Uterine Growth Retardation].

    Science.gov (United States)

    Calaora-Tournadre, D; Ragot, S; Meurice, J C; Pourrat, O; D'Halluin, G; Magnin, G; Pierre, F

    2006-04-01

    To investigate the frequency of main symptoms of Obstructive Sleep Apnea Syndrom (OSAS) and their relationship with Pregnancy Induced-Hypertension (PIH) as well as Intrauterine Growth Retardation (IGR) as suggested by recent studies. Four hundred (and) thirty-eight enquiry forms completed during post-partum period were analysed, after exclusion of multiple pregnancies. Collected data were demographic characteristics, obstetrical events, sleep disorders during last trimester, screening of snoring and vigilance troubles with an Epworth score. Forty-five percentages of the patients reported to have habitual snoring during pregnancy. Among these, 85% were non-snorers before pregnancy. Daytime somnolence concerned 84,5% of the population with an Epworth score significatively increased (P<0,0001). The prevalence of PIH was found to be 4,5%, with two apparently independent risk factors: the body mass index (OR=1,1) and an association between snoring and increased vigilance trouble (OR=2,6). No statistical difference was found concerning IGR. SAS symptoms are frequent during pregnancy and snoring appears to be linked with PIH. However, polysomnographic data are not yet sufficient to explain pathophysiological mechanisms and find relevant diagnostic markers during pregnancy.

  1. Low Birth Weight due to Intrauterine Growth Restriction and/or Preterm Birth: Effects on Nephron Number and Long-Term Renal Health

    Directory of Open Access Journals (Sweden)

    Vladislava Zohdi

    2012-01-01

    Full Text Available Epidemiological studies have clearly demonstrated a strong association between low birth weight and long-term renal disease. A potential mediator of this long-term risk is a reduction in nephron endowment in the low birth weight infant at the beginning of life. Importantly, nephrons are only formed early in life; during normal gestation, nephrogenesis is complete by about 32–36 weeks, with no new nephrons formed after this time during the lifetime of the individual. Hence, given that a loss of a critical number of nephrons is the hallmark of renal disease, an increased severity and acceleration of renal disease is likely when the number of nephrons is already reduced prior to disease onset. Low birth weight can result from intrauterine growth restriction (IUGR or preterm birth; a high proportion of babies born prematurely also exhibit IUGR. In this paper, we describe how IUGR and preterm birth adversely impact on nephrogenesis and how a subsequent reduced nephron endowment at the beginning of life may lead to long-term risk of renal disease, but not necessarily hypertension.

  2. Paraoxonase-2 and paraoxonase-3: comparison of mRNA expressions in the placentae of unexplained intrauterine growth restricted and noncomplicated pregnancies.

    Science.gov (United States)

    Dikbas, Levent; Yapca, Omer Erkan; Dikbas, Neslihan; Gundogdu, Cemal

    2017-05-01

    Recent evidence suggests that oxidative stress is involved in the pathophysiology of many human diseases. It has been demonstrated that oxidative stress is associated with intrauterine growth restriction (IUGR), and the depletion of placental antioxidant systems has been suggested as a key factor in this disease. Our aims were to explore the possible role of antioxidant paraoxonase-2 (PON2) and paraoxonase-3 (PON3) in the pathophysiology of unexplained IUGR. We have studied the expression of mRNA for PON2, PON3 in placental tissues by using RT-qPCR. Two groups, consisting of normal (n = 18) and unexplained IUGR pregnancies (n = 20) were compared. Our results demonstrated that there were no significant differences in the mRNA expressions of PON2, PON3 between the two groups (p = 0.28, p = 0.90, respectively). PON2 and PON3 were down-regulated in IUGR. Antenatal steroid therapy had no effect on the expression mRNA in placentae of unexplained IUGR pregnancies compared to non-treated group. These results suggest that PON2, PON3 mRNA levels were not changed significantly in placentae of IUGR when compared to normal pregnant women.

  3. Dietary Methionine Restriction Alleviates Hyperglycemia in Pigs with Intrauterine Growth Restriction by Enhancing Hepatic Protein Kinase B Signaling and Glycogen Synthesis.

    Science.gov (United States)

    Ying, Zhixiong; Zhang, Hao; Su, Weipeng; Zhou, Le; Wang, Fei; Li, Yue; Zhang, Lili; Wang, Tian

    2017-10-01

    Background: Individuals with intrauterine growth restriction (IUGR) are prone to developing type 2 diabetes mellitus (T2DM). Dietary methionine restriction (MR) improves insulin sensitivity and glucose homeostasis in individuals with normal birth weight (NBW). Objective: This study investigated the effects of MR on plasma glucose concentration and hepatic and muscle glucose metabolism in pigs with IUGR. Methods: Thirty female NBW and 60 same-sex spontaneous IUGR piglets (Landrace × Yorkshire) were selected. After weaning (day 21), the piglets were fed diets with adequate methionine (NBW-CON and IUGR-CON) or 30% less methionine (IUGR-MR) ( n = 6). At day 180, 1 pig with a body weight near the mean of each replication was selected for biochemical analysis. Results: The IUGR-CON group showed 41.6%, 68.6%, and 67.1% higher plasma glucose concentration, hepatic phosphoenolpyruvate carboxykinase activity, and glucose-6-phosphatase activity, respectively, than the NBW-CON group ( P glycogen content and glycogen synthase activity were 36.9% and 38.8% lower, respectively, in the IUGR-CON than the NBW-CON group ( P glycogen content and glycogen synthase activity of the IUGR-MR pigs were 62.9% and 50.8% higher than those of the IUGR-CON pigs ( P glycogen synthesis, implying a potential nutritional strategy to prevent type 2 diabetes mellitus in IUGR offspring. © 2017 American Society for Nutrition.

  4. STRIDER: Sildenafil Therapy In Dismal prognosis Early-onset intrauterine growth Restriction--a protocol for a systematic review with individual participant data and aggregate data meta-analysis and trial sequential analysis.

    Science.gov (United States)

    Ganzevoort, Wessel; Alfirevic, Zarko; von Dadelszen, Peter; Kenny, Louise; Papageorghiou, Aris; van Wassenaer-Leemhuis, Aleid; Gluud, Christian; Mol, Ben Willem; Baker, Philip N

    2014-03-11

    In pregnancies complicated by early-onset extreme fetal growth restriction, there is a high risk of preterm birth and an overall dismal fetal prognosis. Sildenafil has been suggested to improve this prognosis. The first aim of this review is to assess whether sildenafil benefits or harms these babies. The second aim is to analyse if these effects are modified in a clinically meaningful way by factors related to the women or the trial protocol. The STRIDER (Sildenafil Therapy In Dismal prognosis Early-onset intrauterine growth Restriction) Individual Participant Data (IPD) Study Group will conduct a prospective IPD and aggregate data systematic review with meta-analysis and trial sequential analysis. The STRIDER IPD Study Group started trial planning and funding applications in 2012. Three trials will be launched in 2014, recruiting for three years. Further trials are planned to commence in 2015.The primary outcome for babies is being alive at term gestation without evidence of serious adverse neonatal outcome. The latter is defined as severe central nervous system injury (severe intraventricular haemorrhage (grade 3 and 4) or cystic periventricular leukomalacia, demonstrated by ultrasound and/or magnetic resonance imaging) or other severe morbidity (bronchopulmonary dysplasia, retinopathy of prematurity requiring treatment, or necrotising enterocolitis requiring surgery). The secondary outcomes are improved fetal growth velocity assessed by ultrasound abdominal circumference measurements, gestational age and birth weight (centile) at delivery, and age-adequate performance on the two-year Bayley scales of infant and toddler development-III (composite cognitive score and composite motor score). Subgroup and sensitivity analyses in the IPD meta-analysis include assessment of the influence of several patient characteristics: an abnormal or normal serum level of placental growth factor, absent/reversed umbilical arterial end diastolic flow at commencement of treatment

  5. Placental NFE2L2 is discordantly activated in monochorionic twins with selective intrauterine growth restriction and possibly regulated by hypoxia.

    Science.gov (United States)

    Wu, Jing; He, Zhiming; Gao, Yu; Zhang, Guanglan; Huang, Xuan; Fang, Qun

    2017-04-01

    Nuclear factor, erythroid 2 like 2 (NFE2L2) is an important transcription factor that protects cells from oxidative stress (OS). NFE2L2 deficiency in placentas is associated with pregnancy complications. We have demonstrated that elevated OS existed in placental shares of the smaller fetus in selective intrauterine growth restriction (sIUGR); however, the role of NFE2L2 in the development of sIUGR remains unknown. In this study, we examined the levels of NFE2L2 and heme oxygenase 1 (HMOX1), a major antioxidant regulated by NFE2L2, in sIUGR placentas. We also investigated the relationship between hypoxia and NFE2L2 activation, which may be involved in the pathogenesis of sIUGR. Real-time PCR, Western blot, and immunohistochemistry were used to detect the levels of NFE2L2 and HMOX1 in placentas from 30 monochorionic diamniotic (MCDA) twin pregnancies. The trophoblast cell line HTR-8/SVneo was cultured under severe (3%) or mild (10%) hypoxia. NFE2L2 and HMOX1 were both up-regulated in placental shares of the smaller fetus in the sIUGR group. No significant inter-twin differences in NFE2L2 and HMOX1 were detected in the normal group. In vitro, NFE2L2 was suppressed under severe hypoxia (3% O 2 ) but was clearly up-regulated under mild hypoxia (10% O 2 ). Compared with the suppression of NFE2L2 in placentas of fetal growth restriction (FGR) in singleton pregnancies, NFE2L2 was up-regulated in placental shares of the smaller fetus in sIUGR pregnancies. The asymmetrical activation of NFE2L2 in placental shares of sIUGR twins may be a compensation for hypoxia that protects the smaller fetus from OS damage.

  6. Nutrient-intake-level-dependent regulation of intestinal development in newborn intrauterine growth-restricted piglets via glucagon-like peptide-2.

    Science.gov (United States)

    Liu, J; Liu, Z; Gao, L; Chen, L; Zhang, H

    2016-10-01

    The objective of the present study was to investigate the intestinal development of newborn intrauterine growth-restricted (IUGR) piglets subjected to normal nutrient intake (NNI) or restricted nutrient intake (RNI). Newborn normal birth weight (NBW) and IUGR piglets were allotted to NNI or RNI levels for 4 weeks from day 8 postnatal. IUGR piglets receiving NNI had similar growth performance compared with that of NBW piglets. Small intestine length and villous height were greater in IUGR piglets fed the NNI than that of piglets fed the RNI. Lactase activity was increased in piglets fed the NNI compared with piglets fed the RNI. Absorptive function, represented by active glucose transport by the Ussing chamber method and messenger RNA (mRNA) expressions of two main intestinal glucose transporters, Na+-dependent glucose transporter 1 (SGLT1) and glucose transporter 2 (GLUT2), were greater in IUGR piglets fed the NNI compared with piglets fed the RNI regimen. The apoptotic process, characterized by caspase-3 activity (a sign of activated apoptotic cells) and mRNA expressions of p53 (pro-apoptotic), bcl-2-like protein 4 (Bax) (pro-apoptotic) and B-cell lymphoma-2 (Bcl-2) (anti-apoptotic), were improved in IUGR piglets fed the NNI regimen. To test the hypothesis that improvements in intestinal development of IUGR piglets fed NNI might be mediated through circulating glucagon-like peptide-2 (GLP-2), GLP-2 was injected subcutaneously to IUGR piglets fed the RNI from day 8 to day 15 postnatal. Although the intestinal development of IUGR piglets fed the RNI regimen was suppressed compared with those fed the NNI regimen, an exogenous injection of GLP-2 was able to bring intestinal development to similar levels as NNI-fed IUGR piglets. Collectively, our results demonstrate that IUGR neonates that have NNI levels could improve intestinal function via the regulation of GLP-2.

  7. Amino acid-based formula as a rescue strategy in feeding very-low-birth-weight infants with intrauterine growth restriction.

    Science.gov (United States)

    Raimondi, Francesco; Spera, Anna Maria; Sellitto, Maria; Landolfo, Francesca; Capasso, Letizia

    2012-05-01

    Very-low-birth-weight (VLBW) neonates may develop severe intolerance to standard preterm formula especially if they are associated with intrauterine growth restriction (IUGR). We tested the hypothesis that these infants may tolerate an elemental, amino acid-based formula as a rescue feeding strategy. In a prospective, case-control pilot study, we enrolled VLBW IUGR infants enterally fed with standard preterm formula (SPF) at daily increments of 16 mL/kg. If gastric residuals accounted for >70% of milk feed in the previous 24 hours, then feedings were temporarily withheld and then resumed with amino acid formula (AAF) increased at the same speed. Cases on AAF were compared to controls on SPF and with cases themselves while on SPF. Primary outcome was the time to reach full enteral feedings. Secondary outcomes were time on parenteral nutrition, time on central venous catheter, and formula tolerability based on the amount of gastric residual volume. Sixty-four infants (22 cases) were enrolled. Although during the total duration of nutrition, cases had worse primary and secondary outcomes, when on AAF, cases were comparable to controls in time to full enteral feeding (14.4 vs 14 days), time on parenteral nutrition, and time on central venous catheter. Cases on AAF and controls had similar gastric residual volumes. At day 3 after AAF introduction, cases had a significantly reduced number (%) of gastric residual volume >5 mL/kg over total number of feedings (5.6 vs 1.5%; P Growth at 12 months of corrected age was also comparable. In our population of VLBW IUGR newborns with severe feeding intolerance, a short course on AAF was a safe and effective means of nutritional rescue.

  8. Exposure to social defeat stress in adolescence improves the working memory and anxiety-like behavior of adult female rats with intrauterine growth restriction, independently of hippocampal neurogenesis.

    Science.gov (United States)

    Furuta, Miyako; Ninomiya-Baba, Midori; Chiba, Shuichi; Funabashi, Toshiya; Akema, Tatsuo; Kunugi, Hiroshi

    2015-04-01

    Intrauterine growth restriction (IUGR) is a risk factor for memory impairment and emotional disturbance during growth and adulthood. However, this risk might be modulated by environmental factors during development. Here we examined whether exposing adolescent male and female rats with thromboxane A2-induced IUGR to social defeat stress (SDS) affected their working memory and anxiety-like behavior in adulthood. We also used BrdU staining to investigate hippocampal cellular proliferation and BrdU and NeuN double staining to investigate neural differentiation in female IUGR rats. In the absence of adolescent stress, IUGR female rats, but not male rats, scored significantly lower in the T-maze test of working memory and exhibited higher anxiety-like behavior in the elevated-plus maze test compared with controls. Adolescent exposure to SDS abolished these behavioral impairments in IUGR females. In the absence of adolescent stress, hippocampal cellular proliferation was significantly higher in IUGR females than in non-IUGR female controls and was not influenced by adolescent exposure to SDS. Hippocampal neural differentiation was equivalent in non-stressed control and IUGR females. Neural differentiation was significantly increased by adolescent exposure to SDS in controls but not in IUGR females. There was no significant difference in the serum corticosterone concentrations between non-stressed control and IUGR females; however, adolescent exposure to SDS significantly increased serum corticosterone concentration in control females but not in IUGR females. These results demonstrate that adolescent exposure to SDS improves behavioral impairment independent of hippocampal neurogenesis in adult rats with IUGR. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Gestational food restriction decreases placental interleukin-10 expression and markers of autophagy and endoplasmic reticulum stress in murine intrauterine growth restriction.

    Science.gov (United States)

    Chu, Alison; Thamotharan, Shanthie; Ganguly, Amit; Wadehra, Madhuri; Pellegrini, Matteo; Devaskar, Sherin U

    2016-10-01

    Intrauterine growth restriction (IUGR) affects up to 10% of pregnancies and often results in short- and long-term sequelae for offspring. The mechanisms underlying IUGR are poorly understood, but it is known that healthy placentation is essential for nutrient provision to fuel fetal growth, and is regulated by immunologic inputs. We hypothesized that in pregnancy, maternal food restriction (FR) resulting in IUGR would decrease the overall immunotolerant milieu in the placenta, leading to increased cellular stress and death. Our specific objectives were to evaluate (1) key cytokines (eg, IL-10) that regulate maternal-fetal tolerance, (2) cellular processes (autophagy and endoplasmic reticulum [ER] stress) that are immunologically mediated and important for cellular survival and functioning, and (3) the resulting IUGR phenotype and placental histopathology in this animal model. After subjecting pregnant mice to mild and moderate FR from gestational day 10 to 19, we collected placentas and embryos at gestational day 19. We examined RNA sequencing data to identify immunologic pathways affected in IUGR-associated placentas and validated messenger RNA expression changes of genes important in cellular integrity. We also evaluated histopathologic changes in vascular and trophoblastic structures as well as protein expression changes in autophagy, ER stress, and apoptosis in the mouse placentas. Several differentially expressed genes were identified in FR compared with control mice, including a considerable subset that regulates immune tolerance, inflammation, and cellular integrity. In summary, maternal FR decreases the anti-inflammatory effect of IL-10 and suppresses placental autophagic and ER stress responses, despite evidence of dysregulated vascular and trophoblast structures leading to IUGR. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Embryonic mortality and intrauterine growth retardation (IUGR) associated with placental alterations in pregnant rats treated with methyl methanesulfonate (MMS) at the peri-implantation stage.

    Science.gov (United States)

    Yokoi, Ryohei; Hayashi, Morimichi; Tamura, Toru; Kobayashi, Kazuo; Kuroda, Junji; Kusama, Hiroshi; Kagami, Hiroshi; Ono, Tamao

    2008-12-01

    Embryonic mortality and intrauterine growth retardation (IUGR) are induced by exposure of rodents to xenobiotic agents during the pregastrulation period of development. We examined the time course of the effects of methyl methanesulfonate (MMS), an alkylating agent, on conceptus development in order to clarify the relative roles of the embryo and the placenta in their induction. Pregnant rats were treated orally with a single dose of MMS (200 mg/kg) in the morning of gestation day (GD) 6 (peri-implantation stage). Embryonic mortality was increased on GD12 and thereafter by MMS treatment, with newly dead embryos showing placental hypoplasia at GD12. Embryo or fetal weight was also smaller for MMS-treated dams than for control dams from GD14 to GD20. The labyrinth zone and junctional zone (JZ) of the placenta were thinner in MMS-treated rats from GD12 to GD17 and from GD12 to GD20 (except for GD17), respectively. Furthermore, MMS-treated dams showed a smaller number of glycogen cells in the JZ on GD14. In contrast, the placental glycogen concentration was higher and the expression of glucose transporter 1 in the JZ remained at GD20. These results indicate that exposure of pregnant rats to MMS at the peri-implantation stage of embryogenesis affects placental development and growth. The placental impairment induced by MMS was likely responsible for the embryonic death observed 6 days after exposure of dams to this agent as well as for the IUGR of surviving embryos or fetuses throughout the gestation period.

  11. Verification of a model for the detection of intrauterine growth restriction (IUGR) by receiver operating characteristics (ROC)

    Science.gov (United States)

    Liu, Pengbo; Mongelli, Max; Mondry, Adrian

    2004-07-01

    The purpose of this study is to verify by Receiver Operating Characteristics (ROC) a mathematical model supporting the hypothesis that IUGR can be diagnosed by estimating growth velocity. The ROC compare computerized simulation results with clinical data from 325 pregnant British women. Each patient had 6 consecutive ultrasound examinations for fetal abdominal circumference (fac). Customized and un-customized fetal weights were calculated according to Hadlock"s formula. IUGR was diagnosed by the clinical standard, i.e. estimated weight below the tenth percentile. Growth velocity was estimated by calculating the changes of fac (Dzfac/dt) at various time intervals from 3 to 10 weeks. Finally, ROC was used to compare the methods. At 3~4 weeks scan interval, the area under the ROC curve is 0.68 for customized data and 0.66 for the uncustomized data with 95% confidence interval. Comparison between simulation data and real pregnancies verified that the model is clinically acceptable.

  12. Intrauterin graviditet efter Cavatermbehandling

    DEFF Research Database (Denmark)

    Shokouh-Amiri, Ali; Kjaergaard, Niels

    2009-01-01

    A case of intrauterine pregnancy occurring after successful balloon thermal endometrial ablation is described. Although rare, pregnancy after endometrial ablation is possible, and use of a supplemental contraceptive method should be planned. In case of pregnancy after endometrial ablation...

  13. New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism

    Science.gov (United States)

    Horikoshi, Momoko; Yaghootkar, Hanieh; Mook-Kanamori, Dennis O.; Sovio, Ulla; Taal, H. Rob; Hennig, Branwen J.; Bradfield, Jonathan P.; St. Pourcain, Beate; Evans, David M.; Charoen, Pimphen; Kaakinen, Marika; Cousminer, Diana L.; Lehtimäki, Terho; Kreiner-Møller, Eskil; Warrington, Nicole M.; Bustamante, Mariona; Feenstra, Bjarke; Berry, Diane J.; Thiering, Elisabeth; Pfab, Thiemo; Barton, Sheila J.; Shields, Beverley M.; Kerkhof, Marjan; van Leeuwen, Elisabeth M.; Fulford, Anthony J.; Kutalik, Zoltán; Zhao, Jing Hua; den Hoed, Marcel; Mahajan, Anubha; Lindi, Virpi; Goh, Liang-Kee; Hottenga, Jouke-Jan; Wu, Ying; Raitakari, Olli T.; Harder, Marie N.; Meirhaeghe, Aline; Ntalla, Ioanna; Salem, Rany M.; Jameson, Karen A.; Zhou, Kaixin; Monies, Dorota M.; Lagou, Vasiliki; Kirin, Mirna; Heikkinen, Jani; Adair, Linda S.; Alkuraya, Fowzan S.; Al-Odaib, Ali; Amouyel, Philippe; Andersson, Ehm Astrid; Bennett, Amanda J.; Blakemore, Alexandra I.F.; Buxton, Jessica L.; Dallongeville, Jean; Das, Shikta; de Geus, Eco J. C.; Estivill, Xavier; Flexeder, Claudia; Froguel, Philippe; Geller, Frank; Godfrey, Keith M.; Gottrand, Frédéric; Groves, Christopher J.; Hansen, Torben; Hirschhorn, Joel N.; Hofman, Albert; Hollegaard, Mads V.; Hougaard, David M.; Hyppönen, Elina; Inskip, Hazel M.; Isaacs, Aaron; Jørgensen, Torben; Kanaka-Gantenbein, Christina; Kemp, John P.; Kiess, Wieland; Kilpeläinen, Tuomas O.; Klopp, Norman; Knight, Bridget A.; Kuzawa, Christopher W.; McMahon, George; Newnham, John P.; Niinikoski, Harri; Oostra, Ben A.; Pedersen, Louise; Postma, Dirkje S.; Ring, Susan M.; Rivadeneira, Fernando; Robertson, Neil R.; Sebert, Sylvain; Simell, Olli; Slowinski, Torsten; Tiesler, Carla M.T.; Tönjes, Anke; Vaag, Allan; Viikari, Jorma S.; Vink, Jacqueline M.; Vissing, Nadja Hawwa; Wareham, Nicholas J.; Willemsen, Gonneke; Witte, Daniel R.; Zhang, Haitao; Zhao, Jianhua; Wilson, James F.; Stumvoll, Michael; Prentice, Andrew M.; Meyer, Brian F.; Pearson, Ewan R.; Boreham, Colin A.G.; Cooper, Cyrus; Gillman, Matthew W.; Dedoussis, George V.; Moreno, Luis A; Pedersen, Oluf; Saarinen, Maiju; Mohlke, Karen L.; Boomsma, Dorret I.; Saw, Seang-Mei; Lakka, Timo A.; Körner, Antje; Loos, Ruth J.F.; Ong, Ken K.; Vollenweider, Peter; van Duijn, Cornelia M.; Koppelman, Gerard H.; Hattersley, Andrew T.; Holloway, John W.; Hocher, Berthold; Heinrich, Joachim; Power, Chris; Melbye, Mads; Guxens, Mònica; Pennell, Craig E.; Bønnelykke, Klaus; Bisgaard, Hans; Eriksson, Johan G.; Widén, Elisabeth; Hakonarson, Hakon; Uitterlinden, André G.; Pouta, Anneli; Lawlor, Debbie A.; Smith, George Davey; Frayling, Timothy M.; McCarthy, Mark I.; Grant, Struan F.A.; Jaddoe, Vincent W.V.; Jarvelin, Marjo-Riitta; Timpson, Nicholas J.; Prokopenko, Inga; Freathy, Rachel M.

    2012-01-01

    Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood1. Previous genome-wide association studies identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes, and a second variant, near CCNL1, with no obvious link to adult traits2. In an expanded genome-wide association meta-analysis and follow-up study (up to 69,308 individuals of European descent from 43 studies), we have now extended the number of genome-wide significant loci to seven, accounting for a similar proportion of variance to maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes; ADRB1 with adult blood pressure; and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism. PMID:23202124

  14. Intrauterine growth restriction modifies the hedonic response to sweet taste in newborn pups - Role of the accumbal μ-opioid receptors.

    Science.gov (United States)

    Laureano, D P; Dalle Molle, R; Alves, M B; Luft, C; Desai, M; Ross, M G; Silveira, P P

    2016-05-13

    Intrauterine growth restriction (IUGR) is associated with increased preference for palatable foods. The hedonic response to sweet taste, modulated by the nucleus accumbens μ-opioid-receptors, may be involved. We investigated hedonic responses and receptor levels in IUGR and Control animals. From pregnancy day 10, Sprague-Dawley dams received either an ad libitum (Control), or a 50% food restricted (FR) diet. At birth, pups were cross-fostered, and nursed by Adlib fed dams. The hedonic response was evaluated at 1 day after birth and at 90 days of life, by giving sucrose solution or water and analyzing the hedonic facial responses (within 60s). Control pups exposed either to water or sucrose resolved their hedonic responses after 16 and 18s, respectively, while FR hedonic responses to sucrose persisted over 20s. FR pups had deceased phospho-μ-opioid-receptor (p=0.009) and reduced phosphor:total mu opioid receptor ratio compared to controls pups (p=0.003). In adults, there was an interaction between group and solution at the end of the evaluation (p=0.044): Control decreased the response after sucrose solution, FR did not change over time. There were no differences in phosphorylation of μ-opioid-receptor in adults. These results demonstrate IUGR newborn rats exhibit alterations in hedonic response accompanied by a decrease in μ-opioid-receptor phosphorylation, though these alterations do not persist at 3 months of age. Opioid system alterations in early life may contribute to the development of preference for highly palatable foods and contribute to rapid weight gain and obesity in IUGR offspring. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Arginase up-regulation and eNOS uncoupling contribute to impaired endothelium-dependent vasodilation in a rat model of intrauterine growth restriction.

    Science.gov (United States)

    Grandvuillemin, Isabelle; Buffat, Christophe; Boubred, Farid; Lamy, Edouard; Fromonot, Julien; Charpiot, Philippe; Simoncini, Stephanie; Sabatier, Florence; Dignat-George, Françoise; Peyter, Anne-Christine; Simeoni, Umberto; Yzydorczyk, Catherine

    2018-05-09

    Individuals born after intrauterine growth restriction (IUGR) are at increased risk of developing cardiovascular diseases in adulthood, notably hypertension (HTN). Alterations in the vascular system, particularly impaired endothelium-dependent vasodilation, may play an important role in long-term effects of IUGR. Whether such vascular dysfunction precedes HTN has not been fully established in individuals born after IUGR. Moreover, the intimate mechanisms of altered endothelium-dependent vasodilation remain incompletely elucidated. We therefore investigated, using a rat model of IUGR, whether impaired endothelium-dependent relaxation precedes the development of HTN and whether key components of the L-Arginine-nitric oxide (NO) pathway are involved in its pathogenesis. Pregnant rats were fed with a control (CTRL, 23% casein) or low-protein diet (LP, 9% casein) to induce IUGR. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography in 5- and 8-week-old male offspring. Aortic rings were isolated to investigate relaxation to acetylcholine, NO production, eNOS protein content, arginase activity, and superoxide anion production. SBP was not different at 5 weeks, but significantly increased in 8-week-old LP vs. CRTL offspring. In 5-week-old LP vs. CRTL males, endothelium-dependent vasorelaxation was significantly impaired, but restored by pre-incubation with L-Arginine or the arginase inhibitor BEC; NO production was significantly reduced, but restored by L-Arginine pretreatment; total eNOS protein, dimer/monomer ratio, and arginase activity were significantly increased; superoxide anion production was significantly enhanced, but normalized by pretreatment with the NOS inhibitor L-NNA. In this model, IUGR leads to early-impaired endothelium-dependent vasorelaxation, resulting from arginase up-regulation and eNOS uncoupling, which precedes the development of HTN.

  16. Effects of Intrauterine Growth Restriction During Late Pregnancy on the Development of the Ovine Fetal Thymus and the T-Lymphocyte Subpopulation.

    Science.gov (United States)

    Liu, Yingchun; He, Shan; Zhang, Yuan; Xia, Wei; Li, Ming; Zhang, Chongzhi; Gao, Feng

    2015-07-01

    The retarded development of fetal thymus in intrauterine growth restriction (IUGR) from maternal undernutrition during late pregnancy destroys the tridimensional structure and modifies the development of fetal T lymphocytes. The mechanisms, however, remain unclear. The objective of this study was to investigate the effect of IUGR during late pregnancy on the development of the ovine fetal thymus and the T-lymphocyte subpopulation. Eighteen time-mated ewes with singleton fetuses were allocated to three groups at day 90 of pregnancy: restricted group 1 (RG1, 0.18 MJ ME/BW(0.75) /day, n = 6), restricted group 2 (RG2, 0.33 MJ ME/BW(0.75) /day, n = 6) and a control group (CG, ad libitum, 0.67 MJ ME/BW(0.75) /day, n = 6). Fetuses were recovered at slaughter on day 140. Fetuses in RG1 exhibited decreased (P restricted groups. In addition, there was reduced mRNA expression (P < 0.05) of T-cell receptor, apoptosis antigen 1 ligand, and RAG2 in the RG1 group. In contrast, increases in glutathione peroxidase, malondialdehyde, caspase-3, Cytochrome c, and CD4(+) T cells were observed (P < 0.05), and higher mRNA expressions (P < 0.05) of protein 53, Bcl-2 associated X protein (Bax), and apoptosis antigen 1 (Fas) were found in RG1 fetuses; and thymuses of RG2 fetuses had increased caspase-3, and expression of Fas and Bax (P < 0.05), relative to control fetuses. These results indicate that reduced cell proliferation, oxidative stress, and increased cell apoptosis were the potential mechanisms for impaired development and microenvironment of IUGR fetal thymus, and for modifying the maturation of CD4(+) CD8(+) thymocytes underlying their reduced numbers . © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Perinatal supplementation of 4-phenylbutyrate and glutamine attenuates endoplasmic reticulum stress and improves colonic epithelial barrier function in rats born with intrauterine growth restriction.

    Science.gov (United States)

    Désir-Vigné, Axel; Haure-Mirande, Vianney; de Coppet, Pierre; Darmaun, Dominique; Le Dréan, Gwenola; Segain, Jean-Pierre

    2018-05-01

    Intrauterine growth restriction (IUGR) can affect the structure and function of the intestinal barrier and increase digestive disease risk in adulthood. Using the rat model of maternal dietary protein restriction (8% vs. 20%), we found that the colon of IUGR offspring displayed decreased mRNA expression of epithelial barrier proteins MUC2 and occludin during development. This was associated with increased mRNA expression of endoplasmic reticulum (ER) stress marker XBP1s and increased colonic permeability measured in Ussing chambers. We hypothesized that ER stress contributes to colonic barrier alterations and that perinatal supplementation of dams with ER stress modulators, phenylbutyrate and glutamine (PG) could prevent these defects in IUGR offspring. We first demonstrated that ER stress induction by tunicamycin or thapsigargin increased the permeability of rat colonic tissues mounted in Ussing chamber and that PG treatment prevented this effect. Therefore, we supplemented the diet of control and IUGR dams with PG during gestation and lactation. Real-time polymerase chain reaction and histological analysis of colons from 120-day-old offspring revealed that perinatal PG treatment partially prevented the increased expression of ER stress markers but reversed the reduction of crypt depth and goblet cell number in IUGR rats. In dextran sodium sulfate-induced injury and recovery experiments, the colon of IUGR rats without perinatal PG treatment showed higher XBP1s mRNA levels and histological scores of inflammation than IUGR rats with perinatal PG treatment. In conclusion, these data suggest that perinatal supplementation with PG could alleviate ER stress and prevent epithelial barrier dysfunction in IUGR offspring. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Long-term functional outcomes and correlation with regional brain connectivity by MRI diffusion tractography metrics in a near-term rabbit model of intrauterine growth restriction.

    Directory of Open Access Journals (Sweden)

    Miriam Illa

    Full Text Available BACKGROUND: Intrauterine growth restriction (IUGR affects 5-10% of all newborns and is associated with increased risk of memory, attention and anxiety problems in late childhood and adolescence. The neurostructural correlates of long-term abnormal neurodevelopment associated with IUGR are unknown. Thus, the aim of this study was to provide a comprehensive description of the long-term functional and neurostructural correlates of abnormal neurodevelopment associated with IUGR in a near-term rabbit model (delivered at 30 days of gestation and evaluate the development of quantitative imaging biomarkers of abnormal neurodevelopment based on diffusion magnetic resonance imaging (MRI parameters and connectivity. METHODOLOGY: At +70 postnatal days, 10 cases and 11 controls were functionally evaluated with the Open Field Behavioral Test which evaluates anxiety and attention and the Object Recognition Task that evaluates short-term memory and attention. Subsequently, brains were collected, fixed and a high resolution MRI was performed. Differences in diffusion parameters were analyzed by means of voxel-based and connectivity analysis measuring the number of fibers reconstructed within anxiety, attention and short-term memory networks over the total fibers. PRINCIPAL FINDINGS: The results of the neurobehavioral and cognitive assessment showed a significant higher degree of anxiety, attention and memory problems in cases compared to controls in most of the variables explored. Voxel-based analysis (VBA revealed significant differences between groups in multiple brain regions mainly in grey matter structures, whereas connectivity analysis demonstrated lower ratios of fibers within the networks in cases, reaching the statistical significance only in the left hemisphere for both networks. Finally, VBA and connectivity results were also correlated with functional outcome. CONCLUSIONS: The rabbit model used reproduced long-term functional impairments and their

  19. Intrauterine growth restriction increases circulating mitochondrial DNA and Toll-like receptor 9 expression in adult offspring: could aerobic training counteract these adaptations?

    Science.gov (United States)

    Oliveira, V; Silva Junior, S D; de Carvalho, M H C; Akamine, E H; Michelini, L C; Franco, M C

    2017-04-01

    It has been demonstrated that intrauterine growth restriction (IUGR) can program increase cardiometabolic risk. There are also evidences of the correlation between IUGR with low-grade inflammation and, thus can contribute to development of several cardiometabolic comorbidities. Therefore, we investigated the influence of IUGR on circulating mitochondrial DNA (mtDNA)/Toll-like receptor 9 (TLR9) and TNF-α expression in adult offspring. Considering that the aerobic training has anti-inflammatory actions, we also investigated whether aerobic training would improve these inflammatory factors. Pregnant Wistar rats received ad libitum or 50% of ad libitum diet throughout gestation. At 8 weeks of age, male offspring from both groups were randomly assigned to control, trained control, restricted and trained restricted. Aerobic training protocol was performed on a treadmill and after that, we evaluated circulating mtDNA, cardiac protein expression of TLR9, plasma and cardiac TNF-α levels, and left ventricle (LV) mass. We found that IUGR promoted an increase in the circulating mtDNA, TLR9 expression and plasma TNF-α levels. Further, our results revealed that aerobic training can restore mtDNA/TLR9 content and plasma levels of TNF-α among restricted rats. The cardiac TNF-α content and LV mass were not influenced either by IUGR or aerobic training. In conclusion, IUGR can program mtDNA/TLR9 content, which may lead to high levels of TNF-α. However, aerobic training was able to normalize these alterations. These findings evidenced that the association of IUGR and aerobic training seems to exert an important interaction effect regarding pro-inflammatory condition and, aerobic training may be used as a strategy to reduce deleterious adaptations in IUGR offspring.

  20. Long-term functional outcomes and correlation with regional brain connectivity by MRI diffusion tractography metrics in a near-term rabbit model of intrauterine growth restriction.

    Science.gov (United States)

    Illa, Miriam; Eixarch, Elisenda; Batalle, Dafnis; Arbat-Plana, Ariadna; Muñoz-Moreno, Emma; Figueras, Francesc; Gratacos, Eduard

    2013-01-01

    Intrauterine growth restriction (IUGR) affects 5-10% of all newborns and is associated with increased risk of memory, attention and anxiety problems in late childhood and adolescence. The neurostructural correlates of long-term abnormal neurodevelopment associated with IUGR are unknown. Thus, the aim of this study was to provide a comprehensive description of the long-term functional and neurostructural correlates of abnormal neurodevelopment associated with IUGR in a near-term rabbit model (delivered at 30 days of gestation) and evaluate the development of quantitative imaging biomarkers of abnormal neurodevelopment based on diffusion magnetic resonance imaging (MRI) parameters and connectivity. At +70 postnatal days, 10 cases and 11 controls were functionally evaluated with the Open Field Behavioral Test which evaluates anxiety and attention and the Object Recognition Task that evaluates short-term memory and attention. Subsequently, brains were collected, fixed and a high resolution MRI was performed. Differences in diffusion parameters were analyzed by means of voxel-based and connectivity analysis measuring the number of fibers reconstructed within anxiety, attention and short-term memory networks over the total fibers. The results of the neurobehavioral and cognitive assessment showed a significant higher degree of anxiety, attention and memory problems in cases compared to controls in most of the variables explored. Voxel-based analysis (VBA) revealed significant differences between groups in multiple brain regions mainly in grey matter structures, whereas connectivity analysis demonstrated lower ratios of fibers within the networks in cases, reaching the statistical significance only in the left hemisphere for both networks. Finally, VBA and connectivity results were also correlated with functional outcome. The rabbit model used reproduced long-term functional impairments and their neurostructural correlates of abnormal neurodevelopment associated with IUGR

  1. Maternal History and Uterine Artery Doppler in the Assessment of Risk for Development of Early- and Late-Onset Preeclampsia and Intrauterine Growth Restriction

    Directory of Open Access Journals (Sweden)

    Elisa Llurba

    2009-01-01

    Full Text Available Objective. To examine the value of one-step uterine artery Doppler at 20 weeks of gestation in the prediction pre-eclampsia (PE and/or intrauterine growth restriction (IUGR. Methods. A prospective multicentre study that included all women with singleton pregnancies at 19–22 weeks of gestation (w. The mean pulsatility index (mPI of both uterine arteries was calculated. Receiver-operating characteristics curves (ROC were drawn to compare uterine artery Doppler and maternal risk factors for the prediction of early-onset PE and/or IUGR (before 32 w and late-onset PE and/or IUGR. Results. 6,586 women were included in the study. Complete outcome data was recorded for 6,035 of these women (91.6%. PE developed in 75 (1.2% and IUGR in 69 (1.1% cases. Uterine Doppler mPI was 0.99 and the 90th centile was 1.40. For 10% false-positive rate, uterine Doppler mPI identified 70.6% of pregnancies that subsequently developed early-onset PE and 73.3% of pregnancies that developed early-onset IUGR. The test had a lower detection rate for the late-onset forms of the disease (23.5% for PE and 30% for IUGR. Maternal history has a low sensitivity in the detection of early-onset cases, although it is better at detecting late-onset PE. Conclusion. Uterine artery Doppler and maternal risk factors seem to select two different populations - early and late-onset PE which might suggest a different pathogenesis.

  2. Long-Term Functional Outcomes and Correlation with Regional Brain Connectivity by MRI Diffusion Tractography Metrics in a Near-Term Rabbit Model of Intrauterine Growth Restriction

    Science.gov (United States)

    Illa, Miriam; Eixarch, Elisenda; Batalle, Dafnis; Arbat-Plana, Ariadna; Muñoz-Moreno, Emma; Figueras, Francesc; Gratacos, Eduard

    2013-01-01

    Background Intrauterine growth restriction (IUGR) affects 5–10% of all newborns and is associated with increased risk of memory, attention and anxiety problems in late childhood and adolescence. The neurostructural correlates of long-term abnormal neurodevelopment associated with IUGR are unknown. Thus, the aim of this study was to provide a comprehensive description of the long-term functional and neurostructural correlates of abnormal neurodevelopment associated with IUGR in a near-term rabbit model (delivered at 30 days of gestation) and evaluate the development of quantitative imaging biomarkers of abnormal neurodevelopment based on diffusion magnetic resonance imaging (MRI) parameters and connectivity. Methodology At +70 postnatal days, 10 cases and 11 controls were functionally evaluated with the Open Field Behavioral Test which evaluates anxiety and attention and the Object Recognition Task that evaluates short-term memory and attention. Subsequently, brains were collected, fixed and a high resolution MRI was performed. Differences in diffusion parameters were analyzed by means of voxel-based and connectivity analysis measuring the number of fibers reconstructed within anxiety, attention and short-term memory networks over the total fibers. Principal Findings The results of the neurobehavioral and cognitive assessment showed a significant higher degree of anxiety, attention and memory problems in cases compared to controls in most of the variables explored. Voxel-based analysis (VBA) revealed significant differences between groups in multiple brain regions mainly in grey matter structures, whereas connectivity analysis demonstrated lower ratios of fibers within the networks in cases, reaching the statistical significance only in the left hemisphere for both networks. Finally, VBA and connectivity results were also correlated with functional outcome. Conclusions The rabbit model used reproduced long-term functional impairments and their neurostructural

  3. Normalization of similarity-based individual brain networks from gray matter MRI and its association with neurodevelopment in infants with intrauterine growth restriction.

    Science.gov (United States)

    Batalle, Dafnis; Muñoz-Moreno, Emma; Figueras, Francesc; Bargallo, Nuria; Eixarch, Elisenda; Gratacos, Eduard

    2013-12-01

    Obtaining individual biomarkers for the prediction of altered neurological outcome is a challenge of modern medicine and neuroscience. Connectomics based on magnetic resonance imaging (MRI) stands as a good candidate to exhaustively extract information from MRI by integrating the information obtained in a few network features that can be used as individual biomarkers of neurological outcome. However, this approach typically requires the use of diffusion and/or functional MRI to extract individual brain networks, which require high acquisition times and present an extreme sensitivity to motion artifacts, critical problems when scanning fetuses and infants. Extraction of individual networks based on morphological similarity from gray matter is a new approach that benefits from the power of graph theory analysis to describe gray matter morphology as a large-scale morphological network from a typical clinical anatomic acquisition such as T1-weighted MRI. In the present paper we propose a methodology to normalize these large-scale morphological networks to a brain network with standardized size based on a parcellation scheme. The proposed methodology was applied to reconstruct individual brain networks of 63 one-year-old infants, 41 infants with intrauterine growth restriction (IUGR) and 22 controls, showing altered network features in the IUGR group, and their association with neurodevelopmental outcome at two years of age by means of ordinal regression analysis of the network features obtained with Bayley Scale for Infant and Toddler Development, third edition. Although it must be more widely assessed, this methodology stands as a good candidate for the development of biomarkers for altered neurodevelopment in the pediatric population. © 2013 Elsevier Inc. All rights reserved.

  4. Altered small-world topology of structural brain networks in infants with intrauterine growth restriction and its association with later neurodevelopmental outcome.

    Science.gov (United States)

    Batalle, Dafnis; Eixarch, Elisenda; Figueras, Francesc; Muñoz-Moreno, Emma; Bargallo, Nuria; Illa, Miriam; Acosta-Rojas, Ruthy; Amat-Roldan, Ivan; Gratacos, Eduard

    2012-04-02

    Intrauterine growth restriction (IUGR) due to placental insufficiency affects 5-10% of all pregnancies and it is associated with a wide range of short- and long-term neurodevelopmental disorders. Prediction of neurodevelopmental outcomes in IUGR is among the clinical challenges of modern fetal medicine and pediatrics. In recent years several studies have used magnetic resonance imaging (MRI) to demonstrate differences in brain structure in IUGR subjects, but the ability to use MRI for individual predictive purposes in IUGR is limited. Recent research suggests that MRI in vivo access to brain connectivity might have the potential to help understanding cognitive and neurodevelopment processes. Specifically, MRI based connectomics is an emerging approach to extract information from MRI data that exhaustively maps inter-regional connectivity within the brain to build a graph model of its neural circuitry known as brain network. In the present study we used diffusion MRI based connectomics to obtain structural brain networks of a prospective cohort of one year old infants (32 controls and 24 IUGR) and analyze the existence of quantifiable brain reorganization of white matter circuitry in IUGR group by means of global and regional graph theory features of brain networks. Based on global and regional analyses of the brain network topology we demonstrated brain reorganization in IUGR infants at one year of age. Specifically, IUGR infants presented decreased global and local weighted efficiency, and a pattern of altered regional graph theory features. By means of binomial logistic regression, we also demonstrated that connectivity measures were associated with abnormal performance in later neurodevelopmental outcome as measured by Bayley Scale for Infant and Toddler Development, Third edition (BSID-III) at two years of age. These findings show the potential of diffusion MRI based connectomics and graph theory based network characteristics for estimating differences in the

  5. Flexible treatment of gestational diabetes modulated on ultrasound evaluation of intrauterine growth: a controlled randomized clinical trial.

    Science.gov (United States)

    Bonomo, M; Cetin, I; Pisoni, M P; Faden, D; Mion, E; Taricco, E; Nobile de Santis, M; Radaelli, T; Motta, G; Costa, M; Solerte, L; Morabito, A

    2004-06-01

    In order to prevent abnormalities of fetal growth still characterizing pregnancies complicated by Gestational Diabetes (GDM), in the present study we evaluated a therapeutic strategy for GDM based on ultrasound (US) measurement of fetal insulin-sensitive tissues. All GDM women diagnosed before 28th week immediately started diet and self-monitoring of blood glucose; after 2 weeks they were randomized to conventional (C) or modified (M) management. In C the glycemic target (GT) was fixed at 90 fasting/120 post-prandial mg/dl; in M GT varied, according to US measurement of the Abdominal Circumference (AC) centile performed every 2 weeks: 80/100 if AC > or =75th, 100/140 if AC or =75th c. Mean metabolic data were similar in the 2 groups, but in M a tightly-optimized subgroup, resulting from the lowering of GT due to AC > or =75th, coexisted with a less-controlled one, whose higher GT was justified by ACgrowth, with clear advantages on global pregnancy outcome.

  6. Endoglin in pregnancy complicated by fetal intrauterine growth restriction in normotensive and preeclamptic pregnant women: a comparison between preeclamptic patients with appropriate-for-gestational-age weight infants and healthy pregnant women.

    Science.gov (United States)

    Laskowska, Marzena; Laskowska, Katarzyna; Oleszczuk, Jan

    2012-06-01

    The aim of this study was to determine the maternal serum endoglin concentration in pregnancies with intrauterine growth restriction (IUGR) in the presence or absence of preeclampsia and to compare the results with preeclamptic pregnant women with appropriate-for-gestational-age weight infants and with healthy pregnant controls. The study was performed on 52 normotensive pregnant patients with pregnancy complicated by isolated IUGR, 33 patients with preeclampsia complicated by IUGR and 33 preeclamptic patients with appropriate-for-gestational-age weight infants. The control group consisted of 54 healthy normotensive pregnant patients with singleton uncomplicated pregnancies. The maternal serum endoglin concentrations were determined using a sandwich enzyme-linked immunosorbent assay assay. Our study revealed increased levels of endoglin in the serum of women with normotensive pregnancy complicated by isolated IUGR, and in both groups of preeclamptic patients with and without IUGR. The levels of endoglin were the highest in pregnancy complicated by fetal intrauterine growth restriction (IUGR) in the course of preeclampsia. The mean values were 12.2 ± 4.3 ng/ml in the IUGR group, 14.1 ± 3.6 ng/ml in preeclamptic patients with normal intrauterine fetal growth, 15.1 ± 3.2 ng/ml in preeclamptic pregnant women with IUGR and 10.6 ± 3.7 ng/ml in the healthy controls. We also found positive correlations between serum endoglin levels and systolic and diastolic blood pressure and inverse correlations between maternal endoglin and infant birth weight. Our results suggest that increased endoglin concentration may be at least responsible for the pathogenesis of preeclampsia and/or intrauterine fetal growth restriction. It seems that the pathomechanism underlying the development of preeclampsia and isolated IUGR is similar, but that their beginning or intensity may be different in these two pregnancy complications. The positive correlation between endoglin and

  7. Inhibition of the receptor for advanced glycation end-products (RAGE) protects from secondhand smoke (SHS)-induced intrauterine growth restriction IUGR in mice.

    Science.gov (United States)

    Lewis, Joshua B; Mejia, Camilo; Jordan, Clinton; Monson, Troy D; Bodine, Jared S; Dunaway, Todd M; Egbert, Kaleb M; Lewis, Adam L; Wright, Tanner J; Ogden, K Connor; Broberg, Dallin S; Hall, Parker D; Nelson, Shawn M; Hirschi, Kelsey M; Reynolds, Paul R; Arroyo, Juan A

    2017-12-01

    Intrauterine growth restriction (IUGR) is a disease affecting 10% of all pregnancies. IUGR is associated with maternal, fetal, or placental abnormalities. Studies investigating the effects of secondhand smoke (SHS) exposure and IUGR are limited. The receptor for advanced glycation end-products (RAGE) is a pro-inflammatory transmembrane receptor increased by SHS in the placenta. We tested the hypothesis that inhibition of RAGE during SHS exposure protects from smoke-induced IUGR. C57BL/6 mice were exposed to SHS or SHS + semi-synthetic glycosaminoglycan ethers (SAGEs) known to inhibit RAGE signaling. Trophoblast cells were treated with cigarette smoke extract (CSE) with or without SAGEs in order to address the effects of RAGE inhibition during trophoblast invasion in vitro. SHS-treated mice demonstrated a significant reduction in fetal weight (7.35-fold, P ≤ 0.0001) and placental weight (1.13-fold, P ≤ 0.0001) compared with controls. Mice co-treated with SHS and SAGEs were protected from SHS-induced fetal weights decreases. SHS treatment of C57BL/6 mice activated placental extracellular signal-regulated kinase (ERK) (3.0-fold, P ≤ 0.05), JNK (2.4-fold, P ≤ 0.05) and p38 (2.1-fold, P ≤ 0.05) and the expression of inflammatory mediators including TNF-α (1.34-fold, P ≤ 0.05) and IL-1β (1.03-fold, P ≤ 0.05). SHS-mediated activation of these molecules was reduced to basal levels when SAGE was co-administered. Invasion of trophoblast cells decreased 92% (P < 0.002) when treated with CSE and CSE-mediated invasion was completely reversed by SAGEs. We conclude that RAGE inhibition protects against fetal weight loss during SHS-induced IUGR. These studies provide insight into tobacco-mediated IUGR development and clarify avenues that may be helpful in the alleviation of placental complications.

  8. Fetal cardiac function in late-onset intrauterine growth restriction vs small-for-gestational age, as defined by estimated fetal weight, cerebroplacental ratio and uterine artery Doppler.

    Science.gov (United States)

    Pérez-Cruz, M; Cruz-Lemini, M; Fernández, M T; Parra, J A; Bartrons, J; Gómez-Roig, M D; Crispi, F; Gratacós, E

    2015-10-01

    Among late-onset small fetuses, a combination of estimated fetal weight (EFW), cerebroplacental ratio (CPR) and mean uterine artery (UtA) pulsatility index (PI) can predict a subgroup of fetuses with poor perinatal outcome; however, the association of these criteria with fetal cardiac structure and function is unknown. Our aim was to determine the presence and severity of signs indicating cardiac dysfunction in small fetuses, classified as intrauterine growth-restricted (IUGR) or small-for-gestational age (SGA), according to EFW, CPR and UtA-PI. A cohort of 209 late-onset small fetuses that were delivered > 34 weeks of gestation was divided in two categories: SGA (n = 59) if EFW was between the 3(rd) and 9(th) centiles with normal CPR and UtA-PI; and IUGR (n = 150) if EFW was  95(th) centile. The small population was compared with 150 appropriately grown fetuses (controls). Fetal cardiac morphometry and function were assessed by echocardiography using two-dimensional M-mode, conventional and tissue Doppler. Compared with controls, both IUGR and SGA fetuses showed larger and more globular hearts (mean left sphericity index ± SD: controls, 1.8 ± 0.3; SGA, 1.5 ± 0.2; and IUGR, 1.6 ± 0.3; P < 0.01) and showed signs of systolic and diastolic dysfunction, including decreased tricuspid annular plane systolic excursion (mean ± SD: controls, 8.2 ± 1.1; SGA, 7.4 ± 1.2; and IUGR, 6.9 ± 1.1; P < 0.001) and increased left myocardial performance index (mean ± SD: controls, 0.45 ± 0.14; SGA, 0.51 ± 0.08; and IUGR, 0.57 ± 0.1; P < 0.001). Despite a perinatal outcome comparable to that of normal fetuses, the population of so-defined SGA fetuses showed signs of prenatal cardiac dysfunction. This supports the concept that at least a proportion of them are not 'constitutionally small' and that further research is needed. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

  9. Dopplervelocimetria arterial em gestantes com antecedente de crescimento intra-uterino retardado Arterial doppler velocimetry in pregnant women with previous idiopathic intrauterine growth retardation

    Directory of Open Access Journals (Sweden)

    Solange Sasaki

    1998-10-01

    the perinatal results obtained for concepti with retarded intrauterine growth (RIUG with those for concepti considered adequate for gestational age (AGA. Methods: a prospective study of the evolution of doppler ultrasound was made in 38 pregnant women with of idiopathic intrauterine growth retardation (IUGR in previous pregnancy. A relationship was established between this antecedent and the new pregnancy. The pregnant women studied were divided into two groups in agreement with their neonates birthweight. Group 1 was associated with IUGR and group 2 with adequate birth weight. IUGR was confirmed in 23.7% of the cases. Umbilical and uterine artery doppler velocimetry was performed from 20 to 40 weeks of gestation. Middle cerebral artery doppler velocimetry was analyzed after 28 weeks of gestation, twice a month, being the last valued examination before birth. Results: the uterine and umbilical artery ratio at 24 and 28 weeks of gestation, respectively, correlated with the presence of IUGR. There was no difference between the two groups regarding the presence or absence of a small notch in the uterine artery wave form and middle cerebral artery doppler velocimetry ratio, at the last examination before birth. There was a relationship between neonatal stay in hospital for more than three days and the presence of IUGR. Conclusions: doppler ultrasound should be used in the follow-up of cases with a high risk of IUGR. It allows the detection of the fetuses at high risk of hypoxia and, by interrupting the pregnancy, fetal distress-related complications may be avoided.

  10. Levonorgestrel Intrauterine System

    Science.gov (United States)

    ... removed during the first 7 days of your menstrual period, you should start using your new form of birth control 7 days before your intrauterine system is removed.Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

  11. Curvas de crescimento intra-uterino de uma população de alto nível socioeconômico Intrauterine growth curves in a high-income population

    Directory of Open Access Journals (Sweden)

    Conceição A. M. Segre

    2001-06-01

    Full Text Available OBJETIVO: as curvas de percentil constituem uma das formas de avaliação do crescimento intra-uterino e podem predizer doenças do recém-nascido como também caracterizar uma população. Este trabalho teve por objetivo construir as curvas de crescimento intra-uterino dos recém-nascidos da Maternidade do Hospital Albert Einstein (MAE, hospital que atende a uma população de alto nível socioeconômico, e comparar com as curvas de crescimento intra-uterino de uma população norte-americana da Califórnia. MÉTODOS: foram construídas curvas de crescimento intra-uterino a partir do peso do recém-nascido de parto único, tomado logo após o nascimento, e da idade gestacional segundo informações maternas, a partir da 32ª. semana de idade gestacional, abrangendo os nascimentos ocorridos na MAE no período de fevereiro de 1995 a fevereiro de 1999. Foram calculados os percentis 10, 50 e 90 do peso ao nascer para cada idade gestacional e comparados com os das curvas da Califórnia. RESULTADOS: as curvas dos percentis 10 e 50 na população da MAE não diferiram das curvas da Califórnia. Para o percentil 90, a curva da MAE ficou abaixo das curvas da Califórnia. Houve número menor de pequenos e grandes para a idade gestacional (PIG e GIG quando classificados pelas curvas da Califórnia. A classificação em PIG, AIG, GIG mostrou-se relacionada significantemente com o ganho de peso materno nos dois sexos. CONCLUSÕES: as duas populações analisadas segundo as curvas de crescimento intra-uterino são diferentes entre si; deverão ser identificados fatores específicos que atuem na população da MAE.OBJECTIVE: growth curves can be used to assess intrauterine growth, to predict diseases in newborns, and to characterize different populations. The objective of this study was to obtain intrauterine growth curves of newborns from the maternity ward of the Hospital Albert Einstein (MAE and compare them with intrauterine growth curves of a population

  12. INTRAUTERINE FETAL DEATH CASES AT TERTIARY CENTER

    Directory of Open Access Journals (Sweden)

    Babu Lal Bishnoi

    2018-01-01

    Full Text Available BACKGROUND Intrauterine fetal death is a tragic event for the parents and a great cause of stress for the caregiver. It is an important indicator of maternal and perinatal health of a given population. This study was undertaken to study the maternal and fetal factors associated with intrauterine fetal death. Aim and Objective- This was an Analytical study aimed to evaluate and understand the prevalence, socio-epidemiological and etiological factors of IUFD methodology should not be mixed with aims and objectives MATERIALS AND METHODS The study was carried out at March 2017 to June 2017 (4 months study which was conducted at Dr. S. N. Medical College, Jodhpur, Rajasthan. The details were entered in a preformed proforma. IUD is defined as fetal death beyond 20 weeks of gestation and/or birth weight >500g. The details of complaints at admission, obstetrics history, menstrual history, examination findings, per vaginal examination findings, mode and method of delivery and fetal outcomes and investigation reports were recorded. RESULTS A total of 227 intrauterine fetal deaths were reported amongst 6264 deliveries conducted during the study period. The incidence rate of intrauterine fetal death was 36/1000 live births. 192 (84.56% deliveries were unbooked and unsupervised and 133 (58.59% belonged to rural population and 126 (55.5% were preterm and 221 (97.55% were singleton pregnancy. Among the identifiable causes hypertensive disorders (24.22% and severe anemia (13.10% were most common followed by placental causes (9.97%. Congenital malformations were responsible for 12.39% and unidentifiable causes were 11.01%. Induction was done in 103 patients, 94 patients had spontaneous onset of labour and caesarean section was done in 30 patients. Incidence of intrauterine foetal demise gradually decreased as parity advanced. CONCLUSION Institutional deliveries should be promoted to prevent intrapartum fetal deaths. Decrease in the incidence of IUD would

  13. Intrauterine neuromuscular blockade in fetus.

    Science.gov (United States)

    Fan, S Z; Huang, F Y; Lin, S Y; Wang, Y P; Hsieh, F J

    1990-03-01

    Antenatal intrauterine fetal therapy has now become the target of numerous invasive diagnostic and therapeutic maneuvers. Fetal motion during intrauterine fetal therapy not only makes these procedures technically more difficult but also increases the likelihood of trauma to the umbilical vessels and the fetus. Combination of high doses of sedatives, tranquilizers, and narcotics rarely results in adequate suppression of fetal movement. Such medication puts the mother at risk of respiratory depression, regurgitation and aspiration. The use of pancuronium or atracurium to temporarily arrest fetal movement in ten fetus is reported. After an initial ultrasound assessment of fetal lie, placental location, and umbilical cord insertion site, the fetal weight was calculated by the ultrasound parameters of biparietal diameter and abdominal circumference. Under ultrasound guidance, we injected pancuronium 0.15 mg/kg or atracurium 1.0 mg/kg using a 23-gauge spinal needle into the fetal gluteal muscle. Short-term paralysis of the fetus was induced in all cases. Fetal movement stopped by sonographic observation within 5.8 +/- 2.3 min in the pancuronium group and 4.7 +/- 1.8 min in the atracurium group. Fetal movements returned both to maternal sensation or ultrasonic observation by 92 +/- 23 min in the first group and 36 +/- 11 min in the second group. No adverse effect of the relaxant has been observed in any of the mothers. There was no evidence of local soft tissue, nerve or muscle damage at the site of injection on initial examination of the neonates after delivery. The use of neuromuscular relaxant in fetus was a safe and useful method.

  14. Consumo calórico, estado nutricional materno, y retraso del crecimiento intrauterino Energy intake, maternal nutritional status and intrauterine growth retardation

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    Eliana Bender Martins

    2003-02-01

    Full Text Available Para conocer la asociación entre el consumo de energía en el embarazo y el retraso del crecimiento intrauterino (RCIU, se llevó a cabo un estudio de caso-cohorte en tres hospitales de maternidad de la ciudad de México, entre enero y agosto de 1995. De un total de 4.000 partos que ocurrieron en este período, nos referimos en este estudio a los resultados de un análisis de 264 casos de RCIU y 892 controles. Se procedió a un análisis de regresión logística no condicionada, en el que también se ajustaron los factores maternos potencialmente proclives a la confusión. Para el total de los casos no se observó un efecto directo del consumo de energía en el RCIU (RM: 0,99; IC 95%: 0,99-1,00. Sin embargo, entre las mujeres que comenzaron el embarazo con un peso de 50 kilos o menos, el consumo de energía en relación a RCIU mostró una razón de momios de 2,31 (RM: 2,31; IC 95%: 1,59-3,36; para las mujeres primigestas de 1,72 (RM: 1,72; IC 95%: 1,18-2,51; en aquellas con antecedente de bajo peso al nacer de 3,54 (RM: 3,54; IC 95%: 1,93-6,46 y para aquellas que presentaron tensión arterial alta en el embarazo de 1,61 (RM: 1,61; IC 95%: 1,00-2,59.To explore the association between low caloric intake during pregnancy and intrauterine growth retardation (IUGR, a case-control study with 264 cases and 892 controls was conducted in three maternity hospitals in Mexico City from January to August 1995. Nutritional information on pregnancy was recorded using a previously validated food frequency questionnaire. After adjusting for other known maternal risk factors in the non-conditional logistic regression analysis, for the total sample, caloric intake did not present a direct effect on IUGR (OR: 0.99; CI 95%: 0.99-1.00. However the odds ratios were as follows for women: with low pre-gestational weight (OR: 2.31; CI 95%: 1.59-3.36, in first gestation (OR: 1.72; CI 95%: 1.18-2.51, with low birth weight infants (OR: 3.54; CI 95%: 1.93-6.46, and

  15. Growth factor delivery: How surface interactions modulate release in vitro and in vivo

    Science.gov (United States)

    King, William J.; Krebsbach, Paul H.

    2013-01-01

    Biomaterial scaffolds have been extensively used to deliver growth factors to induce new bone formation. The pharmacokinetics of growth factor delivery has been a critical regulator of their clinical success. This review will focus on the surface interactions that control the non-covalent incorporation of growth factors into scaffolds and the mechanisms that control growth factor release from clinically relevant biomaterials. We will focus on the delivery of recombinant human bone morphogenetic protein-2 from materials currently used in the clinical practice, but also suggest how general mechanisms that control growth factor incorporation and release delineated with this growth factor could extend to other systems. A better understanding of the changing mechanisms that control growth factor release during the different stages of preclinical development could instruct the development of future scaffolds for currently untreatable injuries and diseases. PMID:22433783

  16. Aerosol Drug Delivery During Noninvasive Positive Pressure Ventilation: Effects of Intersubject Variability and Excipient Enhanced Growth.

    Science.gov (United States)

    Walenga, Ross L; Longest, P Worth; Kaviratna, Anubhav; Hindle, Michael

    2017-06-01

    Nebulized aerosol drug delivery during the administration of noninvasive positive pressure ventilation (NPPV) is commonly implemented. While studies have shown improved patient outcomes for this therapeutic approach, aerosol delivery efficiency is reported to be low with high variability in lung-deposited dose. Excipient enhanced growth (EEG) aerosol delivery is a newly proposed technique that may improve drug delivery efficiency and reduce intersubject aerosol delivery variability when coupled with NPPV. A combined approach using in vitro experiments and computational fluid dynamics (CFD) was used to characterize aerosol delivery efficiency during NPPV in two new nasal cavity models that include face mask interfaces. Mesh nebulizer and in-line dry powder inhaler (DPI) sources of conventional and EEG aerosols were both considered. Based on validated steady-state CFD predictions, EEG aerosol delivery improved lung penetration fraction (PF) values by factors ranging from 1.3 to 6.4 compared with conventional-sized aerosols. Furthermore, intersubject variability in lung PF was very high for conventional aerosol sizes (relative differences between subjects in the range of 54.5%-134.3%) and was reduced by an order of magnitude with the EEG approach (relative differences between subjects in the range of 5.5%-17.4%). Realistic in vitro experiments of cyclic NPPV demonstrated similar trends in lung delivery to those observed with the steady-state simulations, but with lower lung delivery efficiencies. Reaching the lung delivery efficiencies reported with the steady-state simulations of 80%-90% will require synchronization of aerosol administration during inspiration and reducing the size of the EEG aerosol delivery unit. The EEG approach enabled high-efficiency lung delivery of aerosols administered during NPPV and reduced intersubject aerosol delivery variability by an order of magnitude. Use of an in-line DPI device that connects to the NPPV mask appears to be a

  17. The delivery of medical services in a retail shopping mall: a strategy for growth.

    Science.gov (United States)

    Hayden, K R

    1989-01-01

    The successful medical practice of the future will continually search for growth strategies. This writer believes the location of a primary care medical clinic in a retail shopping mall, with a full menu of primary services, is one strategy for growth. It is an effective method of health care delivery to a community.

  18. Human Growth Hormone Delivery with a Microneedle Transdermal System: Preclinical Formulation, Stability, Delivery and PK of Therapeutically Relevant Doses

    Directory of Open Access Journals (Sweden)

    Mahmoud Ameri

    2014-05-01

    Full Text Available This study evaluated the feasibility of coating formulated recombinant human growth hormone (rhGH on a titanium microneedle transdermal delivery system, Zosano Pharma (ZP-hGH, and assessed preclinical patch delivery performance. Formulation rheology and surface activity were assessed by viscometry and contact angle measurement. rhGH liquid formulation was coated onto titanium microneedles by dip-coating and drying. The stability of coated rhGH was determined by size exclusion chromatography-high performance liquid chromatography (SEC-HPLC. Preclinical delivery and pharmacokinetic studies were conducted in female hairless guinea pigs (HGP using rhGH coated microneedle patches at 0.5 and 1 mg doses and compared to Norditropin® a commercially approved rhGH subcutaneous injection. Studies demonstrated successful rhGH formulation development and coating on microneedle arrays. The ZP-hGH patches remained stable at 40 °C for six months with no significant change in % aggregates. Pharmacokinetic studies showed that the rhGH-coated microneedle patches, delivered with high efficiency and the doses delivered indicated linearity with average Tmax of 30 min. The absolute bioavailability of the microneedle rhGH patches was similar to subcutaneous Norditropin® injections. These results suggest that ZP-transdermal microneedle patch delivery of rhGH is feasible and may offer an effective and patient-friendly alternative to currently marketed rhGH injectables.

  19. Human Growth Hormone Delivery with a Microneedle Transdermal System: Preclinical Formulation, Stability, Delivery and PK of Therapeutically Relevant Doses.

    Science.gov (United States)

    Ameri, Mahmoud; Kadkhodayan, Miryam; Nguyen, Joe; Bravo, Joseph A; Su, Rebeca; Chan, Kenneth; Samiee, Ahmad; Daddona, Peter E

    2014-05-15

    This study evaluated the feasibility of coating formulated recombinant human growth hormone (rhGH) on a titanium microneedle transdermal delivery system, Zosano Pharma (ZP)-hGH, and assessed preclinical patch delivery performance. Formulation rheology and surface activity were assessed by viscometry and contact angle measurement. rhGH liquid formulation was coated onto titanium microneedles by dip-coating and drying. The stability of coated rhGH was determined by size exclusion chromatography-high performance liquid chromatography (SEC-HPLC). Preclinical delivery and pharmacokinetic studies were conducted in female hairless guinea pigs (HGP) using rhGH coated microneedle patches at 0.5 and 1 mg doses and compared to Norditropin® a commercially approved rhGH subcutaneous injection. Studies demonstrated successful rhGH formulation development and coating on microneedle arrays. The ZP-hGH patches remained stable at 40 °C for six months with no significant change in % aggregates. Pharmacokinetic studies showed that the rhGH-coated microneedle patches, delivered with high efficiency and the doses delivered indicated linearity with average Tmax of 30 min. The absolute bioavailability of the microneedle rhGH patches was similar to subcutaneous Norditropin® injections. These results suggest that ZP-transdermal microneedle patch delivery of rhGH is feasible and may offer an effective and patient-friendly alternative to currently marketed rhGH injectables.

  20. [Intrauterine intestinal volvulus].

    Science.gov (United States)

    Gawrych, Elzbieta; Chojnacka, Hanna; Wegrzynowski, Jerzy; Rajewska, Justyna

    2009-07-01

    Intrauterine intestinal volvulus is an extremely rare case of acute congenital intestinal obstruction. The diagnosis is usually possible in the third trimester of a pregnancy. Fetal midgut volvulus is most likely to be recognized by observing a typical clockwise whirlpool sign during color Doppler investigation. Multiple dilated intestinal loops with fluid levels are usually visible during the antenatal ultrasound as well. Physical and radiographic findings in the newborn indicate intestinal obstruction and an emergency surgery is required. The authors describe intrauterine volvulus in 3 female newborns in which surgical treatment was individualized. The decision about primary or delayed anastomosis after resection of the gangrenous part of the small bowel was made at the time of the surgery and depended on the general condition of the newborn, as well as presence or absence of meconium peritonitis. Double loop jejunostomy was performed in case of two newborns, followed by a delayed end-to-end anastomosis. In case of the third newborn, good blood supply of the small intestine after untwisting and 0.25% lignocaine injections into mesentery led to the assumption that the torsion was not complete and ischemia was reversible. In the two cases of incomplete rotation the cecum was sutured to the left abdominal wall to prevent further twisting. The postoperative course was uneventful and oral alimentation caused no problems. Physical development of all these children has been normal (current age: 1-2 years) and the parents have not observed any disorders or problems regarding passage of food through the alimentary canal. Prompt antenatal diagnosis of this surgical emergency and adequate choice of intervention may greatly reduce mortality due to intrauterine volvulus.

  1. Intrauterine supraventricular tachyarrhythmias and transplacental digitalisation.

    Science.gov (United States)

    Nagashima, M; Asai, T; Suzuki, C; Matsushima, M; Ogawa, A

    1986-10-01

    Six newborn infants with intrauterine supraventricular tachyarrhythmias (five cases of atrial flutter and one of supraventricular tachycardia) are described. Transplacental digitalisation was attempted in three cases. Supraventricular tachycardia associated with hydrops fetalis, detected in a fetus at a gestation of 31 weeks, was successfully converted to normal sinus rhythm eight days after the mother began treatment with digoxin. The serum concentration of digoxin in cord blood almost equalled the maternal concentration in three cases. In the remaining three cases treatment with digitalis was effective in converting tachyarrhythmias to sinus rhythm after delivery. With maintenance digoxin therapy, the prognosis of fetal tachyarrhythmias seems to be good, once conversion to sinus rhythm has been accomplished.

  2. A biomimetic growth factor delivery strategy for enhanced regeneration of iliac crest defects

    International Nuclear Information System (INIS)

    Yilgor Huri, Pinar; Huri, Gazi; Yasar, Umit; Dikmen, Nurten; Ucar, Yurdanur; Hasirci, Nesrin; Hasirci, Vasif

    2013-01-01

    The importance of provision of growth factors in the engineering of tissues has long been shown to control the behavior of the cells within the construct and several approaches were applied toward this end. In nature, more than one type of growth factor is known to be effective during the healing of tissue defects and their peak concentrations are not always simultaneous. One of the most recent strategies includes the delivery of a combination of growth factors with the dose and timing to mimic the natural regeneration cascade. The sequential delivery of bone morphogenetic proteins BMP-2 and BMP-7 which are early and late appearing factors during bone regeneration, respectively, was shown in vitro to enhance osteoblastic differentiation of bone marrow derived mesenchymal stem cells. In the present study, the aim was to study the effectiveness of this delivery strategy in a rabbit iliac crest model. 3D plotted poly(ε-caprolactone) scaffolds were loaded with BMP carrying nanoparticles to achieve: (a) single BMP-2 or BMP-7 delivery, and (b) their combined delivery in a simultaneous or (c) sequential (biomimetic) fashion. After eight weeks of implantation, computed tomography and biomechanical tests showed better mineralized matrix formation and bone-implant union strength at the defect site in the case of sequential delivery compared to single or simultaneous delivery modes. Bone mineral density (BMD) and push-out stress were: 33.65±2.25 g cm −3 and 14.5±2.28 MPa, respectively, and almost 2.5 fold higher in comparison to those without growth factors (BMD: 14.14±1.21 g cm −3 ; PS: 6.59±0.65 MPa). This study, therefore, supports those obtained in vitro and emphasizes the importance of mimicking the natural timing of bioavailability of osteogenic factors in improving the regeneration of critical-sized bone defects. (paper)

  3. Double emulsion electrospun nanofibers as a growth factor delivery vehicle for salivary gland regeneration

    Science.gov (United States)

    Foraida, Zahraa I.; Sharikova, Anna; Peerzada, Lubna N.; Khmaladze, Alexander; Larsen, Melinda; Castracane, James

    2017-08-01

    Sustained delivery of growth factors, proteins, drugs and other biologically active molecules is necessary for tissue engineering applications. Electrospun fibers are attractive tissue engineering scaffolds as they partially mimic the topography of the extracellular matrix (ECM). However, they do not provide continuous nourishment to the tissue. In search of a biomimetic scaffold for salivary gland tissue regeneration, we previously developed a blend nanofiber scaffold composed of the protein elastin and the synthetic polymer polylactic-co-glycolic acid (PLGA). The nanofiber scaffold promoted in vivo-like salivary epithelial cell tissue organization and apicobasal polarization. However, in order to enhance the salivary cell proliferation and biomimetic character of the scaffold, sustained growth factor delivery is needed. The composite nanofiber scaffold was optimized to act as a growth factor delivery system using epidermal growth factor (EGF) as a model protein. The nanofiber/EGF hybrid nanofibers were synthesized by double emulsion electrospinning where EGF is emulsified within a water/oil/water (w/o/w) double emulsion system. Successful incorporation of EGF was confirmed using Raman spectroscopy. EGF release profile was characterized using enzyme-linked immunosorbent assay (ELIZA) of the EGF content. Double emulsion electrospinning resulted in slower release of EGF. We demonstrated the potential of the proposed double emulsion electrospun nanofiber scaffold for the delivery of growth factors and/or drugs for tissue engineering and pharmaceutical applications.

  4. Intrauterine thrombosis of umbilical artery - case report

    Directory of Open Access Journals (Sweden)

    Gustavo Henrique de Oliveira

    Full Text Available ABSTRACT: CONTEXT: Umbilical cord thrombosis is related to greater fetal and perinatal morbidity and mortality. It is usually associated with umbilical cord abnormalities that lead to mechanical compression with consequent vascular ectasia. Its correct diagnosis and clinical management remains a challenge that has not yet been resolved. CASE REPORT: This study reports a case of umbilical artery thrombosis that occurred in the second half of a pregnancy. The umbilical cord was long, thin and overly twisted and the fetus presented severe intrauterine growth restriction. The clinical and histopathological findings from this case are described. CONCLUSIONS: This case report emphasizes the difficulty in diagnosing and clinically managing abnormalities of intrauterine life with a high chance of perinatal complications.

  5. Innovations in gene and growth factor delivery systems for diabetic wound healing

    Science.gov (United States)

    Laiva, Ashang Luwang; O'Brien, Fergal J.

    2017-01-01

    Abstract The rise in lower extremity amputations due to nonhealing of foot ulcers in diabetic patients calls for rapid improvement in effective treatment regimens. Administration of growth factors (GFs) are thought to offer an off‐the‐shelf treatment; however, the dose‐ and time‐dependent efficacy of the GFs together with the hostile environment of diabetic wound beds impose a major hindrance in the selection of an ideal route for GF delivery. As an alternative, the delivery of therapeutic genes using viral and nonviral vectors, capable of transiently expressing the genes until the recovery of the wounded tissue offers promise. The development of implantable biomaterial dressings capable of modulating the release of either single or combinatorial GFs/genes may offer solutions to this overgrowing problem. This article reviews the state of the art on gene and protein delivery and the strategic optimization of clinically adopted delivery strategies for the healing of diabetic wounds. PMID:28482114

  6. Aerosol Drug Delivery During Noninvasive Positive Pressure Ventilation: Effects of Intersubject Variability and Excipient Enhanced Growth

    Science.gov (United States)

    Walenga, Ross L.; Kaviratna, Anubhav; Hindle, Michael

    2017-01-01

    Abstract Background: Nebulized aerosol drug delivery during the administration of noninvasive positive pressure ventilation (NPPV) is commonly implemented. While studies have shown improved patient outcomes for this therapeutic approach, aerosol delivery efficiency is reported to be low with high variability in lung-deposited dose. Excipient enhanced growth (EEG) aerosol delivery is a newly proposed technique that may improve drug delivery efficiency and reduce intersubject aerosol delivery variability when coupled with NPPV. Materials and Methods: A combined approach using in vitro experiments and computational fluid dynamics (CFD) was used to characterize aerosol delivery efficiency during NPPV in two new nasal cavity models that include face mask interfaces. Mesh nebulizer and in-line dry powder inhaler (DPI) sources of conventional and EEG aerosols were both considered. Results: Based on validated steady-state CFD predictions, EEG aerosol delivery improved lung penetration fraction (PF) values by factors ranging from 1.3 to 6.4 compared with conventional-sized aerosols. Furthermore, intersubject variability in lung PF was very high for conventional aerosol sizes (relative differences between subjects in the range of 54.5%–134.3%) and was reduced by an order of magnitude with the EEG approach (relative differences between subjects in the range of 5.5%–17.4%). Realistic in vitro experiments of cyclic NPPV demonstrated similar trends in lung delivery to those observed with the steady-state simulations, but with lower lung delivery efficiencies. Reaching the lung delivery efficiencies reported with the steady-state simulations of 80%–90% will require synchronization of aerosol administration during inspiration and reducing the size of the EEG aerosol delivery unit. Conclusions: The EEG approach enabled high-efficiency lung delivery of aerosols administered during NPPV and reduced intersubject aerosol delivery variability by an order of magnitude. Use of an in

  7. Strategies for Controlled Delivery of Growth Factors and Cells for Bone Regeneration

    Science.gov (United States)

    Vo, Tiffany N.; Kasper, F. Kurtis; Mikos, Antonios G.

    2012-01-01

    The controlled delivery of growth factors and cells within biomaterial carriers can enhance and accelerate functional bone formation. The carrier system can be designed with preprogrammed release kinetics to deliver bioactive molecules in a localized, spatiotemporal manner most similar to the natural wound healing process. The carrier can also act as an extracellular matrix-mimicking substrate for promoting osteoprogenitor cellular infiltration and proliferation for integrative tissue repair. This review discusses the role of various regenerative factors involved in bone healing and their appropriate combinations with different delivery systems for augmenting bone regeneration. The general requirements of protein, cell and gene therapy are described, with elaboration on how the selection of materials, configurations and processing affects growth factor and cell delivery and regenerative efficacy in both in vitro and in vivo applications for bone tissue engineering. PMID:22342771

  8. Dissolving Microneedle Patch for Transdermal Delivery of Human Growth Hormone

    Science.gov (United States)

    Lee, Jeong Woo; Choi, Seong-O; Felner, Eric I.

    2014-01-01

    Clinical impact of biotechnology has been constrained by the limitations of traditional hypodermic injection of biopharmaceuticals. Microneedle patches have been proposed as a minimally invasive alternative. In this study, we assess the translation of a dissolving microneedle patch designed for simple, painless self-administration of biopharmacetucials that generates no sharp biohazardous waste. To study pharmacokinetics and safety of this approach, human growth hormone (hGH) was encapsulated in 600 μm long dissolving microneedles composed of carboxymethylcellulose and trehalose using an aqueous, moderate-temperature process that maintained complete hGH activity after encapsulation and retained most activity after storage for up to 15 months at room temperature and humidity. After manual insertion into the skin of hairless rats, hGH pharmacokinetics were similar to conventional subcutaneous injection. After patch removal, the microneedles had almost completely dissolved, leaving behind only blunt stubs. The dissolving microneedle patch was well tolerated, causing only slight, transient erythema. This study suggests that a dissolving microneedle patch can deliver hGH and other biopharmaceuticals in a manner suitable for self-administration without sharp biohazardous waste. PMID:21360810

  9. Antiepileptic drugs and intrauterine death

    DEFF Research Database (Denmark)

    Tomson, Torbjörn; Battino, Dina; Bonizzoni, Erminio

    2015-01-01

    ) after prenatal AED exposure. Using EURAP data, we prospectively monitored pregnancies exposed to the 6 most common AED monotherapies and to polytherapy. Intrauterine death (spontaneous abortion and stillbirth combined) was the primary endpoint. RESULTS: Of 7,055 pregnancies exposed to monotherapy...... with lamotrigine (n = 1,910), carbamazepine (n = 1,713), valproic acid (n = 1,171), levetiracetam (n = 324), oxcarbazepine (n = 262), or phenobarbital (n = 260), and to polytherapy (n = 1,415), 632 ended in intrauterine deaths (592 spontaneous abortions and 40 stillbirths). Rates of intrauterine death were similar...... that the risk was greater with polytherapy vs monotherapy (risk ratio [RR] 1.38; 95% CI 1.14-1.66), parental history of MCMs (RR 1.92; 1.20-3.07), maternal age (RR 1.06; 1.04-1.07), and number of previous intrauterine deaths (RR 1.09; 1.00-1.19). The risk was greater with early enrollment and decreased...

  10. [Delivery of the IUGR fetus].

    Science.gov (United States)

    Perrotin, F; Simon, E G; Potin, J; Laffon, M

    2013-12-01

    The purpose of this paper is to review available data regarding the management of delivery in intra uterine growth retarded fetuses and try to get recommendations for clinical obstetrical practice. Bibliographic research performed by consulting PubMed database and recommendations from scientific societies with the following words: small for gestational age, intra-uterine growth restriction, fetal growth restriction, very low birth weight infants, as well as mode of delivery, induction of labor, cesarean section and operative delivery. The diagnosis of severe IUGR justifies the orientation of the patient to a referral centre with all necessary resources for very low birth weight or premature infants Administration of corticosteroids for fetal maturation (before 34 WG) and a possible neuroprotective treatment by with magnesium sulphate (before 32-33 WG) should be discussed. Although elective caesarean section is common, there is no current evidence supporting the use of systematic cesarean section, especially when the woman is in labor. Induction of labor, even with unfavorable cervix is possible under continuous FHR monitoring, in favorable obstetric situations and in the absence of severe fetal hemodynamic disturbances. Instrumental delivery and routine episiotomy are not recommended. For caesarean section under spinal anesthesia, an adequate anesthetic management must ensure the maintenance of basal blood pressure. Compared with appropriate for gestational age fetus, IUGR fetus is at increased risk of metabolic acidosis or perinatal asphyxia during delivery. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  11. Cesarean Delivery for a Life‑threatening Preterm Placental Abruption

    African Journals Online (AJOL)

    exact etiology is still unclear, however, associated risk factors include maternal hypertension, advanced maternal age, polyhydramnios, multiparity, abdominal trauma, intrauterine growth restriction, intrauterine infection, premature rupture of membranes, threatened miscarriage, and cocaine abuse.[6]. According to Sher and ...

  12. Ted (G.J.) Kloosterman: on intrauterine growth. The significance of prenatal care. Studies on birth weight, placental weight and placental index.

    Science.gov (United States)

    Bleker, O P; Buimer, M; van der Post, J A M; van der Veen, F

    2006-01-01

    In the last century, there was a heated debate on whether fetal growth retardation is caused by a small placenta or whether a placenta is small because the baby is small. One of the active participants in this debate was Kloosterman who studied 80,000 birth weights, and 30,000 placental weights, in relation to gestational age at birth, fetal sex, maternal parity, and perinatal mortality. He found that pregnancies related to heavier placentas last longer. He also found that, from about 32 weeks of gestation onwards, children from primiparous women as compared to those from multiparous women, like twin children as compared to singleton children, are relatively growth retarded, most likely related to prior relatively poor placental growth. He concluded that poor fetal growth is not the cause, but the result of poor placental growth. The clinical implication of all these is that future early detection of poor placental growth may prospect poor fetal growth, and may even allow for early interventions to improve fetal outcome.

  13. Intrauterine Insemination: Fundamentals Revisited.

    Science.gov (United States)

    Allahbadia, Gautam N

    2017-12-01

    Intrauterine insemination (IUI) is an assisted conception technique that involves the deposition of a processed semen sample in the upper uterine cavity, overcoming natural barriers to sperm ascent in the female reproductive tract. It is a cost-effective, noninvasive first-line therapy for selected patients with functionally normal tubes, and infertility due to a cervical factor, anovulation, moderate male factor, unexplained factors, immunological factor, and ejaculatory disorders with clinical pregnancy rates per cycle ranging from 10 to 20%. It, however, has limited use in patients with endometriosis, severe male factor infertility, tubal factor infertility, and advanced maternal age ≥ 35 years. IUI may be performed with or without ovarian stimulation. Controlled ovarian stimulation, particularly with low-dose gonadotropins, with IUI offers significant benefit in terms of pregnancy outcomes compared with natural cycle or timed intercourse, while reducing associated COH complications such as multiple pregnancies and ovarian hyperstimulation syndrome. Important prognostic indicators of success with IUI include age of patient, duration of infertility, stimulation protocol, infertility etiology, number of cycles, timing of insemination, number of preovulatory follicles on the day of hCG, processed total motile sperm > 10 million, and insemination count > 1 × 106 with > 4% normal spermatozoa. Alternative insemination techniques, such as Fallopian tube sperm perfusion, intracervical insemination, and intratubal insemination, provide no additional benefit compared to IUI. A complete couple workup that includes patient history, physical examination, and clinical and laboratory investigations is mandatory to justify the choice in favor of IUI and guide alternative patient management, while individualizing the treatment protocol according to the patient characteristics with a strict cancelation policy to limit multi-follicular development may help optimize IUI

  14. Fundal Height: An Accurate Indicator of Fetal Growth?

    Science.gov (United States)

    ... could indicate conditions such as: Slow fetal growth (intrauterine growth restriction) A significantly larger than average baby (fetal macrosomia) ... Butler Tobah, M.D. Figueras F, et al. Intrauterine growth restriction: New concepts in antenatal surveillance, diagnosis, and management. ...

  15. The role of insulin-like growth factor in prediction and prevention of preterm delivery

    Directory of Open Access Journals (Sweden)

    Bogavac Mirjana

    2010-01-01

    Full Text Available Background/Aim. Prediction and prevention of preterm delivery remain great challenge. It is important to include in everyday medical practice determination of certain markers that could help identifying pregnant women with preterm delivery. Insulin like growth factor (IGF is involved in the control mechanism of fetal and placental growth and development. The aim of this study was to examine the presence of insulin-like growth factor binding protein 1 (IGFBP-1 in cervicovaginal secretion of pregnant women with symptoms of preterm labor, but with apparently intact fetal membranes and to point out a possible application of the strip test for detection of phIGFBP-1 in diagnosis of preterm premature rupture of total membranes (PPROM in everyday medical practice. Methods. The study was performed at the Department for Obstetrics and Gynecology, Clinical Center of Vojvodina between October 2008 and May 2009. The study included 54 pregnant women between 20-35 weeks of gestation (WG, divided into two groups: the study group (16 pregnant women with symptoms of preterm delivery that gave birth before 37 WG and the control group (38 pregnant women with the normal course of pregnancy that gave birth on term. In cervicovaginal secretion of the examined pregnant women the level of IGFBP-1 was determined by the immunochromatographic assay with monoclonal antibodies 6303 as a detecting antibody (Actim PROM test, Medix Biochemica, Kauniainen, Finland. Results. Gestational age (GA at delivery in the study group was 32.6 WG and in the control group it was 38.4 WG. Weight of newborns in the study group was 2,021 g and in the control group 3,430 g. IGFBP test was positive in 15 women (93.75% of the study group, while in the control group it was positive only in 1 woman (2.63%. Conclusion. Test on phIGFBP-1 in cervicovaginal mucus was positive in 93.75% women with preterm delivery, suggesting that this test could be used in diagnosis of silent rupture of fetal

  16. Intrauterine hypoxia: clinical consequences and therapeutic perspectives

    Directory of Open Access Journals (Sweden)

    Thompson LP

    2015-09-01

    Full Text Available Loren P Thompson,1 Sarah Crimmins,1 Bhanu P Telugu,2 Shifa Turan1 1Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA; 2Department of Animal Sciences, University of Maryland, College Park, MD, USA Abstract: Intrauterine hypoxia is a significant clinical challenge in obstetrics that affects both the pregnant mother and fetus. Intrauterine hypoxia can occur in pregnant women living at high altitude and/or with cardiovascular disease. In addition, placental hypoxia can be generated by altered placental development and spiral artery remodeling leading to placental insufficiency and dysfunction. Both conditions can impact normal maternal cardiovascular homeostasis leading to preeclampsia and/or impair transfer of O2/nutrient supply resulting in fetal growth restriction. This review discusses the mechanisms underlying altered placental vessel remodeling, maternal and fetal consequences, patient management, and potential future therapies for improving these conditions. Keywords: fetal growth restriction, oxidative stress, extravillous trophoblast invasion, Doppler ultrasound, pulsatility index, preeclampsia 

  17. Nanotechnological strategies for nerve growth factor delivery: Therapeutic implications in Alzheimer's disease.

    Science.gov (United States)

    Faustino, Célia; Rijo, Patrícia; Reis, Catarina Pinto

    2017-06-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with amyloid-β peptide misfolding and aggregation. Neurotrophic factors, such as nerve growth factor (NGF), can prevent neuronal damage and rescue the cholinergic neurons that undergo cell death in AD, reverse deposition of extracellular amyloid plaques and improve cognitive deficits. However, NGF administration is hampered by the poor pharmacokinetic profile of the therapeutic protein and its inability to cross the blood-brain barrier, which requires specialised drug delivery systems (DDS) for efficient NGF delivery to the brain. This review covers the main therapeutic approaches that have been developed for NGF delivery targeting the brain, from polymeric implants to gene and cell-based therapies, focusing on the role of nanoparticulate systems for the sustained release of NGF in the brain as a neuroprotective and disease-modifying approach toward AD. Lipid- and polymer-based delivery systems, magnetic nanoparticles and quantum dots are specifically addressed as promising nanotechnological strategies to overcome the current limitations of NGF-based therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Management of foetal asphyxia by intrauterine foetal resuscitation

    Science.gov (United States)

    Velayudhareddy, S.; Kirankumar, H

    2010-01-01

    Management of foetal distress is a subject of gynaecological interest, but an anaesthesiologist should know about resuscitation, because he should be able to treat the patient, whenever he is directly involved in managing the parturient patient during labour analgesia and before an emergency operative delivery. Progressive asphyxia is known as foetal distress; the foetus does not breathe directly from the atmosphere, but depends on maternal circulation for its oxygen requirement. The oxygen delivery to the foetus depends on the placental (maternal side), placental transfer and foetal circulation. Oxygen transport to the foetus is reduced physiologically during uterine contractions in labour. Significant impairment of oxygen transport to the foetus, either temporary or permanent may cause foetal distress, resulting in progressive hypoxia and acidosis. Intrauterine foetal resuscitation comprises of applying measures to a mother in active labour, with the intention of improving oxygen delivery to the distressed foetus to the base line, if the placenta is functioning normally. These measures include left lateral recumbent position, high flow oxygen administration, tocolysis to reduce uterine contractions, rapid intravenous fluid administration, vasopressors for correction of maternal hypotension and amnioinfusion for improving uterine blood flow. Intrauterine Foetal Resuscitation measures are easy to perform and do not require extensive resources, but the results are encouraging in improving the foetal well-being. The anaesthesiologist plays a major role in the application of intrauterine foetal resuscitation measures. PMID:21189876

  19. Management of foetal asphyxia by intrauterine foetal resuscitation

    Directory of Open Access Journals (Sweden)

    S Velayudhareddy

    2010-01-01

    Full Text Available Management of foetal distress is a subject of gynaecological interest, but an anaesthesiologist should know about resuscitation, because he should be able to treat the patient, whenever he is directly involved in managing the parturient patient during labour analgesia and before an emergency operative delivery. Progressive asphyxia is known as foetal distress; the foetus does not breathe directly from the atmosphere, but depends on maternal circulation for its oxygen requirement. The oxygen delivery to the foetus depends on the placental (maternal side, placental transfer and foetal circulation. Oxygen transport to the foetus is reduced physiologically during uterine contractions in labour. Significant impairment of oxygen transport to the foetus, either temporary or permanent may cause foetal distress, resulting in progressive hypoxia and acidosis. Intrauterine foetal resuscitation comprises of applying measures to a mother in active labour, with the intention of improving oxygen delivery to the distressed foetus to the base line, if the placenta is functioning normally. These measures include left lateral recumbent position, high flow oxygen administration, tocolysis to reduce uterine contractions, rapid intravenous fluid administration, vasopressors for correction of maternal hypotension and amnioinfusion for improving uterine blood flow. Intrauterine Foetal Resuscitation measures are easy to perform and do not require extensive resources, but the results are encouraging in improving the foetal well-being. The anaesthesiologist plays a major role in the application of intrauterine foetal resuscitation measures.

  20. Cluster analysis to estimate the risk of preeclampsia in the high-risk Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) study

    Science.gov (United States)

    Marttinen, Pekka; Gillberg, Jussi; Lokki, A. Inkeri; Majander, Kerttu; Ordén, Maija-Riitta; Taipale, Pekka; Pesonen, Anukatriina; Räikkönen, Katri; Hämäläinen, Esa; Kajantie, Eero; Laivuori, Hannele

    2017-01-01

    Objectives Preeclampsia is divided into early-onset (delivery before 34 weeks of gestation) and late-onset (delivery at or after 34 weeks) subtypes, which may rise from different etiopathogenic backgrounds. Early-onset disease is associated with placental dysfunction. Late-onset disease develops predominantly due to metabolic disturbances, obesity, diabetes, lipid dysfunction, and inflammation, which affect endothelial function. Our aim was to use cluster analysis to investigate clinical factors predicting the onset and severity of preeclampsia in a cohort of women with known clinical risk factors. Methods We recruited 903 pregnant women with risk factors for preeclampsia at gestational weeks 12+0–13+6. Each individual outcome diagnosis was independently verified from medical records. We applied a Bayesian clustering algorithm to classify the study participants to clusters based on their particular risk factor combination. For each cluster, we computed the risk ratio of each disease outcome, relative to the risk in the general population. Results The risk of preeclampsia increased exponentially with respect to the number of risk factors. Our analysis revealed 25 number of clusters. Preeclampsia in a previous pregnancy (n = 138) increased the risk of preeclampsia 8.1 fold (95% confidence interval (CI) 5.7–11.2) compared to a general population of pregnant women. Having a small for gestational age infant (n = 57) in a previous pregnancy increased the risk of early-onset preeclampsia 17.5 fold (95%CI 2.1–60.5). Cluster of those two risk factors together (n = 21) increased the risk of severe preeclampsia to 23.8-fold (95%CI 5.1–60.6), intermediate onset (delivery between 34+0–36+6 weeks of gestation) to 25.1-fold (95%CI 3.1–79.9) and preterm preeclampsia (delivery before 37+0 weeks of gestation) to 16.4-fold (95%CI 2.0–52.4). Body mass index over 30 kg/m2 (n = 228) as a sole risk factor increased the risk of preeclampsia to 2.1-fold (95%CI 1.1–3

  1. Ted (G.J.) Kloosterman: on intrauterine growth. The significance of prenatal care. Studies on birth weight, placental weight and placental index

    NARCIS (Netherlands)

    Bleker, O. P.; Buimer, M.; van der Post, J. A. M.; van der Veen, F.

    2006-01-01

    In the last century, there was a heated debate on whether fetal growth retardation is caused by a small placenta or whether a placenta is small because the baby is small. One of the active participants in this debate was Kloosterman who studied 80,000 birth weights, and 30,000 placental weights, in

  2. Ethanol-induced impairment of polyamine homeostasis – A potential cause of neural tube defect and intrauterine growth restriction in fetal alcohol syndrome

    International Nuclear Information System (INIS)

    Haghighi Poodeh, Saeid; Alhonen, Leena; Salonurmi, Tuire; Savolainen, Markku J.

    2014-01-01

    Highlights: • Polyamine pools in embryonic and extraembryonic tissues are developmentally regulated. • Alcohol administration perturbs polyamine levels in the tissues with various patterns. • Total absence of polyamines in the embryo head at 9.5 dpc is critical for development. • The deficiency is associated with reduction in endothelial cell sprouting in the head. • Retarded migration of neural crest cells may cause development of neural tube defect. - Abstract: Introduction: Polyamines play a fundamental role during embryogenesis by regulating cell growth and proliferation and by interacting with RNA, DNA and protein. The polyamine pools are regulated by metabolism and uptake from exogenous sources. The use of certain inhibitors of polyamine synthesis causes similar defects to those seen in alcohol exposure e.g. retarded embryo growth and endothelial cell sprouting. Methods: CD-1 mice received two intraperitoneal injections of 3 g/kg ethanol at 4 h intervals 8.75 days post coitum (dpc). The fetal head, trunk, yolk sac and placenta were collected at 9.5 and 12.5 dpc and polyamine concentrations were determined. Results: No measurable quantity of polyamines could be detected in the embryo head at 9.5 dpc, 12 h after ethanol exposure. Putrescine was not detectable in the trunk of the embryo at that time, whereas polyamines in yolk sac and placenta were at control level. Polyamine deficiency was associated with slow cell growth, reduction in endothelial cell sprouting, an altered pattern of blood vessel network formation and consequently retarded migration of neural crest cells and growth restriction. Discussion: Our results indicate that the polyamine pools in embryonic and extraembryonic tissues are developmentally regulated. Alcohol administration, at the critical stage, perturbs polyamine levels with various patterns, depending on the tissue and its developmental stage. The total absence of polyamines in the embryo head at 9.5 dpc may explain why this

  3. Ethanol-induced impairment of polyamine homeostasis – A potential cause of neural tube defect and intrauterine growth restriction in fetal alcohol syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Haghighi Poodeh, Saeid, E-mail: saeid.haghighi@oulu.fi [Institute of Clinical Medicine, Department of Internal Medicine, and Biocenter Oulu, University of Oulu, Oulu (Finland); Medical Research Center, Oulu University Hospital, Oulu (Finland); Alhonen, Leena [Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, Kuopio (Finland); School of Pharmacy, Biocenter Kuopio, University of Eastern Finland, Kuopio (Finland); Salonurmi, Tuire; Savolainen, Markku J. [Institute of Clinical Medicine, Department of Internal Medicine, and Biocenter Oulu, University of Oulu, Oulu (Finland); Medical Research Center, Oulu University Hospital, Oulu (Finland)

    2014-03-28

    Highlights: • Polyamine pools in embryonic and extraembryonic tissues are developmentally regulated. • Alcohol administration perturbs polyamine levels in the tissues with various patterns. • Total absence of polyamines in the embryo head at 9.5 dpc is critical for development. • The deficiency is associated with reduction in endothelial cell sprouting in the head. • Retarded migration of neural crest cells may cause development of neural tube defect. - Abstract: Introduction: Polyamines play a fundamental role during embryogenesis by regulating cell growth and proliferation and by interacting with RNA, DNA and protein. The polyamine pools are regulated by metabolism and uptake from exogenous sources. The use of certain inhibitors of polyamine synthesis causes similar defects to those seen in alcohol exposure e.g. retarded embryo growth and endothelial cell sprouting. Methods: CD-1 mice received two intraperitoneal injections of 3 g/kg ethanol at 4 h intervals 8.75 days post coitum (dpc). The fetal head, trunk, yolk sac and placenta were collected at 9.5 and 12.5 dpc and polyamine concentrations were determined. Results: No measurable quantity of polyamines could be detected in the embryo head at 9.5 dpc, 12 h after ethanol exposure. Putrescine was not detectable in the trunk of the embryo at that time, whereas polyamines in yolk sac and placenta were at control level. Polyamine deficiency was associated with slow cell growth, reduction in endothelial cell sprouting, an altered pattern of blood vessel network formation and consequently retarded migration of neural crest cells and growth restriction. Discussion: Our results indicate that the polyamine pools in embryonic and extraembryonic tissues are developmentally regulated. Alcohol administration, at the critical stage, perturbs polyamine levels with various patterns, depending on the tissue and its developmental stage. The total absence of polyamines in the embryo head at 9.5 dpc may explain why this

  4. Numerical simulations of crystal growth in a transdermal drug delivery system

    Science.gov (United States)

    Zeng, Jianming; Jacob, Karl I.; Tikare, Veena

    2004-02-01

    Grain growth by precipitation and Ostwald ripening in an unstressed matrix of a dissolved crystallizable component was simulated using a kinetic Monte Carlo model. This model was used previously to study Ostwald ripening in the high crystallizable component regime and was shown to correctly simulate solution, diffusion and precipitation. In this study, the same model with modifications was applied to the low crystallizable regime of interest to the transdermal drug delivery system (TDS) community. We demonstrate the model's utility by simulating precipitation and grain growth during isothermal storage at different supersaturation conditions. The simulation results provide a first approximation for the crystallization occurring in TDS. It has been reported that for relatively higher temperature growth of drug crystals in TDS occurs only in the middle third of the polymer layer. The results from the simulations support these findings that crystal growth is limited to the middle third of the region, where the availability of crystallizable components is the highest, for cluster growth at relatively high temperature.

  5. Care-Related and Maternal Risk Factors Associated with the Antenatal Nondetection of Intrauterine Growth Restriction: A Case-Control Study from Bremen, Germany

    Directory of Open Access Journals (Sweden)

    Sinja Alexandra Ernst

    2017-01-01

    Full Text Available Objective. To identify care-related and maternal risk factors for the antenatal nondetection of IUGR. Methods. In this hospital-based case-control study we compared antenatally undetected IUGR neonates (cases to detected IUGR neonates (controls. Data were collected using newborn documentation sheets and standardized personal interviews with the mothers. We calculated antenatal detection rates and used uni- and multivariable logistic regression models to assess the association of antenatal nondetection of IUGR and maternal and care-related factors. Results. A total of 161 neonates from three hospitals were included in the study. Suboptimal fetal growth was identified antenatally in n=77 pregnancies while in n=84 it was not detected antenatally (antenatal detection rate: 47.8%. Severity of IUGR, maternal complications, and a Doppler examination during the course of pregnancy were associated with IUGR detection. We did not find statistically significant differences regarding parental socioeconomic status and maternal migration background. Conclusions. In our study, about half of all pregnancies affected by suboptimal growth remained undetected. Future in-depth studies with larger study populations should further examine factors that could increase antenatal detection rates for IUGR.

  6. Disturbances in Maternal Steroidogenesis and Appearance of Intrauterine Growth Retardation at High-Altitude Environments Are Established from Early Pregnancy. Effects of Treatment with Antioxidant Vitamins.

    Directory of Open Access Journals (Sweden)

    Victor H Parraguez

    Full Text Available Pregnancies at high-altitudes are influenced by hypoxia and oxidative stress and frequently affected by IUGR. However, a common thought is that early pregnant women visiting altitude have no major complications for gestation development, since IUGR is developed during the second half of pregnancy. Thus, using a well-characterized sheep-model, we aimed to determine whether long- and/or short-term exposure to high-altitude may affect maternal steroidogenesis and therefore embryo-fetal growth from conception. The second aim was to differentiate the relative role of hypoxia and oxidative stress by assessing the effects of supplementation with antioxidant agents during this early-pregnancy stage, which were previously found to be useful to prevent IUGR. The results indicate that both long- and short-term exposure to high-altitude causes disturbances in maternal ovarian steroidogenesis and negatively affects embryo-fetal growth already during the very early stages of gestation, with the consequences being even worsened in newcomers to high-altitude. The supply of antioxidant during this period only showed discrete effects for preventing IUGR. In conclusion, the present study gives a warning for clinicians about the risks for early-pregnant women when visiting high-altitude regions and suggests the need for further studies on the effects of the length of exposure and on the interaction of the exposure with the pregnancy stage.

  7. Intrauterine nutrition: long-term consequences for vascular health

    Directory of Open Access Journals (Sweden)

    Szostak-Wegierek D

    2014-07-01

    Full Text Available Dorota Szostak-WegierekDepartment of Human Nutrition, Medical University of Warsaw, Warsaw, Poland Abstract: There is a growing body of evidence that improper intrauterine nutrition may negatively influence vascular health in later life. Maternal malnutrition may result in intrauterine growth retardation and, in turn, metabolic disorders such as insulin resistance, diabetes, hypertension, and dyslipidemia, and also enhanced risk of atherosclerosis and cardiovascular death in the offspring. Energy and/or protein restriction is the most critical determinant for fetal programming. However, it has also been proposed that intrauterine n-3 fatty acid deficiency may be linked to later higher blood pressure levels and reduced insulin sensitivity. Moreover, it has been shown that inadequate supply of micronutrients such as folate, vitamin B12, vitamin A, iron, magnesium, zinc, and calcium may contribute to impaired vascular health in the progeny. In addition, hypertensive disorders of pregnancy that are linked to impaired placental blood flow and suboptimal fetal nutrition may also contribute to intrauterine growth retardation and aggravated cardiovascular risk in the offspring. On the other hand, maternal overnutrition, which often contributes to obesity and/or diabetes, may result in macrosomia and enhanced cardiometabolic risk in the offspring. Progeny of obese and/or diabetic mothers are relatively more prone to develop obesity, insulin resistance, diabetes, and hypertension. It was demonstrated that they may have permanently enhanced appetites. Their atheromatous lesions are usually more pronounced. It seems that, particularly, a maternal high-fat/junk food diet may be detrimental for vascular health in the offspring. Fetal exposure to excessive levels of saturated fatty and/or n-6 fatty acids, sucrose, fructose and salt, as well as a maternal high glycemic index diet, may also contribute to later enhanced cardiometabolic risk. Keywords: maternal

  8. Limited Uptake of Planned Intrauterine Devices During the Postpartum Period.

    Science.gov (United States)

    Salcedo, Jennifer; Moniaga, Natalie; Harken, Tabetha

    2015-08-01

    The primary objective of this study was to determine the percentage of women with a documented plan for postpartum intrauterine device (IUD) insertion who had a device inserted within 8 weeks of delivery. The secondary objective was to determine factors associated with successful initiation of postpartum IUDs as planned. We conducted a retrospective chart review of women who had at least one prenatal visit and delivered a viable pregnancy at our academic medical center. Methods of planned and established postpartum contraceptive methods were recorded, as well as demographic information and documented reasons for failure to initiate planned intrauterine contraception. A total of 110 women planned postpartum IUD placement. Of these women, 84 (76%) presented for at least one postpartum appointment. Only 22.6% (95% confidence interval 13.7-31.5) of those presenting for postpartum follow-up underwent IUD placement within 8 weeks of delivery. Women planning postpartum IUD insertion were just as likely as women with no planned postpartum contraceptive method to fail to establish contraception within 8 weeks (P = 0.55). Failure to establish planned postpartum intrauterine contraception occurs frequently, even in a setting with a high rate of postpartum follow-up.

  9. Enoxaparin for the prevention of preeclampsia and intrauterine growth restriction in women with a history: a randomized trial.

    Science.gov (United States)

    Groom, Katie M; McCowan, Lesley M; Mackay, Laura K; Lee, Arier C; Said, Joanne M; Kane, Stefan C; Walker, Susan P; van Mens, Thijs E; Hannan, Natalie J; Tong, Stephen; Chamley, Larry W; Stone, Peter R; McLintock, Claire

    2017-03-01

    Preeclampsia and small-for-gestational-age pregnancy are major causes of maternal and perinatal morbidity and mortality. Women with a previous pregnancy affected by these conditions are at an increased risk of recurrence in a future pregnancy. Past trials evaluating the effect of low-molecular-weight heparin for the prevention of recurrence of preeclampsia and small-for-gestational-age pregnancy have shown conflicting results with high levels of heterogeneity displayed when trials were compared. We sought to assess the effectiveness of enoxaparin in addition to high-risk care for the prevention of preeclampsia and small-for-gestational-age pregnancy in women with a history of these conditions. This was an open-label randomized controlled trial in 5 tertiary care centers in 3 countries. Women with a viable singleton pregnancy were invited to participate between >6 +0 and women with prior preeclampsia-calcium 1000-1500 mg daily until 36 +0 weeks. In a subgroup of participants serum samples were taken at recruitment and at 20 and 30 weeks' gestation and later analyzed for soluble fms-like tyrosine kinase-1, soluble endoglin, endothelin-1, placental growth factor, and soluble vascular cell adhesion molecule 1. The primary outcome was a composite of preeclampsia and/or small-for-gestational-age women who miscarried <16 weeks' gestation were excluded. The majority of participants (151/156, 97%) received aspirin. The addition of enoxaparin had no effect on the rate of preeclampsia and/or small-for-gestational-age <5th customized birthweight percentile: enoxaparin 18/72 (25%) vs no enoxaparin 17/77 (22.1%) (odds ratio, 1.19; 95% confidence interval, 0.53-2.64). There was also no difference in any of the secondary outcome measures. Levels of soluble fms-like tyrosine kinase-1 and soluble endoglin increased among those who developed preeclampsia, but there was no difference in levels of these antiangiogenic factors (nor any of the other serum analytes measured) among those

  10. Screening and triage of intrauterine growth restriction (IUGR in general population and high risk pregnancies: a systematic review with a focus on reduction of IUGR related stillbirths

    Directory of Open Access Journals (Sweden)

    Siddiqui Saad

    2011-04-01

    Full Text Available Abstract Background There is a strong association between stillbirth and fetal growth restriction. Early detection and management of IUGR can lead to reduce related morbidity and mortality. In this paper we have reviewed effectiveness of fetal movement monitoring and Doppler velocimetry for the detection and surveillance of high risk pregnancies and the effect of this on prevention of stillbirths. We have also reviewed effect of maternal body mass index (BMI screening, symphysial-fundal height measurement and targeted ultrasound in detection and triage of IUGR in the community. Methods We systematically reviewed all published literature to identify studies related to our interventions. We searched PubMed, Cochrane Library, and all World Health Organization Regional Databases and included publications in any language. Quality of available evidence was assessed using GRADE criteria. Recommendations were made for the Lives Saved Tool (LiST based on rules developed by the Child Health Epidemiology Group. Given the paucity of evidence related to the effect of detection and management of IUGR on stillbirths, we undertook Delphi based evaluation from experts in the field. Results There was insufficient evidence to recommend against or in favor of routine use of fetal movement monitoring for fetal well being. (1 Detection and triage of IUGR with the help of (1a maternal BMI screening, (1b symphysial-fundal height measurement and (1c targeted ultrasound can be an effective method of reducing IUGR related perinatal morbidity and mortality. Pooled results from sixteen studies shows that Doppler velocimetry of umbilical and fetal arteries in ‘high risk’ pregnancies, coupled with the appropriate intervention, can reduce perinatal mortality by 29 % [RR 0.71, 95 % CI 0.52-0.98]. Pooled results for impact on stillbirth showed a reduction of 35 % [RR 0.65, 95 % CI 0.41-1.04]; however, the results did not reach the conventional limits of statistical

  11. Hysteroscopic Management Of Intrauterin Adhesion

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    Ayşegül Dikmen

    2013-03-01

    Full Text Available Objective: Assessment of preoperative and postoperative outcomes of patients that were performed hysterescopic intrauterine adhesiolysis. Material and method: We reviewed 24 patients that underwent hysterescopy with the complaints of amenorrhea, hypomenorrhea, recurrent pregnancy loss between 2004-2008. The most complaints of patients were infertilty amenorrhea. Results: Adhesions occurs mainly as a result of trauma to the gravid uterine cavity in 14 patients. When classifying patients with their intrauterine adhesions, Grade 3 was the most frequently seen. Adhesiolisis was performed with hysteresopic scissors in all patients. In postoperative period following synechiolysis, 10 patients were treated with estrogen and progestogen, 11 of them used intrauterine device with estrogen and progestogen therapy, foley catheter was used in 3 patients. Hysterescopy was performed in 5 patients for second time because of adhesion suspicions. The re-adhesiolysis performed to 3 patients because of determined to mild adhesion. Conclusion: After hysterescopic adhesiolysis, all patients with the complaint of amenorrhea had regular menstruation. Pregnancy after treatment occured in 4 patients but live birth rate was 75%.

  12. Blends of synthetic and natural polymers as drug delivery systems for growth hormone.

    Science.gov (United States)

    Cascone, M G; Sim, B; Downes, S

    1995-05-01

    In order to overcome the biological deficiencies of synthetic polymers and to enhance the mechanical characteristics of natural polymers, two synthetic polymers, poly(vinyl alcohol) (PVA) and poly(acrylic acid) (PAA) were blended, in different ratios, with two biological polymers, collagen (C) and hyaluronic acid (HA). These blends were used to prepare films, sponges and hydrogels which were loaded with growth hormone (GH) to investigate their potential use as drug delivery systems. The GH release was monitored in vitro using a specific enzyme-linked immunosorbent assay. The results show that GH can be released from HA/PAA sponges and from HA/PVA and C/PVA hydrogels. The initial GH concentration used for sample loading affected the total quantity of GH released but not the pattern of release. The rate and quantity of GH released was significantly dependent on the HA or C content of the polymers.

  13. Intrauterine Devices Penetrated and Migrated: CT Findings

    International Nuclear Information System (INIS)

    Mejia Restrepo, Jorge; Lopez, Juan Esteban; Aldana Sepulveda, Natalia; Ruiz Zabaleta, Tania; Mazzaro Mauricio

    2011-01-01

    Intrauterine devices have been used for over 40 years, and they constitute the most widely accepted method of contraception among women because of the low rates of complications and low cost. Although uncommon, with the growing use of multidetector CT penetrated and migrated intrauterine devices have become a more common incidental finding. In some cases, intrauterine devices migrate to adjacent viscera, in particular the bladder and bowel and may give rise to symptoms. Consequently tomographic localization and characterization are essential for treatment planning.

  14. Pregnancy-specific stress, fetoplacental haemodynamics, and neonatal outcomes in women with small for gestational age pregnancies: a secondary analysis of the multicentre Prospective Observational Trial to Optimise Paediatric Health in Intrauterine Growth Restriction.

    Science.gov (United States)

    Levine, Terri A; Grunau, Ruth E; Segurado, Ricardo; Daly, Sean; Geary, Michael P; Kennelly, Mairead M; O'Donoghue, Keelin; Hunter, Alyson; Morrison, John J; Burke, Gerard; Dicker, Patrick; Tully, Elizabeth C; Malone, Fergal D; Alderdice, Fiona A; McAuliffe, Fionnuala M

    2017-06-21

    To examine associations between maternal pregnancy-specific stress and umbilical (UA PI) and middle cerebral artery pulsatility indices (MCA PI), cerebroplacental ratio, absent end diastolic flow (AEDF), birthweight, prematurity, neonatal intensive care unit admission and adverse obstetric outcomes in women with small for gestational age pregnancies. It was hypothesised that maternal pregnancy-specific stress would be associated with fetoplacental haemodynamics and neonatal outcomes. This is a secondary analysis of data collected for a large-scale prospective observational study. This study was conducted in the seven major obstetric hospitals in Ireland and Northern Ireland. Participants included 331 women who participated in the Prospective Observational Trial to Optimise Paediatric Health in Intrauterine Growth Restriction. Women with singleton pregnancies between 24 and 36 weeks gestation, estimated fetal weight <10th percentile and no major structural or chromosomal abnormalities were included. Serial Doppler ultrasound examinations of the umbilical and middle cerebral arteries between 20 and 42 weeks gestation, Pregnancy Distress Questionnaire (PDQ) scores between 23 and 40 weeks gestation and neonatal outcomes. Concerns about physical symptoms and body image at 35-40 weeks were associated with lower odds of abnormal UAPI (OR 0.826, 95% CI 0.696 to 0.979, p=0.028). PDQ score (OR 1.073, 95% CI 1.012 to 1.137, p=0.017), concerns about birth and the baby (OR 1.143, 95% CI 1.037 to 1.260, p=0.007) and concerns about physical symptoms and body image (OR 1.283, 95% CI 1.070 to 1.538, p=0.007) at 29-34 weeks were associated with higher odds of abnormal MCA PI. Concerns about birth and the baby at 29-34 weeks (OR 1.202, 95% CI 1.018 to 1.421, p=0.030) were associated with higher odds of AEDF. Concerns about physical symptoms and body image at 35-40 weeks were associated with decreased odds of neonatal intensive care unit admission (OR 0.635, 95% CI 0

  15. Efficacy of Intrauterine Device in the Treatment of Intrauterine Adhesions

    Directory of Open Access Journals (Sweden)

    Umme Salma

    2014-01-01

    Full Text Available The primary purpose of this paper is to assess the efficacy of the use of the intrauterine device (IUD as an adjunctive treatment modality, for intrauterine adhesions (IUAs. All eligible literatures were identified by electronic databases including PubMed, Scopus, and Web of Science. Additional relevant articles were identified from citations in these publications. There were 28 studies included for a systematic review. Of these, 5 studies were eligible for meta-analysis and 23 for qualitative assessment only. Twenty-eight studies related to the use of IUDs as ancillary treatment following adhesiolysis were identified. Of these studies, 25 studies at least one of the following methods were carried out as ancillary treatment: Foley catheter, hyaluronic acid gel, hormonal therapy, or amnion graft in addition to the IUD. There was one study that used IUD therapy as a single ancillary treatment. In 2 studies, no adjunctive therapy was used after adhesiolysis. There was a wide range of reported menstrual and fertility outcomes which were associated with the use of IUD combined with other ancillary treatments. At present, the IUD is beneficial in patients with IUA, regardless of stage of adhesions. However, IUD needs to be combined with other ancillary treatments to obtain maximal outcomes, in particular in patients with moderate to severe IUA.

  16. The relationship between maternal insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and IGFBP-3 to gestational age and preterm delivery.

    LENUS (Irish Health Repository)

    Cooley, Sharon M

    2010-05-01

    To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2), and insulin-like growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and gestational age at delivery.

  17. Long-term delivery of nerve growth factor by encapsulated cell biodelivery in the Göttingen minipig basal forebrain

    DEFF Research Database (Denmark)

    Fjord-Larsen, L; Kusk, P; Tornøe, Jens

    2010-01-01

    Nerve growth factor (NGF) prevents cholinergic degeneration in Alzheimer's disease (AD) and improves memory in AD animal models. In humans, the safe delivery of therapeutic doses of NGF is challenging. For clinical use, we have therefore developed an encapsulated cell (EC) biodelivery device...

  18. Importance of Maternal Diabetes on the Chronological Deregulation of the Intrauterine Development: An Experimental Study in Rat

    Science.gov (United States)

    Salazar García, Marcela; Reyes Maldonado, Elba; Revilla Monsalve, María Cristina; Villavicencio Guzmán, Laura; Reyes López, Alfonso; Sánchez-Gómez, Concepción

    2015-01-01

    We investigated whether maternal diabetes induced in rats using streptozotocin (STZ) on Day 5 of pregnancy affects the intrauterine developmental timeline. A total of 30 pregnant Sprague-Dawley diabetic rats (DRs) and 20 control rats (CRs) were used to obtain 21-day fetuses (F21) and newborn (NB) pups. Gestational age, weight, and body size were recorded as were the maxillofacial morphometry and morphohistological characteristics of the limbs. In DRs, pregnancy continued for ∼1.7 days, and delivery occurred 23 days postcoitus (DPC). In this group, the number of pups was lower, and 13% had maxillofacial defects. F21 in the DR group had lower weights and were smaller; moreover, the morphological characteristics of the maxillofacial structures, derived from the neural crest, were discordant with their chronological gestational age, resembling 18- to 19-day-old fetuses. These deficiencies were counterbalanced in NB pups. We conclude that hyperglycemia, which results from maternal diabetes and precedes embryo implantation, deregulates the intrauterine developmental timeline, restricts embryo-fetal growth, and primarily delays the remodeling and maturation of the structures derived from neural crest cells. PMID:25756053

  19. Importance of Maternal Diabetes on the Chronological Deregulation of the Intrauterine Development: An Experimental Study in Rat

    Directory of Open Access Journals (Sweden)

    Marcela Salazar García

    2015-01-01

    Full Text Available We investigated whether maternal diabetes induced in rats using streptozotocin (STZ on Day 5 of pregnancy affects the intrauterine developmental timeline. A total of 30 pregnant Sprague-Dawley diabetic rats (DRs and 20 control rats (CRs were used to obtain 21-day fetuses (F21 and newborn (NB pups. Gestational age, weight, and body size were recorded as were the maxillofacial morphometry and morphohistological characteristics of the limbs. In DRs, pregnancy continued for ∼1.7 days, and delivery occurred 23 days postcoitus (DPC. In this group, the number of pups was lower, and 13% had maxillofacial defects. F21 in the DR group had lower weights and were smaller; moreover, the morphological characteristics of the maxillofacial structures, derived from the neural crest, were discordant with their chronological gestational age, resembling 18- to 19-day-old fetuses. These deficiencies were counterbalanced in NB pups. We conclude that hyperglycemia, which results from maternal diabetes and precedes embryo implantation, deregulates the intrauterine developmental timeline, restricts embryo-fetal growth, and primarily delays the remodeling and maturation of the structures derived from neural crest cells.

  20. Inhibition of Xenograft tumor growth by gold nanoparticle-DNA oligonucleotide conjugates-assisted delivery of BAX mRNA.

    Directory of Open Access Journals (Sweden)

    Ji-Hyun Yeom

    Full Text Available Use of non-biological agents for mRNA delivery into living systems in order to induce heterologous expression of functional proteins may provide more advantages than the use of DNA and/or biological vectors for delivery. However, the low efficiency of mRNA delivery into live animals, using non-biological systems, has hampered the use of mRNA as a therapeutic molecule. Here, we show that gold nanoparticle-DNA oligonucleotide (AuNP-DNA conjugates can serve as universal vehicles for more efficient delivery of mRNA into human cells, as well as into xenograft tumors generated in mice. Injections of BAX mRNA loaded on AuNP-DNA conjugates into xenograft tumors resulted in highly efficient mRNA delivery. The delivered mRNA directed the efficient production of biologically functional BAX protein, a pro-apoptotic factor, consequently inhibiting tumor growth. These results demonstrate that mRNA delivery by AuNP-DNA conjugates can serve as a new platform for the development of safe and efficient gene therapy.

  1. Epidermal growth factor (EGF) as a potential targeting agent for delivery of boron to malignant gliomas

    International Nuclear Information System (INIS)

    Capala, J.; Barth, R.F.; Adams, D.M.; Bailey, M.Q.; Soloway, A.H.; Carlsson, J.

    1994-01-01

    The majority of high grade gliomas express an amplified epidermal growth factor receptor (EGFR) gene, and this often is associated with an increase in cell surface receptor expression. The rapid internalization and degradation of EGF-EGFR complexes, as well as their high affinity make EGF a potential targeting agent for delivery of 10 B to tumor cells with an amplified number of EGFR. Human glioma cells can expresses as many as 10 5 -10 6 EGF receptors per cell, and if these could be saturated with boronated EGF, then > 10 8 boron atoms would be delivered per cell. Since EGF has a comparatively low molecular weight (∼ 6 kD), this has allowed us to construct relatively small bioconjugates containing ∼ 900 boron atoms per EGF molecule 3 , which also had high affinity for EGFR on tumor cells. In the present study, the feasibility of using EGF receptors as a potential target for therapy of gliomas was investigated by in vivo scintigraphic studies using 131 I- or 99m T c -labeled EGF in a rat brain tumor model. Our results indicate that intratumorally delivered boron- EGF conjugates might be useful for targeting EGFR on glioma cells if the boron containing moiety of the conjugates persisted intracellularly. Further studies are required, however, to determine if this approach can be used for BNCT of the rat glioma

  2. Single chain Fc-dimer-human growth hormone fusion protein for improved drug delivery.

    Science.gov (United States)

    Zhou, Li; Wang, Hsuan-Yao; Tong, Shanshan; Okamoto, Curtis T; Shen, Wei-Chiang; Zaro, Jennica L

    2017-02-01

    Fc fusion protein technology has been successfully used to generate long-acting forms of several protein therapeutics. In this study, a novel Fc-based drug carrier, single chain Fc-dimer (sc(Fc) 2 ), was designed to contain two Fc domains recombinantly linked via a flexible linker. Since the Fc dimeric structure is maintained through the flexible linker, the hinge region was omitted to further stabilize it against proteolysis and reduce FcγR-related effector functions. The resultant sc(Fc) 2 candidate preserved the neonatal Fc receptor (FcRn) binding. sc(Fc) 2 -mediated delivery was then evaluated using a therapeutic protein with a short plasma half-life, human growth hormone (hGH), as the protein drug cargo. This novel carrier protein showed a prolonged in vivo half-life and increased hGH-mediated bioactivity compared to the traditional Fc-based drug carrier. sc(Fc) 2 technology has the potential to greatly advance and expand the use of Fc-technology for improving the pharmacokinetics and bioactivity of protein therapeutics. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Intrauterine growth restriction and differential patterns of hepatic growth and expression of IGF1, PCK2, and HSDL1 mRNA in the sheep fetus in late gestation.

    Science.gov (United States)

    Gentili, Sheridan; Morrison, Janna L; McMillen, I Caroline

    2009-06-01

    Fetal adaptations to periods of substrate deprivation can result in the programming of glucose intolerance, insulin resistance, and metabolic dysfunction in later life. Placental insufficiency can be associated with either sparing or sacrifice of fetal liver growth, and these different responses may have different metabolic consequences. It is unclear what intrahepatic mechanisms determine the differential responses of the fetal liver to substrate restriction. We investigated the effects of placental restriction (PR) on liver growth and the hepatic expression of SLC2A1, IGF1, IGF2, IGF1R, IGF2R, PPARGC1A, PPARA, PRKAA1, PRKAA2, PCK2, and HSDL1 mRNA in fetal sheep at 140-145 days of gestation. A mean gestational arterial partial pressure of oxygen less than 17 mmHg was defined as hypoxic, and a relative liver of weight more than 2 SD below the mean liver weight of controls was defined as reduced liver growth. Fetuses therefore were defined as control-normoxic (C-N; n = 9), PR-normoxic (PR-N; n = 7), PR-hypoxic (PR-H; n = 8), or PR-hypoxic reduced liver growth (PR-H RLG; n = 4). Hepatic SLC2A1 mRNA expression was highest (P fetal substrate restriction may exist that protect the liver from decreased growth and, potentially, from a decreased responsiveness to the actions of insulin in postnatal life.

  4. Diagnóstico precoce da restrição do crescimento fetal pela estimativa ultra-sonográfica do peso fetal Early diagnosis of intra-uterine growth restriction by ultrasonographic estimation of fetal weight

    Directory of Open Access Journals (Sweden)

    Maria Marta Martins

    2005-02-01

    disease, no history of addictions, gemellarity or malformed fetuses. All mothers performed ultrasonographic exams at the 25th and 27th weeks for estimation of the fetal weight. Results: The exams were able to detect the inadequate development of those fetuses small-for-gestational-age group. The cut-off values for echographic fetal weight were established as 775 grams and 1015 grams for the 25th and 27th weeks, respectively A mathematical model was developed, capable of quantifying the probability of newborns exhibiting insufficient intra-uterine growth, being small-for-gestational-age.

  5. A nanoparticulate injectable hydrogel as a tissue engineering scaffold for multiple growth factor delivery for bone regeneration

    Directory of Open Access Journals (Sweden)

    Dyondi D

    2012-12-01

    Full Text Available Deepti Dyondi,1 Thomas J Webster,2 Rinti Banerjee11Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra, India; 2Nanomedicine Laboratories, Division of Engineering and Department of Orthopedics, Brown University, Providence, RI, USAAbstract: Gellan xanthan gels have been shown to be excellent carriers for growth factors and as matrices for several tissue engineering applications. Gellan xanthan gels along with chitosan nanoparticles of 297 ± 61 nm diameter, basic fibroblast growth factor (bFGF, and bone morphogenetic protein 7 (BMP7 were employed in a dual growth factor delivery system to promote the differentiation of human fetal osteoblasts. An injectable system with ionic and temperature gelation was optimized and characterized. The nanoparticle loaded gels showed significantly improved cell proliferation and differentiation due to the sustained release of growth factors. A differentiation marker study was conducted, analyzed, and compared to understand the effect of single vs dual growth factors and free vs encapsulated growth factors. Dual growth factor loaded gels showed a higher alkaline phosphatase and calcium deposition compared to single growth factor loaded gels. The results suggest that encapsulation and stabilization of growth factors within nanoparticles and gels are promising for bone regeneration. Gellan xanthan gels also showed antibacterial effects against Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis, the common pathogens in implant failure.Keywords: bone tissue engineering, bone morphogenetic protein 7 (BMP7, basic fibroblast growth factor (bFGF, hydrogel, nanoparticles, osteoblasts

  6. Adverse Intrauterine Environment and Cardiac miRNA Expression

    Directory of Open Access Journals (Sweden)

    Mitchell C. Lock

    2017-12-01

    Full Text Available Placental insufficiency, high altitude pregnancies, maternal obesity/diabetes, maternal undernutrition and stress can result in a poor setting for growth of the developing fetus. These adverse intrauterine environments result in physiological changes to the developing heart that impact how the heart will function in postnatal life. The intrauterine environment plays a key role in the complex interplay between genes and the epigenetic mechanisms that regulate their expression. In this review we describe how an adverse intrauterine environment can influence the expression of miRNAs (a sub-set of non-coding RNAs and how these changes may impact heart development. Potential consequences of altered miRNA expression in the fetal heart include; Hypoxia inducible factor (HIF activation, dysregulation of angiogenesis, mitochondrial abnormalities and altered glucose and fatty acid transport/metabolism. It is important to understand how miRNAs are altered in these adverse environments to identify key pathways that can be targeted using miRNA mimics or inhibitors to condition an improved developmental response.

  7. Improving the Lung Delivery of Nasally Administered Aerosols During Noninvasive Ventilation—An Application of Enhanced Condensational Growth (ECG)

    Science.gov (United States)

    Tian, Geng; Hindle, Michael

    2011-01-01

    Abstract Background Aerosol drug delivery during noninvasive ventilation (NIV) is known to be inefficient due to high depositional losses. To improve drug delivery efficiency, the concept of enhanced condensational growth (ECG) was recently proposed in which a submicrometer or nanoaerosol reduces extrathoracic deposition and subsequent droplet size increase promotes lung retention. The objective of this study was to provide proof-of-concept that the ECG approach could improve lung delivery of nasally administered aerosols under conditions consistent with NIV. Methods Aerosol deposition and size increase were evaluated in an adult nose–mouth–throat (NMT) replica geometry using both in vitro experiments and CFD simulations. For the ECG delivery approach, separate streams of a submicrometer aerosol and warm (39°C) saturated air were generated and delivered to the right and left nostril inlets, respectively. A control case was also considered in which an aerosol with a mass median aerodynamic diameter (MMAD) of 4.67 μm was delivered to the model. Results In vitro experiments showed that the ECG approach significantly reduced the drug deposition fraction in the NMT geometry compared with the control case [14.8 (1.83)%—ECG vs. 72.6 (3.7)%—control]. Aerosol size increased from an initial MMAD of 900 nm to a size of approximately 2 μm at the exit of the NMT geometry. Results of the CFD model were generally in good agreement with the experimental findings. Based on CFD predictions, increasing the delivery temperature of the aerosol stream from 21 to 35°C under ECG conditions further reduced the total NMT drug deposition to 5% and maintained aerosol growth by ECG to approximately 2 μm. Conclusions Application of the ECG approach may significantly improve the delivery of pharmaceutical aerosols during NIV and may open the door for using the nasal route to routinely deliver pulmonary medications. PMID:21410327

  8. Intracellular protein delivery activity of peptides derived from insulin-like growth factor binding proteins 3 and 5

    International Nuclear Information System (INIS)

    Goda, Natsuko; Tenno, Takeshi; Inomata, Kosuke; Shirakawa, Masahiro; Tanaka, Toshiki; Hiroaki, Hidekazu

    2008-01-01

    Insulin-like growth factor binding proteins (IGFBPs) have various IGF-independent cellular activities, including receptor-independent cellular uptake followed by transcriptional regulation, although mechanisms of cellular entry remain unclear. Herein, we focused on their receptor-independent cellular entry mechanism in terms of protein transduction domain (PTD) activity, which is an emerging technique useful for clinical applications. The peptides of 18 amino acid residues derived from IGFBP-3 and IGFBP-5, which involve heparin-binding regions, mediated cellular delivery of an exogenous protein into NIH3T3 and HeLa cells. Relative protein delivery activities of IGFBP-3/5-derived peptides were approximately 20-150% compared to that of the HIV-Tat peptide, a potent PTD. Heparin inhibited the uptake of the fusion proteins with IGFBP-3 and IGFBP-5, indicating that the delivery pathway is heparin-dependent endocytosis, similar to that of HIV-Tat. The delivery of GST fused to HIV-Tat was competed by either IGFBP-3 or IGFBP-5-derived synthetic peptides. Therefore, the entry pathways of the three PTDs are shared. Our data has shown a new approach for designing protein delivery systems using IGFBP-3/5 derived peptides based on the molecular mechanisms of IGF-independent activities of IGFBPs

  9. Comparison of genital microbial isolates between intrauterine ...

    African Journals Online (AJOL)

    Background:In the past, the use of intrauterine contraceptive device (IUCD), in particular, Dalkon Shield was found to be associated with ... of these residing in Asia. .... to air dry, labeled and transferred to the laboratory for Gram staining.

  10. Low Cost, Simple, Intrauterine Insemination Procedure

    African Journals Online (AJOL)

    AJRH Managing Editor

    quite simple intrauterine insemination technique which may be performed in developing countries, without the need of sophisticated ... Cytoplasmic Sperm Injection (ICSI), are quite ... were administered only once by intramuscular injection ...

  11. Placental weight and birth weight to placental weight ratio in monochorionic and dichorionic growth-restricted and non-growth-restricted twins

    Directory of Open Access Journals (Sweden)

    Mariângela Alves Souza

    Full Text Available OBJECTIVE: The aim of the present study was to compare the placental weight and birth weight/placental weight ratio for intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins. METHODS: This was a retrospective analysis of placentas from twin pregnancies. Placental weight and the birth weight/placental weight ratio were compared in intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins. The association between cord insertion type and placental lesions in intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins was also investigated. RESULTS: A total of 105 monochorionic (intrauterine growth restriction=40; non-intrauterine growth restriction=65 and 219 dichorionic (intrauterine growth restriction=57; non-intrauterine growth restriction=162 placentas were analyzed. A significantly lower placental weight was observed in intrauterine growth-restricted monochorionic (p=0.022 and dichorionic (p<0.001 twins compared to non-intrauterine growth-restricted twins. There was no difference in the birth weight/placental weight ratio between the intrauterine growth restriction and non-intrauterine growth restriction groups for either monochorionic (p=0.36 or dichorionic (p=0.68 twins. Placental weight and the birth weight/placental weight ratio were not associated with cord insertion type or with placental lesions. CONCLUSION: Low placental weight, and consequently reduced functional mass, appears to be involved in fetal growth restriction in monochorionic and dichorionic twins. The mechanism by which low placental weight influences the birth weight/placental weight ratio in intrauterine growth-restricted monochorionic and dichorionic twins needs to be determined in larger prospective studies.

  12. Investigation of sequential growth factor delivery during cuprizone challenge in mice aimed to enhance oligodendrogliogenesis and myelin repair.

    Directory of Open Access Journals (Sweden)

    Jennifer K Sabo

    Full Text Available Repair in multiple sclerosis involves remyelination, a process in which axons are provided with a new myelin sheath by new oligodendrocytes. Bone morphogenic proteins (BMPs are a family of growth factors that have been shown to influence the response of oligodendrocyte progenitor cells (OPCs in vivo during demyelination and remyelination in the adult brain. We have previously shown that BMP4 infusion increases numbers of OPCs during cuprizone-induced demyelination, while infusion of Noggin, an endogenous antagonist of BMP4 increases numbers of mature oligodendrocytes and remyelinated axons following recovery. Additional studies have shown that insulin-like growth factor-1 (IGF-1 promotes the survival of OPCs during cuprizone-induced demyelination. Based on these data, we investigated whether myelin repair could be further enhanced by sequential infusion of these agents firstly, BMP4 to increase OPC numbers, followed by either Noggin or IGF-1 to increase the differentiation and survival of the newly generated OPCs. We identified that sequential delivery of BMP4 and IGF-1 during cuprizone challenge increased the number of mature oligodendrocytes and decreased astrocyte numbers following recovery compared with vehicle infused mice, but did not alter remyelination. However, sequential delivery of BMP4 and Noggin during cuprizone challenge did not alter numbers of oligodendrocytes or astrocytes in the corpus callosum compared with vehicle infused mice. Furthermore, electron microscopy analysis revealed no change in average myelin thickness in the corpus callosum between vehicle infused and BMP4-Noggin infused mice. Our results suggest that while single delivery of Noggin or IGF-1 increased the production of mature oligodendrocytes in vivo in the context of demyelination, only Noggin infusion promoted remyelination. Thus, sequential delivery of BMP4 and Noggin or IGF-1 does not further enhance myelin repair above what occurs with delivery of Noggin

  13. Successful Vaginal Delivery despite a Huge Ovarian Mucinous Cystadenoma Complicating Pregnancy: A Case Report

    Directory of Open Access Journals (Sweden)

    Dipak Mandi

    2013-12-01

    Full Text Available A 22-year-old patient with 9 months of amenorrhea and a huge abdominal swelling was admitted to our institution with an ultrasonography report of a multiloculated cystic space-occupying lesion, almost taking up the whole abdomen (probably of ovarian origin, along with a single live intrauterine fetus. She delivered vaginally a boy baby within 4 hours of admission without any maternal complication, but the baby had features of intrauterine growth restriction along with low birth weight. On the 8th postpartum day, the multiloculated cystic mass, which arose from the right ovary and weighed about 11 kg, was removed via laparotomy. A mucinous cystadenoma with no malignant cells in peritoneal washing was detected in histopathology examination. This report describes a rare case of a successful vaginal delivery despite a huge cystadenoma of the right ovary complicating the pregnancy.

  14. Retardo no crescimento intrauterino, baixo peso ao nascer e prematuridade em recém-nascidos de grávidas com malária, na Colômbia Intrauterine growth retardation, low birth weight and prematurity in neonates of pregnant women with malaria in Colombia

    Directory of Open Access Journals (Sweden)

    Alberto Tobón-Castaño

    2011-06-01

    Full Text Available INTRODUÇÃO: É frequente a associação da malária com complicações como prematuridade, retardo no crescimento intrauterino, baixo peso ao nascer e mortalidade infantil, efeitos pouco estudados em áreas hipoendêmicas para malaria. O objetivo deste estudo foi analisar a relação da malária gestacional com estes efeitos em recém-nascidosnuma região endêmica para malária na Colômbia, entre 1993 e 2007. MÉTODOS: Foram estudadas as características em 1.716 recém-nascidos num estudo de coorte. Fez-se seguimento em 394 gestantes com malária (27% por Plasmodium falciparum e 73% por P. vivax e 1.322 sem malária. RESULTADOS: Foi encontrada uma relação entre a exposição à malária na gestação e o risco maior de baixo peso ao nascer (RR = 1,37; 1,03-1,83, assim como estatura baixa (RR = 1,52; 1,25-1,85, retardo no crescimento intrauterino (RR = 1,29; 1,0-1,66 e prematuridade (RR = 1,68; 1,3-2,17. A frequência de nascimentos prematuros foi maior nas mães com malária por P. falciparum (77% que aquelas com P. vivax (RR = 1,77; IC 95%: 1,2-2,6. CONCLUSÕES: O baixo peso ao nascer e o retardo no crescimento foi associado com malária na gestação na Colômbia. A infecção por P. vivax foi relacionada com efeitos adversos sobre o recém-nascido, de modo semelhante em relação ao P. falciparum.INTRODUCTION: Association between malaria and pregnancy complications, such as prematurity, intrauterine growth restriction, low birthweight and infant mortality has been reported. These effects have been studied widely in areas hyperendemic for malaria, but studies in low-endemic areas are scarce. The study investigated the relation between gestational malaria and low birthweight and intrauterine growth retardation in neonates of a malarial endemic region in Colombia, between 1993 and 2007. METHODS: The pattern of development in 1,716 neonates of women with and without malaria infection during pregnancy was evaluated in a cohort study. A

  15. Intra-uterine contraceptive devices.

    Science.gov (United States)

    Elias, J

    1985-05-01

    Among the advantages of IUDs are the device's high continuation rate, the lack of systemic side effects, and the absence of a need for continual motivation to practice contraception. The effectiveness of plastic IUDs is directly proportional to their surface area, but the degree of excessive bleeding experienced is inversely related to device size. Thus, devices represent a compromise between large size for effectiveness and small size for acceptability. The optimum time to fit an IUD is during the 1st hald of the menstrual cycle. Absolute contraindications to IUD use include the presence of active pelvic inflammatory disease, undiagnosed irregular bleeding, a history of ectopic pregnancy or tubal surgery, and a distorted uteine cavity. Failure rates associated with IUD use range from 2-3% in the 1st year and then decrease. Since the main mechanism of action appears to be production of a sterile inflammatory reaction in the uterine cavity, the IUD prevents intrauterine pregnancy more effectively than ectopic pregnancy. Nonetheless, there is little evidence to suggest that IUD use actually increases the incidence of ectopic pregnancy. Resumption of fertility after IUD removal is not delayed. There is not need to change inert plastic IUDs in women who remain symptom free. The copper devices should be changed every 3-4 years. A search is under way for antifertility agents that can be incorporated into the device to reduce side effects. In general, the IUD is most suitable for older, parous women.

  16. Acute and Impaired Wound Healing: Pathophysiology and Current Methods for Drug Delivery, Part 2: Role of Growth Factors in Normal and Pathological Wound Healing: Therapeutic Potential and Methods of Delivery

    Science.gov (United States)

    Demidova-Rice, Tatiana N.; Hamblin, Michael R.; Herman, Ira M.

    2012-01-01

    This is the second of 2 articles that discuss the biology and pathophysiology of wound healing, reviewing the role that growth factors play in this process and describing the current methods for growth factor delivery into the wound bed. PMID:22820962

  17. Pokemon siRNA Delivery Mediated by RGD-Modified HBV Core Protein Suppressed the Growth of Hepatocellular Carcinoma.

    Science.gov (United States)

    Kong, Jing; Liu, Xiaoping; Jia, Jianbo; Wu, Jinsheng; Wu, Ning; Chen, Jun; Fang, Fang

    2015-10-01

    Hepatocellular carcinoma (HCC) is a deadly human malignant tumor that is among the most common cancers in the world, especially in Asia. Hepatitis B virus (HBV) infection has been well established as a high risk factor for hepatic malignance. Studies have shown that Pokemon is a master oncogene for HCC growth, suggesting it as an ideal therapeutic target. However, efficient delivery system is still lacking for Pokemon targeting treatment. In this study, we used core proteins of HBV, which is modified with RGD peptides, to construct a biomimetic vector for the delivery of Pokemon siRNAs (namely, RGD-HBc-Pokemon siRNA). Quantitative PCR and Western blot assays revealed that RGD-HBc-Pokemon siRNA possessed the highest efficiency of Pokemon suppression in HCC cells. In vitro experiments further indicated that RGD-HBc-Pokemon-siRNA exerted a higher tumor suppressor activity on HCC cell lines, evidenced by reduced proliferation and attenuated invasiveness, than Pokemon-siRNA or RGD-HBc alone. Finally, animal studies demonstrated that RGD-HBc-Pokemon siRNA suppressed the growth of HCC xenografts in mice by a greater extent than Pokemon-siRNA or RGD-HBc alone. Based on the above results, Pokemon siRNA delivery mediated by RGD-modified HBV core protein was shown to be an effective strategy of HCC gene therapy.

  18. Temporally controlled growth factor delivery from a self-assembling peptide hydrogel and electrospun nanofibre composite scaffold.

    Science.gov (United States)

    Bruggeman, Kiara F; Wang, Yi; Maclean, Francesca L; Parish, Clare L; Williams, Richard J; Nisbet, David R

    2017-09-21

    Tissue-specific self-assembling peptide (SAP) hydrogels designed based on biologically relevant peptide sequences have great potential in regenerative medicine. These materials spontaneously form 3D networks of physically assembled nanofibres utilising non-covalent interactions. The nanofibrous structure of SAPs is often compared to that of electrospun scaffolds. These electrospun nanofibers are produced as sheets that can be engineered from a variety of polymers that can be chemically modified to incorporate many molecules including drugs and growth factors. However, their macroscale morphology limits them to wrapping and bandaging applications. Here, for the first time, we combine the benefits of these systems to describe a two-component composite scaffold from these biomaterials, with the design goal of providing a hydrogel scaffold that presents 3D structures, and also has temporal control over drug delivery. Short fibres, cut from electrospun scaffolds, were mixed with our tissue-specific SAP hydrogel to provide a range of nanofibre sizes found in the extracellular matrix (10-300 nm in diameter). The composite material maintained the shear-thinning and void-filling properties of SAP hydrogels that have previously been shown to be effective for minimally invasive material injection, cell delivery and subsequent in vivo integration. Both scaffold components were separately loaded with growth factors, important signaling molecules in tissue regeneration whose rapid degradation limits their clinical efficacy. The two biomaterials provided sequential growth factor delivery profiles: the SAP hydrogel provided a burst release, with the release rate decreasing over 12 hours, while the electrospun nanofibres provided a more constant, sustained delivery. Importantly, this second release commenced 6 days later. The design rules established here to provide temporally distinct release profiles can enable researchers to target specific stages in regeneration, such as the

  19. Sendai viroplexes for epidermal growth factor receptor-directed delivery of interleukin-12 and salmosin genes to cancer cells.

    Science.gov (United States)

    Kim, Jung Seok; Kim, Min Woo; Jeong, Hwa Yeon; Kang, Seong Jae; Park, Sang Il; Lee, Yeon Kyung; Kim, Hong Sung; Kim, Keun Sik; Park, Yong Serk

    2016-07-01

    The effective delivery of therapeutic genes to target cells has been a fundamental goal in cancer gene therapy because of its advantages with respect to both safety and transfection efficiency. In the present, study we describe a tumor-directed gene delivery system that demonstrates remarkable efficacy in gene delivery and minimizes the off-target effects of gene transfection. The system consists of a well-verified cationic O,O'-dimyristyl-N-lysyl glutamate (DMKE), Sendai virus fusion (F) protein and hemagglutinin-neuraminidase (HN) protein, referred to as cationic Sendai F/HN virosomes. To achieve tumor-specific recognition, anti-epidermal growth factor (EGF) receptor antibody was coupled to the surface of the virosomes containing interleukin-12 (IL-12) and/or salmosin genes that have potent anti-angiogenetic functions. Among the virosomal formulations, the anti-EGF receptor (EGFR) viroplexes, prepared via complexation of plasmid DNA (pDNA) with cationic DMKE lipid, exhibited more efficient gene transfection to tumor cells over-expressing EGF receptors compared to the neutrally-charged anti-EGFR virosomes encapsulating pDNA. In addition, the anti-EGFR viroplexes with IL-12 and salmosin genes exhibited the most effective therapeutic efficacy in a mouse tumor model. Especially when combined with doxorubicin, transfection of the two genes via the anti-EGFR viroplexes exhibited an enhanced inhibitory effect on tumor growth and metastasis in lungs. The results of the present study suggest that anti-EGFR viroplexes can be utilized as an effective strategy for tumor-directed gene delivery. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  20. Characterization of respiratory drug delivery with enhanced condensational growth using an individual path model of the entire tracheobronchial airways.

    Science.gov (United States)

    Tian, Geng; Longest, Philip Worth; Su, Guoguang; Hindle, Michael

    2011-03-01

    The objective of this study was to evaluate the delivery of inhaled pharmaceutical aerosols using an enhanced condensational growth (ECG) approach in an airway model extending from the oral cavity to the end of the tracheobronchial (TB) region. The geometry consisted of an elliptical mouth-throat (MT) model, the upper TB airways extending to bifurcation B3, and a subsequent individual path model entering the right lower lobe of the lung. Submicrometer monodisperse aerosols with diameters of 560 and 900 nm were delivered to the mouth inlet under control (25 °C with subsaturated air) or ECG (39 or 42 °C with saturated air) conditions. Flow fields and droplet characteristics were simulated using a computational fluid dynamics model that was previously demonstrated to accurately predict aerosol size growth and deposition. Results indicated that both the control and ECG delivery cases produced very little deposition in the MT and upper TB model (approximately 1%). Under ECG delivery conditions, large size increases of the aerosol droplets were observed resulting in mass median aerodynamic diameters of 2.4-3.3 μm exiting B5. This increase in aerosol size produced an order of magnitude increase in aerosol deposition within the TB airways compared with the controls, with TB deposition efficiencies of approximately 32-46% for ECG conditions. Estimates of downstream pulmonary deposition indicted near full lung retention of the aerosol during ECG delivery. Furthermore, targeting the region of TB deposition by controlling the inlet temperature conditions and initial aerosol size also appeared possible.

  1. Facile modification of gelatin-based microcarriers with multiporous surface and proliferative growth factors delivery to enhance cell growth

    Energy Technology Data Exchange (ETDEWEB)

    Huang Sha [Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China); Wang Yijuan [Key Laboratory for Macromolecular Science of Shaanxi Province, Shaanxi Normal University, Xi' an 710062 (China); Deng, Tianzheng [Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China); Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Jin Fang [Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi' an, 710032 (China); Liu Shouxin [Key Laboratory for Macromolecular Science of Shaanxi Province, Shaanxi Normal University, Xi' an 710062 (China); Zhang Yongjie [Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China); Feng Feng [Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China); Department of Dermatology, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China); Jin Yan [Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China)], E-mail: yanjin@fmmu.edu.cn

    2008-07-28

    The design of microcarriers plays an important role in the success of cell expansion. The present article provides a facile approach to modify the gelatin-based particles and investigates the feasibility of their acting as microcarriers for cell attachment and growth. Gelatin particles (150-320 {mu}m) were modified by cryogenic treatment and lyophilization to develop the surface with the features of multiporous morphology and were incorporated with proliferative growth factors (bFGF) by adsorption during the post-preparation, which enables them to serve as microcarriers for cells amplification, together with the advantages of larger cell-surface contact area and capability of promoting cell propagation. The microstructure and release assay of the modified microcarriers demonstrated that the pores on surface were uniform and bFGF was released in a controlled manner. Through in vitro fibroblast culture, these features resulted in a prominent increase in the cell attachment rate and cell growth rate relative to the conditions without modification. Although the scanning electron microscopy and optical microscopy analysis results indicated that cells attached, spread, and proliferated on all the microcarriers, cell growth clearly showed a significant correlation with the multiporous structure of microcarriers, in particular on bFGF combined ones. These results validate our previous assumption that the facile modification could improve cell growth on the gelatin-based microcarriers obviously and the novel microcarriers may be a promising candidate in tissue engineering.

  2. Facile modification of gelatin-based microcarriers with multiporous surface and proliferative growth factors delivery to enhance cell growth

    International Nuclear Information System (INIS)

    Huang Sha; Wang Yijuan; Deng, Tianzheng; Jin Fang; Liu Shouxin; Zhang Yongjie; Feng Feng; Jin Yan

    2008-01-01

    The design of microcarriers plays an important role in the success of cell expansion. The present article provides a facile approach to modify the gelatin-based particles and investigates the feasibility of their acting as microcarriers for cell attachment and growth. Gelatin particles (150-320 μm) were modified by cryogenic treatment and lyophilization to develop the surface with the features of multiporous morphology and were incorporated with proliferative growth factors (bFGF) by adsorption during the post-preparation, which enables them to serve as microcarriers for cells amplification, together with the advantages of larger cell-surface contact area and capability of promoting cell propagation. The microstructure and release assay of the modified microcarriers demonstrated that the pores on surface were uniform and bFGF was released in a controlled manner. Through in vitro fibroblast culture, these features resulted in a prominent increase in the cell attachment rate and cell growth rate relative to the conditions without modification. Although the scanning electron microscopy and optical microscopy analysis results indicated that cells attached, spread, and proliferated on all the microcarriers, cell growth clearly showed a significant correlation with the multiporous structure of microcarriers, in particular on bFGF combined ones. These results validate our previous assumption that the facile modification could improve cell growth on the gelatin-based microcarriers obviously and the novel microcarriers may be a promising candidate in tissue engineering

  3. Novel drug delivery systems for releasing growth factors to the CNS: focus on Alzheimer's and Parkinson's diseases.

    Science.gov (United States)

    Herran, E; Igartua, M; Pedraz, J L; Hernandez, R M

    2014-01-01

    Alzheimer's disease (AD) and Parkinson's disease (PD) represent the most common neurodegenerative disorders and affect more than 35 million people. Due to the limited effectiveness of available treatments in halting the neurodegenerative process, new therapies, such therapies based on growth factors (GFs), have been investigated. Nevertheless, the efficacies of these new treatments depend not only on the application of neurotrophins but also on the approaches used to deliver these proteins such that they can reach the brain. This review summarises the most widely used drug delivery systems (DDSs) for releasing GFs as possible treatments for AD and PD.

  4. Pulmonary hypoplasia on preterm infant associated with diffuse chorioamniotic hemosiderosis caused by intrauterine hemorrhage due to massive subchorial hematoma: report of a neonatal autopsy case.

    Science.gov (United States)

    Yamada, Sohsuke; Marutani, Takamitsu; Hisaoka, Masanori; Tasaki, Takashi; Nabeshima, Atsunori; Shiraishi, Mika; Sasaguri, Yasuyuki

    2012-08-01

    A male infant born prematurely at 31 weeks of gestation weighed 789 g and had mildly brown-colored oral/tracheal aspirates at delivery. The amniotic fluid was also discolored, and its index was below 5. The patient died of hypoxemic respiratory and cardiac failure 2 hours after birth. The maternal profiles showed placenta previa and intrauterine growth restriction (IUGR) at 22 weeks of gestation, and revealed recurrent episodes of antenatal and substantial vaginal bleeding and oligohydramnios, indicating chronic abruption-oligohydramnios sequence. The thickened placenta, weighing 275 g, grossly displayed unevenness and diffuse opacity with green to brown discoloration in the chorioamniotic surface, and revealed chronic massive subchorial hematomas (Breus' mole) with old peripheral blood clot, circumvallation, and infarction. Microscopically, diffuse Berlin-blue staining-positive hemosiderin deposits were readily encountered in the chorioamniotic layers of the chorionic plate, consistent with diffuse chorioamniotic hemosiderosis (DCH) due to Breus' mole, accompanied by diffuse amniotic necrosis. At autopsy, an external examination showed several surface anomalies and marked pulmonary hypoplasia, 0.006 (less 0.012) of lung:body weight ratio. Since Breus' mole has a close relationship with intrauterine hemorrhage, resulting in DCH, IUGR, and/or pulmonary hypoplasia of the newborn, the present features might be typical. © 2012 The Authors. Pathology International © 2012 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.

  5. Targeted Delivery of Glucan Particle Encapsulated Gallium Nanoparticles Inhibits HIV Growth in Human Macrophages

    Directory of Open Access Journals (Sweden)

    Ernesto R. Soto

    2016-01-01

    Full Text Available Glucan particles (GPs are hollow, porous 3–5 μm microspheres derived from the cell walls of Baker’s yeast (Saccharomyces cerevisiae. The 1,3-β-glucan outer shell provides for receptor-mediated uptake by phagocytic cells expressing β-glucan receptors. GPs have been used for macrophage-targeted delivery of a wide range of payloads (DNA, siRNA, protein, small molecules, and nanoparticles encapsulated inside the hollow GPs or bound to the surface of chemically derivatized GPs. Gallium nanoparticles have been proposed as an inhibitory agent against HIV infection. Here, macrophage targeting of gallium using GPs provides for more efficient delivery of gallium and inhibition of HIV infection in macrophages compared to free gallium nanoparticles.

  6. The Probable Effects of Cytokines in Intrauterine Infections and Perinatal Brain Injury

    Directory of Open Access Journals (Sweden)

    Mehmet Oflaz

    2013-10-01

    Full Text Available Perinatal brain injuries and the subsequent development of cerebral palsy are closely associated with intrauterine infections and inflammatory response. Premature prenatal rupture of membranes and premature births are also closely linked to infections and inflammation, and the presence of both infection / inflammation and premature birth together greatly increase the risk for cerebral palsy. Periventricular leukolamacia, a common neonatal brain white matter lesion, is a major risk factor for cerebral palsy. Inflammatory cytokines released during the course of intrauterine infection play an important role in the genesis of brain white matter lesion. Maternal intrauterine infection appears to increase the risk of preterm delivery, which in turn is associated with an increased risk of intraventricular hemorrhage, neonatal white matter damage, and subsequent cerebral palsy. Proinflammatory cytokines IL-1, IL-6 and Tumor necrosis factor-%u03B1 might be the link between prenatal intrauterine infection and neonatal brain damage, and interrupting the proinflammatory cytokine cascade might prevent later disability in those born near the end of the second trimester.

  7. Neutron capture therapy of epidermal growth factor (+) gliomas using boronated cetuximab (IMC-C225) as a delivery agent

    Energy Technology Data Exchange (ETDEWEB)

    Barth, Rolf F. E-mail: barth.1@osu.edu; Wu Gong; Yang Weilian; Binns, Peter J.; Riley, Kent J.; Patel, Hemant; Coderre, Jeffrey A.; Tjarks, Werner; Bandyopadhyaya, A.K.; Thirumamagal, B.T.S.; Ciesielski, Michael J.; Fenstermaker, Robert A

    2004-11-01

    Cetuximab (IMC-C225) is a monoclonal antibody directed against both the wild-type and mutant vIII isoform of the epidermal growth factor receptor (EGFR). The purpose of the present study was to evaluate the monoclonal antibody (MoAb), cetuximab, as a boron delivery agent for neutron capture therapy (NCT) of brain tumors. Twenty-four hours following intratumoral (i.t.) administration of boronated cetuximab (C225-G5-B{sub 1100}), the mean boron concentration in rats bearing either F98{sub EGFR} or F98{sub WT} gliomas were 92.3{+-}23.3 {mu}g/g and 36.5{+-}18.8 {mu}g/g, respectively. In contrast, the uptake of boronated dendrimer (G5-B{sub 1000}) was 6.7{+-}3.6 {mu}g/g. Based on its favorable in vivo uptake, C225-G5-B{sub 1100} was evaluated as a delivery agent for BNCT in F98{sub EGFR} glioma bearing rats. The mean survival time (MST) of rats that received C225-G5-B{sub 1100}, administered by convection enhanced delivery (CED), was 45{+-}3 d compared to 25{+-}3 d for untreated control animals. A further enhancement in MST to >59 d was obtained by administering C225-G5-B{sub 1100} in combination with i.v. boronophenylalanine (BPA). These data are the first to demonstrate the efficacy of a boronated MoAb for BNCT of an intracerebral (i.c.) glioma and are paradigmatic for future studies using a combination of boronated MoAbs and low molecular weight delivery agents.

  8. In vivo delivery of recombinant human growth hormone from genetically engineered human fibroblasts implanted within Baxter immunoisolation devices.

    Science.gov (United States)

    Josephs, S F; Loudovaris, T; Dixit, A; Young, S K; Johnson, R C

    1999-01-01

    Continuous delivery of therapeutic peptide to the systemic circulation would be the optimal treatment for a variety of diseases. The Baxter TheraCyte system is a membrane encapsulation system developed for implantation of tissues, cells such as endocrine cells or cell lines genetically engineered for therapeutic peptide delivery in vivo. To demonstrate the utility of this system, cell lines were developed which expressed human growth hormone (hGH) at levels exceeding 1 microgram per million cells per day. These were loaded into devices which were then implanted into juvenile nude rats. Significant levels of hGH of up to 2.5 ng/ml were detected in plasma throughout the six month duration of the study. In contrast, animals implanted with free cells showed peak plasma levels of 0.5 to 1.2 ng four days after implantation with no detectable hGH beyond 10 days. Histological examination of explanted devices showed they were vascularized and contained cells that were viable and morphologically healthy. After removal of the implants, no hGH could be detected which confirmed that the source of hGH was from cells contained within the device. The long term expression of human growth hormone as a model peptide has implications for the peptide therapies for a variety of human diseases using membrane encapsulated cells.

  9. Developments in human growth hormone preparations: sustained-release, prolonged half-life, novel injection devices, and alternative delivery routes

    Directory of Open Access Journals (Sweden)

    Cai Y

    2014-07-01

    Full Text Available Yunpeng Cai,1,2 Mingxin Xu,2 Minglu Yuan,2 Zhenguo Liu,1 Weien Yuan2 1Department of Neurology, Xinhua Hospital, School of Medicine, 2School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People’s Republic of China Abstract: Since the availability of recombinant human growth hormone (rhGH enabled the application of human growth hormone both in clinical and research use in the 1980s, millions of patients were prescribed a daily injection of rhGH, but noncompliance rates were high. To address the problem of noncompliance, numerous studies have been carried out, involving: sustained-release preparations, prolonged half-life derivatives, new injectors that cause less pain, and other noninvasive delivery methods such as intranasal, pulmonary and transdermal deliveries. Some accomplishments have been made and launched already, such as the Nutropin Depot® microsphere and injectors (Zomajet®, Serojet®, and NordiFlex®. Here, we provide a review of the different technologies and illustrate the key points of these studies to achieve an improved rhGH product. Keywords: intranasal, pulmonary, transdermal, microsphere, microneedle, hydrogel

  10. Local delivery of cannabinoid-loaded microparticles inhibits tumor growth in a murine xenograft model of glioblastoma multiforme.

    Directory of Open Access Journals (Sweden)

    Dolores Hernán Pérez de la Ossa

    Full Text Available Cannabinoids, the active components of marijuana and their derivatives, are currently investigated due to their potential therapeutic application for the management of many different diseases, including cancer. Specifically, Δ(9-Tetrahydrocannabinol (THC and Cannabidiol (CBD - the two major ingredients of marijuana - have been shown to inhibit tumor growth in a number of animal models of cancer, including glioma. Although there are several pharmaceutical preparations that permit the oral administration of THC or its analogue nabilone or the oromucosal delivery of a THC- and CBD-enriched cannabis extract, the systemic administration of cannabinoids has several limitations in part derived from the high lipophilicity exhibited by these compounds. In this work we analyzed CBD- and THC-loaded poly-ε-caprolactone microparticles as an alternative delivery system for long-term cannabinoid administration in a murine xenograft model of glioma. In vitro characterization of THC- and CBD-loaded microparticles showed that this method of microencapsulation facilitates a sustained release of the two cannabinoids for several days. Local administration of THC-, CBD- or a mixture (1:1 w:w of THC- and CBD-loaded microparticles every 5 days to mice bearing glioma xenografts reduced tumour growth with the same efficacy than a daily local administration of the equivalent amount of those cannabinoids in solution. Moreover, treatment with cannabinoid-loaded microparticles enhanced apoptosis and decreased cell proliferation and angiogenesis in these tumours. Our findings support that THC- and CBD-loaded microparticles could be used as an alternative method of cannabinoid delivery in anticancer therapies.

  11. Evaluation of Enhanced Condensational Growth (ECG) for Controlled Respiratory Drug Delivery in a Mouth-Throat and Upper Tracheobronchial Model

    Science.gov (United States)

    Hindle, Michael; Longest, P. Worth

    2010-01-01

    Purpose The objective of this study is to evaluate the effects of enhanced condensational growth (ECG), as a novel inhalation drug delivery method, on nano-aerosol deposition in a mouth-throat (MT) and upper tracheobronchial (TB) model using in vitro experiments and computational fluid dynamics (CFD) simulations. Methods Separate streams of nebulized nano-aerosols and saturated humidified air (39°C—ECG; 25°C—control) were combined as they were introduced into a realistic MT-TB geometry. Aerosol deposition was determined in the MT, generations G0–G2 (trachea—lobar bronchi) and G3–G5 and compared to CFD simulations. Results Using ECG conditions, deposition of 560 and 900 nm aerosols was low in the MT region of the MT-TB model. Aerosol drug deposition in the G0–G2 and G3–G5 regions increased due to enhanced condensational growth compared to control. CFD-predicted depositions were generally in good agreement with the experimental values. Conclusions The ECG platform appears to offer an effective method of delivering nano-aerosols through the extrathoracic region, with minimal deposition, to the tracheobronchial airways and beyond. Aerosol deposition is then facilitated as enhanced condensational growth increases particle size. Future studies will investigate the effects of physio-chemical drug properties and realistic inhalation profiles on ECG growth characteristics. PMID:20454837

  12. Self-assembling peptide amphiphiles and related methods for growth factor delivery

    Science.gov (United States)

    Stupp, Samuel I [Chicago, IL; Donners, Jack J. J. M.; Silva, Gabriel A [Chicago, IL; Behanna, Heather A [Chicago, IL; Anthony, Shawn G [New Stanton, PA

    2009-06-09

    Amphiphilic peptide compounds comprising one or more epitope sequences for binding interaction with one or more corresponding growth factors, micellar assemblies of such compounds and related methods of use.

  13. Low Cost, Simple, Intrauterine Insemination Procedure with ...

    African Journals Online (AJOL)

    During the last 30 years however, intrauterine insemination has evolved with the introduction of ovulation stimulating protocols and sperm preparation methods taken from assisted reproduction techniques. Costs have risen, but the success rate has not risen to the same extent. We have therefore developed a quite simple ...

  14. Prognostic factors affecting outcome of intrauterine insemination ...

    African Journals Online (AJOL)

    for a rational use of the procedure so that couples do not waste time and money on ineffective therapy if it is not indicated. Objective: ... of intrauterine insemination procedures at a fertility center in Ondo, ... significant reduction in the side effects associated with the .... HMG alone or in combination with other drugs for ovarian.

  15. Intra-uterine insemination for male subfertility

    NARCIS (Netherlands)

    Bensdorp, A. J.; Cohlen, B. J.; Heineman, M. J.; Vandekerckhove, P.

    2007-01-01

    BACKGROUND: Intra-uterine insemination (IUI) is one of the most frequently used fertility treatments for couples with male subfertility. Its use, especially when combined with ovarian hyperstimulation (OH) has been subject of discussion. Although the treatment itself is less invasive and expensive

  16. Dual growth factor delivery from biofunctionalized allografts: Sequential VEGF and BMP-2 release to stimulate allograft remodeling.

    Science.gov (United States)

    Sharmin, Farzana; McDermott, Casey; Lieberman, Jay; Sanjay, Archana; Khan, Yusuf

    2017-05-01

    Autografts have been shown to stimulate osteogenesis, osteoclastogenesis, and angiogenesis, and subsequent rapid graft incorporation. Large structural allografts, however, suffer from limited new bone formation and remodeling, both of which are directly associated with clinical failure due to non-unions, late graft fractures, and infections, making it a priority to improve large structural allograft healing. We have previously shown the osteogenic ability of a polymer-coated allograft that delivers bone morphogenetic protein-2 both in vitro and in vivo through both burst release and sustained release kinetics. In this study, we have demonstrated largely sequential delivery of bone morphogenetic protein-2 and vascular endothelial growth factor from the same coated allograft. Release data showed that loading both growth factors onto a polymeric coating with two different techniques resulted in short-term (95% release within 2 weeks) and long-term (95% release within 5 weeks) delivery kinetics. We have also demonstrated how released VEGF, traditionally associated with angiogenesis, can also provide a stimulus for allograft remodeling via resorption. Bone marrow derived mononuclear cells were co-cultured with VEGF released from the coated allograft and showed a statistically significant (p exposed to VEGF released from the allografts over controls (p < 0.05). These results indicate that by using different loading protocols temporal control can be achieved when delivering multiple growth factors from a polymer-coated allograft. Further, released VEGF can also stimulate osteoclastogenesis that may enhance allograft incorporation, and thus mitigate long-term clinical complications. © 2017 Orthopedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1086-1095, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  17. The relationship between maternal insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and IGFBP-3 to gestational age and preterm delivery.

    LENUS (Irish Health Repository)

    Cooley, Sharon M

    2012-02-01

    AIMS: To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2), and insulin-like growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and gestational age at delivery. METHODS: Prospective cohort study of 1650 low-risk Caucasian women in a London University teaching hospital. Maternal IGF-1, IGF-2 and IGFBP-3 were measured in maternal blood at booking and analyzed with respect to gestational age at delivery. RESULTS: There was no significant association between maternal IGF-1 or IGF-2 and preterm birth (PTB). A significant reduction in mean IGFBP-3 levels was noted with delivery <32 completed weeks (P=0.02). CONCLUSION: Maternal mean IGFBP-3 levels are significantly reduced in cases complicated by delivery <32 completed weeks.

  18. Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction

    Science.gov (United States)

    Shah, Nisarg J.; Hyder, Md. Nasim; Quadir, Mohiuddin A.; Dorval Courchesne, Noémie-Manuelle; Seeherman, Howard J.; Nevins, Myron; Spector, Myron; Hammond, Paula T.

    2014-01-01

    Traumatic wounds and congenital defects that require large-scale bone tissue repair have few successful clinical therapies, particularly for craniomaxillofacial defects. Although bioactive materials have demonstrated alternative approaches to tissue repair, an optimized materials system for reproducible, safe, and targeted repair remains elusive. We hypothesized that controlled, rapid bone formation in large, critical-size defects could be induced by simultaneously delivering multiple biological growth factors to the site of the wound. Here, we report an approach for bone repair using a polyelectrolye multilayer coating carrying as little as 200 ng of bone morphogenetic protein-2 and platelet-derived growth factor-BB that were eluted over readily adapted time scales to induce rapid bone repair. Based on electrostatic interactions between the polymer multilayers and growth factors alone, we sustained mitogenic and osteogenic signals with these growth factors in an easily tunable and controlled manner to direct endogenous cell function. To prove the role of this adaptive release system, we applied the polyelectrolyte coating on a well-studied biodegradable poly(lactic-co-glycolic acid) support membrane. The released growth factors directed cellular processes to induce bone repair in a critical-size rat calvaria model. The released growth factors promoted local bone formation that bridged a critical-size defect in the calvaria as early as 2 wk after implantation. Mature, mechanically competent bone regenerated the native calvaria form. Such an approach could be clinically useful and has significant benefits as a synthetic, off-the-shelf, cell-free option for bone tissue repair and restoration. PMID:25136093

  19. Fabrication and characterization of a novel microparticle with gyrus-patterned surface and growth factor delivery for cartilage tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Huang Sha [Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China); Wang Yijuan [Key Laboratory for Macromolecular Science of Shaanxi Province, Shaanxi Normal University, Xi' an 710062 (China); Liang Tang [Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China); Jin Fang [Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Liu Shouxin [Key Laboratory for Macromolecular Science of Shaanxi Province, Shaanxi Normal University, Xi' an 710062 (China); Jin Yan, E-mail: yanjin@fmmu.edu.cn [Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China)

    2009-05-05

    Microparticles can serve as substrates for cell amplification and deliver the expanded cells to the site of the defect. It was hypothesized that a novel microparticle combined of sustained and localized delivery of proliferative growth factors and gyrus-patterned surface would influence the cell behaviours of adherence and expansion on the microparticle in the present study. To test the hypothesis, gelatin particles with diameter ranging from 280 to 350 {mu}m were fabricated and were modified by cryogenic freeze-drying treatment and basic fibroblast growth factor (bFGF) incorporation. The results of in vitro chondrocyte culture illustrated that cells could proliferate more obviously on the microparticles with bFGF addition, but no correlation between attachment rate and bFGF was observed. On the other hand, microparticles with gyrus-patterned surface demonstrated the highest cell attachment rate and higher rate of cell growth, in particular on bFGF combined ones. It seems to be a promising candidate as a chondrocyte microparticle and could be the potential application in cartilage tissue engineering.

  20. Fabrication and characterization of a novel microparticle with gyrus-patterned surface and growth factor delivery for cartilage tissue engineering

    International Nuclear Information System (INIS)

    Huang Sha; Wang Yijuan; Liang Tang; Jin Fang; Liu Shouxin; Jin Yan

    2009-01-01

    Microparticles can serve as substrates for cell amplification and deliver the expanded cells to the site of the defect. It was hypothesized that a novel microparticle combined of sustained and localized delivery of proliferative growth factors and gyrus-patterned surface would influence the cell behaviours of adherence and expansion on the microparticle in the present study. To test the hypothesis, gelatin particles with diameter ranging from 280 to 350 μm were fabricated and were modified by cryogenic freeze-drying treatment and basic fibroblast growth factor (bFGF) incorporation. The results of in vitro chondrocyte culture illustrated that cells could proliferate more obviously on the microparticles with bFGF addition, but no correlation between attachment rate and bFGF was observed. On the other hand, microparticles with gyrus-patterned surface demonstrated the highest cell attachment rate and higher rate of cell growth, in particular on bFGF combined ones. It seems to be a promising candidate as a chondrocyte microparticle and could be the potential application in cartilage tissue engineering.

  1. Dual growth factor delivery from bilayered, biodegradable hydrogel composites for spatially-guided osteochondral tissue repair

    NARCIS (Netherlands)

    Lu, S.; Lam, J.; Trachtenberg, J.E.; Lee, E.J.; Seyednejad, H.; van den Beucken, J.J.; Tabata, Y.; Wong, M.E.; Jansen, J.A.; Mikos, A.G.; Kasper, F.K.

    2014-01-01

    The present work investigated the use of biodegradable hydrogel composite scaffolds, based on the macromer oligo(poly(ethylene glycol) fumarate) (OPF), to deliver growth factors for the repair of osteochondral tissue in a rabbit model. In particular, bilayered OPF composites were used to mimic the

  2. Drug delivery system of basic fibroblast growth factor using gelatin hydrogel for restoration of acute vocal fold scar.

    Science.gov (United States)

    Kobayashi, Toshiki; Mizuta, Masanobu; Hiwatashi, Nao; Kishimoto, Yo; Nakamura, Tatsuo; Kanemaru, Shin-Ichi; Hirano, Shigeru

    2017-02-01

    There continue to be therapeutic challenges in the management of vocal fold scarring. We previously showed that basic fibroblast growth factor (bFGF) injection has therapeutic potential for vocal fold scarring. However, the working time of bFGF is relatively short, and multiple injections were required in many cases to obtain the regenerative effect. An efficacious delivery system for bFGF has yet to be established. We designed a method of sustained drug delivery system (DDS) of bFGF by using a gelatin hydrogel. Hydrogel has been developed for targeted delivery and controlled release of bFGF. Hydrogel of the particle type is also injectable and commercially available. The current study aims to investigate the effects of a single injection of bFGF-DDS on acute vocal fold scarring using a canine model. Vocal folds from eight beagles were unilaterally scarred by stripping the lamina propria. One month later, hydrogels (0.5ml) containing 10μg of bFGF were injected into the scarred vocal folds of four beagles (FGF-hydrogel group). Saline (0.5ml) was injected into the other four beagles (sham group). Vibratory and histological examination of excised larynges was performed 5 months after treatment. Comparative analysis between the current data and our previous data with repeated injection of bFGF solution was also completed. Vibratory examination demonstrated significantly improved vibration in the bFGF hydrogel-treated group. Histological examination of the bFGF hydrogel group showed restoration of hyaluronic acid in the lamina propria as compared to sham. Comparison between the DDS system and our previous bFGF solution injection indicated better effects of the DDS system on vibratory amplitude. A single injection of bFGF hydrogel has regenerative effects on acute vocal fold scarring, which is at least similar to repeated injection of bFGF solution. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Thermoresponsive nanocomposite gel for local drug delivery to suppress the growth of glioma by inducing autophagy.

    Science.gov (United States)

    Ding, Li; Wang, Qi; Shen, Ming; Sun, Ying; Zhang, Xiangyu; Huang, Can; Chen, Jianhua; Li, Rongxin; Duan, Yourong

    2017-07-03

    Although the treatments of malignant glioma include surgery, radiotherapy and chemotherapy by oral drug administration, the prognosis of patients with glioma remains very poor. We developed a polyethylene glycol-dipalmitoylphosphatidyle- thanoiamine (mPEG-DPPE) calcium phosphate nanoparticles (NPs) injectable thermoresponsive hydrogel (nanocomposite gel) that could provide a sustained and local delivery of paclitaxel (PTX) and temozolomide (TMZ). In addition, the proportion of PTX and TMZ for the optimal synergistic antiglioma effect on C6 cells was determined to be 1:100 (w/w) by the Chou and Talalay method. Our results clearly indicated that the autophagy induced by PTX:TMZ NPs plays an important role in regulating tumor cell death, while autophagy inhibition dramatically reverses the antitumor effect of PTX:TMZ NPs, suggesting that antiproliferative autophagy occurs in response to PTX:TMZ NPs treatment. The antitumor efficacy of the PTX:TMZ NP-loaded gel was evaluated in situ using C6 tumor-bearing rats, and the PTX:TMZ NP-loaded gel exhibited superior antitumor performance. The antitumor effects of the nanocomposite gel in vivo were shown to correlate with autophagic cell death in this study. The in vivo results further confirmed the advantages of such a strategy. The present study may provide evidence supporting the development of nanomedicine for potential clinical application.

  4. Immunohistochemical structural pecularities of uterine tube of fetuses with signs of intrauterine infection

    Directory of Open Access Journals (Sweden)

    Лариса Сергеевна Куприянова

    2015-05-01

    Full Text Available Aim - immunohistochemical detection of structural features of the uterine tubes of fetuses with signs of intrauterine infection.Methods: anthropometric, macroscopic, organometric, histological, immunohistochemical, statistical.Object of research - the uterine tubes of antenatal dead fetuses. The control group consisted of 25 fetuses of healthy mothers; the comparison group is 15 fetuses with signs of intrauterine infection. Fetal infection confirmed by laboratory methods; the presence of TORCH infections, cytomegalovirus, herpes infection and chlamydial infection is determined.Results: indicators of weight and body length of the fetus of the comparison group were significantly reduced. Unidirectional changes are established in the definition of the mass and the length of the uterine tubes of fetuses with signs of intrauterine infection. Massive growth of connective tissue in the mucosa, the mucous membrane and muscle membrane of wall of the uterine tube of fetus in the comparison group is shown by histological methods. Violation of collagen formation in the connective tissue in the uterine tubes of fetuses with signs of intrauterine infection is found by immunohistochemistry method.Conclusions: The reduction of anthropometric and organometric indicators in fetuses of comparison group is shown. Sclerosis and atrophy, as well as violations of collagen-synthesizing function are predominated in the main structural components of the wall of the uterine tube of fetuses in the comparison group. The revealed changes in the future ontogenesis may lead to the development of primary infertility

  5. Intrauterine fertilization capsules--a clinical trial

    DEFF Research Database (Denmark)

    Lenz, S; Lindenberg, S; Sundberg, K

    1991-01-01

    Treatment of 26 women with tubal infertility was attempted using intrauterine capsules loaded with oocytes and spermatozoa. The stimulation protocol was as used for in vitro fertilization and embryo transfer and consisted of short-term use of Buserelin, human menopausal gonadotropin, and human...... and piston from an intrauterine device. Six complete capsules and parts of two other capsules were expelled. None of the women became pregnant, compared with a pregnancy rate of 21% per aspiration following in vitro fertilization and embryo transfer during the same period....... chorionic gonadotropin. Oocytes were collected by ultrasonically guided transvaginal aspiration, and spermatozoa were prepared by swim-up technique. The gametes were placed in agar capsules 4 hr after oocyte collection, and the capsules were introduced to the uterine fundus using an insertion tube...

  6. Microporous silk fibroin scaffolds embedding PLGA microparticles for controlled growth factor delivery in tissue engineering.

    Science.gov (United States)

    Wenk, Esther; Meinel, Anne J; Wildy, Sarah; Merkle, Hans P; Meinel, Lorenz

    2009-05-01

    The development of prototype scaffolds for either direct implantation or tissue engineering purposes and featuring spatiotemporal control of growth factor release is highly desirable. Silk fibroin (SF) scaffolds with interconnective pores, carrying embedded microparticles that were loaded with insulin-like growth factor I (IGF-I), were prepared by a porogen leaching protocol. Treatments with methanol or water vapor induced water insolubility of SF based on an increase in beta-sheet content as analyzed by FTIR. Pore interconnectivity was demonstrated by SEM. Porosities were in the range of 70-90%, depending on the treatment applied, and were better preserved when methanol or water vapor treatments were prior to porogen leaching. IGF-I was encapsulated into two different types of poly(lactide-co-glycolide) microparticles (PLGA MP) using uncapped PLGA (50:50) with molecular weights of either 14 or 35 kDa to control IGF-I release kinetics from the SF scaffold. Embedded PLGA MP were located in the walls or intersections of the SF scaffold. Embedment of the PLGA MP into the scaffolds led to more sustained release rates as compared to the free PLGA MP, whereas the hydrolytic degradation of the two PLGA MP types was not affected. The PLGA types used had distinct effects on IGF-I release kinetics. Particularly the supernatants of the lower molecular weight PLGA formulations turned out to release bioactive IGF-I. Our studies justify future investigations of the developed constructs for tissue engineering applications.

  7. Diabetic Foot Ulcers and Epidermal Growth Factor: Revisiting the Local Delivery Route for a Successful Outcome

    Directory of Open Access Journals (Sweden)

    Jorge Berlanga-Acosta

    2017-01-01

    Full Text Available Soon after epidermal growth factor (EGF discovery, some in vivo models appeared demonstrating its property to enhance cutaneous wound healing. EGF was the first growth factor (GF introduced in the clinical arena as a healing enhancer, exerting its mitogenic effects on epithelial, fibroblastoid, and endothelial cells via a tyrosine kinase membrane receptor. Compelling evidences from the 90s documented that, for EGF, locally prolonged bioavailability and hourly interaction with the receptor were necessary for a successful tissue response. Eventually, the enthusiasm on the clinical use of EGF to steer the healing process was wiped out as the topical route to deliver proteins started to be questioned. The simultaneous in vivo experiments, emphasizing the impact of the parenterally administered EGF on epithelial and nonepithelial organs in terms of mitogenesis and cytoprotection, rendered the theoretical fundamentals for the injectable use of EGF and shaped the hypothesis that locally infiltrating the diabetic ulcers would lead to an effective healing. Although the diabetic chronic wounds microenvironment is hostile for local GFs bioavailability, EGF local infiltration circumvented the limitations of its topical application, thus expanding its therapeutic prospect. Our clinical pharmacovigilance and basic studies attest the significance of the GF local infiltration for chronic wounds healing.

  8. Causes and Mechanisms of Intrauterine Hypoxia and Its Impact on the Fetal Cardiovascular System: A Review

    Directory of Open Access Journals (Sweden)

    Damian Hutter

    2010-01-01

    Full Text Available Until today the role of oxygen in the development of the fetus remains controversially discussed. It is still believed that lack of oxygen in utero might be responsible for some of the known congenital cardiovascular malformations. Over the last two decades detailed research has given us new insights and a better understanding of embryogenesis and fetal growth. But most importantly it has repeatedly demonstrated that oxygen only plays a minor role in the early intrauterine development. After organogenesis has taken place hypoxia becomes more important during the second and third trimester of pregnancy when fetal growth occurs. This review will briefly adress causes and mechanisms leading to intrauterine hypoxia and their impact on the fetal cardiovascular system.

  9. A prospective observational study of early fetal growth velocity and its association with birth weight, gestational age at delivery, preeclampsia, and perinatal mortality

    Energy Technology Data Exchange (ETDEWEB)

    Vasudeva, Akhila, E-mail: akhilavasudeva@gmail.com [Department of Obstetrics and Gynaecology, Kasturba Medical College, Manipal University, Manipal 576104, Karnataka State (India); Abraham, Anu Annie, E-mail: anuannieabraham@yahoo.com [Department of Obstetrics and Gynaecology, Kasturba Medical College, Manipal University, Manipal 576104, Karnataka State (India); Kamath, Asha, E-mail: aashakamat@gmail.com [Department of Community Medicine, Kasturba Medical College, Manipal, A Constituent College of Manipal University (India)

    2013-08-15

    Objectives: We aimed to measure early fetal growth velocity and to correlate this with the birth weight, gestational age at delivery, and with the incidence of adverse pregnancy outcomes specifically preeclampsia and perinatal mortality. Methods: A data based prospective observational study, wherein sonographic biometry data and specific pregnancy outcome related data were collected from pregnant women's records, starting soon after their first antenatal visit. Early fetal growth velocity was measured using BPD growth between 11 and 14 weeks scan and anomaly scan and standardizing this by Z scoring. Results: Out of 607 fetuses, 41 (6.7%) were slow growing, 531 (87.4%) normally growing, and 35 (5.7%) fast growing (Z scoring <10th{sup ,} 10–90th, and >90th percentiles respectively). As fetal growth velocity increased, the mean birth weight decreased from 2958.7 ± 388.9 (<10th centile), 2742.1 ± 576.6 (10–90th centile), to 2339.3 ± 729.4 (>90th centile); and gestational age at delivery decreased from 38.5 ± 1.3 (<10th centile), 37.5 ± 2.1 (10–90th centile), to 36.4 ± 2.2 (>90th centile), and both these trends were statistically significant (p < 0.001).Faster growing fetuses had a higher risk of preterm delivery(spontaneous + indicated) compared to other 2 groups [OR 4.42 (2.18,8.98)], and slower growing fetuses had a higher risk of postdated deliveries compared to other 2 groups [OR 3.042 (1.44, 6.45)].We found no significant association between early fetal growth velocity and incidence of small for gestational age at birth/low birth weight at term, preeclampsia, and perinatal mortality. Conclusions: Early fetal growth velocity between first and second trimesters, may be one of the important factors influencing ultimate birthweight and gestational age at delivery.

  10. A prospective observational study of early fetal growth velocity and its association with birth weight, gestational age at delivery, preeclampsia, and perinatal mortality

    International Nuclear Information System (INIS)

    Vasudeva, Akhila; Abraham, Anu Annie; Kamath, Asha

    2013-01-01

    Objectives: We aimed to measure early fetal growth velocity and to correlate this with the birth weight, gestational age at delivery, and with the incidence of adverse pregnancy outcomes specifically preeclampsia and perinatal mortality. Methods: A data based prospective observational study, wherein sonographic biometry data and specific pregnancy outcome related data were collected from pregnant women's records, starting soon after their first antenatal visit. Early fetal growth velocity was measured using BPD growth between 11 and 14 weeks scan and anomaly scan and standardizing this by Z scoring. Results: Out of 607 fetuses, 41 (6.7%) were slow growing, 531 (87.4%) normally growing, and 35 (5.7%) fast growing (Z scoring <10th , 10–90th, and >90th percentiles respectively). As fetal growth velocity increased, the mean birth weight decreased from 2958.7 ± 388.9 (<10th centile), 2742.1 ± 576.6 (10–90th centile), to 2339.3 ± 729.4 (>90th centile); and gestational age at delivery decreased from 38.5 ± 1.3 (<10th centile), 37.5 ± 2.1 (10–90th centile), to 36.4 ± 2.2 (>90th centile), and both these trends were statistically significant (p < 0.001).Faster growing fetuses had a higher risk of preterm delivery(spontaneous + indicated) compared to other 2 groups [OR 4.42 (2.18,8.98)], and slower growing fetuses had a higher risk of postdated deliveries compared to other 2 groups [OR 3.042 (1.44, 6.45)].We found no significant association between early fetal growth velocity and incidence of small for gestational age at birth/low birth weight at term, preeclampsia, and perinatal mortality. Conclusions: Early fetal growth velocity between first and second trimesters, may be one of the important factors influencing ultimate birthweight and gestational age at delivery

  11. Fetal monitoring indications for delivery and 2-year outcome in 310 infants with fetal growth restriction delivered before 32 weeks' gestation in the TRUFFLE study

    NARCIS (Netherlands)

    Visser, G.H.A.; Bilardo, Caterina M.; Derks, J. B.; Ferrazzi, E.; Fratelli, Nicola; Frusca, T.; Ganzevoort, W.; Lees, Christoph C.; Napolitano, Raffaele; Todros, T.; Wolf, H.; Hecher, K.; Marlow, N.; Arabin, B.; Brezinka, C.; Diemert, A.; Duvekot, Johannes J.; Martinelli, P.; Ostermayer, E.; Papageorghiou, Aris T.; Schlembach, D.; Schneider, K. T M; Thilaganathan, B.; Valcamonico, A.; Aktas, Ayse; Borgione, Silvia; Chaoui, Rabih; Cornette, Jerome M J; Diehl, Thilo; van Eyck, J.; van Haastert, I. C.; Kingdom, J.C.; Lobmaier, Silvia; Lopriore, E.; Missfelder-Lobos, Hannah; Mansi, Giuseppina; Martelli, Paola; Maso, Gianpaolo; Marsal, K.; Maurer-Fellbaum, Ute; Mensing van Charante, N.; Mulder-De Tollenaer, Susanne; Oberto, Manuela; Oepkes, D.; Ogge, Giovanna; van der Post, Joris A. M.; Prefumo, Federico; Preston, Lucy; Raimondi, Francesco; Rattue, H.; Reiss, Irwin K M; Scheepers, L. S.; Skabar, Aldo; Spaanderman, M.; Thornton, J.G.; Valensise, H.; Weisglas-Kuperus, N.; Zimmermann, Andrea

    2017-01-01

    Objective: In the TRUFFLE (Trial of Randomized Umbilical and Fetal Flow in Europe) study on the outcome of early fetal growth restriction, women were allocated to one of three groups of indication for delivery according to the following monitoring strategies: (1) reduced fetal heart rate (FHR)

  12. How to monitor pregnancies complicated by fetal growth restriction and delivery before 32 weeks : post-hoc analysis of TRUFFLE study

    NARCIS (Netherlands)

    Ganzevoort, W.; Mensing van Charante, N.; Thilaganathan, B.; Prefumo, Federico; Arabin, B.; Bilardo, Caterina M.; Brezinka, C.; Derks, J. B.; Diemert, A.; Duvekot, Johannes J.; Ferrazzi, E.; Frusca, T.; Hecher, K.; Marlow, N.; Martinelli, P.; Ostermayer, E.; Papageorghiou, Aris T.; Schlembach, D.; Schneider, K. T M; Todros, T.; Valcamonico, A.; Visser, G. H.A.; van Wassenaer-Leemhuis, A.; Lees, Christoph C.; Wolf, H.; Aktas, Ayse; Borgione, Silvia; Chaoui, Rabih; Cornette, Jerome M J; Diehl, Thilo; van Eyck, J.; Fratelli, Nicola; van Haastert, I. C.; Lobmaier, Silvia; Lopriore, E.; Missfelder-Lobos, Hannah; Mansi, Giuseppina; Martelli, Paola; Maso, Gianpaolo; Maurer-Fellbaum, Ute; Mulder-De Tollenaer, Susanne; Napolitano, Raffaele; Oberto, Manuela; Oepkes, D.; Ogge, Giovanna; van der Post, Joris A. M.; Preston, Lucy; Raimondi, Francesco; Rattue, H.; Reiss, Irwin K M; Scheepers, L. S.; Skabar, Aldo; Spaanderman, M.; Weisglas-Kuperus, N.; Zimmermann, Andrea

    2017-01-01

    Objectives: In the recent TRUFFLE study, it appeared that, in pregnancies complicated by fetal growth restriction (FGR) between 26 and 32 weeks' gestation, monitoring of the fetal ductus venosus (DV) waveform combined with computed cardiotocography (CTG) to determine timing of delivery increased the

  13. Fetal growth restriction is associated with malaria in pregnancy

    DEFF Research Database (Denmark)

    Briand, Valérie; Saal, Jessica; Ghafari, Caline

    2016-01-01

    BACKGROUND: Few studies have evaluated the effect of malaria on intrauterine growth restriction on the basis of the fetal growth rate, rather than just the small-for-gestational age z score. Here, we assessed the impact of malaria on IUGR, using data from a longitudinal, ultrasonography-based fol......BACKGROUND: Few studies have evaluated the effect of malaria on intrauterine growth restriction on the basis of the fetal growth rate, rather than just the small-for-gestational age z score. Here, we assessed the impact of malaria on IUGR, using data from a longitudinal, ultrasonography......-based follow-up study of Beninese women. METHODS: A total of 1016 women were followed up from gestational week 17 to delivery. Malaria was detected every month. Women underwent ultrasonography 4 times for gestational age determination and fetal biometry. We assessed the effect of malaria on birth weight......-for-gestational age z score (n = 735 women) and fetal growth velocity (n = 664), defined as a change in fetal weight z score over time. RESULTS: Malaria was detected in 43% of women. Fetal growth velocity was negative overall, decreasing further at the end of the third trimester. Women with ≥2 malarial parasite...

  14. Continuous delivery of propranolol from liposomes-in-microspheres significantly inhibits infantile hemangioma growth

    Directory of Open Access Journals (Sweden)

    Guo XN

    2017-09-01

    Full Text Available Xiaonan Guo,1,* Xiaoshuang Zhu,1,* Dakan Liu,1 Yubin Gong,1 Jing Sun,2 Changxian Dong1 1Department of Hemangioma and Vascular Malformation, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 2Department of Pharmacy, Second Military Medical University, Shanghai, People’s Republic of China *These authors contributed equally to this work Purpose: To reduce the adverse effects and high frequency of administration of propranolol to treat infantile hemangioma, we first utilized propranolol-loaded liposomes-in-microsphere (PLIM as a novel topical release system to realize sustained release of propranolol.Methods: PLIM was developed from encapsulating propranolol-loaded liposomes (PLs in microspheres made of poly(lactic-co-glycolic acid-b-poly(ethylene glycol-b-poly(lactic-co-glycolic acid copolymers (PLGA-PEG-PLGA. The release profile of propranolol from PLIM was evaluated, and its biological activity was investigated in vitro using proliferation assays on hemangioma stem cells (HemSCs. Tumor inhibition was studied in nude mice bearing human subcutaneous infantile hemangioma.Results: The microspheres were of desired particle size (~77.8 µm and drug encapsulation efficiency (~23.9% and achieved sustained drug release for 40 days. PLIM exerted efficient inhibition of the proliferation of HemSCs and significantly reduced the expression of two angiogenesis factors (vascular endothelial growth factor-A [VEGF-A] and basic fibroblast growth factor [bFGF] in HemSCs. Notably, the therapeutic effect of PLIM in hemangioma was superior to that of propranolol and PL in vivo, as reflected by significantly reduced hemangioma volume, weight, and microvessel density. The mean hemangioma weight of the PLIM-treated group was significantly lower than that of other groups (saline =0.28 g, propranolol =0.21 g, PL =0.13 g, PLIM =0.03 g; PLIM vs saline: P<0.001, PLIM vs propranolol: P<0.001, PLIM vs PL: P<0.001. The mean microvessel density of

  15. Prolonged controlled delivery of nerve growth factor using porous silicon nanostructures.

    Science.gov (United States)

    Zilony, Neta; Rosenberg, Michal; Holtzman, Liran; Schori, Hadas; Shefi, Orit; Segal, Ester

    2017-07-10

    Although nerve growth factor (NGF) is beneficial for the treatment of numerous neurological and non-neurological diseases, its therapeutic administration represents a significant challenge, due to the difficulty to locally deliver relevant doses in a safe and non-invasive manner. In this work, we employ degradable nanostructured porous silicon (PSi) films as carriers for NGF, allowing its continuous and prolonged release, while retaining its bioactivity. The PSi carriers exhibit high loading efficacy (up to 90%) of NGF and a continuous release, with no burst, over a period of>26days. The released NGF bioactivity is compared to that of free NGF in both PC12 cells and dissociated dorsal root ganglion (DRG) neurons. We show that the NGF has retained its bioactivity and induces neurite outgrowth and profound differentiation (of >50% for PC12 cells) throughout the period of release within a single administration. Thus, this proof-of-concept study demonstrates the immense therapeutic potential of these tunable carriers as long-term implants of NGF reservoirs and paves the way for new localized treatment strategies of neurodegenerative diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. A suspicious reason for Raynaud's phenomenon: Intrauterine device.

    Science.gov (United States)

    Diken, Adem I; Yalçınkaya, Adnan; Aksoy, Eray; Yılmaz, Seyhan; Çağlı, Kerim

    2015-06-01

    Primary Raynaud's phenomenon may be insistent in patients under medical therapy, and intrauterine devices may be an unnoticed reason in these patients. Fluctuations in female sex hormone status were reported to be associated with the emergence of primary Raynaud's phenomenon symptoms. The use of intrauterine devices was not reported to be associated with Raynaud's phenomenon previously. Intrauterine device may stimulate vascular hyperactivity regarding hormonal or unknown mechanisms that result in Raynaud's phenomenon. We present a postmenopausal patient who complained of primary Raynaud's phenomenon symptoms and had recovery after the removal of her copper intrauterine device. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  17. Association of cord blood chemokines and other biomarkers with neonatal complications following intrauterine inflammation.

    Directory of Open Access Journals (Sweden)

    Yoshikazu Otsubo

    Full Text Available Intrauterine inflammation has been associated with preterm birth and neonatal complications. Few reports have comprehensively investigated multiple cytokine profiles in cord blood and precisely identified surrogate markers for intrauterine inflammation.To identify the cytokines and surrogate markers associated with intrauterine inflammation and subsequent neonatal complications.We analyzed cord blood samples from 135 patients admitted to the neonatal intensive care unit at Sasebo City General Hospital. We retrospectively determined the associations between the presence of neonatal complications and cord blood cytokines, prenatal factors, and laboratory data at birth. A total of 27 cytokines in the cord blood were measured using a bead-based array sandwich immunoassay.Both Th1 and Th2 cytokine levels were low, whereas the levels of growth factors and chemokines were high. In particular, chemokines IL-8, MCP-1, and MIP-1α were significantly higher in very premature neonates when compared with more mature neonates. In addition, some have been shown to be associated with multiple neonatal complications, including patent ductus arteriosus (PDA, respiratory distress syndrome (RDS, and chronic lung disease (CLD. Similarly, the levels of N-terminal pro-brain natriuretic peptide, nucleated RBC, and urinary β2-microglobulin were associated with these complications and chemokine levels.Our results suggest the association of inflammatory chemokines IL-8, MCP-1, and MIP-1α with intrauterine inflammation, premature birth, and neonatal complications in these perinatal subjects. Furthermore, the association of the aforementioned biomarkers with PDA, RDS, and CLD may help establish early diagnostic measures to predict such neonatal complications following intrauterine inflammation.

  18. STRIDER: Sildenafil Therapy In Dismal prognosis Early-onset intrauterine growth Restriction--a protocol for a systematic review with individual participant data and aggregate data meta-analysis and trial sequential analysis

    NARCIS (Netherlands)

    Ganzevoort, Wessel; Alfirevic, Zarko; von Dadelszen, Peter; Kenny, Louise; Papageorghiou, Aris; van Wassenaer-Leemhuis, Aleid; Gluud, Christian; Mol, Ben Willem; Baker, Philip N.

    2014-01-01

    In pregnancies complicated by early-onset extreme fetal growth restriction, there is a high risk of preterm birth and an overall dismal fetal prognosis. Sildenafil has been suggested to improve this prognosis. The first aim of this review is to assess whether sildenafil benefits or harms these

  19. The Effects of Intrauterine Malnutrition on Maternal-Fetal Cholesterol Transport and Fetal Lipid Synthesis in Mice

    NARCIS (Netherlands)

    van Meer, Hester; van Straten, Esther M. E.; Baller, Julius F. W.; van Dijk, Theo H.; Kuipers, Folkert; Verkade, Henkjan J.; Plosch, Torsten

    Intrauterine malnutrition is associated with increased susceptibility to chronic diseases in adulthood. Growth-restricted infants display a less favorable lipid profile already shortly postnatal. Maternal low protein diet (LPD) during gestation is a well-defined model of fetal programming in rodents

  20. Local myocardial insulin-like growth factor 1 (IGF-1) delivery with biotinylated peptide nanofibers improves cell therapy for myocardial infarction

    Science.gov (United States)

    Davis, Michael E.; Hsieh, Patrick C. H.; Takahashi, Tomosaburo; Song, Qing; Zhang, Shuguang; Kamm, Roger D.; Grodzinsky, Alan J.; Anversa, Piero; Lee, Richard T.

    2006-05-01

    Strategies for cardiac repair include injection of cells, but these approaches have been hampered by poor cell engraftment, survival, and differentiation. To address these shortcomings for the purpose of improving cardiac function after injury, we designed self-assembling peptide nanofibers for prolonged delivery of insulin-like growth factor 1 (IGF-1), a cardiomyocyte growth and differentiation factor, to the myocardium, using a "biotin sandwich" approach. Biotinylated IGF-1 was complexed with tetravalent streptavidin and then bound to biotinylated self-assembling peptides. This biotin sandwich strategy allowed binding of IGF-1 but did not prevent self-assembly of the peptides into nanofibers within the myocardium. IGF-1 that was bound to peptide nanofibers activated Akt, decreased activation of caspase-3, and increased expression of cardiac troponin I in cardiomyocytes. After injection into rat myocardium, biotinylated nanofibers provided sustained IGF-1 delivery for 28 days, and targeted delivery of IGF-1 in vivo increased activation of Akt in the myocardium. When combined with transplanted cardiomyocytes, IGF-1 delivery by biotinylated nanofibers decreased caspase-3 cleavage by 28% and increased the myocyte cross-sectional area by 25% compared with cells embedded within nanofibers alone or with untethered IGF-1. Finally, cell therapy with IGF-1 delivery by biotinylated nanofibers improved systolic function after experimental myocardial infarction, demonstrating how engineering the local cellular microenvironment can improve cell therapy. engineering | maturation | scaffold

  1. Effects of Adenovirus-Mediated Delivery of the Human Hepatocyte Growth Factor Gene in Experimental Radiation-Induced Heart Disease

    International Nuclear Information System (INIS)

    Hu Shunying; Chen Yundai; Li Libing; Chen Jinlong; Wu Bin; Zhou, Xiao; Zhi Guang; Li Qingfang; Wang Rongliang; Duan Haifeng; Guo Zikuan; Yang Yuefeng; Xiao Fengjun; Wang Hua; Wang Lisheng

    2009-01-01

    Purpose: Irradiation to the heart may lead to late cardiovascular complications. The purpose of this study was to investigate whether adenovirus-mediated delivery of the human hepatocyte growth factor gene could reduce post-irradiation damage of the rat heart and improve heart function. Methods and Materials: Twenty rats received single-dose irradiation of 20 Gy gamma ray locally to the heart and were randomized into two groups. Two weeks after irradiation, these two groups of rats received Ad-HGF or mock adenovirus vector intramyocardial injection, respectively. Another 10 rats served as sham-irradiated controls. At post-irradiation Day 120, myocardial perfusion was tested by myocardial contrast echocardiography with contrast agent injected intravenously. At post-irradiation Day 180, cardiac function was assessed using the Langendorff technique with an isolated working heart model, after which heart samples were collected for histological evaluation. Results: Myocardial blood flow was significantly improved in HGF-treated animals as measured by myocardial contrast echocardiography at post-irradiation Day 120 . At post-irradiation Day 180, cardiac function was significantly improved in the HGF group compared with mock vector group, as measured by left ventricular peak systolic pressure (58.80 ± 9.01 vs. 41.94 ± 6.65 mm Hg, p < 0.05), the maximum dP/dt (5634 ± 1303 vs. 1667 ± 304 mm Hg/s, p < 0.01), and the minimum dP/dt (3477 ± 1084 vs. 1566 ± 499 mm Hg/s, p < 0.05). Picrosirius red staining analysis also revealed a significant reduction of fibrosis in the HGF group. Conclusion: Based on the study findings, hepatocyte growth factor gene transfer can attenuate radiation-induced cardiac injury and can preserve cardiac function.

  2. Intrauterine photoacoustic and ultrasound imaging probe

    Science.gov (United States)

    Miranda, Christopher; Barkley, Joel; Smith, Barbara S.

    2018-04-01

    Intrauterine photoacoustic and ultrasound imaging are probe-based imaging modalities with translational potential for use in detecting endometrial diseases. This deep-tissue imaging probe design allows for the retrofitting of commercially available endometrial sampling curettes. The imaging probe presented here has a 2.92-mm diameter and approximate length of 26 cm, which allows for entry into the human endometrial cavity, making it possible to use photoacoustic imaging and high-resolution ultrasound to characterize the uterus. We demonstrate the imaging probes' ability to provide structural information of an excised pig uterus using ultrasound imaging and detect photoacoustic signals at a radial depth of 1 cm.

  3. Effect of perioperative fetal intrauterine hypoxia on maternal oxidative stress injury after cesarean section

    Directory of Open Access Journals (Sweden)

    Xue-Hong Zou

    2017-03-01

    Full Text Available Objective: To study the effect of perioperative fetal intrauterine hypoxia on maternal oxidative stress injury after cesarean section. Methods: 37 puerperae receiving cesarean section for fetal intrauterine hypoxia between May 2014 and December 2016 were selected as hypoxia group and 40 puerperae receiving cesarean section during the same period and without complications during pregnancy or fetal intrauterine hypoxia were selected as control group. Umbilical arterial blood was collected after delivery of placenta for blood gas analysis, and the placenta tissue and serum samples were collected to test the content of oxidative stress products and antioxidants. Results: Umbilical arterial blood gas analysis parameters pH value as well as PO2, HCO3 - and BE content of hypoxia group were significantly lower than those of control group (P<0.05; NADPH, reactive oxide species (ROS and reactive nitrogen species (RNS content in placenta tissue of hypoxia group were significantly higher than those of control group (P <0.05 while glutathione S-transferase (GST, glutathione peroxidase (GPx, superoxide dismutase (SOD, Trx, vitamin C (VitC, VitE and coenzyme Q10 (CoQ10 content were significantly lower than those of control group (P<0.05; serum malondialdehyde (MDA and 8-iso-prostaglandin F2α (8-iso-PGF2α content of hypoxia group were significantly higher than those of control group (P<0.05. Conclusions: Perioperative fetal intrauterine hypoxia can lead to maternal oxidative stress injury after cesarean section and increase the generation of free radicals and the consumption of antioxidants.

  4. Vesical Calculus 10 Years Post Missing Intrauterine Contraceptive ...

    African Journals Online (AJOL)

    Vesical Calculus 10 Years Post Missing Intrauterine. Contraceptive Device. Abdullahi Abdulwahab-Ahmed, Oluwagbemiga Olabisi Ogunleye. INTRODUCTION. Intrauterine contraceptive devices (IUCD) are acceptable means of contraception world over.[1-4] There have been reports of its migration to other adjourning sites ...

  5. A survey of four years intrauterine insemination at Shariati Hospital

    Directory of Open Access Journals (Sweden)

    Aghahosseini M

    1998-08-01

    Full Text Available Intrauterine insemination (IUI has been practiced since the late 1800's primarily for idiopathic infertility, and in men with deficient semen parameters. The procedure is done by placing washed sperm in uterus a few hours before ovulation. The records of 427 couples receiving IUI for treatment of infertility at Shariati hospital in 1370-74 were reviewed retrospectively. These patients had IUI in 574 cycles. Eighty patients became pregnant and delivery rate was 14% per cycle. Pregnancy rate is impressive when ovulation induction is combined with insemination timed just before ovulation. The success rate in Shariati hospital is comparable to other infertility centers in the world and cost of a cycle of IUI with HMG superovulation is approximately one third the cost of IVF-ET or GIFT cycle and avoids invasive oocyte retrieval and extracorporeal fertilization. So we suggest that women with refractory infertility without anatomic distortion of pelvis can have at least 3-6 cycles of IUI before IVF or GIFT.

  6. Targeted delivery of polyamidoamine-paclitaxel conjugate functionalized with anti-human epidermal growth factor receptor 2 trastuzumab

    Directory of Open Access Journals (Sweden)

    Ma P

    2015-03-01

    Full Text Available Pengkai Ma,1 Xuemei Zhang,1 Ling Ni,2 Jinming Li,2 Fengpu Zhang,1 Zheng Wang,1 Shengnan Lian,1 Kaoxiang Sun1 1School of Pharmacy, Yantai University, Yantai, Shandong Province, People’s Republic of China; 2State Key Laboratory of Long-acting and Targeting Drug Delivery System, Yantai, Shandong Province, People’s Republic of China Background: Antibody-dendrimer conjugates have the potential to improve the targeting and release of chemotherapeutic drugs at the tumor site while reducing adverse side effects caused by drug accumulation in healthy tissues. In this study, trastuzumab (TMAB, which binds to human epidermal growth factor receptor 2 (HER2, was used as a targeting agent in a TMAB-polyamidoamine (PAMAM conjugate carrying paclitaxel (PTX specifically to cells overexpressing HER2. Methods: TMAB was covalently linked to a PAMAM dendrimer via bifunctional polyethylene glycol (PEG. PTX was conjugated to PAMAM using succinic anhydride as a cross-linker, yielding TMAB-PEG-PAMAM-PTX. Dynamic light scattering and transmission electron microscopy were used to characterize the conjugates. The cellular uptake and in vivo biodistribution were studied by fluorescence microscopy, flow cytometry, and Carestream In Vivo FX, respectively. Results: Nuclear magnetic resonance spectroscopy demonstrated that PEG, PTX, fluorescein isothiocyanate, and cyanine7 were conjugated to PAMAM. Ultraviolet-visible spectroscopy and sodium dodecyl sulfate polyacrylamide gel electrophoresis demonstrated that TMAB was conjugated to PEG-PAMAM. Dynamic light scattering and transmission electron microscopy measurements revealed that the different conjugates ranged in size between 10 and 35 nm and had a spherical shape. In vitro cellular uptake demonstrated that the TMAB-conjugated PAMAM was taken up by HER2-overexpressing BT474 cells more efficiently than MCF-7 cells that expressed lower levels of HER2. Co-localization experiments indicated that TMAB-conjugated PAMAM was

  7. Fetal uptake of intra-amniotically delivered dendrimers in a mouse model of intrauterine inflammation and preterm birth.

    Science.gov (United States)

    Burd, Irina; Zhang, Fan; Dada, Tahani; Mishra, Manoj K; Borbiev, Talaibek; Lesniak, Wojciech G; Baghlaf, Haitham; Kannan, Sujatha; Kannan, Rangaramanujam M

    2014-08-01

    Intrauterine inflammation is associated with preterm birth and can lead to fetal neuroinflammation and neurobehavioral disorders in newborns. Dendrimers can intrinsically target and deliver drugs for the treatment of neuroinflammation. We explore whether hydroxyl polyamidoamine (PAMAM) dendrimer (G4-OH)-based nanomedicines can be delivered to the fetus by intra-amniotic administration, in a mouse model of intrauterine inflammation. The time-dependent accumulation of G4-OH-fluorophore conjugate was quantified by fluorescence. These studies suggest that, after intra-amniotic administration, there is significant accumulation of dendrimer in the fetus gut and brain. In addition, there is some fetal-maternal transport of the dendrimer. Confocal microscopy confirmed the presence of G4-OH in the fetal brain, with a large accumulation in the brain blood vessels and the brain parenchyma, and some microglial uptake. We believe that intra-amniotic administration of G4-OH-drug nanomedicines may enable the treatment of diseases related to intrauterine inflammation and fetal neuroinflammation. Using a mouse model of intrauterin inflammation leading to neuroinflammation in the fetus, these investigators demonstrate that intra-amniotic delivery of hydroxyl polyamidoamine (PAMAM) dendrimer (G4-OH)-based nanomedicines may provide an effective method in preventing this complication. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Using maize as a model to study pollen tube growth and guidance, cross-incompatibility and sperm delivery in grasses.

    Science.gov (United States)

    Dresselhaus, Thomas; Lausser, Andreas; Márton, Mihaela L

    2011-09-01

    In contrast to animals and lower plants such as mosses and ferns, sperm cells of flowering plants (angiosperms) are immobile and require transportation to the female gametes via the vegetative pollen tube cell to achieve double fertilization. The path of the pollen tube towards the female gametophyte (embryo sac) has been intensively studied in many intra- and interspecific crossing experiments with the aim of increasing the gene pool of crop plants for greater yield, improved biotic and abiotic stress resistance, and for introducing new agronomic traits. Many attempts to hybridize different species or genotypes failed due to the difficulty for the pollen tubes in reaching the female gametophyte. Detailed studies showed that these processes are controlled by various self-incompatible (intraspecific) and cross-incompatible (interspecific) hybridization mechanisms. Understanding the molecular mechanisms of crossing barriers is therefore of great interest in plant reproduction, evolution and breeding research. In particular, pre-zygotic hybridization barriers related to pollen tube germination, growth, guidance and sperm delivery, which are considered the major hybridization controls in nature and thus also contribute to species isolation and speciation, have been intensively investigated. Despite this general interest, surprisingly little is known about these processes in the most important agronomic plant family, the Gramineae, Poaceae or grasses. Small polymorphic proteins and their receptors, degradation of sterility locus proteins and general compounds such as calcium, γ-aminobutyric acid or nitric oxide have been shown to be involved in progamic pollen germination, adhesion, tube growth and guidance, as well as sperm release. Most advances have been made in the Brassicaceae, Papaveraceae, Linderniaceae and Solanaceae families including their well-understood self-incompatibility (SI) systems. Grass species evolved similar mechanisms to control the penetration

  9. Abnormal cortical development after premature birth shown by altered allometric scaling of brain growth.

    Directory of Open Access Journals (Sweden)

    Olga Kapellou

    2006-08-01

    Full Text Available We postulated that during ontogenesis cortical surface area and cerebral volume are related by a scaling law whose exponent gives a quantitative measure of cortical development. We used this approach to investigate the hypothesis that premature termination of the intrauterine environment by preterm birth reduces cortical development in a dose-dependent manner, providing a neural substrate for functional impairment.We analyzed 274 magnetic resonance images that recorded brain growth from 23 to 48 wk of gestation in 113 extremely preterm infants born at 22 to 29 wk of gestation, 63 of whom underwent neurodevelopmental assessment at a median age of 2 y. Cortical surface area was related to cerebral volume by a scaling law with an exponent of 1.29 (95% confidence interval, 1.25-1.33, which was proportional to later neurodevelopmental impairment. Increasing prematurity and male gender were associated with a lower scaling exponent (p < 0.0001 independent of intrauterine or postnatal somatic growth.Human brain growth obeys an allometric scaling relation that is disrupted by preterm birth in a dose-dependent, sexually dimorphic fashion that directly parallels the incidence of neurodevelopmental impairments in preterm infants. This result focuses attention on brain growth and cortical development during the weeks following preterm delivery as a neural substrate for neurodevelopmental impairment after premature delivery.

  10. Continuation of copper and levonorgestrel intrauterine devices: a retrospective cohort study.

    Science.gov (United States)

    Phillips, Sharon J; Hofler, Lisa G; Modest, Anna M; Harvey, Lara F B; Wu, Lily H; Hacker, Michele R

    2017-07-01

    Studies conflict on whether the duration of use of the copper intrauterine device is longer than that of the levonorgestrel intrauterine device, and whether women who continue using intrauterine devices differ from those who discontinue. We sought to assess continuation rates and performance of levonorgestrel intrauterine devices compared with copper intrauterine devices over a 5-year period. We performed a retrospective cohort study of 1164 individuals who underwent intrauterine device placement at an urban academic medical center. The analysis focused on a comparison of continuation rates between those using levonorgestrel intrauterine device and copper intrauterine device, factors associated with discontinuation, and intrauterine device performance. We assessed the differences in continuation at discrete time points, pregnancy, and expulsion rates using χ 2 tests and calculated hazard ratios using a multivariable Cox model. Of 1164 women who underwent contraceptive intrauterine device insertion, 956 had follow-up data available. At 2 years, 64.9% of levonorgestrel intrauterine device users continued their device, compared with 57.7% of copper intrauterine device users (P = .11). At 4 years, continuation rates were 45.1% for levonorgestre