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Sample records for human fetal growth

  1. Human fetal growth is constrained below optimal for perinatal survival

    NARCIS (Netherlands)

    Vasak, B.; Koenen, S. V.; Koster, M. P. H.; Hukkelhoven, C. W. P. M.; Franx, A.; Hanson, M. A.; Visser, GHA

    ObjectiveThe use of fetal growth charts assumes that the optimal size at birth is at the 50(th) birth-weight centile, but interaction between maternal constraints on fetal growth and the risks associated with small and large fetal size at birth may indicate that this assumption is not valid for

  2. GLI3 Links Environmental Arsenic Exposure and Human Fetal Growth

    Directory of Open Access Journals (Sweden)

    Emily F. Winterbottom

    2015-06-01

    Full Text Available Although considerable evidence suggests that in utero arsenic exposure affects children's health, these data are mainly from areas of the world where groundwater arsenic levels far exceed the World Health Organization limit of 10 μg/L. We, and others, have found that more common levels of in utero arsenic exposure may also impact children's health. However, the underlying molecular mechanisms are poorly understood. To address this issue, we analyzed the expression of key developmental genes in fetal placenta in a birth cohort of women using unregulated water supplies in a US region with elevated groundwater arsenic. We identified several genes whose expression associated with maternal arsenic exposure in a fetal sex-specific manner. In particular, expression of the HEDGEHOG pathway component, GLI3, in female placentae was both negatively associated with arsenic exposure and positively associated with infant birth weight. This suggests that modulation of GLI3 in the fetal placenta, and perhaps in other fetal tissues, contributes to arsenic's detrimental effects on fetal growth. We showed previously that arsenic-exposed NIH3T3 cells have reduced GLI3 repressor protein. Together, these studies identify GLI3 as a key signaling node that is affected by arsenic, mediating a subset of its effects on developmental signaling and fetal health.

  3. Effect of placental factors on growth and function of the human fetal adrenal in vitro.

    Science.gov (United States)

    Riopel, L; Branchaud, C L; Goodyer, C G; Zweig, M; Lipowski, L; Adkar, V; Lefebvre, Y

    1989-11-01

    Conditioned medium from human placental monolayer cultures (PM) had a marked stimulatory effect on proliferation (3H-thymidine uptake) of human fetal zone adrenal cells in primary monolayer culture, even in the absence of serum. Epidermal growth factor (EGF) and fibroblast growth factor (FGF) also significantly stimulated fetal adrenal cell growth. However, the effects of PM differed from those of EGF and FGF in several respects: 1) maximal response to PM was 2-5 times greater; 2) mitogenic effects of EGF and FGF were suppressed by adrenocorticotropic hormone (ACTH), whereas that of 50% PM was not; 3) PM inhibited ACTH-stimulated steroidogenesis (dehydroepiandrosterone sulfate and cortisol), but EGF and FGF did not. Preliminary characterization studies have indicated that approximately half of the placental growth-promoting activity is heat resistant and sensitive to bacterial proteases, and that 50-60% of the activity is lost after dialysis with membranes having a molecular weight cutoff of 3500. These findings suggest a role for the placenta in the growth and differentiated function of the human fetal adrenal gland.

  4. Effect of placental factors on growth and function of the human fetal adrenal in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Riopel, L.; Branchaud, C.L.; Goodyer, C.G.; Zweig, M.; Lipowski, L.; Adkar, V.; Lefebvre, Y. (McGill Univ.-Montreal Children' s Hospital Research Institute, Quebec (Canada))

    1989-11-01

    Conditioned medium from human placental monolayer cultures (PM) had a marked stimulatory effect on proliferation (3H-thymidine uptake) of human fetal zone adrenal cells in primary monolayer culture, even in the absence of serum. Epidermal growth factor (EGF) and fibroblast growth factor (FGF) also significantly stimulated fetal adrenal cell growth. However, the effects of PM differed from those of EGF and FGF in several respects: (1) maximal response to PM was 2-5 times greater; (2) mitogenic effects of EGF and FGF were suppressed by adrenocorticotropic hormone (ACTH), whereas that of 50% PM was not; (3) PM inhibited ACTH-stimulated steroidogenesis (dehydroepiandrosterone sulfate and cortisol), but EGF and FGF did not. Preliminary characterization studies have indicated that approximately half of the placental growth-promoting activity is heat resistant and sensitive to bacterial proteases, and that 50-60% of the activity is lost after dialysis with membranes having a molecular weight cutoff of 3500. These findings suggest a role for the placenta in the growth and differentiated function of the human fetal adrenal gland.

  5. Effect of placental factors on growth and function of the human fetal adrenal in vitro

    International Nuclear Information System (INIS)

    Riopel, L.; Branchaud, C.L.; Goodyer, C.G.; Zweig, M.; Lipowski, L.; Adkar, V.; Lefebvre, Y.

    1989-01-01

    Conditioned medium from human placental monolayer cultures (PM) had a marked stimulatory effect on proliferation (3H-thymidine uptake) of human fetal zone adrenal cells in primary monolayer culture, even in the absence of serum. Epidermal growth factor (EGF) and fibroblast growth factor (FGF) also significantly stimulated fetal adrenal cell growth. However, the effects of PM differed from those of EGF and FGF in several respects: (1) maximal response to PM was 2-5 times greater; (2) mitogenic effects of EGF and FGF were suppressed by adrenocorticotropic hormone (ACTH), whereas that of 50% PM was not; (3) PM inhibited ACTH-stimulated steroidogenesis (dehydroepiandrosterone sulfate and cortisol), but EGF and FGF did not. Preliminary characterization studies have indicated that approximately half of the placental growth-promoting activity is heat resistant and sensitive to bacterial proteases, and that 50-60% of the activity is lost after dialysis with membranes having a molecular weight cutoff of 3500. These findings suggest a role for the placenta in the growth and differentiated function of the human fetal adrenal gland

  6. Hypoglycemia and the origin of hypoxia-induced reduction in human fetal growth.

    Directory of Open Access Journals (Sweden)

    Stacy Zamudio

    2010-01-01

    Full Text Available The most well known reproductive consequence of residence at high altitude (HA >2700 m is reduction in fetal growth. Reduced fetoplacental oxygenation is an underlying cause of pregnancy pathologies, including intrauterine growth restriction and preeclampsia, which are more common at HA. Therefore, altitude is a natural experimental model to study the etiology of pregnancy pathophysiologies. We have shown that the proximate cause of decreased fetal growth is not reduced oxygen availability, delivery, or consumption. We therefore asked whether glucose, the primary substrate for fetal growth, might be decreased and/or whether altered fetoplacental glucose metabolism might account for reduced fetal growth at HA.Doppler and ultrasound were used to measure maternal uterine and fetal umbilical blood flows in 69 and 58 residents of 400 vs 3600 m. Arterial and venous blood samples from mother and fetus were collected at elective cesarean delivery and analyzed for glucose, lactate and insulin. Maternal delivery and fetal uptakes for oxygen and glucose were calculated.The maternal arterial - venous glucose concentration difference was greater at HA. However, umbilical venous and arterial glucose concentrations were markedly decreased, resulting in lower glucose delivery at 3600 m. Fetal glucose consumption was reduced by >28%, but strongly correlated with glucose delivery, highlighting the relevance of glucose concentration to fetal uptake. At altitude, fetal lactate levels were increased, insulin concentrations decreased, and the expression of GLUT1 glucose transporter protein in the placental basal membrane was reduced.Our results support that preferential anaerobic consumption of glucose by the placenta at high altitude spares oxygen for fetal use, but limits glucose availability for fetal growth. Thus reduced fetal growth at high altitude is associated with fetal hypoglycemia, hypoinsulinemia and a trend towards lactacidemia. Our data support that

  7. Evaluation of Fetal Intestinal Cell Growth and Antimicrobial Biofunctionalities of Donor Human Milk After Preparative Processes.

    Science.gov (United States)

    Kanaprach, Pasinee; Pongsakul, Nutkridta; Apiwattanakul, Nopporn; Muanprasat, Chatchai; Supapannachart, Sarayut; Nuntnarumit, Pracha; Chutipongtanate, Somchai

    2018-04-01

    Donor human milk is considered the next best nutrition following mother's own milk to prevent neonatal infection and necrotizing enterocolitis in preterm infants who are admitted at neonatal intensive care unit. However, donor milk biofunctionalities after preparative processes have rarely been documented. To evaluate biofunctionalities preserved in donor milk after preparative processes by cell-based assays. Ten pools of donor milk were produced from 40 independent specimens. After preparative processes, including bacterial elimination methods (holder pasteurization and cold-sterilization microfiltration) and storage conditions (-20°C freezing storage and lyophilization) with varied duration of storage (0, 3, and 6, months), donor milk biofunctionalities were examined by fetal intestinal cell growth and antimicrobial assays. At baseline, raw donor milk exhibited 193.1% ± 12.3% of fetal intestinal cell growth and 42.4% ± 11.8% of antimicrobial activities against Escherichia coli. After bacteria eliminating processes, growth promoting activity was better preserved in pasteurized donor milk than microfiltrated donor milk (169.5% ± 14.3% versus 146.0% ± 11.8%, respectively; p pasteurized donor milk was further examined for the effects of storage conditions at 3 and 6 months. Freezing storage, but not lyophilization, could preserve higher growth-promoting activity during 6 months of storage (163.0% ± 9.4% versus 72.8% ± 6.2%, respectively; p < 0.005). Nonetheless, antimicrobial activity was lost at 6 months, regardless of the storage methods. This study revealed that fetal intestinal cell growth and antimicrobial assays could be applied to measure donor milk biofunctionalities and support the utilization of donor milk within 3 months after preparative processes.

  8. Fetal Mesenchymal Stromal Cells Differentiating towards Chondrocytes Acquire a Gene Expression Profile Resembling Human Growth Plate Cartilage

    NARCIS (Netherlands)

    van Gool, S.A.; Emons, J.A.M.; Leijten, Jeroen Christianus Hermanus; Decker, E.; Sticht, C.; van Houwelingen, J.C.; Goeman, J.J.; Kleijburg, C.; Scherjon, S.; Gretz, N.; Wit, J.M.; Rappold, G.; Post, Janine Nicole; Karperien, Hermanus Bernardus Johannes

    2012-01-01

    Abstract We used human fetal bone marrow-derived mesenchymal stromal cells (hfMSCs) differentiating towards chondrocytes as an alternative model for the human growth plate (GP). Our aims were to study gene expression patterns associated with chondrogenic differentiation to assess whether

  9. Transforming growth factor-β (TGF-β) signaling in healthy human fetal skin: a descriptive study.

    Science.gov (United States)

    Walraven, M; Beelen, R H J; Ulrich, M M W

    2015-05-01

    TGF-β plays an important role in growth and development but is also involved in scarring and fibrosis. Differences for this growth factor are known between scarless fetal wound healing and adult wound healing. Nonetheless, most of the data in this area are from animal studies or in vitro studies and, thus, information about the human situation is incomplete and scarce. The aim of this study was to compare the canonical TGF-β signaling in unwounded human fetal and adult skin. Q-PCR, immunohistochemistry, Western Blot and Luminex assays were used to determine gene expression, protein levels and protein localization of components of this pathway in healthy skin. All components of the canonical TGF-β pathway were present in unwounded fetal skin. Compared to adult skin, fetal skin had differential concentrations of the TGF-β isoforms, had high levels of phosphorylated receptor-Smads, especially in the epidermis, and had low expression of several fibrosis-associated target genes. Further, the results indicated that the processes of receptor endocytosis might also differ between fetal and adult skin. This descriptive study showed that there are differences in gene expression, protein concentrations and protein localization for most components of the canonical TGF-β pathway between fetal and adult skin. The findings of this study can be a starting point for further research into the role of TGF-β signaling in scarless healing. Copyright © 2015 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  10. Human fetal liver stromal cells that overexpress bFGF support growth and maintenance of human embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Jiafei Xi

    Full Text Available In guiding hES cell technology toward the clinic, one key issue to be addressed is to culture and maintain hES cells much more safely and economically in large scale. In order to avoid using mouse embryonic fibroblasts (MEFs we isolated human fetal liver stromal cells (hFLSCs from 14 weeks human fetal liver as new human feeder cells. hFLSCs feeders could maintain hES cells for 15 passages (about 100 days. Basic fibroblast growth factor (bFGF is known to play an important role in promoting self-renewal of human embryonic stem (hES cells. So, we established transgenic hFLSCs that stably express bFGF by lentiviral vectors. These transgenic human feeder cells--bFGF-hFLSCs maintained the properties of H9 hES cells without supplementing with any exogenous growth factors. H9 hES cells culturing under these conditions maintained all hES cell features after prolonged culture, including the developmental potential to differentiate into representative tissues of all three embryonic germ layers, unlimited and undifferentiated proliferative ability, and maintenance of normal karyotype. Our results demonstrated that bFGF-hFLSCs feeder cells were central to establishing the signaling network among bFGF, insulin-like growth factor 2 (IGF-2, and transforming growth factor β (TGF-β, thereby providing the framework in which hES cells were instructed to self-renew or to differentiate. We also found that the conditioned medium of bFGF-hFLSCs could maintain the H9 hES cells under feeder-free conditions without supplementing with bFGF. Taken together, bFGF-hFLSCs had great potential as feeders for maintaining pluripotent hES cell lines more safely and economically.

  11. 125I-human epidermal growth factor specific binding to placentas and fetal membranes from varoius pregnancy states

    International Nuclear Information System (INIS)

    Hofmann, G.E.; Siddiqi, T.A.; Rao, Ch. V.; Carman, F.R.

    1988-01-01

    Specific binding of 125 I-human epidermal growth factor (hEGF) to homogenates of term human placentas and fetal membranes from normal and appropriate for gestational age (N = 20), intrauterine growth retarded (N = 9), twin (N = 11), White class A/B diabetic (N = 12), and large for gestational age (N = 13) pregnancies was measured. In all pregnancy states, placentas bound approximately four times more 125 I-hEGF than did fetal membranes (P 125 I-hEGF binding to fetal membranes from the various pregnancy states (P 125 I-hEGF specific binding to placentas from intrauterine growth retarded or twin pregnancies was significantly greater compared with placentas from normal and appropriate for gestational age pregnancies (P 125 I-hEGF specific binding did not differ between placentas from intrauterine growth retarded or twin pregnancies (P 125 I-hEGF binding did not vary with fetal sex, maternal race, placental weight, or gestational age between 37 to 42 weeks (P 125 I-hEGF binding increased with increasing infant weight when appropriate for gestational age and large for gestational age infants were included (P<0.05, r = 0.38, N = 32) but not for intrauterine growth retarded, appropriate for gestational age, or large for gestational age infants alone. (author)

  12. /sup 125/I-human epidermal growth factor specific binding to placentas and fetal membranes from varoius pregnancy states

    Energy Technology Data Exchange (ETDEWEB)

    Hofmann, G.E.; Siddiqi, T.A.; Rao, Ch. V.; Carman, F.R.

    1988-01-01

    Specific binding of /sup 125/I-human epidermal growth factor (hEGF) to homogenates of term human placentas and fetal membranes from normal and appropriate for gestational age (N = 20), intrauterine growth retarded (N = 9), twin (N = 11), White class AB diabetic (N = 12), and large for gestational age (N = 13) pregnancies was measured. In all pregnancy states, placentas bound approximately four times more /sup 125/I-hEGF than did fetal membranes (P<0.0001). There was no significant differnce in /sup 125/I-hEGF binding to fetal membranes from the various pregnancy states (P<0.05). /sup 125/I-hEGF specific binding to placentas from intrauterine growth retarded or twin pregnancies was significantly greater compared with placentas from normal and appropriate for gestational age pregnancies (P<0.05). The binding to placentas from pregnancies complicated by White class AB diabetes or large for gestational age infants, on the other hand, was not significantly different from that to placentas from normal and appropriate for gestational age pregnancies. /sup 125/I-hEGF specific binding did not differ between placentas from intrauterine growth retarded or twin pregnancies (P<0.05). Placental and fetal membrane /sup 125/I-hEGF binding did not vary with fetal sex, maternal race, placental weight, or gestational age between 37 to 42 weeks (P<0.05). Placental but not fetal membrane /sup 125/I-hEGF binding increased with increasing infant weight when appropriate for gestational age and large for gestational age infants were included (P<0.05, r = 0.38, N = 32) but not for intrauterine growth retarded, appropriate for gestational age, or large for gestational age infants alone.

  13. Growth-inhibitory effect of TGF-B on human fetal adrenal cells in primary monolayer culture.

    Science.gov (United States)

    Riopel, L; Branchaud, C L; Goodyer, C G; Adkar, V; Lefebvre, Y

    1989-08-01

    We examined the effects of transforming-growth factor-B (TGF-B) on growth ([3H]-thymidine uptake) and function (dehydroepiandrosterone sulfate [DHAS] and cortisol production) of human fetal zone adrenal cells. Results indicate that TGF-B significantly inhibits, in a dose-related manner, both basal and epidermal growth factor (EGF)-stimulated cell growth: IC50 = 0.1-0.25 ng/ml. EGF is ineffective in overcoming the inhibitory effect of TGF-B, suggesting a noncompetitive antagonism between the two factors. Also, the inhibitory effect of TGF-B is additive to that of adrenocorticotropic hormone (ACTH). On the other hand, TGF-B (1 ng/ml) does not significantly change basal or ACTH-stimulated DHAS or cortisol secretion. We conclude that, unlike its effect on other steroid-producing cells, TGF-B inhibits growth of fetal zone cells and does not appear to have a significant inhibitory effect on steroidogenesis.

  14. Influence of the fetal bovine serum proteins on the growth of human osteoblast cells on graphene

    Czech Academy of Sciences Publication Activity Database

    Kalbáčová, M.; Brož, A.; Kalbáč, Martin

    100A, č. 11 (2012), s. 3001-3007 ISSN 1549-3296 R&D Projects: GA AV ČR IAA400400911; GA AV ČR KAN200100801; GA ČR GAP204/10/1677; GA ČR(CZ) GAP208/12/1062; GA MŠk ME09060 Institutional support: RVO:61388955 Keywords : human osteoblast * graphene * fetal bovine serum Subject RIV: CG - Electrochemistry Impact factor: 2.834, year: 2012

  15. Serial measurements of serum human placental lactogen (hPL) and serial ultrasound examinations in the evaluation of fetal growth

    DEFF Research Database (Denmark)

    Sørensen, Steen; von Tabouillot, D; Schioler, V

    2000-01-01

    Serial serum hPL measurements and serial ultrasound fetometry were compared in the evaluation of fetal growth by relating these two parameters to size at birth and to clinical factors known to influence size at birth. The data were from a prospective study of 1000 consecutive pregnant women...... considered to be at risk for fetal growth retardation with retrospective analysis. Serum hPL was measured by radioimmunoassay and fetal weight estimated by ultrasound every 3 weeks during the last trimester. hPL values were expressed as multiples of the median (MoM) and linear regression analysis of the h......PL MoM values was carried out for each pregnancy to find the slope of the line (hPL-slope); at least 3 serum hPL values were required. The estimated fetal weight and weight-for-age at birth was expressed in Z-scores. The individual intrauterine growth velocity was calculated by regression analysis...

  16. The effect of fetal sex on customized fetal growth charts.

    Science.gov (United States)

    Rizzo, Giuseppe; Prefumo, Federico; Ferrazzi, Enrico; Zanardini, Cristina; Di Martino, Daniela; Boito, Simona; Aiello, Elisa; Ghi, Tullio

    2016-12-01

    To evaluate the effect of fetal sex on singleton pregnancy growth charts customized for parental characteristics, race, and parity Methods: In a multicentric cross-sectional study, 8070 ultrasonographic examinations from low-risk singleton pregnancies between 16 and 40 weeks of gestation were considered. The fetal measurements obtained were biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL). Quantile regression was used to examine the impact of fetal sex across the biometric percentiles of the fetal measurements considered together with parents' height, weight, parity, and race. Fetal gender resulted to be a significant covariate for BDP, HC, and AC with higher values for male fetuses (p ≤ 0.0009). Minimal differences were found among sexes for FL. Parity, maternal race, paternal height and maternal height, and weight resulted significantly related to the fetal biometric parameters considered independently from fetal gender. In this study, we constructed customized biometric growth charts for fetal sex, parental, and obstetrical characteristics using quantile regression. The use of gender-specific charts offers the advantage to define individualized normal ranges of fetal biometric parameters at each specific centile. This approach may improve the antenatal identification of abnormal fetal growth.

  17. Fetal growth and developmental programming.

    Science.gov (United States)

    Galjaard, Sander; Devlieger, Roland; Van Assche, Frans A

    2013-01-01

    The environment in utero and in early neonatal life may induce a permanent response in the fetus and the newborn, leading to enhanced susceptibility to later diseases. This review concentrates on the role and mechanisms of events during the antenatal and immediate postnatal period resulting in later life diseases, concentrating on abnormal growth patterns of the fetus. Fetal overgrowth is related to exposure to a diabetic intra uterine environment, increasing the vulnerability to transgenerational obesity and hence an increased sensitivity to more diabetic mothers. This effect has been supported by animal data. Fetal growth restriction is complex due to malnutrition in utero, catch up growth due to a high caloric intake and low physical activity in later life. Metabolic changes and a transgenerational effect of intra uterine malnutrition has been supported by animal data. In recent years the discovery of alterations of the genome due to different influences during embryonic life, called epigenetics, has led to the phenomenon of fetal programming resulting in changing transgenerational metabolic effects.

  18. Fetal mesenchymal stromal cells differentiating towards chondrocytes acquire a gene expression profile resembling human growth plate cartilage.

    Directory of Open Access Journals (Sweden)

    Sandy A van Gool

    Full Text Available We used human fetal bone marrow-derived mesenchymal stromal cells (hfMSCs differentiating towards chondrocytes as an alternative model for the human growth plate (GP. Our aims were to study gene expression patterns associated with chondrogenic differentiation to assess whether chondrocytes derived from hfMSCs are a suitable model for studying the development and maturation of the GP. hfMSCs efficiently formed hyaline cartilage in a pellet culture in the presence of TGFβ3 and BMP6. Microarray and principal component analysis were applied to study gene expression profiles during chondrogenic differentiation. A set of 232 genes was found to correlate with in vitro cartilage formation. Several identified genes are known to be involved in cartilage formation and validate the robustness of the differentiating hfMSC model. KEGG pathway analysis using the 232 genes revealed 9 significant signaling pathways correlated with cartilage formation. To determine the progression of growth plate cartilage formation, we compared the gene expression profile of differentiating hfMSCs with previously established expression profiles of epiphyseal GP cartilage. As differentiation towards chondrocytes proceeds, hfMSCs gradually obtain a gene expression profile resembling epiphyseal GP cartilage. We visualized the differences in gene expression profiles as protein interaction clusters and identified many protein clusters that are activated during the early chondrogenic differentiation of hfMSCs showing the potential of this system to study GP development.

  19. The Navigation Guide - evidence-based medicine meets environmental health: integration of animal and human evidence for PFOA effects on fetal growth.

    Science.gov (United States)

    Lam, Juleen; Koustas, Erica; Sutton, Patrice; Johnson, Paula I; Atchley, Dylan S; Sen, Saunak; Robinson, Karen A; Axelrad, Daniel A; Woodruff, Tracey J

    2014-10-01

    The Navigation Guide is a novel systematic review method to synthesize scientific evidence and reach strength of evidence conclusions for environmental health decision making. Our aim was to integrate scientific findings from human and nonhuman studies to determine the overall strength of evidence for the question "Does developmental exposure to perfluorooctanoic acid (PFOA) affect fetal growth in humans?" We developed and applied prespecified criteria to systematically and transparently a) rate the quality of the scientific evidence as "high," "moderate," or "low"; b) rate the strength of the human and nonhuman evidence separately as "sufficient," "limited," "moderate," or "evidence of lack of toxicity"; and c) integrate the strength of the human and nonhuman evidence ratings into a strength of the evidence conclusion. We identified 18 epidemiology studies and 21 animal toxicology studies relevant to our study question. We rated both the human and nonhuman mammalian evidence as "moderate" quality and "sufficient" strength. Integration of these evidence ratings produced a final strength of evidence rating in which review authors concluded that PFOA is "known to be toxic" to human reproduction and development based on sufficient evidence of decreased fetal growth in both human and nonhuman mammalian species. We concluded that developmental exposure to PFOA adversely affects human health based on sufficient evidence of decreased fetal growth in both human and nonhuman mammalian species. The results of this case study demonstrate the application of a systematic and transparent methodology, via the Navigation Guide, for reaching strength of evidence conclusions in environmental health.

  20. The World Health Organization Fetal Growth Charts

    DEFF Research Database (Denmark)

    Kiserud, Torvid; Piaggio, Gilda; Carroli, Guillermo

    2017-01-01

    BACKGROUND: Perinatal mortality and morbidity continue to be major global health challenges strongly associated with prematurity and reduced fetal growth, an issue of further interest given the mounting evidence that fetal growth in general is linked to degrees of risk of common noncommunicable...... longitudinal study of fetal growth in low-risk singleton pregnancies of women of high or middle socioeconomic status and without known environmental constraints on fetal growth. Centers in ten countries (Argentina, Brazil, Democratic Republic of the Congo, Denmark, Egypt, France, Germany, India, Norway...

  1. Growth assessment in diagnosis of Fetal Growth Restriction. Review.

    Science.gov (United States)

    Albu, A R; Horhoianu, I A; Dumitrascu, M C; Horhoianu, V

    2014-06-15

    The assessment of fetal growth represents a fundamental step towards the identification of the true growth restricted fetus that is associated to important perinatal morbidity and mortality. The possible ways of detecting abnormal fetal growth are taken into consideration in this review and their strong and weak points are discussed. An important debate still remains about how to discriminate between the physiologically small fetus that does not require special surveillance and the truly growth restricted fetus who is predisposed to perinatal complications, even if its parameters are above the cut-off limits established. In this article, we present the clinical tools of fetal growth assessment: Symphyseal-Fundal Height (SFH) measurement, the fetal ultrasound parameters widely taken into consideration when discussing fetal growth: Abdominal Circumference (AC) and Estimated Fetal Weight (EFW); several types of growth charts and their characteristics: populational growth charts, standard growth charts, individualized growth charts, customized growth charts and growth trajectories.

  2. Maternal serum placental growth hormone, but not human placental lactogen or insulin growth factor-1, is positively associated with fetal growth in the first half of pregnancy

    DEFF Research Database (Denmark)

    Pedersen, N G; Juul, A; Christiansen, M

    2010-01-01

    To investigate if maternal levels of human placental lactogen (hPL), placental growth hormone (PGH) and insulin-like growth factor-1 (IGF-1) are associated with growth rate of the biparietal diameter (BPD) in the first half of pregnancy.......To investigate if maternal levels of human placental lactogen (hPL), placental growth hormone (PGH) and insulin-like growth factor-1 (IGF-1) are associated with growth rate of the biparietal diameter (BPD) in the first half of pregnancy....

  3. The relationship between human placental morphometry and ultrasonic measurements of utero-placental blood flow and fetal growth.

    Science.gov (United States)

    Salavati, N; Sovio, U; Mayo, R Plitman; Charnock-Jones, D S; Smith, G C S

    2016-02-01

    Ultrasonic fetal biometry and arterial Doppler flow velocimetry are widely used to assess the risk of pregnancy complications. There is an extensive literature on the relationship between pregnancy outcomes and the size and shape of the placenta. However, ultrasonic fetal biometry and arterial Doppler flow velocimetry have not previously been studied in relation to postnatal placental morphometry in detail. We conducted a prospective cohort study of nulliparous women in The Rosie Hospital, Cambridge (UK). We studied a group of 2120 women who had complete data on uterine and umbilical Doppler velocimetry and fetal biometry at 20, 28 and 36 weeks' gestational age, digital images of the placenta available, and delivered a liveborn infant at term. Associations were expressed as the difference in the standard deviation (SD) score of the gestational age adjusted ultrasound measurement (z-score) comparing the lowest and highest decile of the given placental morphometric measurement. The lowest decile of placental surface area was associated with 0.87 SD higher uterine artery Doppler mean pulsatility index (PI) at 20 weeks (95% CI: 0.68 to 1.07, P flow, respectively, and both are associated with fetal growth rate. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Cumulative effects of prenatal-exposure to exogenous chemicals and psychosocial stress on fetal growth: Systematic-review of the human and animal evidence.

    Science.gov (United States)

    Vesterinen, Hanna M; Morello-Frosch, Rachel; Sen, Saunak; Zeise, Lauren; Woodruff, Tracey J

    2017-01-01

    Adverse effects of prenatal stress or environmental chemical exposures on fetal growth are well described, yet their combined effect remains unclear. To conduct a systematic review on the combined impact and interaction of prenatal exposure to stress and chemicals on developmental outcomes. We used the first three steps of the Navigation Guide systematic review. We wrote a protocol, performed a robust literature search to identify relevant animal and human studies and extracted data on developmental outcomes. For the most common outcome (fetal growth), we evaluated risk of bias, calculated effect sizes for main effects of individual and combined exposures, and performed a random effects meta-analysis of those studies reporting on odds of low birthweight (LBW) by smoking and socioeconomic status (SES). We identified 17 human- and 22 animal-studies of combined chemical and stress exposures and fetal growth. Human studies tended to have a lower risk of bias across nine domains. Generally, we found stronger effects for chemicals than stress, and these exposures were associated with reduced fetal growth in the low-stress group and the association was often greater in high stress groups, with limited evidence of effect modification. We found smoking associated with significantly increased odds of LBW, with a greater effect for high stress (low SES; OR 4.75 (2.46-9.16)) compared to low stress (high SES; OR 1.95 (95% CI 1.53-2.48)). Animal studies generally had a high risk of bias with no significant combined effect or effect modification. We found that despite concern for the combined effects of environmental chemicals and stress, this is still an under-studied topic, though limited available human studies indicate chemical exposures exert stronger effects than stress, and this effect is generally larger in the presence of stress.

  5. Prenatal cerebellar growth trajectories and the impact of periconceptional maternal and fetal factors

    NARCIS (Netherlands)

    Koning, I V; Dudink, J; Groenenberg, I A L; Willemsen, S P; Reiss, I K M; Steegers-Theunissen, R P M

    2017-01-01

    STUDY QUESTION: CAN WE assess human prenatal cerebellar growth from the first until the third trimester of pregnancy and create growth trajectories to investigate associations with periconceptional maternal and fetal characteristics? SUMMARY ANSWER: Prenatal growth trajectories of the human

  6. The Navigation Guide—Evidence-Based Medicine Meets Environmental Health: Systematic Review of Human Evidence for PFOA Effects on Fetal Growth

    Science.gov (United States)

    Sutton, Patrice; Atchley, Dylan S.; Koustas, Erica; Lam, Juleen; Sen, Saunak; Robinson, Karen A.; Axelrad, Daniel A.; Woodruff, Tracey J.

    2014-01-01

    Background: The Navigation Guide methodology was developed to meet the need for a robust method of systematic and transparent research synthesis in environmental health science. We conducted a case study systematic review to support proof of concept of the method. Objective: We applied the Navigation Guide systematic review methodology to determine whether developmental exposure to perfluorooctanoic acid (PFOA) affects fetal growth in humans. Methods: We applied the first 3 steps of the Navigation Guide methodology to human epidemiological data: 1) specify the study question, 2) select the evidence, and 3) rate the quality and strength of the evidence. We developed a protocol, conducted a comprehensive search of the literature, and identified relevant studies using prespecified criteria. We evaluated each study for risk of bias and conducted meta-analyses on a subset of studies. We rated quality and strength of the entire body of human evidence. Results: We identified 18 human studies that met our inclusion criteria, and 9 of these were combined through meta-analysis. Through meta-analysis, we estimated that a 1-ng/mL increase in serum or plasma PFOA was associated with a –18.9 g (95% CI: –29.8, –7.9) difference in birth weight. We concluded that the risk of bias across studies was low, and we assigned a “moderate” quality rating to the overall body of human evidence. Conclusion: On the basis of this first application of the Navigation Guide systematic review methodology, we concluded that there is “sufficient” human evidence that developmental exposure to PFOA reduces fetal growth. Citation: Johnson PI, Sutton P, Atchley DS, Koustas E, Lam J, Sen S, Robinson KA, Axelrad DA, Woodruff TJ. 2014. The Navigation Guide—evidence-based medicine meets environmental health: systematic review of human evidence for PFOA effects on fetal growth. Environ Health Perspect 122:1028–1039; http://dx.doi.org/10.1289/ehp.1307893 PMID:24968388

  7. The Navigation Guide—Evidence-Based Medicine Meets Environmental Health: Integration of Animal and Human Evidence for PFOA Effects on Fetal Growth

    Science.gov (United States)

    Koustas, Erica; Sutton, Patrice; Johnson, Paula I.; Atchley, Dylan S.; Sen, Saunak; Robinson, Karen A.; Axelrad, Daniel A.; Woodruff, Tracey J.

    2014-01-01

    Background: The Navigation Guide is a novel systematic review method to synthesize scientific evidence and reach strength of evidence conclusions for environmental health decision making. Objective: Our aim was to integrate scientific findings from human and nonhuman studies to determine the overall strength of evidence for the question “Does developmental exposure to perfluorooctanoic acid (PFOA) affect fetal growth in humans?” Methods: We developed and applied prespecified criteria to systematically and transparently a) rate the quality of the scientific evidence as “high,” “moderate,” or “low”; b) rate the strength of the human and nonhuman evidence separately as “sufficient,” “limited,” “moderate,” or “evidence of lack of toxicity”; and c) integrate the strength of the human and nonhuman evidence ratings into a strength of the evidence conclusion. Results: We identified 18 epidemiology studies and 21 animal toxicology studies relevant to our study question. We rated both the human and nonhuman mammalian evidence as “moderate” quality and “sufficient” strength. Integration of these evidence ratings produced a final strength of evidence rating in which review authors concluded that PFOA is “known to be toxic” to human reproduction and development based on sufficient evidence of decreased fetal growth in both human and nonhuman mammalian species. Conclusion: We concluded that developmental exposure to PFOA adversely affects human health based on sufficient evidence of decreased fetal growth in both human and nonhuman mammalian species. The results of this case study demonstrate the application of a systematic and transparent methodology, via the Navigation Guide, for reaching strength of evidence conclusions in environmental health. Citation: Lam J, Koustas E, Sutton P, Johnson PI, Atchley DS, Sen S, Robinson KA, Axelrad DA, Woodruff TJ. 2014. The Navigation Guide—evidence-based medicine meets environmental health

  8. Octreotide therapy and restricted fetal growth

    DEFF Research Database (Denmark)

    Geilswijk, Marianne; Andersen, Lise Lotte Torvin; Frost, Morten

    2017-01-01

    that octreotide treatment in pregnancy, as well as hypoglycemia in itself, may pose a risk of fetal growth restriction. During pregnancy, management of blood glucose levels in familial hyperinsulinemic hypoglycemia thus forms a medical dilemma. We report on pregnancy outcomes in a woman with symptomatic familial...... hyperinsulinemic hypoglycemia, type 3. During the patient's first pregnancy with a viable fetus octreotide treatment was instituted in gestational age 23 weeks to prevent severe hypoglycemic incidences. Fetal growth velocity declined, and at 37 weeks of gestation, intrauterine growth retardation was evident...... growth velocity was normal. We conclude that octreotide treatment during pregnancy may pose a risk of fetal growth restriction and warrants careful consideration. In some cases of familial hyperinsulinemic hypoglycemia, blood glucose levels can be successfully managed through diet only, also during...

  9. Prenatal smoking exposure and asymmetric fetal growth restriction

    NARCIS (Netherlands)

    Delpisheh, Ali; Brabin, Loretta; Drummond, Sandra; Brabin, Bernard J.

    2008-01-01

    Background: Prenatal smoking exposure causes intrauterine fetal growth restriction ( IUGR), although its effects on fetal proportionality are less clearly defined. Aim: The present study assessed fetal proportionality in babies with IUGR using maternal salivary cotinine to indicate maternal smoking

  10. Assisted Reproduction Causes Reduced Fetal Growth Associated with Downregulation of Paternally Expressed Imprinted Genes That Enhance Fetal Growth in Mice.

    Science.gov (United States)

    Li, Bo; Chen, Shuqiang; Tang, Na; Xiao, Xifeng; Huang, Jianlei; Jiang, Feng; Huang, Xiuying; Sun, Fangzhen; Wang, Xiaohong

    2016-02-01

    Alteration of intrauterine growth trajectory is linked to metabolic diseases in adulthood. In mammalian and, specifically, human species, pregnancies through assisted reproductive technology (ART) are associated with changes in intrauterine growth trajectory. However, it is still unclear how ART alters intrauterine growth trajectory, especially reduced fetal growth in early to midgestation. In this study, using a mouse model, it was found that ART procedures reduce fetal and placental growth at Embryonic Day 10.5. Furthermore, ART leads to decreased methylation levels at H19, KvDMR1, and Snrpn imprinting control regions in the placentae, instead of fetuses. Furthermore, in the placenta, ART downregulated a majority of parentally expressed imprinted genes, which enhance fetal growth, whereas it upregulated a majority of maternally expressed genes which repress fetal growth. Additionally, the expression of genes that regulate placental development was also affected by ART. ART also downregulated a majority of placental nutrient transporters. Disruption of genomic imprinting and abnormal expression of developmentally and functionally relevant genes in placenta may influence the placental development and function, which affect fetal growth and reprogramming. © 2016 by the Society for the Study of Reproduction, Inc.

  11. 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. ...

  12. Growth assessment in diagnosis of Fetal Growth Restriction. Review

    OpenAIRE

    Albu, AR; Horhoianu, IA; Dumitrascu, MC; Horhoianu, V

    2014-01-01

    Abstract The assessment of fetal growth represents a fundamental step towards the identification of the true growth restricted fetus that is associated to important perinatal morbidity and mortality. The possible ways of detecting abnormal fetal growth are taken into consideration in this review and their strong and weak points are discussed. An important debate still remains about how to discriminate between the physiologically small fetus that does not require special surveillance and the t...

  13. The Navigation Guide - evidence-based medicine meets environmental health: systematic review of human evidence for PFOA effects on fetal growth.

    Science.gov (United States)

    Johnson, Paula I; Sutton, Patrice; Atchley, Dylan S; Koustas, Erica; Lam, Juleen; Sen, Saunak; Robinson, Karen A; Axelrad, Daniel A; Woodruff, Tracey J

    2014-10-01

    The Navigation Guide methodology was developed to meet the need for a robust method of systematic and transparent research synthesis in environmental health science. We conducted a case study systematic review to support proof of concept of the method. We applied the Navigation Guide systematic review methodology to determine whether developmental exposure to perfluorooctanoic acid (PFOA) affects fetal growth in humans. We applied the first 3 steps of the Navigation Guide methodology to human epidemiological data: 1) specify the study question, 2) select the evidence, and 3) rate the quality and strength of the evidence. We developed a protocol, conducted a comprehensive search of the literature, and identified relevant studies using prespecified criteria. We evaluated each study for risk of bias and conducted meta-analyses on a subset of studies. We rated quality and strength of the entire body of human evidence. We identified 18 human studies that met our inclusion criteria, and 9 of these were combined through meta-analysis. Through meta-analysis, we estimated that a 1-ng/mL increase in serum or plasma PFOA was associated with a -18.9 g (95% CI: -29.8, -7.9) difference in birth weight. We concluded that the risk of bias across studies was low, and we assigned a "moderate" quality rating to the overall body of human evidence. On the basis of this first application of the Navigation Guide systematic review methodology, we concluded that there is "sufficient" human evidence that developmental exposure to PFOA reduces fetal growth.

  14. The relationship between human placental morphometry and ultrasonic measurements of utero-placental blood flow and fetal growth

    NARCIS (Netherlands)

    Salavati, Nastaran; Sovio, U.; Mayo, R. Plitman; Charnock-Jones, D. S.; Smith, G. C. S.

    Introduction: Ultrasonic fetal biometry and arterial Doppler flow velocimetry are widely used to assess the risk of pregnancy complications. There is an extensive literature on the relationship between pregnancy outcomes and the size and shape of the placenta. However, ultrasonic fetal biometry and

  15. Mathematical models of human cerebellar development in the fetal period.

    Science.gov (United States)

    Dudek, Krzysztof; Nowakowska-Kotas, Marta; Kędzia, Alicja

    2018-04-01

    The evaluation of cerebellar growth in the fetal period forms a part of a widely used examination to identify any features of abnormalities in early stages of human development. It is well known that the development of anatomical structures, including the cerebellum, does not always follow a linear model of growth. The aim of the study was to analyse a variety of mathematical models of human cerebellar development in fetal life to determine their adequacy. The study comprised 101 fetuses (48 males and 53 females) between the 15th and 28th weeks of fetal life. The cerebellum was exposed and measurements of the vermis and hemispheres were performed, together with statistical analyses. The mathematical model parameters of fetal growth were assessed for crown-rump length (CRL) increases, transverse cerebellar diameter and ventrodorsal dimensions of the cerebellar vermis in the transverse plane, and rostrocaudal dimensions of the cerebellar vermis and hemispheres in the frontal plane. A variety of mathematical models were applied, including linear and non-linear functions. Taking into consideration the variance between models and measurements, as well as correlation parameters, the exponential and Gompertz models proved to be the most suitable for modelling cerebellar growth in the second and third trimesters of pregnancy. However, the linear model gave a satisfactory approximation of cerebellar growth, especially in older fetuses. The proposed models of fetal cerebellar growth constructed on the basis of anatomical examination and objective mathematical calculations could be useful in the estimation of fetal development. © 2018 Anatomical Society.

  16. Human fetal anatomy: MR imaging.

    Science.gov (United States)

    Weinreb, J C; Lowe, T; Cohen, J M; Kutler, M

    1985-12-01

    Twenty-four pregnant women carrying 26 fetuses (two sets of twins) were imaged with magnetic resonance (MR) imaging at 0.35 T following sonographic evaluation. Each study was retrospectively evaluated to determine which of 33 normal fetal structures were visible on the images and which imaging parameters were most useful for depicting fetal anatomy. Fetal motion degraded fetal images in all but two cases, both with oligohydramnios and in the third trimester of gestation. Nevertheless, many fetal structures were identifiable, particularly in the third trimester. Visualization of fetal anatomy improved with intravenous maternal sedation in five cases. Relatively T1-weighted images occasionally offered the advantage of less image degradation owing to fetal motion and improved contrast between different fetal structures. More T2 weighting was believed to be advantageous in one case for outlining the fetal head and in one case for delineation of the brain. In many cases, structures were similarly identifiable (though with different signal intensities) regardless of the parameters selected. The authors conclude that MR imaging of many fetal structures is currently unsatisfactory and is probably of limited value, particularly in the first and second trimesters. However, the relative frequency and detail with which the fetal head and liver can be depicted indicate that these may be areas for further investigation, and the potential utility of imaging fetal fat warrants further investigation.

  17. Fetal growth disorders in twin gestations.

    LENUS (Irish Health Repository)

    Breathnach, Fionnuala M

    2012-06-01

    Twin growth is frequently mismatched. This review serves to explore the pathophysiologic mechanisms that underlie growth aberrations in twin gestations, the prenatal recognition of abnormal twin growth, and the critical importance of stratifying management of abnormal twin growth by chorionicity. Although poor in utero growth of both twins may reflect maternal factors resulting in global uteroplacental dysfunction, discordant twin growth may be attributed to differences in genetic potential between co-twins, placental dysfunction confined to one placenta only, or one placental territory within a shared placenta. In addition, twin-twin transfusion syndrome represents a distinct entity of which discordant growth is a common feature. Discordant growth is recognized as an independent risk factor for adverse perinatal outcome. Intertwin birth weight disparity of 18% or more should be considered to represent a discordance threshold, which serves as an independent risk factor for adverse perinatal outcome. At this cutoff, perinatal morbidity is found to increase both for the larger and the smaller twin within a discordant pair. There remains uncertainty surrounding the sonographic parameters that are most predictive of discordance. Although heightening of fetal surveillance in the face of discordant twin growth follows the principles applied to singleton gestations complicated by fetal growth restriction, the timing of intervention is largely influenced by chorionicity.

  18. Insulin-like growth factors in embryonic and fetal growth and skeletal development (Review).

    Science.gov (United States)

    Agrogiannis, Georgios D; Sifakis, Stavros; Patsouris, Efstratios S; Konstantinidou, Anastasia E

    2014-08-01

    The insulin-like growth factors (IGF)-I and -II have a predominant role in fetal growth and development. IGFs are involved in the proliferation, differentiation and apoptosis of fetal cells in vitro and the IGF serum concentration has been shown to be closely correlated with fetal growth and length. IGF transcripts and peptides have been detected in almost every fetal tissue from as early in development as pre‑implantation to the final maturation stage. Furthermore, IGFs have been demonstrated to be involved in limb morphogenesis. However, although ablation of Igf genes in mice resulted in growth retardation and delay in skeletal maturation, no impact on outgrowth and patterning of embryonic limbs was observed. Additionally, various molecular defects in the Igf1 and Igf1r genes in humans have been associated with severe intrauterine growth retardation and impaired skeletal maturation, but not with truncated limbs or severe skeletal dysplasia. The conflicting data between in vitro and in vivo observations with regard to bone morphogenesis suggests that IGFs may not be the sole trophic factors involved in fetal skeletal growth and that redundant mechanisms may exist in chondro- and osteogenesis. Further investigation is required in order to elucidate the functions of IGFs in skeletal development.

  19. Longitudinal study of computerized cardiotocography in early fetal growth restriction

    NARCIS (Netherlands)

    Wolf, H.; Arabin, B.; Lees, Christoph C.; Oepkes, D.; Prefumo, Federico; Thilaganathan, B.; Todros, T.; Visser, G.H.A.; Bilardo, Caterina M.; Derks, J. B.; Diemert, A.; Duvekot, Johannes J.; Ferrazzi, E.; Frusca, T.; Hecher, K.; Marlow, N.; Martinelli, P.; Ostermayer, E.; Papageorghiou, Aris T.; Scheepers, Hubertina C. J.; Schlembach, D.; Schneider, K. T M; Valcamonico, A.; van Wassenaer-Leemhuis, A.; Ganzevoort, W.; Aktas, Ayse; Borgione, Silvia; Brezinka, Christoph; Calvert, Sandra; Chaoui, Rabih; Cornette, Jerome M J; Diehl, Thilo; van Eyck, Jim; Fratelli, Nicola; van Haastert, Inge Lot; Johnson, Samantha; Lobmaier, Silvia; Lopriore, Enrico; Mansi, Giuseppina; Missfelder-Lobos, Hannah; Martelli, Paola; Maso, Gianpaolo; Maurer-Fellbaum, Ute; Van Charante, Nico Mensing; De Tollenaer, Susanne Mulder; Moore, Tamanna; Napolitano, Raffaele; Oberto, Manuela; Ogge, Giovanna; van der Post, Joris Am; Preston, Lucy; Raimondi, Francesco; Reiss, Irwin K M; Rigano, Serena; Schuit, Ewoud; Skabar, Aldo; Spaanderman, Marc E.; Weisglas-Kuperus, Nynke; Zimmermann, Andrea

    2017-01-01

    Objectives: To explore whether, in early fetal growth restriction (FGR), the longitudinal pattern of fetal heart rate (FHR) short-term variation (STV) can be used to identify imminent fetal distress and whether abnormalities of FHR recordings are associated with 2-year infant outcome. Methods: The

  20. MicroRNA-26a modulates transforming growth factor beta-1-induced proliferation in human fetal lung fibroblasts

    International Nuclear Information System (INIS)

    Li, Xiaoou; Liu, Lian; Shen, Yongchun; Wang, Tao; Chen, Lei; Xu, Dan; Wen, Fuqiang

    2014-01-01

    Highlights: • Endogenous miR-26a inhibits TGF-beta 1 induced proliferation of lung fibroblasts. • miR-26a induces G1 arrest through directly targeting 3′-UTR of CCND2. • TGF indispensable receptor, TGF-beta R I, is regulated by miR-26a. • miR-26a acts through inhibiting TGF-beta 2 feedback loop to reduce TGF-beta 1. • Collagen type I and connective tissue growth factor are suppressed by miR-26a. - Abstract: MicroRNA-26a is a newly discovered microRNA that has a strong anti-tumorigenic capacity and is capable of suppressing cell proliferation and activating tumor-specific apoptosis. However, whether miR-26a can inhibit the over-growth of lung fibroblasts remains unclear. The relationship between miR-26a and lung fibrosis was explored in the current study. We first investigated the effect of miR-26a on the proliferative activity of human lung fibroblasts with or without TGF-beta1 treatment. We found that the inhibition of endogenous miR-26a promoted proliferation and restoration of mature miR-26a inhibited the proliferation of human lung fibroblasts. We also examined that miR-26a can block the G1/S phase transition via directly targeting 3′-UTR of CCND2, degrading mRNA and decreasing protein expression of Cyclin D2. Furthermore, we showed that miR-26a mediated a TGF-beta 2-TGF-beta 1 feedback loop and inhibited TGF-beta R I activation. In addition, the overexpression of miR-26a also significantly suppressed the TGF-beta 1-interacting-CTGF–collagen fibrotic pathway. In summary, our studies indicated an essential role of miR-26a in the anti-fibrotic mechanism in TGF-beta1-induced proliferation in human lung fibroblasts, by directly targeting Cyclin D2, regulating TGF-beta R I as well as TGF-beta 2, and suggested the therapeutic potential of miR-26a in ameliorating lung fibrosis

  1. MicroRNA-26a modulates transforming growth factor beta-1-induced proliferation in human fetal lung fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiaoou [Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Department of Respiratory Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Liu, Lian [Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Shen, Yongchun; Wang, Tao; Chen, Lei; Xu, Dan [Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Department of Respiratory Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Wen, Fuqiang, E-mail: wenfuqiang.scu@gmail.com [Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Department of Respiratory Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China)

    2014-11-28

    Highlights: • Endogenous miR-26a inhibits TGF-beta 1 induced proliferation of lung fibroblasts. • miR-26a induces G1 arrest through directly targeting 3′-UTR of CCND2. • TGF indispensable receptor, TGF-beta R I, is regulated by miR-26a. • miR-26a acts through inhibiting TGF-beta 2 feedback loop to reduce TGF-beta 1. • Collagen type I and connective tissue growth factor are suppressed by miR-26a. - Abstract: MicroRNA-26a is a newly discovered microRNA that has a strong anti-tumorigenic capacity and is capable of suppressing cell proliferation and activating tumor-specific apoptosis. However, whether miR-26a can inhibit the over-growth of lung fibroblasts remains unclear. The relationship between miR-26a and lung fibrosis was explored in the current study. We first investigated the effect of miR-26a on the proliferative activity of human lung fibroblasts with or without TGF-beta1 treatment. We found that the inhibition of endogenous miR-26a promoted proliferation and restoration of mature miR-26a inhibited the proliferation of human lung fibroblasts. We also examined that miR-26a can block the G1/S phase transition via directly targeting 3′-UTR of CCND2, degrading mRNA and decreasing protein expression of Cyclin D2. Furthermore, we showed that miR-26a mediated a TGF-beta 2-TGF-beta 1 feedback loop and inhibited TGF-beta R I activation. In addition, the overexpression of miR-26a also significantly suppressed the TGF-beta 1-interacting-CTGF–collagen fibrotic pathway. In summary, our studies indicated an essential role of miR-26a in the anti-fibrotic mechanism in TGF-beta1-induced proliferation in human lung fibroblasts, by directly targeting Cyclin D2, regulating TGF-beta R I as well as TGF-beta 2, and suggested the therapeutic potential of miR-26a in ameliorating lung fibrosis.

  2. Growth perturbations in a phenotype with rapid fetal growth preceding preterm labor and term birth.

    Science.gov (United States)

    Lampl, Michelle; Kusanovic, Juan Pedro; Erez, Offer; Gotsch, Francesca; Espinoza, Jimmy; Goncalves, Luis; Lee, Wesley; Gomez, Ricardo; Nien, Jyh Kae; Frongillo, Edward A; Romero, Roberto

    2009-01-01

    The variability in fetal growth rates and gestation duration in humans is not well understood. Of interest are women presenting with an episode of preterm labor and subsequently delivering a term neonate, who is small relative to peers of similar gestational age. To further understand these relationships, fetal growth patterns predating an episode of preterm labor were investigated. Retrospective analysis of fetal biometry assessed by serial ultrasound in a prospectively studied sample of pregnancies in Santiago, Chile, tested the hypothesis that fetal growth patterns among uncomplicated pregnancies (n = 3,706) and those with an episode of preterm labor followed by term delivery (n = 184) were identical across the time intervals 16-22 weeks, 22-28 weeks, and 28-34 weeks in a multilevel mixed-effects regression. The hypothesis was not supported. Fetal weight growth rate was faster from 16 weeks among pregnancies with an episode of preterm labor (P < 0.05), declined across midgestation (22-28 weeks, P < 0.05), and rebounded between 28 and 34 weeks (P = 0.06). This was associated with perturbations in abdominal circumference growth and proportionately larger biparietal diameter from 22 gestational weeks (P = 0.03), greater femur (P = 0.01), biparietal diameter (P = 0.001) and head circumference (P = 0.02) dimensions relative to abdominal circumference across midgestation (22-28 weeks), followed by proportionately smaller femur diaphyseal length (P = 0.02) and biparietal diameter (P = 0.03) subsequently. A distinctive rapid growth phenotype characterized fetal growth preceding an episode of preterm labor among this sample of term-delivered neonates. Perturbations in abdominal circumference growth and patterns of proportionality suggest an altered growth strategy pre-dating the preterm labor episode.

  3. An EG-VEGF-dependent decrease in homeobox gene NKX3.1 contributes to cytotrophoblast dysfunction: a possible mechanism in human fetal growth restriction.

    Science.gov (United States)

    Murthi, P; Brouillet, S; Pratt, A; Borg, Aj; Kalionis, B; Goffin, F; Tsatsaris, V; Munaut, C; Feige, Jj; Benharouga, M; Fournier, T; Alfaidy, N

    2015-07-21

    Idiopathic fetal growth restriction (FGR) is frequently associated with placental insufficiency. Previous reports have provided evidence that EG-VEGF (endocrine gland derived-vascular endothelial growth factor), a placental secreted protein, is expressed during the first trimester of pregnancy, controls both trophoblast proliferation and invasion, and its increased expression is associated with human FGR. In this study, we hypothesise that EG-VEGF-dependent change in placental homeobox gene expressions contribute to trophoblast dysfunction in idiopathic FGR. The changes in EG-VEGF-dependent homeobox gene expressions were determined using a Homeobox gene cDNA array on placental explants of 8-12 weeks' gestation after stimulation with EG-VEGF in vitro for 24 hours. The Homeobox gene array identified a >5-fold increase in HOXA9, HOXC8, HOXC10, HOXD1, HOXD8, HOXD9 and HOXD11, while NKX 3.1 showed a >2 fold-decrease in mRNA expression compared to untreated controls. Homeobox gene NKX3.1 was selected as a candidate because it is a downstream target of EG-VEGF and its expression and functional role are largely unknown in control and idiopathic FGR-affected placentae. Real-time PCR and immunoblotting showed a significant decrease in NKX3.1 mRNA and protein levels, respectively, in placentae from FGR compared to control pregnancies. Gene inactivation in vitro using short-interference RNA specific for NKX3.1 demonstrated an increase in BeWo cell differentiation and a decrease in HTR8-SVneo proliferation. We conclude that the decreased expression of homeobox gene NKX3.1 down-stream of EG-VEGF may contribute to the trophoblast dysfunction associated with idiopathic FGR pregnancies.

  4. Metabolism of lipoproteins by human fetal hepatocytes

    International Nuclear Information System (INIS)

    Carr, B.R.

    1987-01-01

    The rate of clearance of lipoproteins from plasma appears to play a role in the development of atherogenesis. The liver may account for as much as two thirds of the removal of low-density lipoprotein and one third of the clearance of high-density lipoprotein in certain animal species and humans, mainly by receptor-mediated pathways. The purpose of the present investigation was to determine if human fetal hepatocytes maintained in vitro take up and degrade lipoproteins. We first determined that the maximal binding capacity of iodine 125-iodo-LDL was approximately 300 ng of low-density lipoprotein protein/mg of membrane protein and an apparent dissociation constant of approximately 60 micrograms low-density lipoprotein protein/ml in membranes prepared from human fetal liver. We found that the maximal uptake of [ 125 I]iodo-LDL and [ 125 I]iodo-HDL by fetal hepatocytes occurred after 12 hours of incubation. Low-density lipoprotein uptake preceded the appearance of degradation products by 4 hours, and thereafter the degradation of low-density lipoprotein increased linearly for at least 24 hours. In contrast, high-density lipoprotein was not degraded to any extent by fetal hepatocytes. [ 125 I]Iodo-LDL uptake and degradation were inhibited more than 75% by preincubation with low-density lipoprotein but not significantly by high-density lipoprotein, whereas [ 125 I]iodo-HDL uptake was inhibited 70% by preincubation with high-density lipoprotein but not by low-density lipoprotein. In summary, human fetal hepatocytes take up and degrade low-density lipoprotein by a receptor-mediated process similar to that described for human extrahepatic tissues

  5. Screening for fetal growth restriction using fetal biometry combined with maternal biomarkers.

    Science.gov (United States)

    Gaccioli, Francesca; Aye, Irving L M H; Sovio, Ulla; Charnock-Jones, D Stephen; Smith, Gordon C S

    2018-02-01

    Fetal growth restriction is a major determinant of perinatal morbidity and mortality. Screening for fetal growth restriction is a key element of prenatal care but it is recognized to be problematic. Screening using clinical risk assessment and targeting ultrasound to high-risk women is the standard of care in the United States and United Kingdom, but the approach is known to have low sensitivity. Systematic reviews of randomized controlled trials do not demonstrate any benefit from universal ultrasound screening for fetal growth restriction in the third trimester, but the evidence base is not strong. Implementation of universal ultrasound screening in low-risk women in France failed to reduce the risk of complications among small-for-gestational-age infants but did appear to cause iatrogenic harm to false positives. One strategy to making progress is to improve screening by developing more sensitive and specific tests with the key goal of differentiating between healthy small fetuses and those that are small through fetal growth restriction. As abnormal placentation is thought to be the major cause of fetal growth restriction, one approach is to combine fetal biometry with an indicator of placental dysfunction. In the past, these indicators were generally ultrasonic measurements, such as Doppler flow velocimetry of the uteroplacental circulation. However, another promising approach is to combine ultrasonic suspicion of small-for-gestational-age infant with a blood test indicating placental dysfunction. Thus far, much of the research on maternal serum biomarkers for fetal growth restriction has involved the secondary analysis of tests performed for other indications, such as fetal aneuploidies. An exemplar of this is pregnancy-associated plasma protein A. This blood test is performed primarily to assess the risk of Down syndrome, but women with low first-trimester levels are now serially scanned in later pregnancy due to associations with placental causes of

  6. Sildenafil Citrate Increases Fetal Weight in a Mouse Model of Fetal Growth Restriction with a Normal Vascular Phenotype

    Science.gov (United States)

    Dilworth, Mark Robert; Andersson, Irene; Renshall, Lewis James; Cowley, Elizabeth; Baker, Philip; Greenwood, Susan; Sibley, Colin Peter; Wareing, Mark

    2013-01-01

    Fetal growth restriction (FGR) is defined as the inability of a fetus to achieve its genetic growth potential and is associated with a significantly increased risk of morbidity and mortality. Clinically, FGR is diagnosed as a fetus falling below the 5th centile of customised growth charts. Sildenafil citrate (SC, Viagra™), a potent and selective phosphodiesterase-5 inhibitor, corrects ex vivo placental vascular dysfunction in FGR, demonstrating potential as a therapy for this condition. However, many FGR cases present without an abnormal vascular phenotype, as assessed by Doppler measures of uterine/umbilical artery blood flow velocity. Thus, we hypothesized that SC would not increase fetal growth in a mouse model of FGR, the placental-specific Igf2 knockout mouse, which has altered placental exchange capacity but normal placental blood flow. Fetal weights were increased (by 8%) in P0 mice following maternal SC treatment (0.4 mg/ml) via drinking water. There was also a trend towards increased placental weight in treated P0 mice (P = 0.056). Additionally, 75% of the P0 fetal weights were below the 5th centile, the criterion used to define human FGR, of the non-treated WT fetal weights; this was reduced to 51% when dams were treated with SC. Umbilical artery and vein blood flow velocity measures confirmed the lack of an abnormal vascular phenotype in the P0 mouse; and were unaffected by SC treatment. 14C-methylaminoisobutyric acid transfer (measured to assess effects on placental nutrient transporter activity) per g placenta was unaffected by SC, versus untreated, though total transfer was increased, commensurate with the trend towards larger placentas in this group. These data suggest that SC may improve fetal growth even in the absence of an abnormal placental blood flow, potentially affording use in multiple sub-populations of individuals presenting with FGR. PMID:24204949

  7. Sildenafil citrate increases fetal weight in a mouse model of fetal growth restriction with a normal vascular phenotype.

    Directory of Open Access Journals (Sweden)

    Mark Robert Dilworth

    Full Text Available Fetal growth restriction (FGR is defined as the inability of a fetus to achieve its genetic growth potential and is associated with a significantly increased risk of morbidity and mortality. Clinically, FGR is diagnosed as a fetus falling below the 5(th centile of customised growth charts. Sildenafil citrate (SC, Viagra™, a potent and selective phosphodiesterase-5 inhibitor, corrects ex vivo placental vascular dysfunction in FGR, demonstrating potential as a therapy for this condition. However, many FGR cases present without an abnormal vascular phenotype, as assessed by Doppler measures of uterine/umbilical artery blood flow velocity. Thus, we hypothesized that SC would not increase fetal growth in a mouse model of FGR, the placental-specific Igf2 knockout mouse, which has altered placental exchange capacity but normal placental blood flow. Fetal weights were increased (by 8% in P0 mice following maternal SC treatment (0.4 mg/ml via drinking water. There was also a trend towards increased placental weight in treated P0 mice (P = 0.056. Additionally, 75% of the P0 fetal weights were below the 5(th centile, the criterion used to define human FGR, of the non-treated WT fetal weights; this was reduced to 51% when dams were treated with SC. Umbilical artery and vein blood flow velocity measures confirmed the lack of an abnormal vascular phenotype in the P0 mouse; and were unaffected by SC treatment. (14C-methylaminoisobutyric acid transfer (measured to assess effects on placental nutrient transporter activity per g placenta was unaffected by SC, versus untreated, though total transfer was increased, commensurate with the trend towards larger placentas in this group. These data suggest that SC may improve fetal growth even in the absence of an abnormal placental blood flow, potentially affording use in multiple sub-populations of individuals presenting with FGR.

  8. Hormonal influences on growth of the fetal pig

    International Nuclear Information System (INIS)

    Spencer, G.S.

    1986-01-01

    Although there is considerable information on hormonal systems regulating growth postnatally, little is known about hormonal influences on growth in the fetuw. It has long been postulated that insulin is the major fetal growth promoting hormone. However, chronic administration of insulin to the fetal pig during 14 days in utero, although producing hyperinsulinaemia and elevated somatomedin levels, did not stimulate an increase in length, weight or cell number. Postnatally the principal growth promoting hormones are the growth hormone dependent somatomedins. It is thought that multiplication stimulating activity (MSA) is the fetal somatomedin. However, under similar conditions to those used for insulin administration, MSA did not affect growth in the fetal pig. Administration of somatostatin to chronically catheterized fetuses inhibited (p≤0.01) and thyrotrophin releasing factor stimulated (≤0.01) GH release. However, chronic administration of SRIF did not inhibit fetal growth. Thus there does seem to be some hypothalamic control over GH secretion but this may not play a major role in regulating fetal growth

  9. Infertility, infertility treatment, and fetal growth restriction

    DEFF Research Database (Denmark)

    Zhu, Jin Liang; Obel, Carsten; Hammer Bech, Bodil

    2007-01-01

    mortality and SGA among infertile couples (treated and untreated), but the odds ratios (ORs) of perinatal mortality among infertile couples were attenuated after adjustment for maternal age and body mass index (1.32, 95% confidence interval [CI] 0.95-1.84 among untreated and 1.26, 95% CI 0.86-1.85 among......OBJECTIVE: To examine the association between infertility, with or without treatment, and fetal growth, as well as perinatal and infant mortality. METHODS: From the Danish National Birth Cohort (1997-2003), we identified 51,041 singletons born of fertile couples (time to pregnancy 12 months or less...... treated couples). The elevated risk of SGA among infertile couples persisted after adjustment for maternal age, parity, and smoking (OR 1.24, 95% CI 1.10-1.40 among untreated, and OR 1.40, 95% CI 1.23-1.60 among treated). The risk of SGA increased with time to pregnancy, and a longer time to pregnancy...

  10. Maternal depression and anxiety and fetal-neonatal growth

    Directory of Open Access Journals (Sweden)

    Tiago Miguel Pinto

    2017-09-01

    Conclusion: This study demonstrates the independent longitudinal effect of maternal anxiety on major markers of fetal-neonatal growth outcomes and trajectories, simultaneously considering the effect of maternal depression and anxiety.

  11. Prevention of fetal demise and growth restriction in a mouse model of fetal alcohol syndrome.

    Science.gov (United States)

    Spong, C Y; Abebe, D T; Gozes, I; Brenneman, D E; Hill, J M

    2001-05-01

    Two peptides [NAPVSIPQ (NAP) and SALLRSIPA (ADNF-9)], that are associated with novel glial proteins regulated by vasoactive intestinal peptide, are shown now to provide protective intervention in a model of fetal alcohol syndrome. Fetal demise and growth restrictions were produced after intraperitoneal injection of ethanol to pregnant mice during midgestation (E8). Death and growth abnormalities elicited by alcohol treatment during development are believed to be associated, in part, with severe oxidative damage. NAP and ADNF-9 have been shown to exhibit antioxidative and antiapoptotic actions in vitro. Pretreatment with an equimolar combination of the peptides prevented the alcohol-induced fetal death and growth abnormalities. Pretreatment with NAP alone resulted in a significant decrease in alcohol-associated fetal death; whereas ADNF-9 alone had no detectable effect on fetal survival after alcohol exposure, indicating a pharmacological distinction between the peptides. Biochemical assessment of the fetuses indicated that the combination peptide treatment prevented the alcohol-induced decreases in reduced glutathione. Peptide efficacy was evident with either 30-min pretreatment or with 1-h post-alcohol administration. Bioavailability studies with [(3)H]NAPVSIPQ indicated that 39% of the total radioactivity comigrated with intact peptide in the fetus 60 min after administration. These studies demonstrate that fetal death and growth restriction associated with prenatal alcohol exposure were prevented by combinatorial peptide treatment and suggest that this therapeutic strategy be explored in other models/diseases associated with oxidative stress.

  12. 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...

  13. A radiographic study of the human fetal spine

    International Nuclear Information System (INIS)

    Bagnall, K.M.; Harris, P.F.; Jones, P.R.M.

    1979-01-01

    Regression equations are presented which describe the growth in length of the various regions of the vertebral column in the human fetus. From 8 weeks on the thoracic is always the longest region and the sacral the shortest, while the lumbar region is longer than the cervical. From the regression equations predictions of fetal vertebral length can be made from fetal age: this should be useful in obstetric practice when diagnostic ultrasound techniques are being employed for the diagnosis of growth disorders and skeletal abnormalities. A different development pattern emerges when average 'vertebral units' for each region are compared. The lumbar vertebrae are always the largest with the thoracic, cervical and sacral vertebrae being progressively smaller. (author)

  14. The World Health Organization fetal growth charts: concept, findings, interpretation, and application.

    Science.gov (United States)

    Kiserud, Torvid; Benachi, Alexandra; Hecher, Kurt; Perez, Rogelio González; Carvalho, José; Piaggio, Gilda; Platt, Lawrence D

    2018-02-01

    weight was strongest on the lowest percentiles and smallest on the highest percentiles for estimated fetal weight. (3) When adjustment was made for maternal covariates, there was still a significant effect of country as covariate that indicated that ethnic, cultural, and geographic variation play a role. (4) Variation between populations was not restricted to fetal size because there were also differences in growth trajectories. (5) The wide physiologic ranges, as illustrated by the 5th-95th percentile for estimated fetal weight being 2205-3538 g at 37 weeks gestation, signify that human fetal growth under optimized maternal conditions is not uniform. Rather, it has a remarkable variation that largely is unexplained by commonly known factors. We suggest this variation could be part of our common biologic strategy that makes human evolution extremely successful. The World Health Organization fetal growth charts are intended to be used internationally based on low-risk pregnancies from populations in Africa, Asia, Europe, and South America. We consider it prudent to test and monitor whether the growth charts' performance meets the local needs, because refinements are possible by a change in cut-offs or customization for fetal sex, maternal factors, and populations. In the same line, the study finding of variations emphasizes the need for carefully adjusted growth charts that reflect optimal local growth when public health issues are addressed. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. STEREOLOGICAL STUDIES ON FETAL VASCULAR DEVELOPMENT IN HUMAN PLACENTAL VILLI

    Directory of Open Access Journals (Sweden)

    Terry M Mayhew

    2011-05-01

    Full Text Available In human pregnancy, fetal well-being depends on the development of placental villi and the creation and maintenance of fetal microvessels within them. The aim of this study was to define stereological measures of the growth, capillarization and maturation of villi and of fetoplacental angiogenesis and capillary remodelling. Placentas were collected at 12-41 weeks of gestation and assigned to six age groups spanning equal age ranges. Tissue samples were randomised for position and orientation. Overall growth of peripheral (intermediate and terminal villi and their capillaries was evaluated using total volumes, surface areas and lengths. Measures of villous capillarization comprised capillary volume, surface and length densities and capillary:villus surface and length ratios. Size and shape remodelling of villi and capillaries was assessed using mean cross-sectional areas, perimeters and shape coefficients (perimeter2/area. Group comparisons were drawn by analysis of variance. Villous and capillary volumes, surfaces and lengths increased significantly throughout gestation. Villous maturation involved phasic (capillary:villus surface and length ratios or progressive (volume, surface and length densities increases in indices of villous capillarization. It also involved isomorphic thinning (cross-sectional areas and perimeters declined but shape coefficients did not alter. In contrast, growth of capillaries did not involve changes in luminal areas or perimeters. The results show that villous growth and fetal angiogenesis involve increases in overall length rather than calibre and that villous differentiation involves increased capillarization. Although they do not distinguish between increases in the lengths versus numbers of capillary segments, other studies have shown that capillaries switch from branching to non-branching angiogenesis during gestation. Combined with maintenance of capillary calibres, these processes will contribute to the reduced

  16. Fetal first trimester growth is not associated with kidney outcomes in childhood.

    Science.gov (United States)

    Bakker, Hanneke; Gaillard, Romy; Hofman, Albert; Reiss, Irwin K; Steegers, Eric A P; Jaddoe, Vincent W V

    2017-04-01

    Impaired fetal growth is associated with increased risks of kidney diseases in later life. Because human development rates are highest during the first trimester, this trimester may be a particularly critical period for kidney outcomes. We have therefore examined the association of fetal first trimester growth with kidney outcomes in childhood. This study was embedded in a prospective population-based cohort study among 1176 pregnant women and their children. We used fetal first trimester crown-length as the growth measure among mothers with a regular menstrual cycle and a known first day of the last menstrual period. At the childhood age of 6 (median 5.7-6.8) years, we measured combined kidney volume, microalbuminuria and estimated glomerular filtration rate (eGFR) based on serum creatinine and cystatin C concentrations. No consistent associations of fetal first trimester crown-rump length with childhood combined kidney volume, eGFR and microalbuminuria were observed. Compared to children with a fetal first trimester crown-rump length in the highest quintile, those in the lowest quintile had a larger childhood combined kidney volume (difference 5.32 cm 3 , 95 % confidence interval 1.06 to 9.57), but no differences in kidney function. Our results do not support the hypothesis that fetal first trimester growth restriction affects kidney size and function in childhood. Further studies are needed to focus on critical periods in early life for kidney function and disease in later life.

  17. Immunohistochemical distribution of regulatory peptides in the human fetal adenohypophysis

    Science.gov (United States)

    Reyes, R; Valladares, F; Gutiérrez, R; González, M; Bello, A R

    2008-01-01

    We have studied here the cellular distribution of several regulatory peptides in hormone-producing cells of the human pituitary during the fetal period. Immunohistochemistry was used to show the expression of several regulatory peptides, namely Angiotensin-II, Neurotensin and Galanin, at successive gestational stages and their co-localization with hormones in the human fetal adenohypophysis. Somatotrophs, gonadotrophs and thyrotrophs were differentiated earliest. At gestational week 9, Angiotensin-II immunoreactivity was co-localized only with growth hormone immunoreactivity in somatotrophs, one of the first hormone-producing cells to differentiate. This co-localization remained until week 37. Neurotensin immunoreactivity was present in gonadotrophs and thyrotrophs in week 23, after FSH and TSH hormone differentiation. Galanin immunoreactivity was present in all hormone-producing cell types except corticotrophs. The different pro-opiomelanocortin-derived peptides were detected at different stages of gestation and adrenocorticotrophic hormone immunoreaction was the last to be detected. Our results show an interesting relationship between regulatory peptides and hormones during human fetal development, which could imply that these peptides play a regulatory role in the development of pituitary function. PMID:18510508

  18. The customized fetal growth potential: a standard for Ireland.

    LENUS (Irish Health Repository)

    Unterscheider, Julia

    2013-01-01

    To identify maternal and pregnancy-related physiological and pathological variables associated with fetal growth and birthweight in Ireland and to develop customized birthweight centile charts for the Irish population that will aid in appropriate identification and selection of growth-restricted fetuses requiring increased antenatal surveillance.

  19. Isolating the role of elevated Phlda2 in asymmetric late fetal growth restriction in mice

    Directory of Open Access Journals (Sweden)

    Simon J. Tunster

    2014-10-01

    Full Text Available Pleckstrin homology-like domain family A member 2 (PHLDA2 is a maternally expressed imprinted gene whose elevated expression has been linked to fetal growth restriction in a number of human studies. In mice, Phlda2 negatively regulates placental growth and limits the accumulation of placental glycogen. We previously reported that a three-copy transgene spanning the Phlda2 locus drove a fetal growth restriction phenotype late in gestation, suggesting a causative role for PHLDA2 in human growth restriction. However, in this mouse model, Phlda2 was overexpressed by fourfold, alongside overexpression of a second imprinted gene, Slc22a18. Here, we genetically isolate the role of Phlda2 in driving late fetal growth restriction in mice. We furthermore show that this Phlda2-driven growth restriction is asymmetrical, with a relative sparing of the brain, followed by rapid catch-up growth after birth, classic features of placental insufficiency. Strikingly, fetal growth restriction showed strain-specific differences, being apparent on the 129S2/SvHsd (129 genetic background and absent on the C57BL6 (BL6 background. A key difference between these two strains is the placenta. Specifically, BL6 placentae possess a more extensive endocrine compartment and substantially greater stores of placental glycogen. Taken together, these data support a direct role for elevated Phlda2 in limiting fetal growth but also suggest that growth restriction only manifests when there is limited placental reserve. These findings should be taken into account in interpreting the results from human studies.

  20. Early fetal size and growth as predictors of adverse outcome

    DEFF Research Database (Denmark)

    Pedersen, Nina Gros; Figueras, Francesc; Wøjdemann, Karen R

    2008-01-01

    OBJECTIVE: To evaluate the association between fetal size and growth between the first and second trimesters and subsequent adverse pregnancy outcome. METHODS: A cohort was created of 7,642 singleton pregnancies cared for in three obstetric units associated with Copenhagen University. Data were...... obtained from ultrasound measurements at 11-14 weeks (crown-rump length, biparietal diameter) and 17-21 weeks (biparietal diameter). Fetal size was assessed by gestation-specific z scores, and fetal growth between the first and second trimester was calculated individually using conditional centiles....... The main outcome measures were preterm delivery, smallness for gestational age, and perinatal death. RESULTS: Slow growth of the biparietal diameter less than the 10th and less than the 2.5th conditional centiles between first and second trimesters occurred in 10.4% and 3.6% of the population, respectively...

  1. Placental adaptations to the maternal-fetal environment: implications for fetal growth and developmental programming.

    Science.gov (United States)

    Sandovici, Ionel; Hoelle, Katharina; Angiolini, Emily; Constância, Miguel

    2012-07-01

    The placenta is a transient organ found in eutherian mammals that evolved primarily to provide nutrients for the developing fetus. The placenta exchanges a wide array of nutrients, endocrine signals, cytokines and growth factors with the mother and the fetus, thereby regulating intrauterine development. Recent studies show that the placenta is not just a passive organ mediating maternal-fetal exchange. It can adapt its capacity to supply nutrients in response to intrinsic and extrinsic variations in the maternal-fetal environment. These dynamic adaptations are thought to occur to maximize fetal growth and viability at birth in the prevailing conditions in utero. However, some of these adaptations may also affect the development of individual fetal tissues, with patho-physiological consequences long after birth. Here, this review summarizes current knowledge on the causes, possible mechanisms and consequences of placental adaptive responses, with a focus on the regulation of transporter-mediated processes for nutrients. This review also highlights the emerging roles that imprinted genes and epigenetic mechanisms of gene regulation may play in placental adaptations to the maternal-fetal environment. Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  2. Review: Adiponectin – The Missing Link between Maternal Adiposity, Placental Transport and Fetal Growth?

    Science.gov (United States)

    Aye, Irving L. M. H.; Powell, Theresa L.; Jansson, Thomas

    2012-01-01

    Adiponectin has well-established insulin-sensitizing effects in non-pregnant individuals. Pregnant women who are obese or have gestational diabetes typically have low circulating levels of adiponectin, which is associated with increased fetal growth. Lean women, on the other hand, have high circulating levels of adiponectin. As a result, maternal serum adiponectin is inversely correlated to fetal growth across the full range of birth weights, suggesting that maternal adiponectin may limit fetal growth. In the mother, adiponectin is predicted to promote insulin sensitivity and stimulate glucose uptake in maternal skeletal muscle thereby reducing nutrient availability for placental transfer. Adiponectin prevents insulin-stimulated amino acid uptake in cultured primary human trophoblast cells by modulating insulin receptor substrate phosphorylation. Furthermore, chronic administration of adiponectin to pregnant mice inhibits placental insulin and mammalian target of rapamycin complex 1 (mTORC1) signaling, down-regulates the activity and expression of key placental nutrient transporters and decreases fetal growth. Preliminary findings indicate that adiponectin binds to the adiponectin receptor-2 on the trophoblast cell and activates p38 MAPK and PPAR-α, which inhibits the insulin/IGF-1 signaling pathway. In contrast to maternal adiponectin, recent reports suggest that fetal adiponectin may promote expansion of adipose tissue and stimulate fetal growth. Regulation of placental function by adiponectin constitutes a novel physiological mechanism by which the endocrine functions of maternal adipose tissue influence fetal growth. These findings may help us better understand the factors determining birth weight in normal pregnancies and in pregnancy complications associated with altered maternal adiponectin levels such as obesity and gestational diabetes. PMID:23245987

  3. Distribution of melatonin receptor in human fetal brain

    Institute of Scientific and Technical Information of China (English)

    WANG Guo-quan; SHAO Fu-yuan; ZHAO Ying; LIU Zhi-min

    2001-01-01

    Objective: To study the distribution of 2 kinds of melatonin receptor subtypes (mtl and MT2) in human fetal brain. Methods: The fetal brain tissues were sliced and the distribution ofmelatonin receptors in human fetal brain were detected using immunohistochemistry and in situ hybridization. Results: Melatonin receptor mtl existed in the cerebellun and hypothalamus, melatonin receptor MT2 exists in hypothalamus, occipital and medulla. Conclusion: Two kinds of melatonin receptors, mtl and MT2 exist in the membrane and cytosol of brain cells, indicating that human fetal brain is a target organ of melatonin.

  4. Fetal growth and later maternal death, cardiovascular disease and diabetes

    DEFF Research Database (Denmark)

    Lykke, Jacob A; Paidas, Michael J; Triche, Elizabeth W

    2012-01-01

    Low birthweight of the offspring has been associated with increased risk of early death and ischemic heart disease in the mother. However, other measurements of fetal growth than the basic birthweight are more accurate. We investigated the relation between the standardized birthweight by gestatio......Low birthweight of the offspring has been associated with increased risk of early death and ischemic heart disease in the mother. However, other measurements of fetal growth than the basic birthweight are more accurate. We investigated the relation between the standardized birthweight...... by gestational age and gender and the ponderal index and the mother's subsequent mortality and cardiovascular morbidity....

  5. Fetal plasma erythropoietin concentration in severe growth retardation.

    Science.gov (United States)

    Snijders, R J; Abbas, A; Melby, O; Ireland, R M; Nicolaides, K H

    1993-02-01

    The aim of this study was to determine whether hypoxemia induces an increase in plasma erythropoietin concentration in human fetal life and, if so, whether this response stimulates fetal erythropoiesis. The plasma erythropoietin concentration in blood samples from 33 small-for-gestational-age fetuses at 26 to 38 weeks' gestation was measured. Measurements were compared with the reference range for gestation, and associations with PO2, pH, and erythroblast and erythrocyte counts were examined. The mean plasma erythropoietin concentration in the small-for-gestational-age fetuses was significantly increased, and the degree of increase was significantly associated both with fetal acidemia and, more strongly, with fetal erythroblastosis. Erythropoietin production in response to tissue hypoxia occurs from at least 26 weeks' gestation with measurable physiologic effects on erythropoiesis. Furthermore, more accurate assessment of tissue oxygenation may be obtained by measuring the erythroblast count rather than the blood pH.

  6. Fetal first trimester growth is not associated with kidney outcomes in childhood

    NARCIS (Netherlands)

    H. Bakker (Hanneke); R. Gaillard (Romy); A. Hofman (Albert); I.K.M. Reiss (Irwin); E.A.P. Steegers (Eric); V.W.V. Jaddoe (Vincent)

    2017-01-01

    textabstractBackground: Impaired fetal growth is associated with increased risks of kidney diseases in later life. Because human development rates are highest during the first trimester, this trimester may be a particularly critical period for kidney outcomes. We have therefore examined the

  7. Fetal thrombocytopenia in pregnancies with fetal human parvovirus-B19 infection.

    Science.gov (United States)

    Melamed, Nir; Whittle, Wendy; Kelly, Edmond N; Windrim, Rory; Seaward, P Gareth R; Keunen, Johannes; Keating, Sarah; Ryan, Greg

    2015-06-01

    Fetal infection with human parvovirus B19 (hParvo-B19) has been associated mainly with fetal anemia, although data regarding other fetal hematologic effects are limited. Our aim was to assess the rate and consequences of severe fetal thrombocytopenia after fetal hParvo-B19 infection. We conducted a retrospective study of pregnancies that were complicated by fetal hParvo-B19 infection that underwent fetal blood sampling (FBS). The characteristics and outcomes of fetuses with severe thrombocytopenia (B19 infection. A total of 37 pregnancies that were affected by fetal hParvo-B19 infection were identified. Of the 29 cases that underwent FBS and had information regarding fetal platelets, 11 cases (38%) were complicated by severe fetal thrombocytopenia. Severely thrombocytopenic fetuses were characterized by a lower hemoglobin concentration (2.6 ± 0.9 g/dL vs 5.5 ± 3.6 g/dL; P = .01), lower reticulocyte count (9.1% ± 2.8% vs 17.3% ± 10.6%; P = .02), and lower gestational age at the time of diagnosis (21.4 ± 3.1 wk vs 23.6 ± 2.2 wk; P = .03). Both the fetal death rate within 48 hours of FBS (27.3% vs 0%; P = .02) and the risk of prematurity (100.0% vs 13.3%; P B19 infection, can be further worsened by IUT, and may be associated with an increased risk of procedure-related fetal loss after either FBS or IUT. Copyright © 2015. Published by Elsevier Inc.

  8. Fetal magnetic resonance imaging and human genetics

    International Nuclear Information System (INIS)

    Hengstschlaeger, Markus

    2006-01-01

    The use of fetal magnetic resonance imaging (MRI), in addition to prenatal genetic testing and sonography, has the potential to improve prenatal diagnosis of genetic disorders. MRI plays an important role in the evaluation of fetal abnormalities and malformations. Fetal MRI often enables a differential diagnosis, a determination of the extent of the disorder, the prognosis, and an improvement in therapeutic management. For counseling of parents, as well as to basically understand how genetic aberrations affect fetal development, it is of great importance to correlate different genotypes with fetal MRI data

  9. Fetal magnetic resonance imaging and human genetics

    Energy Technology Data Exchange (ETDEWEB)

    Hengstschlaeger, Markus [Medical Genetics, Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria)]. E-mail: markus.hengstschlaeger@meduniwien.ac.at

    2006-02-15

    The use of fetal magnetic resonance imaging (MRI), in addition to prenatal genetic testing and sonography, has the potential to improve prenatal diagnosis of genetic disorders. MRI plays an important role in the evaluation of fetal abnormalities and malformations. Fetal MRI often enables a differential diagnosis, a determination of the extent of the disorder, the prognosis, and an improvement in therapeutic management. For counseling of parents, as well as to basically understand how genetic aberrations affect fetal development, it is of great importance to correlate different genotypes with fetal MRI data.

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

    Science.gov (United States)

    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. Impacts of maternal dietary protein intake on fetal survival, growth, and development.

    Science.gov (United States)

    Herring, Cassandra M; Bazer, Fuller W; Johnson, Gregory A; Wu, Guoyao

    2018-03-01

    Maternal nutrition during gestation, especially dietary protein intake, is a key determinant in embryonic survival, growth, and development. Low maternal dietary protein intake can cause embryonic losses, intra-uterine growth restriction, and reduced postnatal growth due to a deficiency in specific amino acids that are important for cell metabolism and function. Of note, high maternal dietary protein intake can also result in intra-uterine growth restriction and embryonic death, due to amino acid excesses, as well as the toxicity of ammonia, homocysteine, and H 2 S that are generated from amino acid catabolism. Maternal protein nutrition has a pronounced impact on fetal programming and alters the expression of genes in the fetal genome. As a precursor to the synthesis of molecules (e.g. nitric oxide, polyamines, and creatine) with cell signaling and metabolic functions, L-arginine (Arg) is essential during pregnancy for growth and development of the conceptus. With inadequate maternal dietary protein intake, Arg and other important amino acids are deficient in mother and fetus. Dietary supplementation of Arg during gestation has been effective in improving embryonic survival and development of the conceptus in many species, including humans, pigs, sheep, mice, and rats. Both the balance among amino acids and their quantity are critical for healthy pregnancies and offspring. Impact statement This review aims at: highlighting adverse effects of elevated levels of ammonia in mother or fetus on embryonic/fetal survival, growth, and development; helping nutritionists and practitioners to understand the mechanisms whereby elevated levels of ammonia in mother or fetus results in embryonic/fetal death, growth restriction, and developmental abnormalities; and bringing, into the attention of nutritionists and practitioners, the problems of excess or inadequate dietary intake of protein or amino acids on pregnancy outcomes in animals and humans. The article provides new

  12. Cholesterol synthesis by human fetal hepatocytes: effect of lipoproteins

    International Nuclear Information System (INIS)

    Carr, B.R.; Simpson, E.R.

    1984-01-01

    The purpose of the present investigation was to determine the effect of various lipoproteins on the rate of cholesterol synthesis of human fetal liver cells maintained in culture. This was accomplished by measuring the rate of incorporation of tritium from tritiated water or carbon 14-labeled acetate into cholesterol in human fetal liver cells. Optimal conditions for each assay were determined. When human fetal liver cells were maintained in the presence of low-density lipoprotein, cholesterol synthesis was inhibited in a concentration-dependent fashion. Intermediate--density lipoprotein and very-low-density lipoprotein also suppressed cholesterol synthesis in human fetal liver cells. In contrast, high-density lipoprotein stimulated cholesterol synthesis in human fetal liver cells. The results of the present as well as our previous investigations suggest that multiple interrelationships exist between fetal liver cholesterol synthesis and lipoprotein-cholesterol utilization by the human fetal adrenal gland and that these processes serve to regulate the lipoprotein-cholesterol levels in fetal plasma

  13. A crucial role for maternal dietary methyl donor intake in epigenetic programming and fetal growth outcomes.

    Science.gov (United States)

    McGee, Meghan; Bainbridge, Shannon; Fontaine-Bisson, Bénédicte

    2018-06-01

    The fetal origins of health and disease framework has identified extremes in fetal growth and birth weight as factors associated with the lifelong generation of chronic diseases such as obesity, diabetes, cardiovascular disease, and hypertension. Maternal nutrition plays a critical role in fetal and placental development, in part by providing the methyl groups required to establish the fetus's genome structure and function, notably through DNA methylation. The goal of this narrative review is to describe the role of maternal dietary methyl donor (methionine, folate, and choline) and cofactor (zinc and vitamins B2, B6, and B12) intake in one-carbon metabolism and DNA methylation in the fetus and placenta, as well as their impacts on fetal growth and lifelong health outcomes, with specific examples in animals and humans. Based on the available evidence, it is concluded that intake of different amounts of dietary methyl donors and cofactors during pregnancy may alter fetal growth and development, thus establishing a major link between early environmental exposure and disease development in the offspring later in life.

  14. Role of uteroplacental and fetal Doppler in identifying fetal growth restriction at term.

    OpenAIRE

    Khalil, A; Thilaganathan, B

    2017-01-01

    Identification of the fetus at risk of adverse outcome at term is a challenge to both clinicians and researchers alike. Despite the fact that fetal growth restriction (FGR) is a known risk factor for stillbirth, at least two thirds of the stillbirth cases at term are not small for gestational age (SGA) - a commonly used proxy for FGR. However, the majority of SGA fetuses are constitutionally small babies and do not suffer from adverse perinatal outcome. The cerebroplacental ratio (CPR) is eme...

  15. Placental Dysfunction Underlies Increased Risk of Fetal Growth Restriction and Stillbirth in Advanced Maternal Age Women.

    Science.gov (United States)

    Lean, Samantha C; Heazell, Alexander E P; Dilworth, Mark R; Mills, Tracey A; Jones, Rebecca L

    2017-08-29

    Pregnancies in women of advanced maternal age (AMA) are susceptible to fetal growth restriction (FGR) and stillbirth. We hypothesised that maternal ageing is associated with utero-placental dysfunction, predisposing to adverse fetal outcomes. Women of AMA (≥35 years) and young controls (20-30 years) with uncomplicated pregnancies were studied. Placentas from AMA women exhibited increased syncytial nuclear aggregates and decreased proliferation, and had increased amino acid transporter activity. Chorionic plate and myometrial artery relaxation was increased compared to controls. AMA was associated with lower maternal serum PAPP-A and sFlt and a higher PlGF:sFlt ratio. AMA mice (38-41 weeks) at E17.5 had fewer pups, more late fetal deaths, reduced fetal weight, increased placental weight and reduced fetal:placental weight ratio compared to 8-12 week controls. Maternofetal clearance of 14 C-MeAIB and 3 H-taurine was reduced and uterine arteries showed increased relaxation. These studies identify reduced placental efficiency and altered placental function with AMA in women, with evidence of placental adaptations in normal pregnancies. The AMA mouse model complements the human studies, demonstrating high rates of adverse fetal outcomes and commonalities in placental phenotype. These findings highlight placental dysfunction as a potential mechanism for susceptibility to FGR and stillbirth with AMA.

  16. Biopsychosocial determinants of pregnancy length and fetal growth.

    Science.gov (United States)

    St-Laurent, Jennifer; De Wals, Philippe; Moutquin, Jean-Marie; Niyonsenga, Theophile; Noiseux, Manon; Czernis, Loretta

    2008-05-01

    The causes and mechanisms related to preterm delivery and intrauterine growth restriction are poorly understood. Our objective was to assess the direct and indirect effects of psychosocial and biomedical factors on the duration of pregnancy and fetal growth. A self-administered questionnaire was distributed to pregnant women attending prenatal ultrasound clinics in nine hospitals in the Montérégie region in the province of Quebec, Canada, from November 1997 to May 1998. Prenatal questionnaires were linked with birth certificates. Theoretical models explaining pregnancy length and fetal growth were developed and tested, using path analysis. In order to reduce the number of variables from the questionnaire, a principal component analysis was performed, and the three most important new dimensions were retained as explanatory variables in the final models. Data were available for 1602 singleton pregnancies. The biophysical score, covering both maternal age and the pre-pregnancy body mass index, was the only variable statistically associated with pregnancy length. Smoking, obstetric history, maternal health and biophysical indices were direct predictors of fetal growth. Perceived stress, social support and self-esteem were not directly related to pregnancy outcomes, but were determinants of smoking and the above-mentioned biomedical variables. More studies are needed to identify the mechanisms by which adverse psychosocial factors are translated into adverse biological effects.

  17. Maternal endotoxin-induced fetal growth restriction in rats: Fetal responses in toll-like receptor

    Directory of Open Access Journals (Sweden)

    Banun Kusumawardani

    2012-09-01

    Full Text Available Background: Porphyromonas gingivalis as a major etiology of periodontal disease can produce virulence factor, lipopolysaccharide/LPS, which is expected to play a role in the intrauterine fetal growth. Trophoblast at the maternal-fetal interface actively participates in response to infection through the expression of a family of natural immune receptors, toll-like receptor (TLR. Purpose: the aims of study were to identify endotoxin concentration in maternal blood serum of Porphyromonas gingivalis-infected pregnant rats, to characterize the TLR-4 expression in trophoblast cells, and to determine its effect on fetal growth. Methods: Female rats were infected with live-Porphyromonas gingivalis at concentration of 2 x 109 cells/ml into subgingival sulcus area of the maxillary first molar before and/or during pregnancy. They were sacrified on 14th and 20th gestational day. Fetuses were evaluated for weight and length. Endotoxin was detected by limulus amebocyte lysate assay in the maternal blood serum. The TLR-4 expression in trophoblast cells was detected by immunohistochemistry. WHO multicentre study for the development of growth standards from fetal life to childhood: the fetal component.

    Science.gov (United States)

    Merialdi, Mario; Widmer, Mariana; Gülmezoglu, Ahmet Metin; Abdel-Aleem, Hany; Bega, George; Benachi, Alexandra; Carroli, Guillermo; Cecatti, Jose Guilherme; Diemert, Anke; Gonzalez, Rogelio; Hecher, Kurt; Jensen, Lisa N; Johnsen, Synnøve L; Kiserud, Torvid; Kriplani, Alka; Lumbiganon, Pisake; Tabor, Ann; Talegawkar, Sameera A; Tshefu, Antoinette; Wojdyla, Daniel; Platt, Lawrence

    2014-05-02

    In 2006 WHO presented the infant and child growth charts suggested for universal application. However, major determinants for perinatal outcomes and postnatal growth are laid down during antenatal development. Accordingly, monitoring fetal growth in utero by ultrasonography is important both for clinical and scientific reasons. The currently used fetal growth references are derived mainly from North American and European population and may be inappropriate for international use, given possible variances in the growth rates of fetuses from different ethnic population groups. WHO has, therefore, made it a high priority to establish charts of optimal fetal growth that can be recommended worldwide. This is a multi-national study for the development of fetal growth standards for international application by assessing fetal growth in populations of different ethnic and geographic backgrounds. The study will select pregnant women of high-middle socioeconomic status with no obvious environmental constraints on growth (adequate nutritional status, non-smoking), and normal pregnancy history with no complications likely to affect fetal growth. The study will be conducted in centres from ten developing and industrialized countries: Argentina, Brazil, Democratic Republic of Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand. At each centre, 140 pregnant women will be recruited between 8 + 0 and 12 + 6 weeks of gestation. Subsequently, visits for fetal biometry will be scheduled at 14, 18, 24, 28, 32, 36, and 40 weeks (+/- 1 week) to be performed by trained ultrasonographers.The main outcome of the proposed study will be the development of fetal growth standards (either global or population specific) for international applications. The data from this study will be incorporated into obstetric practice and national health policies at country level in coordination with the activities presently conducted by WHO to implement the use of the Child Growth Standards.

  18. The INTERGROWTH-21st fetal growth standards: toward the global integration of pregnancy and pediatric care.

    Science.gov (United States)

    Papageorghiou, Aris T; Kennedy, Stephen H; Salomon, Laurent J; Altman, Douglas G; Ohuma, Eric O; Stones, William; Gravett, Michael G; Barros, Fernando C; Victora, Cesar; Purwar, Manorama; Jaffer, Yasmin; Noble, Julia A; Bertino, Enrico; Pang, Ruyan; Cheikh Ismail, Leila; Lambert, Ann; Bhutta, Zulfiqar A; Villar, José

    2018-02-01

    The purpose of the INTERGROWTH-21 st project was to develop international, prescriptive standards for fetal growth assessed by ultrasound and fundal height, preterm postnatal growth, newborn size and body composition, maternal weight gain, and infant development at the age of 2 years. Hence, we have produced, based on World Health Organization recommendations, the first comprehensive set of international standards of optimal fetal and newborn growth that perfectly match the existing World Health Organization child growth standards. Uniquely, the same population was followed up longitudinally from 9 weeks of fetal life to 2 years of age, with growth, health, and nutritional status assessment at 2 years supporting the appropriateness of the population for construction of growth standards. The resulting package of clinical tools allows, for the first time, growth and development to be monitored from early pregnancy to infancy. The INTERGROWTH-21 st fetal growth standards, which are based on observing >4500 healthy pregnancies, nested in a study of >59,000 pregnancies from populations with low rates of adverse perinatal outcomes, show how fetuses should grow-rather than the more limited objective of past references, which describe how they have grown at specific times and locations. Our work has confirmed the fundamental biological principle that variation in human growth across different populations is mostly dependent on environmental, nutritional, and socioeconomic factors. We found that when mothers' nutritional and health needs are met and there are few environmental constraints on growth, st newborn size standards. We suggest that misclassification of these infants by using local charts could affect the delivery of optimal health care. Copyright © 2018. Published by Elsevier Inc.

  19. Fetal growth velocity and body proportion in the assessment of growth.

    Science.gov (United States)

    Hiersch, Liran; Melamed, Nir

    2018-02-01

    Fetal growth restriction implies failure of a fetus to meet its growth potential and is associated with increased perinatal mortality and morbidity. Therefore, antenatal detection of fetal growth restriction is of major importance in an attempt to deliver improved clinical outcomes. The most commonly used approach towards screening for fetal growth restriction is by means of sonographic fetal weight estimation, to detect fetuses small for gestational age, defined by an estimated fetal weight <10th percentile for gestational age. However, the predictive accuracy of this approach is limited both by suboptimal detection rate (as it may overlook non-small-for-gestational-age growth-restricted fetuses) and by a high false-positive rate (as most small-for-gestational-age fetuses are not growth restricted). Here, we review 2 strategies that may improve the diagnostic accuracy of sonographic fetal biometry for fetal growth restriction. The first strategy involves serial ultrasound evaluations of fetal biometry. The information obtained through these serial assessments can be interpreted using several different approaches including fetal growth velocity, conditional percentiles, projection-based methods, and individualized growth assessment that can be viewed as mathematical techniques to quantify any decrease in estimated fetal weight percentile, a phenomenon that many care providers assess and monitor routinely in a qualitative manner. This strategy appears promising in high-risk pregnancies where it seems to improve the detection of growth-restricted fetuses at increased risk of adverse perinatal outcomes and, at the same time, decrease the risk of falsely diagnosing healthy constitutionally small-for-gestational-age fetuses as growth restricted. Further studies are needed to determine the utility of this strategy in low-risk pregnancies as well as to optimize its performance by determining the optimal timing and interval between exams. The second strategy refers to the

  1. 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.

  2. Impact of placental insufficiency on fetal skeletal muscle growth

    Science.gov (United States)

    Hay, William W.

    2016-01-01

    Intrauterine growth restriction (IUGR) caused by placental insufficiency is one of the most common and complex problems in perinatology, with no known cure. In pregnancies affected by placental insufficiency, a poorly functioning placenta restricts nutrient supply to the fetus and prevents normal fetal growth. Among other significant deficits in organ development, the IUGR fetus characteristically has less lean body and skeletal muscle mass than their appropriately-grown counterparts. Reduced skeletal muscle growth is not fully compensated after birth, as individuals who were born small for gestational age (SGA) from IUGR have persistent reductions in muscle mass and strength into adulthood. The consequences of restricted muscle growth and accelerated postnatal “catch-up” growth in the form of adiposity may contribute to the increased later life risk for visceral adiposity, peripheral insulin resistance, diabetes, and cardiovascular disease in individuals who were formerly IUGR. This review will discuss how an insufficient placenta results in impaired fetal skeletal muscle growth and how lifelong reductions in muscle mass might contribute to increased metabolic disease risk in this vulnerable population. PMID:26994511

  3. Dietary -carbamylglutamate and rumen-protected -arginine supplementation ameliorate fetal growth restriction in undernourished ewes.

    Science.gov (United States)

    Zhang, H; Sun, L W; Wang, Z Y; Deng, M T; Zhang, G M; Guo, R H; Ma, T W; Wang, F

    2016-05-01

    This study was conducted with an ovine intrauterine growth restriction (IUGR) model to test the hypothesis that dietary -carbamylglutamate (NCG) and rumen-protected -Arg (RP-Arg) supplementation are effective in ameliorating fetal growth restriction in undernourished ewes. Beginning on d 35 of gestation, ewes were fed a diet providing 100% of NRC-recommended nutrient requirements, 50% of NRC recommendations (50% NRC), 50% of NRC recommendations supplemented with 20 g/d RP-Arg (providing 10 g/d of Arg), and 50% of NRC recommendations supplemented with 5 g/d NCG product (providing 2.5 g/d of NCG). On d 110, maternal, fetal, and placental tissues and fluids were collected and weighed. Ewe weights were lower ( ewes compared with adequately fed ewes. Maternal RP-Arg or NCG supplementation did not alter ( = 0.26) maternal BW in nutrient-restricted ewes. Weights of most fetal organs were increased ( ewes compared with 50% NRC-fed ewes. Supplementation of RP-Arg or NCG reduced ( ewes but had no effect on concentrations of lactate and GH. Maternal RP-Arg or NCG supplementation markedly improved ( ewes. These novel results indicate that dietary NCG and RP-Arg supplementation to underfed ewes ameliorated fetal growth restriction, at least in part, by increasing the availability of AA in the conceptus and provide support for its clinical use to ameliorate IUGR in humans and sheep industry production.

  4. Fetal head circumference growth in children with specific language impairment.

    Science.gov (United States)

    Whitehouse, Andrew J O; Zubrick, Stephen R; Blair, Eve; Newnham, John P; Hickey, Martha

    2012-01-01

    To characterise fetal brain growth in children with specific language impairment (SLI). A nested case-control study. Perth, Western Australia. Thirty children meeting criteria for SLI at age 10 years were individually matched with a typically developing comparison child on sex, non-verbal ability, fetal gestational age, maternal age at conception, smoking and alcohol intake during pregnancy. Occipitofrontal head circumference (HC) was measured using ultrasonography at approximately 18 weeks gestation. Femur length provided a measure of fetal length. Occipitofrontal HC was measured at birth and at the 1-year postnatal follow-up using a precise paper tape measure, while crown-heel length acted as an index of body length at both time points. Raw data were transformed to z-scores using reference norms. The SLI group had a significantly smaller mean HC than the typically developing comparison children at birth, but there was no group difference at 18 weeks gestation or at the 1-year postnatal follow-up. Individual analyses found that 12 SLI children had an HC z-score less than -1 at birth, with three of these cases meeting criteria for microcephaly. There was no group difference in the indices of overall body size at any time point. Children with SLI are more likely to have a small HC at birth but not at 18 weeks gestation or infancy, suggesting growth asynchrony in brain development during the second half of pregnancy.

  5. Normative biometrics for fetal ocular growth using volumetric MRI reconstruction.

    Science.gov (United States)

    Velasco-Annis, Clemente; Gholipour, Ali; Afacan, Onur; Prabhu, Sanjay P; Estroff, Judy A; Warfield, Simon K

    2015-04-01

    To determine normative ranges for fetal ocular biometrics between 19 and 38 weeks gestational age (GA) using volumetric MRI reconstruction. The 3D images of 114 healthy fetuses between 19 and 38 weeks GA were created using super-resolution volume reconstructions from MRI slice acquisitions. These 3D images were semi-automatically segmented to measure fetal orbit volume, binocular distance (BOD), interocular distance (IOD), and ocular diameter (OD). All biometry correlated with GA (Volume, Pearson's correlation coefficient (CC) = 0.9680; BOD, CC = 0.9552; OD, CC = 0.9445; and IOD, CC = 0.8429), and growth curves were plotted against linear and quadratic growth models. Regression analysis showed quadratic models to best fit BOD, IOD, and OD and a linear model to best fit volume. Orbital volume had the greatest correlation with GA, although BOD and OD also showed strong correlation. The normative data found in this study may be helpful for the detection of congenital fetal anomalies with more consistent measurements than are currently available. © 2015 John Wiley & Sons, Ltd. © 2015 John Wiley & Sons, Ltd.

  6. What is the value of ultrasound soft tissue measurements in the prediction of abnormal fetal growth?

    LENUS (Irish Health Repository)

    Farah, N

    2012-02-01

    Abnormal fetal growth increases the complications of pregnancy not only for the baby but also for the mother. Growth abnormalities also have lifelong consequences. These babies are at increased risk of insulin resistance, diabetes and hypertension later in life. It is important to identify these babies antenatally to optimise their clinical care. Although used extensively antenatally to monitor fetal growth, ultrasound has its limitations. Despite the use of more than 50 different formulae to estimate fetal weight, their performance has been poor at the extremes of fetal weight. Over the past 20 years there has been emerging interest in studying fetal soft tissue measurements to improve detection of growth abnormalities. This review paper outlines the value of soft tissue measurements in identifying fetal growth abnormalities, in estimating fetal weight and in managing diabetes mellitus in pregnancy.

  7. Overexpression of microRNA-375 impedes platelet-derived growth factor-induced proliferation and migration of human fetal airway smooth muscle cells by targeting Janus kinase 2.

    Science.gov (United States)

    Ji, Yamei; Yang, Xin; Su, Huixia

    2018-02-01

    The abnormal proliferation and migration of airway smooth muscle (ASM) cells play a critical role in airway remodeling during the development of asthma. MicroRNAs (miRNAs) have emerged as critical regulators of ASM cell proliferation and migration in airway remodeling. In this study, we aimed to investigate the potential role of miR-375 in the regulation of platelet-derived growth factor (PDGF)-induced fetal ASM cell proliferation and migration. Our results showed that miR-375 expression was significantly decreased in fetal ASM cells that were treated with PDGF. Functional data showed that overexpression of miR-375 inhibited the proliferation and migration of fetal ASM cells, whereas inhibition of miR-375 enhanced the proliferation and migration of fetal ASM cells. The results of bioinformatics analysis and a dual-luciferase reporter assay showed that miR-375 binds directly to the 3'-untranslated region of Janus kinase 2 (JAK2). Further data confirmed that miR-375 negatively regulates the expression of JAK2 in fetal ASM cells. Moreover, miR-375 also impeded the PDGF-induced activation of signal transducer and activator of transcription 3 (STAT3) in fetal ASM cells. However, restoration of JAK2 expression partially reversed the inhibitory effect of miR-375 on fetal ASM cell proliferation and migration. Overall, our results demonstrate that miR-375 inhibits fetal ASM cell proliferation and migration by targeting JAK2/STAT3 signaling. Our study provides a potential therapeutic target for the development of novel treatment strategies for pediatric asthma. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  8. Amniotic oxytocin and vasopressin in relation to human fetal development and labour

    NARCIS (Netherlands)

    Oosterbaan, H. P.; Swaab, D. F.

    1989-01-01

    Previous experiments in rats revealed increased amniotic oxytocin (OXT) levels in the course of normal development and increased vasopressin (AVP) levels in retarded fetal growth. In order to see whether similar changes would also occur in human, OXT and AVP levels were determined in amniotic fluid,

  9. Maternal Therapy with Ad.VEGF-A165 Increases Fetal Weight at Term in a Guinea-Pig Model of Fetal Growth Restriction.

    Science.gov (United States)

    Swanson, Anna M; Rossi, Carlo A; Ofir, Keren; Mehta, Vedanta; Boyd, Michael; Barker, Hannah; Ledwozyw, Agata; Vaughan, Owen; Martin, John; Zachary, Ian; Sebire, Neil; Peebles, Donald M; David, Anna L

    2016-12-01

    In a model of growth-restricted sheep pregnancy, it was previously demonstrated that transient uterine artery VEGF overexpression can improve fetal growth. This approach was tested in guinea-pig pregnancies, where placental physiology is more similar to humans. Fetal growth restriction (FGR) was attained through peri-conceptual nutrient restriction in virgin guinea pigs. Ad.VEGF-A 165 or Ad.LacZ (1 × 10 10 vp) was applied at mid-gestation via laparotomy, delivered externally to the uterine circulation with thermosensitive gel. At short-term (3-8 days post surgery) or at term gestation, pups were weighed, and tissues were sampled for vector spread analysis, VEGF expression, and its downstream effects. Fetal weight at term was increased (88.01 ± 13.36 g; n = 26) in Ad.VEGF-A 165 -treated animals compared with Ad.LacZ-treated animals (85.52 ± 13.00 g; n = 19; p = 0.028). The brain, liver, and lung weight and crown rump length were significantly larger in short-term analyses, as well as VEGF expression in transduced tissues. At term, molecular analyses confirmed the presence of VEGF transgene in target tissues but not in fetal samples. Tissue histology analysis and blood biochemistry/hematological examination were comparable with controls. Uterine artery relaxation in Ad.VEGF-A 165 -treated dams was higher compared with Ad.LacZ-treated dams. Maternal uterine artery Ad.VEGF-A 165 increases fetal growth velocity and term fetal weight in growth-restricted guinea-pig pregnancy.

  10. O6-methylguanine DNA methyltransferase in human fetal tissues: fetal and maternal factors

    International Nuclear Information System (INIS)

    D'Ambrosio, S.M.; Samuel, M.J.; Dutta-Choudhury, T.A.; Wani, A.A.

    1986-01-01

    O 6 -Methylguanine methyltransferase (O 6 -MT) was measured and compared in extracts of 7 human fetal tissues obtained from 21 different fetal specimens as a function of fetal age and race, and maternal smoking and drug usage. Activity was determined from the proteinase-K solubilized radioactivity transferred from the DNA to the O 6 -MT. S9 homogenates were incubated with a heat depurinated [ 3 H]-methylnitrosourea alkylated DNA. Liver exhibited the highest activity followed by kidney, lung, small intestine, large intestine, skin and brain. Each of the tissues exhibited a 3- to 5-fold level of interindividual variation of O 6 -MT. There did not appear to be any significant difference of O 6 -MT in the tissues obtained from mothers who smoked cigarettes during pregnancy. Also, fetal race and age did not appear to account for the level of variation of O 6 -MT. The fetal tissues obtained from an individual using phenobarbital and smoking exhibited 4-fold increases in O 6 -MT activity. The tissues obtained from another individual on kidney dialysis were 2- to 3-fold higher than the normal population. These data suggest that the variation in human O 6 -MT can not be explained by racial or smoking factors, but may be modulated by certain drugs

  11. Fetal deficiency of Lin28 programs life-long aberrations in growth and glucose metabolism

    Science.gov (United States)

    Shinoda, Gen; Shyh-Chang, Ng; de Soysa, T. Yvanka; Zhu, Hao; Seligson, Marc T.; Shah, Samar P.; Abo-Sido, Nora; Yabuuchi, Akiko; Hagan, John P.; Gregory, Richard I.; Asara, John M.; Cantley, Lewis C.; Moss, Eric G.; Daley, George Q.

    2013-01-01

    LIN28A/B are RNA binding proteins implicated by genetic association studies in human growth and glucose metabolism. Mice with ectopic over-expression of Lin28a have shown related phenotypes. Here we describe the first comprehensive analysis of the physiologic consequences of Lin28a and Lin28b deficiency in knockout (KO) mice. Lin28a/b-deficiency led to dwarfism starting at different ages, and compound gene deletions showed a cumulative dosage effect on organismal growth. Conditional gene deletion at specific developmental stages revealed that fetal but neither neonatal nor adult deficiency resulted in growth defects and aberrations in glucose metabolism. Tissue-specific KO mice implicated skeletal muscle-deficiency in the abnormal programming of adult growth and metabolism. The effects of Lin28b KO can be rescued by Tsc1 haplo-insufficiency in skeletal muscles. Our data implicate fetal expression of Lin28a/b in the regulation of life-long effects on metabolism and growth, and demonstrate that fetal Lin28b acts at least in part via mTORC1 signaling. PMID:23666760

  12. Role of the placental Vitamin D receptor in modulating feto-placental growth in Fetal growth restriction and Preeclampsia-affected pregnancies.

    Directory of Open Access Journals (Sweden)

    Padma eMurthi

    2016-02-01

    Full Text Available Fetal growth restriction (FGR is a common pregnancy complication that affects up to 5% of pregnancies worldwide. Recent studies demonstrate that Vitamin D deficiency is implicated in reduced fetal growth, which may be rescued by supplementation of Vitamin D. Despite this, the pathway(s by which Vitamin D modulate fetal growth remains to be investigated. Our own studies demonstrate that the Vitamin D receptor (VDR is significantly decreased in placentae from human pregnancies complicated by FGR and contributes to abnormal placental trophoblast apoptosis and differentiation and regulation of cell-cycle genes in vitro. Thus, Vitamin D signalling is important for normal placental function and fetal growth. This review discusses the association of Vitamin D with fetal growth, the function of Vitamin D and its receptor in pregnancy, as well as the functional significance of a placental source of Vitamin D in FGR. Additionally, we propose that for Vitamin D to be clinically effective to prevent and manage FGR, the molecular mechanisms of Vitamin D and its receptor in modulating fetal growth requires further investigation.

  13. Cross-hemispheric functional connectivity in the human fetal brain.

    Science.gov (United States)

    Thomason, Moriah E; Dassanayake, Maya T; Shen, Stephen; Katkuri, Yashwanth; Alexis, Mitchell; Anderson, Amy L; Yeo, Lami; Mody, Swati; Hernandez-Andrade, Edgar; Hassan, Sonia S; Studholme, Colin; Jeong, Jeong-Won; Romero, Roberto

    2013-02-20

    Compelling evidence indicates that psychiatric and developmental disorders are generally caused by disruptions in the functional connectivity (FC) of brain networks. Events occurring during development, and in particular during fetal life, have been implicated in the genesis of such disorders. However, the developmental timetable for the emergence of neural FC during human fetal life is unknown. We present the results of resting-state functional magnetic resonance imaging performed in 25 healthy human fetuses in the second and third trimesters of pregnancy (24 to 38 weeks of gestation). We report the presence of bilateral fetal brain FC and regional and age-related variation in FC. Significant bilateral connectivity was evident in half of the 42 areas tested, and the strength of FC between homologous cortical brain regions increased with advancing gestational age. We also observed medial to lateral gradients in fetal functional brain connectivity. These findings improve understanding of human fetal central nervous system development and provide a basis for examining the role of insults during fetal life in the subsequent development of disorders in neural FC.

  14. Histochemical and radioautographic studies of normal human fetal colon

    International Nuclear Information System (INIS)

    Lev, R.; Orlic, D.; New York Medical Coll., N.Y.

    1974-01-01

    Twenty fetal and infant colons ranging from 10 weeks in utero to 20 months postpartum, and 12 adult human colons were examined using histochemical techniques in conjunction with in vitro radioautography using Na 2 35 SO 4 as a sulfomucin precursor. Only the sulfated components of mucus in fetal goblet cells was found to differ significantly from adult colonic mucins. In the fetus sulfomucin staining was much weaker than in the adult, and was more intense in the left colon which is the reverse of the adult pattern. Sulfomucin was concentrated in the crypts throughout the fetal colon whereas in the adult right colon it predominated in the surface cells. As in the adult, saponification liberated carboxyl groups, possibly belonging to sialic acid, and vicinal hydroxyl groups from fetal mucins suggesting that this procedure hydrolyses an ester linkage between these 2 reactive groups. During the middle trimester of fetal life the colon possesses villi whose constituent cells display alkaline phosphatase in their surface coat. These and other morphological and histochemical similarities to fetal small intestine suggest that the fetal colon may have a limited capacity to absorb materials contained within swallowed amniotic fluid during this period. (orig.) [de

  15. Distinct functional programming of human fetal and adult monocytes.

    Science.gov (United States)

    Krow-Lucal, Elisabeth R; Kim, Charles C; Burt, Trevor D; McCune, Joseph M

    2014-03-20

    Preterm birth affects 1 out of 9 infants in the United States and is the leading cause of long-term neurologic handicap and infant mortality, accounting for 35% of all infant deaths in 2008. Although cytokines including interferon-γ (IFN-γ), interleukin-10 (IL-10), IL-6, and IL-1 are produced in response to in utero infection and are strongly associated with preterm labor, little is known about how human fetal immune cells respond to these cytokines. We demonstrate that fetal and adult CD14(+)CD16(-) classical monocytes are distinct in terms of basal transcriptional profiles and in phosphorylation of signal transducers and activators of transcription (STATs) in response to cytokines. Fetal monocytes phosphorylate canonical and noncanonical STATs and respond more strongly to IFN-γ, IL-6, and IL-4 than adult monocytes. We demonstrate a higher ratio of SOCS3 to IL-6 receptor in adult monocytes than in fetal monocytes, potentially explaining differences in STAT phosphorylation. Additionally, IFN-γ signaling results in upregulation of antigen presentation and costimulatory machinery in adult, but not fetal, monocytes. These findings represent the first evidence that primary human fetal and adult monocytes are functionally distinct, potentially explaining how these cells respond differentially to cytokines implicated in development, in utero infections, and the pathogenesis of preterm labor.

  16. BMP signaling in the human fetal ovary is developmentally regulated and promotes primordial germ cell apoptosis.

    Science.gov (United States)

    Childs, Andrew J; Kinnell, Hazel L; Collins, Craig S; Hogg, Kirsten; Bayne, Rosemary A L; Green, Samira J; McNeilly, Alan S; Anderson, Richard A

    2010-08-01

    Primordial germ cells (PGCs) are the embryonic precursors of gametes in the adult organism, and their development, differentiation, and survival are regulated by a combination of growth factors collectively known as the germ cell niche. Although many candidate niche components have been identified through studies on mouse PGCs, the growth factor composition of the human PGC niche has not been studied extensively. Here we report a detailed analysis of the expression of components of the bone morphogenetic protein (BMP) signaling apparatus in the human fetal ovary, from postmigratory PGC proliferation to the onset of primordial follicle formation. We find developmentally regulated and reciprocal patterns of expression of BMP2 and BMP4 and identify germ cells to be the exclusive targets of ovarian BMP signaling. By establishing long-term cultures of human fetal ovaries in which PGCs are retained within their physiological niche, we find that BMP4 negatively regulates postmigratory PGC numbers in the human fetal ovary by promoting PGC apoptosis. Finally, we report expression of both muscle segment homeobox (MSX)1 and MSX2 in the human fetal ovary and reveal a selective upregulation of MSX2 expression in human fetal ovary in response to BMP4, suggesting this gene may act as a downstream effector of BMP-induced apoptosis in the ovary, as in other systems. These data reveal for the first time growth factor regulation of human PGC development in a physiologically relevant context and have significant implications for the development of cultures systems for the in vitro maturation of germ cells, and their derivation from pluripotent stem cells.

  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. Sildenafil citrate (Viagra) enhances vasodilatation in fetal growth restriction.

    Science.gov (United States)

    Wareing, Mark; Myers, Jenny E; O'Hara, Maureen; Baker, Philip N

    2005-05-01

    Fetal growth restriction (FGR) affects up to 8% of all pregnancies and has massive short-term (increased fetal morbidity and mortality) and long-term (increased incidence of cardiovascular disease in adulthood) health implications. Doppler waveform analysis of pregnancies complicated by FGR suggests compromised uteroplacental circulation and placental hypoperfusion. Our aim was to determine whether myometrial small artery function was aberrant in FGR and to assess whether sildenafil citrate could improve vasodilatation in FGR pregnancies. Small arteries dissected from myometrial biopsies obtained at cesarean section from normal pregnant women (n = 27) or women whose pregnancies were complicated by FGR (n = 12) were mounted on wire myographs. Vessels were constricted (with arginine vasopressin or U46619) and relaxed (with bradykinin) before and after incubation with a phosphodiesterase-5 inhibitor, sildenafil citrate. We demonstrated increased myometrial small artery vasoconstriction and decreased endothelium-dependent vasodilatation in vessels from women whose pregnancies were complicated by FGR. Sildenafil citrate significantly reduced vasoconstriction and significantly improved relaxation of FGR small arteries. We conclude that sildenafil citrate improves endothelial function of myometrial vessels from women whose pregnancies are complicated by intrauterine growth restriction. Sildenafil citrate may offer a potential therapeutic strategy to improve uteroplacental blood flow in FGR pregnancies.

  20. Anti-inflammatory Elafin in human fetal membranes.

    Science.gov (United States)

    Stalberg, Cecilia; Noda, Nathalia; Polettini, Jossimara; Jacobsson, Bo; Menon, Ramkumar

    2017-02-01

    Elafin is a low molecular weight protein with antileukoproteinase, anti-inflammatory, antibacterial and immunomodulating properties. The profile of Elafin in fetal membranes is not well characterized. This study determined the changes in Elafin expression and concentration in human fetal membrane from patients with preterm prelabor rupture of membranes (PPROM) and in vitro in response to intra-amniotic polymicrobial pathogens. Elafin messenger RNA (mRNA) expressions were studied in fetal membranes from PPROM, normal term as well as in normal term not in labor membranes in an organ explant system treated (24 h) with lipopolysaccharide (LPS), using quantitative reverse transcription-polymerase chain reaction (RT-PCR). Enzyme-linked immunosorbent assay (ELISA) measured Elafin concentrations in culture supernatants from tissues treated with LPS and polybacterial combinations of heat-inactivated Mycoplasma hominis (MH), Ureaplasma urealyticum (UU) and Gardnerella vaginalis (GV). Elafin mRNA expression in fetal membranes from women with PPROM was significantly higher compared to women who delivered at term after normal pregnancy (5.09±3.50 vs. 11.71±2.21; Pmembranes showed a significantly increased Elafin m-RNA expression (Pmembranes also showed no changes in Elafin protein concentrations compared to untreated controls. Higher Elafin expression in PPROM fetal membranes suggests a host response to an inflammatory pathology. However, lack of Elafin response to LPS and polymicrobial treatment is indicative of the minimal anti-inflammatory impact of this molecule in fetal membranes.

  1. Sexual dimorphism in epigenomicresponses of stem cells to extreme fetal growth

    Science.gov (United States)

    Delahaye, Fabien; Wijetunga, N. Ari; Heo, Hye J.; Tozour, Jessica N.; Zhao, Yong Mei; Greally, John M.; Einstein, Francine H.

    2014-01-01

    Extreme fetal growth is associated with increased susceptibility to a range of adult diseases through an unknown mechanism of cellular memory. We tested whether heritable epigenetic processes in long-lived CD34+ hematopoietic stem/progenitor cells (HSPCs) showed evidence for re-programming associated with the extremes of fetal growth. Here we show that both fetal growth restriction and over-growth are associated with global shifts towards DNA hypermethylation, targeting cis-regulatory elements in proximity to genes involved in glucose homeostasis and stem cell function. We find a sexually dimorphic response; intrauterine growth restriction (IUGR) is associated with substantially greater epigenetic dysregulation in males, whereas large for gestational age (LGA) growth predominantly affects females. The findings are consistent with extreme fetal growth interacting with variable fetal susceptibility to influence cellular aging and metabolic characteristics through epigenetic mechanisms, potentially generating biomarkers that could identify infants at higher risk for chronic disease later in life. PMID:25300954

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

    Directory of Open Access Journals (Sweden)

    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.

  3. MicroRNA-20b-5p inhibits platelet-derived growth factor-induced proliferation of human fetal airway smooth muscle cells by targeting signal transducer and activator of transcription 3.

    Science.gov (United States)

    Tang, Jin; Luo, Lingying

    2018-06-01

    Pediatric asthma is still a health threat to the pediatric population in recent years. The airway remodeling induced by abnormal airway smooth muscle (ASM) cell proliferation is an important cause of asthma. MicroRNAs (miRNAs) are important regulators of ASM cell proliferation. Numerous studies have reported that miR-20b-5p is a critical regulator for cell proliferation. However, whether miR-20b-5p is involved in regulating ASM cell proliferation remains unknown. In this study, we aimed to investigate the potential role of miR-20b-5p in regulating the proliferation of fetal ASM cell induced by platelet-derived growth factor (PDGF). Here, we showed that miR-20b-5p was significantly decreased in fetal ASM cells treated with PDGF. Biological experiments showed that the overexpression of miR-20b-5p inhibited the proliferation while miR-20b-5p inhibition markedly promoted the proliferation of fetal ASM cells. Bioinformatics analysis and luciferase reporter assay showed that miR-20b-5p directly targeted the 3'-UTR of signal transducer and activator of transcription 3 (STAT3). Further data showed that miR-20b-5p negatively regulated the expression of STAT3 in fetal ASM cells. Moreover, miR-20b-5p regulates the transcriptional activity of STAT3 in fetal ASM cells. Overexpression of STAT3 reversed the inhibitory effect of miR-20b-5p overexpression on fetal ASM cell proliferation while the knockdown of STAT3 abrogated the promoted effect of miR-20b-5p inhibition on fetal ASM cell proliferation. Overall, our results show that miR-20b-5p impedes PDGF-induced proliferation of fetal ASM cells through targeting STAT3. Our study suggests that miR-20b-5p may play an important role in airway remodeling during asthma and suggests that miR-20b-5p may serve as a potential therapeutic target for pediatric asthma. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  4. 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.

  5. Programmed Fetal Membrane Senescence and Exosome-Mediated Signaling: A Mechanism Associated With Timing of Human Parturition

    Directory of Open Access Journals (Sweden)

    Ramkumar Menon

    2017-08-01

    Full Text Available Human parturition is an inflammatory process that involves both fetal and maternal compartments. The precise immune cell interactions have not been well delineated in human uterine tissues during parturition, but insights into human labor initiation have been informed by studies in animal models. Unfortunately, the timing of parturition relative to fetal maturation varies among viviparous species—indicative of different phylogenetic clocks and alarms—but what is clear is that important common pathways must converge to control the birth process. Herein, we hypothesize a novel signaling mechanism initiated by human fetal membrane aging and senescence-associated inflammation. Programmed events of fetal membrane aging coincide with fetal growth and organ maturation. Mechanistically, senescence involves in telomere shortening and activation of p38 mitogen-activated signaling kinase resulting in aging-associated phenotypic transition. Senescent tissues release inflammatory signals that are propagated via exosomes to cause functional changes in maternal uterine tissues. In vitro, oxidative stress causes increased release of inflammatory mediators (senescence-associated secretory phenotype and damage-associated molecular pattern markers that can be packaged inside the exosomes. These exosomes traverse through tissues layers, reach maternal tissues to increase overall inflammatory load transitioning them from a quiescent to active state. Animal model studies have shown that fetal exosomes can travel from fetal to the maternal side. Thus, aging fetal membranes and membrane-derived exosomes cargo fetal signals to the uterus and cervix and may trigger parturition. This review highlights a novel hypothesis in human parturition research based on data from ongoing research using human fetal membrane model system.

  6. The effects of smoking and hypertensive disorders on fetal growth

    Directory of Open Access Journals (Sweden)

    Irgens Lorentz M

    2006-04-01

    Full Text Available Abstract Background It is well known that smoking and pregnancy induced hypertension (PIH are associated with decreased fetal growth. It has been reported that in preeclampsia the fetal growth deficit attributable to smoking is higher, which has been contradicted in other studies. We therefore evaluated the effects on fetal growth of early- and late onset PIH and chronic hypertension and how cigarette smoking modify these effects. We also quantified the proportion of small for gestational age (SGA cases attributable to PIH, chronic hypertension, and smoking. Methods Population-based study based on record of 215598 singleton pregnancies from the Medical Birth Registry of Norway. Results In severe preeclampsia, mild preeclampsia, transient hypertension, and normotension in term birth, odds ratios (ORs of SGA in smokers compared with non-smokers were 1.4 (95% confidence interval 0.9, 2.2, 1.6 (1.3, 1.9, 2.3 (1.8, 3.1, and 2.0 (1.9, 2.1, respectively. For preterm births, corresponding ORs were 1.3 (0.9, 2.0, 1.8 (1.1, 3.0, 4.1 (1.9, 9.0, and 1.7 (1.4, 2.0, respectively. The effect of early onset PIH was stronger than that in term births, while the effect of smoking was equal in preterm and term newborns. Only in non-smokers who delivered at term, the rates of SGA significantly increased with the severity of PIH (ORs = 1.3 (1.1, 1.5, 1.8 (1.7, 2.0, and 2.5 (2.2, 3.0 for transient hypertension, mild-, and severe preeclampsia, respectively. The combined effects of smoking and hypertension were generally not synergistic. The effect of smoking was not stronger in women who had chronic hypertension. Nor were the effects of chronic hypertension stronger in smokers. PIH explained 21.9 and 2.5% of preterm and term cases of SGA, respectively, while smoking explained 12% of SGA cases. Conclusion The effects of hypertensive disorder and smoking were generally not synergistic, which suggest that they may exert their main actions on separate sites or work through

  7. A new customized fetal growth standard for African American women: the PRB/NICHD Detroit Study

    Science.gov (United States)

    Tarca, Adi L.; Romero, Roberto; Gudicha, Dereje W.; Erez, Offer; Hernandez-Andrade, Edgar; Yeo, Lami; Bhatti, Gaurav; Pacora, Percy; Maymon, Eli; Hassan, Sonia S.

    2018-01-01

    Background The assessment of fetal growth disorders requires a standard. Current nomograms for the assessment of fetal growth in African American women have been derived either from neonatal (rather than fetal) biometry data or have not been customized for maternal ethnicity, weight, height, parity, and fetal sex. Objective We sought to 1) develop a new customized fetal growth standard for African American mothers; and 2) compare such a standard to three existing standards for the classification of fetuses as small (SGA) or large (LGA) for gestational age. Study Design A retrospective cohort study included 4,183 women (4,001 African American and 182 Caucasian) from the Detroit metropolitan area who underwent ultrasound examinations between 14 and 40 weeks of gestation (the median number of scans per pregnancy was 5, interquartile range 3-7) and for whom relevant covariate data were available. Longitudinal quantile regression was used to build models defining the “normal” estimated fetal weight (EFW) centiles for gestational age in African American women, adjusted for maternal height, weight, parity, and fetal sex, and excluding pathologic factors with a significant effect on fetal weight. The resulting Perinatology Research Branch/Eunice Kennedy Shriver National Institute of Child Health and Human Development (hereinafter, PRB/NICHD) growth standard was compared to 3 other existing standards—the customized gestation-related optimal weight (GROW) standard; the Eunice Kennedy Shriver National Institute of Child Health and Human Development (hereinafter, NICHD) African American standard; and the multinational World Health Organization (WHO) standard—utilized to screen fetuses for SGA (90th centile) based on the last available ultrasound examination for each pregnancy. Results 1) First, the mean birthweight at 40 weeks was 133g higher for neonates born to Caucasian than to African American mothers and 150g higher for male than female neonates; maternal weight

  8. Malaria and fetal growth alterations in the 3(rd) trimester of pregnancy

    DEFF Research Database (Denmark)

    Schmiegelow, Christentze; Minja, Daniel Thomas; Oesterholt, Mayke

    2013-01-01

    Pregnancy associated malaria is associated with decreased birth weight, but in-utero evaluation of fetal growth alterations is rarely performed. The objective of this study was to investigate malaria induced changes in fetal growth during the 3(rd) trimester using trans-abdominal ultrasound....

  9. Characterization of the fetal blood transcriptome and proteome in maternal anti-fetal rejection: evidence of a distinct and novel type of human fetal systemic inflammatory response.

    Science.gov (United States)

    Lee, Joonho; Romero, Roberto; Chaiworapongsa, Tinnakorn; Dong, Zhong; Tarca, Adi L; Xu, Yi; Chiang, Po Jen; Kusanovic, Juan Pedro; Hassan, Sonia S; Yeo, Lami; Yoon, Bo Hyun; Than, Nandor Gabor; Kim, Chong Jai

    2013-10-01

    The human fetus is able to mount a systemic inflammatory response when exposed to microorganisms. This stereotypic response has been termed the 'fetal inflammatory response syndrome' (FIRS), defined as an elevation of fetal plasma interleukin-6 (IL-6). FIRS is frequently observed in patients whose preterm deliveries are associated with intra-amniotic infection, acute inflammatory lesions of the placenta, and a high rate of neonatal morbidity. Recently, a novel form of fetal systemic inflammation, characterized by an elevation of fetal plasma CXCL10, has been identified in patients with placental lesions consistent with 'maternal anti-fetal rejection'. These lesions include chronic chorioamnionitis, plasma cell deciduitis, and villitis of unknown etiology. In addition, positivity for human leukocyte antigen (HLA) panel-reactive antibodies (PRA) in maternal sera can also be used to increase the index of suspicion for maternal anti-fetal rejection. The purpose of this study was to determine (i) the frequency of pathologic lesions consistent with maternal anti-fetal rejection in term and spontaneous preterm births; (ii) the fetal serum concentration of CXCL10 in patients with and without evidence of maternal anti-fetal rejection; and (iii) the fetal blood transcriptome and proteome in cases with a fetal inflammatory response associated with maternal anti-fetal rejection. Maternal and fetal sera were obtained from normal term (n = 150) and spontaneous preterm births (n = 150). A fetal inflammatory response associated with maternal anti-fetal rejection was diagnosed when the patients met two or more of the following criteria: (i) presence of chronic placental inflammation; (ii) ≥80% of maternal HLA class I PRA positivity; and (iii) fetal serum CXCL10 concentration >75th percentile. Maternal HLA PRA was analyzed by flow cytometry. The concentrations of fetal CXCL10 and IL-6 were determined by ELISA. Transcriptome analysis was undertaken after the extraction of total RNA

  10. Perfluoroalkyl Acids in Maternal Serum and Indices of Fetal Growth

    DEFF Research Database (Denmark)

    Bach, Cathrine C; Bech, Bodil H; Nohr, Ellen A

    2015-01-01

    BACKGROUND: Previous studies indicated an association between intrauterine exposure to perfluorooctane sulfonate (PFOS) or perfluorooctanoate (PFOA) and lower birth weight. However, these perfluoroalkyl acids (PFAAs) have to some extent been substituted by other compounds on which little is known...... was restricted to term births (n=1426). For PFOS, the birth weight estimates for the highest versus lowest quartile were -50 [95 % CI: -123; 23] g in all births and -62 [95 % CI: -126; 3] g in term births. For the other PFAAs, the direction of the associations was inconsistent, and no overall association...... with birth weight was apparent. No PFAAs were associated with birth length or head circumference at birth. CONCLUSIONS: Overall, we did not find strong or consistent associations between PFAAs and birth weight or other indices of fetal growth, though estimated mean birth weights were lower among those...

  11. Maternal-fetal hepatic and placental metabolome profiles are associated with reduced fetal growth in a rat model of maternal obesity

    DEFF Research Database (Denmark)

    Mumme, Karen; Gray, Clint; Reynolds, Clare M.

    2016-01-01

    : Metabolomic profiling was used to reveal altered maternal and fetal metabolic pathways in a model of diet induced obesity during pregnancy, leading to reduced fetal growth. Methods: We examined the metabolome of maternal and fetal livers, and placenta following a high fat and salt intake. Sprague–Dawley rats...

  12. 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)

  13. 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.

  14. Sex Differences in Placental Mitochondrial Function Associated with Ozone-Induced Fetal Growth Restriction

    Science.gov (United States)

    Fetal growth restriction is a major underlying cause of infant mortality worldwide. Despite knowledge of risk factors for adverse pregnancy outcomes, the mechanisms that drive compromised growth during pregnancy have not been well established. Placental maladaptation, particularl...

  15. Comparison of the biological features between human fetal hepatocyte and immortalized L-02 hepatocyte in vitro

    International Nuclear Information System (INIS)

    Kong Weiwei; Teng Gaojun

    2004-01-01

    Objective: To evaluate the feasibilities of the potential donors in liver cell transplantation using the human fetal hepatocytes and immortalized L-02 hepatocytes by comparing their biological features. Methods: Human fetal hepatocytes were isolated from aborted fetal livers (gestational ages from 14 w to 24 w) by an improved two-stage perfusion method and cultured in a conditioned medium without any growth factors. α-fetal protein (AFP) and albumin (ALB) were detected by radioimmunoassay (RIA) and cytokeratin-19 (CK-19 ) was identified by cellular immunochemistry study. Immortalized L-02 hepatocytes were cultured in the same condition and the characteristic proteins were detected by the same methods. Results: The viability of human fetal hepatocytes was approximately 95% using the perfusion method, and the maximum survival time of the cultured hepatocytes was 3 weeks. The expression of AFP, ALB, and CK19 was detected at the same time, especially during Day 3 to Day 7 in the culture. By comparison, the proliferation ability of L-02 hepatocyte was greater, although with a lower level of ALB secretion. The expression of AFP and CK19 was not detected. Furthermore, during the long culture, L-02 hepatocytes may undergo a morphologic change and fail to express ALB. Conclusion: Human fetal hepatocyte may be a practical donor for hepatocyte transplantation with its high-level protein expression and potential bi-differentiation ability. In view of the absent expression of ALB and the morphologic change in culture, although with better proliferation, L-02 hepatocyte seems not useful for hepatocyte transplantation

  16. Fetal programming: prenatal testosterone excess leads to fetal growth retardation and postnatal catch-up growth in sheep.

    Science.gov (United States)

    Manikkam, Mohan; Crespi, Erica J; Doop, Douglas D; Herkimer, Carol; Lee, James S; Yu, Sunkyung; Brown, Morton B; Foster, Douglas L; Padmanabhan, Vasantha

    2004-02-01

    Alterations in the maternal endocrine, nutritional, and metabolic environment disrupt the developmental trajectory of the fetus, leading to adult diseases. Female offspring of rats, subhuman primates, and sheep treated prenatally with testosterone (T) develop reproductive/metabolic defects during adult life similar to those that occur after intrauterine growth retardation. In the present study we determined whether prenatal T treatment produces growth-retarded offspring. Cottonseed oil or T propionate (100 mg, im) was administered twice weekly to pregnant sheep between 30-90 d gestation (term = 147 d; cottonseed oil, n = 16; prenatal T, n = 32). Newborn weight and body dimensions were measured the day after birth, and postnatal weight gain was monitored for 4 months in all females and in a subset of males. Consistent with its action, prenatal T treatment produced females and males with greater anogenital distances relative to controls. Prenatal T treatment reduced body weights and heights of newborns from both sexes and chest circumference of females. Prenatally T-treated females, but not males, exhibited catch-up growth during 2-4 months of postnatal life. Plasma IGF-binding protein-1 and IGF-binding protein-2, but not IGF-I, levels of prenatally T-treated females were elevated in the first month of life, a period when the prenatally T-treated females were not exhibiting catch-up growth. This is suggestive of reduced IGF availability and potential contribution to growth retardation. These findings support the concept that fetal growth retardation and postnatal catch-up growth, early markers of future adult diseases, can also be programmed by prenatal exposure to excess sex steroids.

  17. More than fetal urine: enteral uptake of amniotic fluid as a major predictor for fetal growth during late gestation

    NARCIS (Netherlands)

    Bagci, S.; Brosens, E.; Tibboel, D.; Klein, A.; Ijsselstijn, H.; Wijers, C.H.W.; Roeleveld, N.; Blaauw, I. de; Broens, P.M.; Rooij, I.A.L.M. van; Holscher, A.; Boemers, T.M.; Pauly, M.; Munsterer, O.J.; Schmiedeke, E.; Schafer, M.; Ure, B.E.; Lacher, M.; Choinitzki, V.; Schumacher, J.; Zwink, N.; Jenetzky, E.; Katzer, D.; Arand, J.; Bartmann, P.; Reutter, H.M.

    2016-01-01

    The purpose of our study was to investigate the importance of amniotic fluid (AF) for fetal growth during late gestation using esophageal atresia (EA) patients as a model. In this retrospective cohort study, we compared the z-scores adapted for birth weights (BW z-scores) for each of 517 European

  18. APOPTOSIS DURING HUMAN FETAL KIDNEY DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Rade Čukuranović

    2005-01-01

    Full Text Available Kidney morphogenesis is a complex and stepwise process. The formation of mature kidney in mammals is preceded by two primitive embryonic kidneys known as pronephros and mesonephros. Metanephros develops as a result of reciprocal inductive interactions between two primordial mesodermal derivates: ureteric bud, an epithelial outgrowth of the Wolffian duct, and metanephric blastema, a group of mesenchymal cells. The ureteric bud induces the metanephric mesenchyme to differentiate and form nephrons, whilst the metanephric mesenchyme induces the ureteric bud to grow and branch to form collecting ducts. The nephron goes through four developmental stages, which are described as: 1 vesicle, 2 comma-shaped and S-shaped stages, 3 developing capillary loop, and finally 4 maturing glomerulus. Apoptosis (programmed cell death is a predominant form of physiological cell death, by which organism eliminate unwanted or damaged cells. It is the major component of normal development and disease. Apoptosis is the result of series of biochemical processes happening in certain order in a dying cell, among which the most important is activation of enzyme families called caspases which influence different cell components. Apoptosis is characterized by membrane blebbing, shrinkage of the cell, nuclear fragmentation and chromatin condensation. Organelles are preserved almost intact. Cell surface molecules change. A variety of physiological and pathological stimuli can initiate apoptosis. They act via receptor mechanisms, through biochemical agents, or cause DNA and cell membrane damage. Apoptosis is an important component of fetal development. It is thought that apoptosis is the one of the main regulatory events involved in kidney morphogenesis, considering that among great number of developed cells, only a few of them are involved in the developing program by escaping apoptosis. In any period during kidney development about 3 to 5%of cells are apoptotic. Thorough

  19. Lens artifacts in human fetal eyes - the challenge of interpreting the histomorphology of human fetal lenses.

    Science.gov (United States)

    Herwig, Martina C; Müller, Annette M; Klarmann-Schulz, Ute; Holz, Frank G; Loeffler, Karin U

    2014-01-01

    Evaluation of the lens, including cataractous changes, is often of paramount importance in the classification of fetal syndromes or forensic questions. On histology, the crystalline lens is - especially in fetal and infant eyes - an organ susceptible to numerous artifacts. Thus, the aim of our study was to study various factors (including fixatives) that might have an impact on lens histomorphology. Twenty eyes from ten fetuses (formalin fixation: n = 10, glutaraldehyde fixation: n = 10), matched for gestational age and abortion (spontaneous vs. induced), were investigated macroscopically and by light microscopy. Sections were stained with routine hematoxylin & eosin (H&E), and periodic acid schiff (PAS). The age of the fetal eyes ranged from 15 to 36 weeks of gestation. Lens artifacts were analyzed and compared to fetal and adult lenses with definitive cataractous changes. In addition, 34 eyes from 27 fetuses with trisomy 21 were investigated for lens changes. All lenses showed artifacts of varying extent, in particular globules, vacuoles, clefts, anterior/posterior capsular separation, subcapsular proteinaceous material, fragmentation of the lens capsule/epithelium, and a posterior umbilication. Glutaraldehyde-fixed lenses displayed less artifacts compared to those fixed in formalin. Slight differences in the appearance of artifacts were found dependent on the fixative (formaldehyde vs glutaraldehyde) and the kind of abortion (iatrogenous vs spontaneous). The gestational age did not have a significant influence on the type and extent of lens artifacts. The lenses from fetuses with trisomy 21 displayed similar lens artifacts with no specific findings. Alterations in fetal lens morphology are extremely frequent and variable. These artifacts have to be carefully taken into account when interpreting post-mortem findings. Thus, the postmortem diagnosis of a fetal cataract should be made with great caution, and should include, in adherence to our proposed

  20. The relationship between maternal and fetal vitamin D, insulin resistance, and fetal growth.

    LENUS (Irish Health Repository)

    Walsh, Jennifer M

    2013-05-01

    Evidence for a role of vitamin D in maintaining normal glucose homeostasis is inconclusive. We sought to clarify the relationship between maternal and fetal insulin resistance and vitamin D status. This is a prospective cohort study of 60 caucasian pregnant women. Concentrations of 25-hydroxyvitamin D (25-OHD), glucose, insulin, and leptin were measured in early pregnancy and at 28 weeks. Ultrasound at 34 weeks assessed fetal anthropometry including abdominal wall width, a marker of fetal adiposity. At delivery birth weight was recorded and fetal 25-OHD, glucose, C-peptide, and leptin measured in cord blood. Insulin resistance was calculated using the Homeostasis Model Assessment (HOMA) equation. We found that those with lower 25-OHD in early pregnancy had higher HOMA indices at 28 weeks, (r = -.32, P = .02). No significant relationship existed between maternal or fetal leptin and 25-OHD, or between maternal or fetal 25-OHD and fetal anthropometry or birth weight. The incidence of vitamin D deficiency was high at each time point (15%-45%). These findings lend support to routine antenatal supplementation with vitamin D in at risk populations.

  1. Maternal hemodynamics, fetal biometry and Dopplers in pregnancies followed up for suspected fetal growth restriction.

    Science.gov (United States)

    Roberts, Llinos A; Ling, Hua Zen; Poon, Liona; Nicolaides, Kypros H; Kametas, Nikos A

    2018-04-01

    To assess whether in a cohort of patients with small for gestational age (SGA) foetuses with estimated fetal weight ≤10 th percentile, maternal hemodynamics, fetal biometry and Dopplers at presentation, can predict the subsequent development of abnormal fetal Dopplers or delivery with birthweight Cheetah), mean arterial pressure, fetal biometry, umbilical artery (UA), middle cerebral artery (MCA) and uterine artery (UT) pulsatility index (PI) and the deepest vertical pool (DVP) of amniotic fluid. Z-scores of these variables were calculated based on reported reference ranges and the values were compared between those with evidence of abnormal fetal Dopplers at presentation (group 1), those that developed abnormal Dopplers in subsequent visits (group 2) and those who did not develop abnormal Dopplers throughout pregnancy (group 3). Abnormal fetal Dopplers were defined as UAPI >95 th percentile, or MCA PI <5 th percentile. Differences in measured variables at presentation were also compared between pregnancies delivering a baby with birthweight <3 rd and ≥3 rd percentile. Multivariate logistic regression analysis was used to determine significant predictors of birthweight <3 rd percentile and evolution from normal fetal Dopplers to abnormal fetal Dopplers in groups 2 and 3. In the study population 14 (16%) cases were in group 1, 19 (22%) in group 2 and 53 (62%) in group 3. The birthweight was <3 rd percentile in 39 (45%) cases and ≥3 rd percentile in 47 (55%). In the study groups, compared to normal populations, there was decreased cardiac output and stroke volume and increased peripheral vascular resistance and mean arterial pressure (MAP) and the deviations from normal were most marked in group 1. Pregnancies with a birthweight <3 rd , compared to those ≥3 rd percentile, had higher deviations from normal in fetal biometry, maternal cardiac output, stroke volume, heart rate and peripheral vascular resistance and UT-PI. Multivariate logistic regression

  2. Fish intake during pregnancy, fetal growth, and gestational length in 19 European birth cohort studies

    NARCIS (Netherlands)

    Leventakou, Vasiliki; Roumeliotaki, Theano; Martinez, David; Barros, Henrique; Brantsaeter, Anne Lise; Casas, Maribel; Charles, Marie Aline; Cordier, Sylvaine; Eggesbø, Merete; Van Eijsden, Manon; Forastiere, Francesco; Gehring, Ulrike; Govarts, Eva; Halldórsson, Thorhallur I.; Hanke, Wojciech; Haugen, Margaretha; Heppe, Denise H M; Heude, Barbara; Inskip, Hazel M.; Jaddoe, Vincent W V; Jansen, Maria; Kelleher, Cecily; Meltzer, Helle Margrete; Merletti, Franco; Moltó-Puigmartí, Carolina; Mommers, Monique; Murcia, Mario; Oliveira, Andreia; Olsen, Sjúrour F.; Pele, Fabienne; Polanska, Kinga; Porta, Daniela; Richiardi, Lorenzo; Robinson, Siân M.; Stigum, Hein; Strøm, Marin; Sunyer, Jordi; Thijs, Carel; Viljoen, Karien; Vrijkotte, Tanja G M; Wijga, Alet H.; Kogevinas, Manolis; Vrijheid, Martine; Chatzi, Leda

    2014-01-01

    Background: Fish is a rich source of essential nutrients for fetal development, but in contrast, it is also a well-known route of exposure to environmental pollutants. Objective: We assessed whether fish intake during pregnancy is associated with fetal growth and the length of gestation in a panel

  3. Mother's educational level and fetal growth: The genesis of health inequalities

    NARCIS (Netherlands)

    L.M. Silva (Lindsay); P.W. Jansen (Pauline); R.P.M. Steegers-Theunissen (Régine); V.W.V. Jaddoe (Vincent); L.R. Arends (Lidia); H.W. Tiemeier (Henning); F.C. Verhulst (Frank); H.A. Moll (Henriëtte); A. Hofman (Albert); J.P. Mackenbach (Johan); H. Raat (Hein)

    2010-01-01

    textabstractBackground: Women of low socio-economic status (SES) give birth to lighter babies. It is unknown from which moment during pregnancy socio-economic differences in fetal weight can be observed, whether low SES equally affects different fetal-growth components, or what the effect of low SES

  4. Fetal growth, cognitive function, and brain volumes in childhood and adolescence.

    Science.gov (United States)

    Rogne, Tormod; Engstrøm, Andreas Aass; Jacobsen, Geir Wenberg; Skranes, Jon; Østgård, Heidi Furre; Martinussen, Marit

    2015-03-01

    To evaluate the association between fetal growth pattern and cognitive function at 5 and 9 years and regional brain volumes at 15 years. Eighty-three term-born small-for-gestational-age (SGA) neonates and 105 non-SGA neonates in a control group were available for follow-up. Based on serial fetal ultrasound measurements from gestational weeks 25-37, SGA neonates were classified with fetal growth restriction (n=13) or non-fetal growth restriction (n=36). Cognitive function was assessed at 5 and 9 years, and brain volumes were estimated with cerebral magnetic resonance imaging at 15 years. Small-for-gestational-age children had lower performance intelligence quotient at 5 years compared with those in a control group (107.3 compared with 112.5, Pgrowth restriction and control groups, the SGA fetal growth restriction group had significantly lower performance intelligence quotient at 5 years (103.5 compared with 112.5, Pgrowth restriction and control groups for thalamic (17.4 compared with 18.6 cm, Pintelligence quotient scores at 5 and 9 years and smaller brain volumes at 15 years compared with those in the control group, but these findings were only found in those with fetal growth restriction, indicating a possible relationship to decelerated fetal growth. II.

  5. Fetal growth versus birthweight: the role of placenta versus other determinants.

    Directory of Open Access Journals (Sweden)

    Marie Cecilie Paasche Roland

    Full Text Available INTRODUCTION: Birthweight is used as an indicator of intrauterine growth, and determinants of birthweight are widely studied. Less is known about determinants of deviating patterns of growth in utero. We aimed to study the effects of maternal characteristics on both birthweight and fetal growth in third trimester and introduce placental weight as a possible determinant of both birthweight and fetal growth in third trimester. METHODS: The STORK study is a prospective cohort study including 1031 healthy pregnant women of Scandinavian heritage with singleton pregnancies. Maternal determinants (age, parity, body mass index (BMI, gestational weight gain and fasting plasma glucose of birthweight and fetal growth estimated by biometric ultrasound measures were explored by linear regression models. Two models were fitted, one with only maternal characteristics and one which included placental weight. RESULTS: Placental weight was a significant determinant of birthweight. Parity, BMI, weight gain and fasting glucose remained significant when adjusted for placental weight. Introducing placental weight as a covariate reduced the effect estimate of the other variables in the model by 62% for BMI, 40% for weight gain, 33% for glucose and 22% for parity. Determinants of fetal growth were parity, BMI and weight gain, but not fasting glucose. Placental weight was significant as an independent variable. Parity, BMI and weight gain remained significant when adjusted for placental weight. Introducing placental weight reduced the effect of BMI on fetal growth by 23%, weight gain by 14% and parity by 17%. CONCLUSION: In conclusion, we find that placental weight is an important determinant of both birthweight and fetal growth. Our findings indicate that placental weight markedly modifies the effect of maternal determinants of both birthweight and fetal growth. The differential effect of third trimester glucose on birthweight and growth parameters illustrates that

  6. Perinatal Programming of Childhood Asthma: Early Fetal Size, Growth Trajectory during Infancy, and Childhood Asthma Outcomes

    Directory of Open Access Journals (Sweden)

    Steve Turner

    2012-01-01

    Full Text Available The “fetal origins hypothesis” or concept of “developmental programming” suggests that faltering fetal growth and subsequent catch-up growth are implicated in the aetiology of cardiovascular disease. Associations between reduced birth weight, rapid postnatal weight gain, and asthma suggest that there are fetal origins to respiratory disease. The present paper first summarises the literature relating birth weight and post natal growth trajectories to asthma outcomes. Second, issues regarding the interpretation of antenatal fetal ultrasound measurements are discussed. Finally, recent reports linking antenatal measurement and growth trajectory to early childhood asthma outcomes are discussed. Understanding the nature and timing of factors which influence antenatal growth may give important insight into the antecedents of early-onset asthma with implications for interventions.

  7. Perinatal programming of childhood asthma: early fetal size, growth trajectory during infancy, and childhood asthma outcomes.

    Science.gov (United States)

    Turner, Steve

    2012-01-01

    The "fetal origins hypothesis" or concept of "developmental programming" suggests that faltering fetal growth and subsequent catch-up growth are implicated in the aetiology of cardiovascular disease. Associations between reduced birth weight, rapid postnatal weight gain, and asthma suggest that there are fetal origins to respiratory disease. The present paper first summarises the literature relating birth weight and post natal growth trajectories to asthma outcomes. Second, issues regarding the interpretation of antenatal fetal ultrasound measurements are discussed. Finally, recent reports linking antenatal measurement and growth trajectory to early childhood asthma outcomes are discussed. Understanding the nature and timing of factors which influence antenatal growth may give important insight into the antecedents of early-onset asthma with implications for interventions.

  8. Growth and development symposium: Fetal programming in animal agriculture

    Science.gov (United States)

    Fetal programming is the ability to improve animal production and well-being by altering the maternal environment and holds enormous challenges and great opportunities for researchers and the animal industry. A symposium was held to provide an overview of current knowledge of fetal programming in re...

  9. DNA Methylation Landscapes of Human Fetal Development

    NARCIS (Netherlands)

    Slieker, Roderick C.; Roost, Matthias S.; van Iperen, Liesbeth; Suchiman, H. Eka D; Tobi, Elmar W.; Carlotti, Françoise; de Koning, Eelco J P; Slagboom, P. Eline; Heijmans, Bastiaan T.; Chuva de Sousa Lopes, Susana M.

    2015-01-01

    Remodelling the methylome is a hallmark of mammalian development and cell differentiation. However, current knowledge of DNA methylation dynamics in human tissue specification and organ development largely stems from the extrapolation of studies in vitro and animal models. Here, we report on the DNA

  10. Human platelet lysate: Replacing fetal bovine serum as a gold standard for human cell propagation?

    Science.gov (United States)

    Burnouf, Thierry; Strunk, Dirk; Koh, Mickey B C; Schallmoser, Katharina

    2016-01-01

    The essential physiological role of platelets in wound healing and tissue repair builds the rationale for the use of human platelet derivatives in regenerative medicine. Abundant growth factors and cytokines stored in platelet granules can be naturally released by thrombin activation and clotting or artificially by freeze/thaw-mediated platelet lysis, sonication or chemical treatment. Human platelet lysate prepared by the various release strategies has been established as a suitable alternative to fetal bovine serum as culture medium supplement, enabling efficient propagation of human cells under animal serum-free conditions for a multiplicity of applications in advanced somatic cell therapy and tissue engineering. The rapidly increasing number of studies using platelet derived products for inducing human cell proliferation and differentiation has also uncovered a considerable variability of human platelet lysate preparations which limits comparability of results. The main variations discussed herein encompass aspects of donor selection, preparation of the starting material, the possibility for pooling in plasma or additive solution, the implementation of pathogen inactivation and consideration of ABO blood groups, all of which can influence applicability. This review outlines the current knowledge about human platelet lysate as a powerful additive for human cell propagation and highlights its role as a prevailing supplement for human cell culture capable to replace animal serum in a growing spectrum of applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. A placenta clinic approach to the diagnosis and management of fetal growth restriction.

    Science.gov (United States)

    Kingdom, John C; Audette, Melanie C; Hobson, Sebastian R; Windrim, Rory C; Morgen, Eric

    2018-02-01

    Effective detection and management of fetal growth restriction is relevant to all obstetric care providers. Models of best practice to care for these patients and their families continue to evolve. Since much of the disease burden in fetal growth restriction originates in the placenta, the concept of a multidisciplinary placenta clinic program, managed primarily within a maternal-fetal medicine division, has gained popularity. In this context, fetal growth restriction is merely one of many placenta-related disorders that can benefit from an interdisciplinary approach, incorporating expertise from specialist perinatal ultrasound and magnetic resonance imaging, reproductive genetics, neonatal pediatrics, internal medicine subspecialties, perinatal pathology, and nursing. The accurate diagnosis and prognosis for women with fetal growth restriction is established by comprehensive clinical review and detailed sonographic evaluation of the fetus, combined with uterine artery Doppler and morphologic assessment of the placenta. Diagnostic accuracy for placenta-mediated fetal growth restriction may be enhanced by quantification of maternal serum biomarkers including placenta growth factor alone or combined with soluble fms-like tyrosine kinase-1. Uterine artery Doppler is typically abnormal in most instances of early-onset fetal growth restriction and is associated with coexistent preeclampsia and underlying maternal vascular malperfusion pathology of the placenta. By contrast, rare but potentially more serious underlying placental diagnoses, such as massive perivillous fibrinoid deposition, chronic histiocytic intervillositis, or fetal thrombotic vasculopathy, may be associated with normal uterine artery Doppler waveforms. Despite minor variations in placental size, shape, and cord insertion, placental function remains, largely normal in the general population. Consequently, morphologic assessment of the placenta is not currently incorporated into current screening

  12. 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.

  13. Differing levels of excision repair in human fetal dermis and brain cells

    International Nuclear Information System (INIS)

    Gibson, R.E.; D'Ambrosio, S.M.; Ohio State Univ., Columbus

    1982-01-01

    The levels of DNA excision repair, as measured by unscheduled DNA synthesis (UDS) and the UV-endonuclease sensitive site assay, were compared in cells derived from human fetal brain and dermal tissues. The level of UDS induced following ultraviolet (UV) irradiation was found to be lower (approx. 60%) in the fetal brain cells than in fetal dermal cells. It was determined, using the UV-endonuclease sensitive site assay to confirm the UDS observation, that 50% of the dimers induced by UV in fetal dermal cells were repaired in 8 h. while only 15% were removed in the fetal brain cells during the same period of time. Even after 24 h. only 44% of the dimers induced by UV in the fetal brain cells were repaired, while 65% were removed in the dermal cells. These data suggest that cultured human fetal brain cells exhibit lower levels of excision repair compared to cultured human fetal dermal cells. (author)

  14. Correlation between maternal and cord blood leptin and fetal growth

    African Journals Online (AJOL)

    SERVER

    2007-09-05

    Sep 5, 2007 ... IL -2 and growth hormone. The long form of the leptin receptor functions similarly to cytokine ... regulation of leptin synthesis and the risk for obesity in the offspring. In species such as the human and sheep, ..... Hormonal regulation of leptin levels in the fetus and neonate might be different from the endocrine ...

  15. Maternal psychological distress and fetal growth trajectories : The Generation R Study

    NARCIS (Netherlands)

    Henrichs, Jens; Schenk, J. J.; Roza, S. J.; van den Berg, M. P.; Schmidt, H. G.; Steegers, E. A. P.; Hofman, A.; Jaddoe, V. W. V.; Verhulst, F. C.; Tiemeier, H.

    Background. Previous research suggests, though not consistently, that maternal psychological distress during pregnancy leads to adverse birth outcomes. We investigated whether maternal psychological distress affects fetal growth during the period of mid-pregnancy until birth. Method. Pregnant women

  16. Quaternary structure and spin state of human fetal methemoglobin

    International Nuclear Information System (INIS)

    Chevion, M.; Navok, T.; Ilan, Y.A.; Czapski, G.

    1981-01-01

    Using the pulse-radiolysis technique, solutions of fetal human methemoglobin were irradiated in order to reduce a single heme-iron within the protein tetramers. The valence-hybrids thus formed ere reacted wjth oxygen. Kinetics of the reactions were studied. The effects of p and inositol-hexaphosphate (IHP) were examined. The kinetics of the ligation of oxygen to stripped valence-hybrids showed a single-phase behaviour at the pH range 7-9. As the pH was lowered below 6.5, a second slower phase became apparent. This slow phase consisted of approximately 50% at pH 5.8. In the presence of IHP above pH 7.4, the kinetics of oxygen-binding was of a single-phase. As the pH was lowered a transition to a second, slower phase was noticed. Below pH 7 the slower phase was the only detectable one. The analysis of the relative contribution of the faster phase to the total reaction, as a function of the pH, showed a typical sigmoidal transition curve characterized by a pK = 7.2 and a Hill parameter n = 3.06. On this basis it is concluded that stripped, fetal human methemoglobin resides in an R quaternary structure while the presence of IHP stabilizes the T structure at pH below 7.2. The switch between the high spin aquomet- and the low spin hydroxymet-derivatives of adult and fetal human hemoglobins was studied optically in detail. These switches were found to be only slightly affected by IHP, and exhibited very low cooperativity (pK = 8.04; n = 1.1 and pK = 8.10; n = 1.3 for adult methemoglobin when stripped and in the presence of IHP, respectively; pK = 8.18; n = 1.11 and pK = 8.21; n = 1.28 for fetal methemoglobin when stripped and in the presence of IHP, respectively). These findings lead to the conclusion that the transition between quaternary structures in either human or fetal methemoglobins is not coupled to the switch of the spin state of the ferric heme. (author)

  17. Physical exercise during pregnancy and fetal growth measures: a study within the Danish National Birth Cohort

    DEFF Research Database (Denmark)

    Juhl, Mette; Olsen, Jørn; Andersen, Per Kragh

    2010-01-01

    OBJECTIVE: The objective of the study was to examine the association between physical exercise during pregnancy and fetal growth measures. STUDY DESIGN: Data on 79,692 liveborn singletons from the Danish National Birth Cohort were collected between 1996 and 2002. Mean differences in birthweight, ...... effects on fetal growth measures related to exercise apart from a modest decreased risk of small- and large-for-gestational-age infants. These findings do not speak against advising pregnant women to be physically active during pregnancy....

  18. Socioeconomic Status Accounts for Rapidly Increasing Geographic Variation in the Incidence of Poor Fetal Growth

    Science.gov (United States)

    Ball, Stephen J.; Jacoby, Peter; Zubrick, Stephen R.

    2013-01-01

    Fetal growth is an important risk factor for infant morbidity and mortality. In turn, socioeconomic status is a key predictor of fetal growth; however, other sociodemographic factors and environmental effects may also be important. This study modelled geographic variation in poor fetal growth after accounting for socioeconomic status, with a fixed effect for socioeconomic status and a combination of spatially-correlated and spatially-uncorrelated random effects. The dataset comprised 88,246 liveborn singletons, aggregated within suburbs in Perth, Western Australia. Low socioeconomic status was strongly associated with an increased risk of poor fetal growth. An increase in geographic variation of poor fetal growth from 1999–2001 (interquartile odds ratio among suburbs = 1.20) to 2004–2006 (interquartile odds ratio = 1.40) indicated a widening risk disparity by socioeconomic status. Low levels of residual spatial patterns strengthen the case for targeting policies and practices in areas of low socioeconomic status for improved outcomes. This study indicates an alarming increase in geographic inequalities in poor fetal growth in Perth which warrants further research into the specific aspects of socioeconomic status that act as risk factors. PMID:23799513

  19. 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.

  20. Protein structure of fetal antigen 1 (FA1). A novel circulating human epidermal-growth-factor-like protein expressed in neuroendocrine tumors and its relation to the gene products of dlk and pG2

    DEFF Research Database (Denmark)

    Jensen, Charlotte Harken; Krogh, Thomas N; Højrup, Peter

    1994-01-01

    The present paper describes the primary structure, glycosylation and tissue localization of fetal antigen 1 (FA1) isolated from second-trimester human amniotic fluid. FA1 is a single-chained, heterogeneous glycoprotein of 225-262 amino acid residues. FA1 has six well conserved epidermal...... extends with minor corrections to the human adrenal-specific mRNA, pG2 as well. Immunohistochemical analysis demonstrated the presence of FA1 in 10 out of 14 lung tumors containing neuroendocrine elements, and in the placental villi where FA1 was exclusively seen in stromal cells in close contact...... to the vascular structure. In the pancreas, FA1 co-localized with insulin in the insulin secretory granules of the beta cells within the islets of Langerhans. Our findings suggest that FA1 is synthesized as a membrane anchored protein and released into the circulation after enzymic cleavage, and that circulating...

  1. Assessment of fetal activity concentration and fetal dose for selected radionuclides based on animal and human data

    International Nuclear Information System (INIS)

    Roedler, H.D.

    1987-01-01

    Biokinetic data of selected radionuclide compounds from investigations in man and animal were taken from literature references with the purpose to provide a basis for a comparative assessment of fetal and adult radiation doses after intake or administration of radionuclides. The following ratios of fetal to adult doses were derived from human data: 0.5 for caesium 137 and total body, 2.3 for iron 59 and liver, 0.06 - 0.3 - 1.1 for iodine 131 and thyroid, and 0.1 - 0.3 for strontium 90 and bone. The ratios of activity concentrations in fetal and adult tissues are of considerable variability - up to three orders of magnitude. Further studies on fetal and adult biokinetics specifically designed for comparative dose assessment are indispensable. 106 refs.; 6 tabs

  2. Somatomedin-C/insulin-like growth factor-I and Insulin-like growth factor-II mRNAs in rate fetal and adult tissues

    International Nuclear Information System (INIS)

    Lund, P.K.; Moats-Staats, B.M.; Hynes, M.A.; Simmons, J.G.; Jansen, M.; D'ercole, A.J.; Van Wyk, J.J.

    1986-01-01

    Somatomedin-C or insulin-like growth factor I (Sm-C/IGF-I) and insulin-like growth factor II (IGF-II) have been implicated in the regulation of fetal growth and development. In the present study 32 P-labeled complementary DNA probes encoding human and mouse Sm-C/IGF-I and human IGF-II were used in Northern blot hybridizations to analyze rat Sm-C/IGF-I and IGF-II mRNAs in poly(A + ) RNAs from intestine, liver, lung, and brain of adult rats and fetal rats between day 14 and 17 of gestation. In fetal rats, all four tissues contained a major mRNA of 1.7 kilobase (kb) that hybridized with the human Sm-C/IGF-I cDNA and mRNAs of 7.5, 4.7, 1.7, and 1.2 kb that hybridized with the mouse Sm-C/IGF-I cDNA. Adult rat intestine, liver, and lung also contained these mRNAs but Sm-C/IGF-I mRNAs were not detected in adult rat brain. These findings provide direct support for prior observations that multiple tissues in the fetus synthesize immunoreactive Sm-C/IGF-I and imply a role for Sm-C/IGF-I in fetal development as well as postnatally. Multiple IGF-II mRNAs of estimated sizes 4.7, 3.9, 2.2, 1.75, and 1.2 kb were observed in fetal rat intestine, liver, lung, and brain. The 4.7- and 3.9-kb mRNAs were the major hybridizing IGF-II mRNAs in all fetal tissues. Higher abundance of IGF-II mRNAs in rat fetal tissues compared with adult tissues supports prior hypotheses, based on serum IGF-II concentrations, that IGF-II is predominantly a fetal somatomedin. IGF-II mRNAs are present, however, in some poly(A + ) RNAs from adult rat tissues. The brain was the only tissue in the adult rat where the 4.7- and 3.9-kb IGF-II mRNAs were consistently detected. These findings suggest that a role for IGF-II in the adult rat, particularly in the central nervous system, cannot be excluded

  3. Fetal abdominal magnetic resonance imaging

    International Nuclear Information System (INIS)

    Brugger, Peter C.; Prayer, Daniela

    2006-01-01

    This review deals with the in vivo magnetic resonance imaging (MRI) appearance of the human fetal abdomen. Imaging findings are correlated with current knowledge of human fetal anatomy and physiology, which are crucial to understand and interpret fetal abdominal MRI scans. As fetal MRI covers a period of more than 20 weeks, which is characterized not only by organ growth, but also by changes and maturation of organ function, a different MR appearance of the fetal abdomen results. This not only applies to the fetal intestines, but also to the fetal liver, spleen, and adrenal glands. Choosing the appropriate sequences, various aspects of age-related and organ-specific function can be visualized with fetal MRI, as these are mirrored by changes in signal intensities. Knowledge of normal development is essential to delineate normal from pathological findings in the respective developmental stages

  4. Fetal abdominal magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Brugger, Peter C. [Center of Anatomy and Cell Biology, Integrative Morphology Group, Medical University of Vienna, Waehringerstrasse 13, 1090 Vienna (Austria)]. E-mail: peter.brugger@meduniwien.ac.at; Prayer, Daniela [Department of Radiology, Medical University of Vienna, Waehringerguertel 18-20, 1090 Vienna (Austria)

    2006-02-15

    This review deals with the in vivo magnetic resonance imaging (MRI) appearance of the human fetal abdomen. Imaging findings are correlated with current knowledge of human fetal anatomy and physiology, which are crucial to understand and interpret fetal abdominal MRI scans. As fetal MRI covers a period of more than 20 weeks, which is characterized not only by organ growth, but also by changes and maturation of organ function, a different MR appearance of the fetal abdomen results. This not only applies to the fetal intestines, but also to the fetal liver, spleen, and adrenal glands. Choosing the appropriate sequences, various aspects of age-related and organ-specific function can be visualized with fetal MRI, as these are mirrored by changes in signal intensities. Knowledge of normal development is essential to delineate normal from pathological findings in the respective developmental stages.

  5. Placental responses to changes in the maternal environment determine fetal growth

    Directory of Open Access Journals (Sweden)

    Kris Genelyn eDimasuay

    2016-01-01

    Full Text Available Placental responses to maternal perturbations are complex and remain poorly understood. Altered maternal environment during pregnancy such as hypoxia, stress, obesity, diabetes, toxins, altered nutrition, inflammation, and reduced utero-placental blood flow may influence fetal development, which can predispose to diseases later in life. The placenta being a metabolically active tissue responds to these perturbations by regulating the fetal supply of nutrients and oxygen and secretion of hormones into the maternal and fetal circulation. We have proposed that placental nutrient sensing integrates maternal and fetal nutritional cues with information from intrinsic nutrient sensing signaling pathways to balance fetal demand with the ability of the mother to support pregnancy by regulating maternal physiology, placental growth, and placental nutrient transport. Emerging evidence suggests that the nutrient-sensing signaling pathway mechanistic target of rapamycin (mTOR plays a central role in this process. Thus, placental nutrient sensing plays a critical role in modulating maternal-fetal resource allocation, thereby affecting fetal growth and the life-long health of the fetus.

  6. SERIAL ULTRASOUND TO ESTIMATE FETAL GROWTH CURVES IN SOUTHERN TAMANDUA (TAMANDUA TETRADACTYLA).

    Science.gov (United States)

    Thompson, Rachel; Wolf, Tiffany M; Robertson, Heather; Colburn, Margarita Woc; Moreno, Alexis; Moresco, Anneke; Napier, Anne Elise; Nofs, Sally A

    2017-06-01

    From 2012 to 2015, 16 pregnancies were monitored by ultrasonography in nine tamanduas ( Tamandua tetradactyla ) housed in three zoological facilities. Sonographic measurements were recorded to establish fetal growth curves using thoracic and skull landmarks described for giant anteaters ( Myrmecophaga tridactyla ). All pregnancies resulted in the uncomplicated delivery of healthy offspring, thus gestational development was considered normal. These data may be used as a reference for normal fetal development with potential for estimating parturition date in the absence of breeding data.

  7. The impact of fetal growth restriction on latency in the setting of expectant management of preeclampsia.

    Science.gov (United States)

    McKinney, David; Boyd, Heather; Langager, Amanda; Oswald, Michael; Pfister, Abbey; Warshak, Carri R

    2016-03-01

    Fetal growth restriction is a common complication of preeclampsia. Expectant management for qualifying patients has been found to have acceptable maternal safety while improving neonatal outcomes. Whether fetal growth restriction influences the duration of latency during expectant management of preeclampsia is unknown. The objective of the study was to determine whether fetal growth restriction is associated with a reduced interval to delivery in women with preeclampsia being expectantly managed prior to 34 weeks. We performed a retrospective cohort of singleton, live-born, nonanomalous deliveries at the University of Cincinnati Medical Center between 2008 and 2013. Patients were included in our analysis if they were diagnosed with preeclampsia prior to 34 completed weeks and if the initial management plan was to pursue expectant management beyond administration of steroids for fetal lung maturity. Two study groups were determined based on the presence or absence of fetal growth restriction. Patients were delivered when they developed persistent neurological symptoms, severe hypertension refractory to medical therapy, renal insufficiency, nonreassuring fetal status, pulmonary edema, or hemolysis elevated liver low platelet syndrome or when they reached 37 weeks if they remained stable without any other indication for delivery. Our primary outcome was the interval from diagnosis of preeclampsia to delivery, measured in days. Secondary outcomes included indications for delivery, rates of induction and cesarean delivery, development of severe morbidities of preeclampsia, and select neonatal outcomes. We performed a multivariate logistic regression analysis comparing those with fetal growth restriction with those with normally grown fetuses to determine whether there is an association between fetal growth restriction and a shortened interval to delivery, neonatal intensive care unit admission, prolonged neonatal stay, and neonatal mortality. A total of 851 patients met

  8. 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.

  9. Periconceptional growth hormone treatment alters fetal growth and development in lambs.

    Science.gov (United States)

    Koch, J M; Wilmoth, T A; Wilson, M E

    2010-05-01

    Research in the area of fetal programming has focused on intrauterine growth restriction. Few studies have attempted to examine programming mechanisms that ultimately lead to lambs with a greater potential for postnatal growth. We previously demonstrated that treatment of ewes with GH at the time of breeding led to an increase in birth weight. Therefore, the objective of this study was to determine the effects of a single injection of sustained-release GH given during the periconceptional period on fetal growth and development and to determine if the GH axis would be altered in these offspring. Estrus was synchronized using 2 injections of PGF(2alpha); at the time of the second injection, ewes assigned to treatment were also given an injection of sustained-release GH. A maternal jugular vein sample was taken weekly to analyze IGF-I as a proxy for GH to estimate the duration of the treatment effect. In ewes treated with GH, IGF-I increased (P brain weights were obtained, as well as left and right ventricular wall thicknesses. On postnatal d 100, a subset of ewe lambs were weighed and challenged with an intravenous injection of GHRH. Lambs from treated ewes had increased (P left ventricular wall was thinner (P development. Lambs born to ewes treated with GH were larger at birth and had altered organ development, which may indicate that early maternal GH treatment may lead to permanent changes in the developing fetus. The ewe lambs maintained their growth performance to at least 100 d of postnatal life and appeared to have an altered GH axis, as demonstrated by the altered response to GHRH.

  10. Characterization of fetal growth by repeated ultrasound measurements in the wild guinea pig (Cavia aperea).

    Science.gov (United States)

    Schumann, K; Guenther, A; Göritz, F; Jewgenow, K

    2014-08-01

    Fetal growth during pregnancy has previously been studied in the domesticated guinea pig (Cavia aperea f. porcellus) after dissecting pregnant females, but there are no studies describing the fetal growth in their wild progenitor, the wild guinea pig (C aperea). In this study, 50 pregnancies of wild guinea pig sows were investigated using modern ultrasound technique. The two most common fetal growth parameters (biparietal diameter [BPD] and crown-rump-length [CRL]) and uterine position were measured. Data revealed similar fetal growth patterns in the wild guinea pig and domesticated guinea pig in the investigated gestation period, although they differ in reproductive milestones such as gestation length (average duration of pregnancy 68 days), average birth weight, and litter mass. In this study, pregnancy lasted on average 60.2 days with a variance of less than a day (0.96 days). The measured fetal growth parameters are strongly correlated with each (R = 0.91; P guinea pig. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Optimal fetal growth for the Caucasian singleton and assessment of appropriateness of fetal growth: an analysis of a total population perinatal database

    Directory of Open Access Journals (Sweden)

    Lawrence David M

    2005-05-01

    Full Text Available Abstract Background The appropriateness of an individual's intra uterine growth is now considered an important determinant of both short and long term outcomes, yet currently used measures have several shortcomings. This study demonstrates a method of assessing appropriateness of intrauterine growth based on the estimation of each individual's optimal newborn dimensions from routinely available perinatal data. Appropriateness of growth can then be inferred from the ratio of the value of the observed dimension to that of the optimal dimension. Methods Fractional polynomial regression models including terms for non-pathological determinants of fetal size (gestational duration, fetal gender and maternal height, age and parity were used to predict birth weight, birth length and head circumference from a population without any major risk factors for sub-optimal intra-uterine growth. This population was selected from a total population of all singleton, Caucasian births in Western Australia 1998–2002. Births were excluded if the pregnancy was exposed to factors known to influence fetal growth pathologically. The values predicted by these models were treated as the optimal values, given infant gender, gestational age, maternal height, parity, and age. Results The selected sample (N = 62,746 comprised 60.5% of the total Caucasian singleton birth cohort. Equations are presented that predict optimal birth weight, birth length and head circumference given gestational duration, fetal gender, maternal height, age and parity. The best fitting models explained 40.5% of variance for birth weight, 32.2% for birth length, and 25.2% for head circumference at birth. Conclusion Proportion of optimal birth weight (length or head circumference provides a method of assessing appropriateness of intrauterine growth that is less dependent on the health of the reference population or the quality of their morphometric data than is percentile position on a birth weight

  12. In utero glucocorticoid (GLC) exposure reduces fetal skeletal muscle growth in rats

    Science.gov (United States)

    Maternal undernutrition and stress expose the fetus to above normal levels of GLC and predispose to intrauterine growth restriction. The aim of this study was to determine if fetal GLC exposure impairs skeletal muscle growth independently of maternal undernutrition. Three groups (n=7/group) of timed...

  13. Fetal Growth in Pregnancies Conceived after Gastric Bypass Surgery in Relation to Surgery-to-Conception Interval

    DEFF Research Database (Denmark)

    Nørgaard, Lone Nikoline; Gjerris, Anne Cathrine Roslev; Kirkegaard, Ida

    2014-01-01

    Medicine Database). Main outcome measures were early and late fetal growth in relation to time from bariatric surgery to conception of the pregnancy. Early fetal growth was expressed as "Fetal Growth Index": the ratio between the estimated number of days from first trimester ultrasound to second trimester......OBJECTIVE: To describe early and late fetal growth in pregnancies conceived after gastric bypass surgery in relation to time from surgery to conception of pregnancy. METHODS: National cohort study on 387 Danish women, who had laparoscopic or open gastric bypass surgery prior to a singleton...... ultrasound biometries and the actual calender time elapsed in days. Late fetal growth was expressed as the observed versus expected birthweight according to gestational age (GA). RESULTS: The surgery-to-conception interval ranged from 3 to 1851 days with a mean value of 502 (SD, 351) days. The mean "fetal...

  14. Isolation and characterization of neural stem cells from human fetal striatum

    International Nuclear Information System (INIS)

    Li Xiaoxia; Xu Jinchong; Bai Yun; Wang Xuan; Dai Xin; Liu Yinan; Zhang Jun; Zou Junhua; Shen Li; Li Lingsong

    2005-01-01

    This paper described that neural stem cells (hsNSCs) were isolated and expanded rapidly from human fetal striatum in adherent culture. The population was serum- and growth factor-dependent and expressed neural stem cell markers. They were capable of multi-differentiation into neurons, astrocytes, and oligodendrocytes. When plated in the dopaminergic neuron inducing medium, human striatum neural stem cells could differentiate into tyrosine hydroxylase positive neurons. hsNSCs were morphologically homogeneous and possessed high proliferation ability. The population doubled every 44.28 h and until now it has divided for more than 82 generations in vitro. Normal human diploid karyotype was unchanged throughout the in vitro culture period. Together, this study has exploited a method for continuous and rapid expansion of human neural stem cells as pure population, which maintained the capacity to generate almost fifty percent neurons. The availability of such cells may hold great interest for basic and applied neuroscience

  15. International standards for fetal growth based on serial ultrasound measurements: the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project.

    Science.gov (United States)

    Papageorghiou, Aris T; Ohuma, Eric O; Altman, Douglas G; Todros, Tullia; Cheikh Ismail, Leila; Lambert, Ann; Jaffer, Yasmin A; Bertino, Enrico; Gravett, Michael G; Purwar, Manorama; Noble, J Alison; Pang, Ruyan; Victora, Cesar G; Barros, Fernando C; Carvalho, Maria; Salomon, Laurent J; Bhutta, Zulfiqar A; Kennedy, Stephen H; Villar, José

    2014-09-06

    In 2006, WHO produced international growth standards for infants and children up to age 5 years on the basis of recommendations from a WHO expert committee. Using the same methods and conceptual approach, the Fetal Growth Longitudinal Study (FGLS), part of the INTERGROWTH-21(st) Project, aimed to develop international growth and size standards for fetuses. The multicentre, population-based FGLS assessed fetal growth in geographically defined urban populations in eight countries, in which most of the health and nutritional needs of mothers were met and adequate antenatal care was provided. We used ultrasound to take fetal anthropometric measurements prospectively from 14 weeks and 0 days of gestation until birth in a cohort of women with adequate health and nutritional status who were at low risk of intrauterine growth restriction. All women had a reliable estimate of gestational age confirmed by ultrasound measurement of fetal crown-rump length in the first trimester. The five primary ultrasound measures of fetal growth--head circumference, biparietal diameter, occipitofrontal diameter, abdominal circumference, and femur length--were obtained every 5 weeks (within 1 week either side) from 14 weeks to 42 weeks of gestation. The best fitting curves for the five measures were selected using second-degree fractional polynomials and further modelled in a multilevel framework to account for the longitudinal design of the study. We screened 13,108 women commencing antenatal care at less than 14 weeks and 0 days of gestation, of whom 4607 (35%) were eligible. 4321 (94%) eligible women had pregnancies without major complications and delivered live singletons without congenital malformations (the analysis population). We documented very low maternal and perinatal mortality and morbidity, confirming that the participants were at low risk of adverse outcomes. For each of the five fetal growth measures, the mean differences between the observed and smoothed centiles for the 3rd

  16. Is Placental Mitochondrial Function a Regulator that Matches Fetal and Placental Growth to Maternal Nutrient Intake in the Mouse?

    Directory of Open Access Journals (Sweden)

    Marcos R Chiaratti

    Full Text Available Effective fetal growth requires adequate maternal nutrition coupled to active transport of nutrients across the placenta, which, in turn requires ATP. Epidemiological and experimental evidence has shown that impaired maternal nutrition in utero results in an adverse postnatal phenotype for the offspring. Placental mitochondrial function might link maternal food intake to fetal growth since impaired placental ATP production, in response to poor maternal nutrition, could be a pathway linking maternal food intake to reduced fetal growth.We assessed the effects of maternal diet on placental water content, ATP levels and mitochondrial DNA (mtDNA content in mice at embryonic (E day 18 (E18. Females maintained on either low- (LPD or normal- (NPD protein diets were mated with NPD males.Fetal dry weight and placental efficiency (embryo/placental fresh weight were positively correlated (r = 0.53, P = 0.0001. Individual placental dry weight was reduced by LPD (P = 0.003, as was the expression of amino acid transporter Slc38a2 and of growth factor Igf2. Placental water content, which is regulated by active transport of solutes, was increased by LPD (P = 0.0001. However, placental ATP content was also increased (P = 0.03. To investigate the possibility of an underlying mitochondrial stress response, we studied cultured human trophoblast cells (BeWos. High throughput imaging showed that amino acid starvation induces changes in mitochondrial morphology that suggest stress-induced mitochondrial hyperfusion. This is a defensive response, believed to increase mitochondrial efficiency, that could underlie the increase in ATP observed in placenta.These findings reinforce the pathophysiological links between maternal diet and conceptus mitochondria, potentially contributing to metabolic programming. The quiet embryo hypothesis proposes that pre-implantation embryo survival is best served by a relatively low level of metabolism. This may extend to post

  17. WHO multicentre study for the development of growth standards from fetal life to childhood

    DEFF Research Database (Denmark)

    Merialdi, Mario; Widmer, Mariana; Gülmezoglu, Ahmet Metin

    2014-01-01

    backgrounds. The study will select pregnant women of high-middle socioeconomic status with no obvious environmental constraints on growth (adequate nutritional status, non-smoking), and normal pregnancy history with no complications likely to affect fetal growth. The study will be conducted in centres from...... ten developing and industrialized countries: Argentina, Brazil, Democratic Republic of Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand. At each centre, 140 pregnant women will be recruited between 8 + 0 and 12 + 6 weeks of gestation. Subsequently, visits for fetal biometry...

  18. Maternal factors associated with fetal growth and birthweight are independent determinants of placental weight and exhibit differential effects by fetal sex.

    Directory of Open Access Journals (Sweden)

    Marie Cecilie Paasche Roland

    Full Text Available INTRODUCTION: Maternal nutritional and metabolic factors influence the developmental environment of the fetus. Virtually any nutritional factor in the maternal blood has to pass the placental membranes to reach the fetal blood. Placental weight is a commonly used measure to summarize placental growth and function. Placental weight is an independent determinant of fetal growth and birthweight and modifies the associations between maternal metabolic factors and fetal growth. We hypothesized that maternal factors known to be related to fetal growth, newborn size and body composition are determinants of placental weight and that effects of maternal metabolic factors on placental weight differ between the genders. METHODS: The STORK study is a prospective longitudinal study including 1031 healthy pregnant women of Scandinavian heritage with singleton pregnancies. Maternal determinants (parity, body mass index, gestational weight gain and fasting plasma glucose of placental weight were explored by linear regression models, stratified by fetal sex. RESULTS: Parity, maternal BMI, gestational weight gain and fasting glucose had positive effects on placental weight. There was a sex specific effect in these associations. Fasting glucose was significantly associated with placental weight in females but not in males. CONCLUSION: Maternal factors known to influence fetal growth, birthweight and neonatal body composition are determinants of placental weight. The effect of maternal factors on placental weight is influenced by sex as illustrated in the relation between maternal glucose and placental weight.

  19. Mother's educational level and fetal growth: the genesis of health inequalities.

    Science.gov (United States)

    Silva, Lindsay M; Jansen, Pauline W; Steegers, Eric A P; Jaddoe, Vincent W V; Arends, Lidia R; Tiemeier, Henning; Verhulst, Frank C; Moll, Henriëtte A; Hofman, Albert; Mackenbach, Johan P; Raat, Hein

    2010-10-01

    Women of low socio-economic status (SES) give birth to lighter babies. It is unknown from which moment during pregnancy socio-economic differences in fetal weight can be observed, whether low SES equally affects different fetal-growth components, or what the effect of low SES is after taking into account mediating factors. In 3545 pregnant women participating in the Generation R Study, we studied the association of maternal educational level (high, mid-high, mid-low and low) as a measure of SES with fetal weight, head circumference, abdominal circumference and femur length. We did this before and after adjusting for potential mediators, including maternal height, pre-pregnancy body mass index and smoking. In fetuses of low-educated women relative to those of high-educated women, fetal growth was slower, leading to a lower fetal weight that was observable from late pregnancy onwards. In these fetuses, growth of the head [-0.16 mm/week; 95% confidence interval (CI): -0.25 to -0.07; P = 0.0004], abdomen (-0.10 mm/week; 95% CI: -0.21 to 0.01; P = 0.08) and femur (-0.03 mm/week; 95% CI: -0.05 to -0.006; P = 0.01) were all slower; from mid-pregnancy onwards, head circumference was smaller, and from late pregnancy onwards, femur length was also smaller. The negative effect of low education was greatest for head circumference (difference in standard deviation score in late pregnancy: -0.26; 95% CI: -0.36 to -0.15; P effect persevered even after adjustment for the potential mediators (adjusted difference: -0.14; 95% CI: -0.25 to -0.03; P = 0.01). Low maternal education is associated with a slower fetal growth and this effect appears stronger for growth of the head than for other body parts.

  20. Ethnic differences in fetal size and growth in a multi-ethnic population.

    Science.gov (United States)

    Sletner, Line; Rasmussen, Svein; Jenum, Anne Karen; Nakstad, Britt; Jensen, Odd Harald Rognerud; Vangen, Siri

    2015-09-01

    Impaired or excessive fetal growth is associated with adverse short- and long-term health outcomes that differ between ethnic groups. We explored ethnic differences in fetal size and growth from mid pregnancy until birth. Data are from the multi-ethnic STORK-Groruddalen study, a population-based, prospective cohort of 823 pregnant women and their offspring in Oslo, Norway. Measures were z-scores of estimated fetal weight (EFW), head circumference (HC), abdominal circumference (AC) and femur length (FL), in gestational week 24, 32 and 37, measured by ultrasound, and similar measures at birth. Differences in fetal size and growth were assessed using separate Linear Mixed Models including all four time points, with ethnic Europeans as reference. In week 24 South Asian fetuses had smaller AC, but larger FL than Europeans, and slightly lower EFW (-0.17 SD (-0.33, -0.01), p=0.04). Middle East/North African fetuses also had larger FL, but similar AC, and hence slightly higher EFW (0.18 (0.003, 0.36), p=0.05). Both groups had slower growth of AC, FL and EFW from this time until birth, and had -0.61 SD (-0.73, -0.49) and -0.28 SD (-0.41, -0.15) lower birth weight respectively. Ethnic East Asians, on the other hand, were smaller throughout pregnancy and had -0.58 SD (-0.82, -0.34) lower birth weight. Significant ethnic differences remained after adjusting for maternal factors. We observed ethnic differences in fetal size and body proportions already in gestational week 24, and in fetal growth from this time until birth, which were only partly explained by key maternal factors. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Development of the penis during the human fetal period (13 to 36 weeks after conception).

    Science.gov (United States)

    Gallo, Carla B M; Costa, Waldemar S; Furriel, Angelica; Bastos, Ana L; Sampaio, Francisco J B

    2013-11-01

    We analyzed the development of the area of the penis and erectile structures (corpora cavernosa and corpus spongiosum) and the thickness of the tunica albuginea during the fetal period (13 to 36 weeks after conception) in humans to establish normative patterns of growth. We studied 56 male human fetuses at 13 to 36 weeks after conception. We used histochemical and morphometric techniques to analyze the parameters of total penile area, area of corpora cavernosa, area of corpus spongiosum, and thickness of tunica albuginea in the dorsal and ventral regions using ImageJ software (National Institutes of Health, Bethesda, Maryland). Between 13 and 36 weeks after conception the area of the penis varies from 0.95 to 24.25 mm2. The area of the corpora cavernosa varies from 0.28 to 9.12 mm2, and the area of the corpus spongiosum varies from 0.14 to 3.99 mm2. The thickness of the tunica albuginea varies from 0.029 to 0.296 mm in the dorsal region and from 0.014 to 0.113 mm in the ventral region of the corpora cavernosa. We found a strong correlation between the total penile area, corpora cavernosa and corpus spongiosum with fetal age (weeks following conception). The growth rate was more intense during the second trimester (13 to 24 weeks of gestation) compared to the third trimester (25 to 36 weeks). Tunica albuginea thickness also was strongly correlated with fetal age and this structure was thicker in the dorsal vs ventral region. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  2. Octreotide therapy and restricted fetal growth: pregnancy in familial hyperinsulinemic hypoglycemia

    Directory of Open Access Journals (Sweden)

    Marianne Geilswijk

    2017-02-01

    Full Text Available Hypoglycemia during pregnancy can have serious health implications for both mother and fetus. Although not generally recommended in pregnancy, synthetic somatostatin analogues are used for the management of blood glucose levels in expectant hyperinsulinemic mothers. Recent reports suggest that octreotide treatment in pregnancy, as well as hypoglycemia in itself, may pose a risk of fetal growth restriction. During pregnancy, management of blood glucose levels in familial hyperinsulinemic hypoglycemia thus forms a medical dilemma. We report on pregnancy outcomes in a woman with symptomatic familial hyperinsulinemic hypoglycemia, type 3. During the patient’s first pregnancy with a viable fetus octreotide treatment was instituted in gestational age 23 weeks to prevent severe hypoglycemic incidences. Fetal growth velocity declined, and at 37 weeks of gestation, intrauterine growth retardation was evident. During the second pregnancy with a viable fetus, blood glucose levels were managed through dietary intervention alone. Thus, the patient was advised to take small but frequent meals high in fiber and low in carbohydrates. Throughout pregnancy, no incidences of severe hypoglycemia occurred and fetal growth velocity was normal. We conclude that octreotide treatment during pregnancy may pose a risk of fetal growth restriction and warrants careful consideration. In some cases of familial hyperinsulinemic hypoglycemia, blood glucose levels can be successfully managed through diet only, also during pregnancy.

  3. Low PAPP-A in the first trimester is associated with reduced fetal growth rate prior to gestational week 20

    DEFF Research Database (Denmark)

    Salvig, J D; Kirkegaard, I; Winding, Trine Nøhr

    2010-01-01

    To evaluate the association between maternal pregnancy-associated plasma protein-A (PAPP-A) and fetal growth from the first to the second trimester.......To evaluate the association between maternal pregnancy-associated plasma protein-A (PAPP-A) and fetal growth from the first to the second trimester....

  4. Fetal growth trajectory and risk for eczema in a Saudi population.

    Science.gov (United States)

    AlMakoshi, Amel; Ellahi, Awaiss; Sallout, Bala; Devereux, Graham; Turner, Steve

    2015-12-01

    Recent studies in Western cohorts have identified associations between increasing fetal abdominal circumference (AC) during mid-pregnancy and increased risk for eczema and atopy. We sought to replicate these findings in a Saudi population where antenatal environmental exposures are different compared with Western countries. A Saudi birth cohort was recruited to relate maternal dietary intake and fetal growth to wheeze, eczema, and rhinitis in the first 2 yrs. Fetal size was determined from routine ultrasound scan measurements in the second and third trimesters and birthweight was noted. Parent-reported outcomes during the first 2 yrs were acquired by telephone-administered questionnaire. There were 1076 mothers recruited. AC was determined in 562 for the second, in 632 for the third, and in 281 for both second and third trimesters. A history of eczema was determined in 814 children at 2 yrs of age. There was an inverse relationship between change in abdominal circumference between the second and third trimesters for eczema (OR 0.66 per z score increase in AC [95% CI 0.49, 0.89]), and the quartile with the greatest faltering growth were at increased risk compared with other groups (p ≤ 0.045). Change in fetal size between the third trimester and birth was not associated with altered eczema risk. There were no associations between fetal growth and wheeze at the age of 2 yrs. Our findings contrast observations made in Western populations but nonetheless suggest that factors associated with changing fetal growth trajectory in the second half of pregnancy are also relevant to atopy development on the global setting. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. The effect of copper deficiency on fetal growth and liver anti-oxidant capacity in the Cohen diabetic rat model

    Energy Technology Data Exchange (ETDEWEB)

    Ergaz, Zivanit, E-mail: zivanit@hadassah.org.il [Hebrew University Hadassah Medical School, Jerusalem (Israel); Shoshani-Dror, Dana [Hebrew University Hadassah Medical School, Jerusalem (Israel); Guillemin, Claire [Department of Pharmacology and Therapeutics, McGill University, Montreal (Canada); Neeman-azulay, Meytal; Fudim, Liza [Hebrew University Hadassah Medical School, Jerusalem (Israel); Weksler-Zangen, Sarah [Diabetes Research Unit, Hebrew University Hadassah Medical School and Hospital, Jerusalem (Israel); Stodgell, Christopher J.; Miller, Richard K. [Department of Obstetrics and Gynecology, University of Rochester, Rochester, MN (United States); Ornoy, Asher [Hebrew University Hadassah Medical School, Jerusalem (Israel)

    2012-12-01

    High sucrose low copper diet induces fetal growth restriction in the three strains of the Cohen diabetic rats: an inbred copper deficient resistant (CDr), an inbred copper deficient sensitive (CDs that become diabetic on high sucrose low copper diet -HSD) and an outbred Wistar derived Sabra rats. Although those growth restricted fetuses also exhibit increased oxidative stress, antioxidants do not restore normal growth. In the present study, we evaluated the role of copper deficiency in the HSD induced fetal growth restriction by adding to the drinking water of the rats 1 ppm or 2 ppm of copper throughout their pregnancy. Fetal and placental growth in correlation with fetal liver copper content and anti-oxidant capacity was evaluated on day 21 of pregnancy. HSD compared to regular chow induced fetal growth restriction, which was most significant in the Cohen diabetic sensitive animals. The addition of 1 ppm and 2 ppm copper to the drinking water normalized fetal growth in a dose dependent manner and reduced the degree of hyperglycemia in the diabetes sensitive rats. The CDs fetuses responded to the HSD with lower catalase like activity, and less reduced superoxide dismutase levels compared to the Sabra strain, and had high malondialdehyde levels even when fed regular chow. Immunostaining was higher for nitrotyrosine among the CDr and higher for hypoxia factor 1 α among the CDs. We conclude that in our model of dietary-induced fetal growth restriction, copper deficiency plays a major etiologic role in the decrease of fetal growth and anti-oxidant capacity. -- Highlights: ► High sucrose low copper diet restricted fetal growth in the Cohen diabetic rat model ► Maternal copper blood levels directly correlated with fetal liver copper content ► Copper supplementation decreased embryonic resorption in the inbred strains ► Copper supplementation reduced hyperglycemia in the sucrose sensitive inbred strain ► Copper supplementation alleviated growth restriction and

  6. The effect of copper deficiency on fetal growth and liver anti-oxidant capacity in the Cohen diabetic rat model

    International Nuclear Information System (INIS)

    Ergaz, Zivanit; Shoshani-Dror, Dana; Guillemin, Claire; Neeman-azulay, Meytal; Fudim, Liza; Weksler-Zangen, Sarah; Stodgell, Christopher J.; Miller, Richard K.; Ornoy, Asher

    2012-01-01

    High sucrose low copper diet induces fetal growth restriction in the three strains of the Cohen diabetic rats: an inbred copper deficient resistant (CDr), an inbred copper deficient sensitive (CDs that become diabetic on high sucrose low copper diet -HSD) and an outbred Wistar derived Sabra rats. Although those growth restricted fetuses also exhibit increased oxidative stress, antioxidants do not restore normal growth. In the present study, we evaluated the role of copper deficiency in the HSD induced fetal growth restriction by adding to the drinking water of the rats 1 ppm or 2 ppm of copper throughout their pregnancy. Fetal and placental growth in correlation with fetal liver copper content and anti-oxidant capacity was evaluated on day 21 of pregnancy. HSD compared to regular chow induced fetal growth restriction, which was most significant in the Cohen diabetic sensitive animals. The addition of 1 ppm and 2 ppm copper to the drinking water normalized fetal growth in a dose dependent manner and reduced the degree of hyperglycemia in the diabetes sensitive rats. The CDs fetuses responded to the HSD with lower catalase like activity, and less reduced superoxide dismutase levels compared to the Sabra strain, and had high malondialdehyde levels even when fed regular chow. Immunostaining was higher for nitrotyrosine among the CDr and higher for hypoxia factor 1 α among the CDs. We conclude that in our model of dietary-induced fetal growth restriction, copper deficiency plays a major etiologic role in the decrease of fetal growth and anti-oxidant capacity. -- Highlights: ► High sucrose low copper diet restricted fetal growth in the Cohen diabetic rat model ► Maternal copper blood levels directly correlated with fetal liver copper content ► Copper supplementation decreased embryonic resorption in the inbred strains ► Copper supplementation reduced hyperglycemia in the sucrose sensitive inbred strain ► Copper supplementation alleviated growth restriction and

  7. Maternal smoking during pregnancy and fetal organ growth: a magnetic resonance imaging study.

    Directory of Open Access Journals (Sweden)

    Devasuda Anblagan

    Full Text Available To study whether maternal cigarette smoking during pregnancy is associated with alterations in the growth of fetal lungs, kidneys, liver, brain, and placenta.A case-control study, with operators performing the image analysis blinded.Study performed on a research-dedicated magnetic resonance imaging (MRI scanner (1.5 T with participants recruited from a large teaching hospital in the United Kingdom.A total of 26 pregnant women (13 current smokers, 13 non smokers were recruited; 18 women (10 current smokers, 8 nonsmokers returned for the second scan later in their pregnancy.Each fetus was scanned with MRI at 22-27 weeks and 33-38 weeks gestational age (GA.Images obtained with MRI were used to measure volumes of the fetal brain, kidneys, lungs, liver and overall fetal size, as well as placental volumes.Exposed fetuses showed lower brain volumes, kidney volumes, and total fetal volumes, with this effect being greater at visit 2 than at visit 1 for brain and kidney volumes, and greater at visit 1 than at visit 2 for total fetal volume. Exposed fetuses also demonstrated lower lung volume and placental volume, and this effect was similar at both visits. No difference was found between the exposed and nonexposed fetuses with regards to liver volume.Magnetic resonance imaging has been used to show that maternal smoking is associated with reduced growth of fetal brain, lung and kidney; this effect persists even when the volumes are corrected for maternal education, gestational age, and fetal sex. As expected, the fetuses exposed to maternal smoking are smaller in size. Similarly, placental volumes are smaller in smoking versus nonsmoking pregnant women.

  8. Effects of chronic carbon monoxide exposure on fetal growth and development in mice

    Directory of Open Access Journals (Sweden)

    Venditti Carolina C

    2011-12-01

    Full Text Available Abstract Background Carbon monoxide (CO is produced endogenously, and can also be acquired from many exogenous sources: ie. cigarette smoking, automobile exhaust. Although toxic at high levels, low level production or exposure lends to normal physiologic functions: smooth muscle cell relaxation, control of vascular tone, platelet aggregation, anti- inflammatory and anti-apoptotic events. In pregnancy, it is unclear at what level maternal CO exposure becomes toxic to the fetus. In this study, we hypothesized that CO would be embryotoxic, and we sought to determine at what level of chronic CO exposure in pregnancy embryo/fetotoxic effects are observed. Methods Pregnant CD1 mice were exposed to continuous levels of CO (0 to 400 ppm from conception to gestation day 17. The effect on fetal/placental growth and development, and fetal/maternal CO concentrations were determined. Results Maternal and fetal CO blood concentrations ranged from 1.12- 15.6 percent carboxyhemoglobin (%COHb and 1.0- 28.6%COHb, respectively. No significant difference was observed in placental histological morphology or in placental mass with any CO exposure. At 400 ppm CO vs. control, decreased litter size and fetal mass (p Conclusions Exposure to levels at or below 300 ppm CO throughout pregnancy has little demonstrable effect on fetal growth and development in the mouse.

  9. Retinoic Acid signalling and the control of meiotic entry in the human fetal gonad.

    Directory of Open Access Journals (Sweden)

    Andrew J Childs

    Full Text Available The development of mammalian fetal germ cells along oogenic or spermatogenic fate trajectories is dictated by signals from the surrounding gonadal environment. Germ cells in the fetal testis enter mitotic arrest, whilst those in the fetal ovary undergo sex-specific entry into meiosis, the initiation of which is thought to be mediated by selective exposure of fetal ovarian germ cells to mesonephros-derived retinoic acid (RA. Aspects of this model are hard to reconcile with the spatiotemporal pattern of germ cell differentiation in the human fetal ovary, however. We have therefore examined the expression of components of the RA synthesis, metabolism and signalling pathways, and their downstream effectors and inhibitors in germ cells around the time of the initiation of meiosis in the human fetal gonad. Expression of the three RA-synthesising enzymes, ALDH1A1, 2 and 3 in the fetal ovary and testis was equal to or greater than that in the mesonephros at 8-9 weeks gestation, indicating an intrinsic capacity within the gonad to synthesise RA. Using immunohistochemistry to detect RA receptors RARα, β and RXRα, we find germ cells to be the predominant target of RA signalling in the fetal human ovary, but also reveal widespread receptor nuclear localization indicative of signalling in the testis, suggesting that human fetal testicular germ cells are not efficiently shielded from RA by the action of the RA-metabolising enzyme CYP26B1. Consistent with this, expression of CYP26B1 was greater in the human fetal ovary than testis, although the sexually-dimorphic expression patterns of the germ cell-intrinsic regulators of meiotic initiation, STRA8 and NANOS2, appear conserved. Finally, we demonstrate that RA induces a two-fold increase in STRA8 expression in cultures of human fetal testis, but is not sufficient to cause widespread meiosis-associated gene expression. Together, these data indicate that while local production of RA within the fetal ovary may

  10. Retinoic Acid Signalling and the Control of Meiotic Entry in the Human Fetal Gonad

    Science.gov (United States)

    Kinnell, Hazel L.; Anderson, Richard A.; Saunders, Philippa T. K.

    2011-01-01

    The development of mammalian fetal germ cells along oogenic or spermatogenic fate trajectories is dictated by signals from the surrounding gonadal environment. Germ cells in the fetal testis enter mitotic arrest, whilst those in the fetal ovary undergo sex-specific entry into meiosis, the initiation of which is thought to be mediated by selective exposure of fetal ovarian germ cells to mesonephros-derived retinoic acid (RA). Aspects of this model are hard to reconcile with the spatiotemporal pattern of germ cell differentiation in the human fetal ovary, however. We have therefore examined the expression of components of the RA synthesis, metabolism and signalling pathways, and their downstream effectors and inhibitors in germ cells around the time of the initiation of meiosis in the human fetal gonad. Expression of the three RA-synthesising enzymes, ALDH1A1, 2 and 3 in the fetal ovary and testis was equal to or greater than that in the mesonephros at 8–9 weeks gestation, indicating an intrinsic capacity within the gonad to synthesise RA. Using immunohistochemistry to detect RA receptors RARα, β and RXRα, we find germ cells to be the predominant target of RA signalling in the fetal human ovary, but also reveal widespread receptor nuclear localization indicative of signalling in the testis, suggesting that human fetal testicular germ cells are not efficiently shielded from RA by the action of the RA-metabolising enzyme CYP26B1. Consistent with this, expression of CYP26B1 was greater in the human fetal ovary than testis, although the sexually-dimorphic expression patterns of the germ cell-intrinsic regulators of meiotic initiation, STRA8 and NANOS2, appear conserved. Finally, we demonstrate that RA induces a two-fold increase in STRA8 expression in cultures of human fetal testis, but is not sufficient to cause widespread meiosis-associated gene expression. Together, these data indicate that while local production of RA within the fetal ovary may be important in

  11. Maternal milk consumption, fetal growth, and the risks of neonatal complications: The Generation R Study

    NARCIS (Netherlands)

    D.H.M. Heppe (Denise); R.M. van Dam (Rob); S.P. Willemsen (Sten); H. den Breeijen (Hanneke); H. Raat (Hein); A. Hofman (Albert); E.A.P. Steegers (Eric); V.W.V. Jaddoe (Vincent)

    2011-01-01

    textabstractBackground: Maternal cow-milk consumption may increase birth weight. Previous studies did not assess the association of maternal milk consumption with trimester-specific fetal growth. Objective: The objective was to assess associations of first-trimester maternal milk consumption with

  12. Plasmodium falciparum infection early in pregnancy has profound consequences for fetal growth

    DEFF Research Database (Denmark)

    Schmiegelow, Christentze; Matondo, Sungwa; Minja, Daniel T R

    2017-01-01

    Malaria during pregnancy constitutes a large health problem in areas of endemicity. The World Health Organization recommends that interventions are initiated at the first antenatal visit, and these improve pregnancy outcomes. This study evaluated fetal growth by ultrasonography and birth outcomes...

  13. Fetal Growth Restriction with Brain Sparing: Neurocognitive and Behavioral Outcomes at 12 Years of Age

    NARCIS (Netherlands)

    Beukers, Fenny; Aarnoudse-Moens, Cornelieke S. H.; van Weissenbruch, Mirjam M.; Ganzevoort, Wessel; van Goudoever, Johannes B.; van Wassenaer-Leemhuis, Aleid G.

    2017-01-01

    Objective To study neurocognitive functions and behavior in children with a history of fetal growth restriction (FGR) with brain sparing. We hypothesized that children with FGR would have poorer outcomes on these domains. Study design Subjects were 12-year-old children with a history of FGR born to

  14. Prepregnancy low-plasma volume and predisposition to preeclampsia and fetal growth restriction

    NARCIS (Netherlands)

    Scholten, R.R.; Sep, S.; Peeters, L.; Hopman, M.T.E.; Lotgering, F.K.; Spaanderman, M.E.A.

    2011-01-01

    OBJECTIVE: To estimate whether recurrence risks of preeclampsia, preterm birth, and fetal growth restriction relate to prepregnancy plasma volume. METHODS: We conducted a retrospective cohort study in 580 formerly preeclamptic women and a control group. In all women we measured plasma volume

  15. Anthropometry of fetal growth in rural Malawi in relation to maternal malaria and HIV status

    NARCIS (Netherlands)

    Kalanda, B.F.; Buuren, S. van; Verhoeff, F.H.; Brabin, B.J.

    2005-01-01

    Objective: To describe fetal growth centiles in relation to maternal malaria and HIV status, using cross sectional measurements at birth. Design: A cross sectional study of pregnant women and their babies. Data on maternal socioeconomic status and current pregnancy, including HIV status and newborn

  16. Physically demanding work, fetal growth and the risk of adverse birth outcomes. The Generation R Study

    NARCIS (Netherlands)

    C.A. Snijder (Claudia); T. Brand (Teus); V.W.V. Jaddoe (Vincent); A. Hofman (Albert); J.P. Mackenbach (Johan); E.A.P. Steegers (Eric); A. Burdorf (Alex)

    2012-01-01

    textabstractObjectives: Work-related risk factors, such as long work hours, and physically demanding work have been suggested to adversely influence pregnancy outcome. The authors aimed to examine associations between various aspects of physically demanding work with fetal growth in different

  17. Physically demanding work, fetal growth and the risk of adverse birth outcomes. The Generation R Study

    NARCIS (Netherlands)

    Snijder, Claudia A.; Brand, Teus; Jaddoe, Vincent; Hofman, Albert; Mackenbach, Johan P.; Steegers, Eric A. P.; Burdorf, Alex

    2012-01-01

    Objectives Work-related risk factors, such as long work hours, and physically demanding work have been suggested to adversely influence pregnancy outcome. The authors aimed to examine associations between various aspects of physically demanding work with fetal growth in different trimesters during

  18. ABSORPTION-SPECTRA OF HUMAN FETAL AND ADULT OXYHEMOGLOBIN, DE-OXYHEMOGLOBIN, CARBOXYHEMOGLOBIN, AND METHEMOGLOBIN

    NARCIS (Netherlands)

    ZIJLSTRA, WG; MEEUWSENVANDERROEST, WP

    We determined the millimolar absorptivities of the four clinically relevant derivatives of fetal and adult human hemoglobin in the visible and near-infrared spectral range (450-1000 nm). As expected, spectral absorption curves of similar shape were found, but the small differences between fetal and

  19. MSCs can be differentially isolated from maternal, middle and fetal segments of the human umbilical cord.

    Science.gov (United States)

    Lim, Jezamine; Razi, Zainul Rashid Mohamad; Law, Jiaxian; Nawi, Azmawati Mohammed; Idrus, Ruszymah Binti Haji; Ng, Min Hwei

    2016-12-01

    Human Wharton's jelly-derived mesenchymal stromal cells (hWJMSCs) are possibly the most suitable allogeneic cell source for stromal cell therapy and tissue engineering applications because of their hypo-immunogenic and non-tumorigenic properties, easy availability and minimal ethical concerns. Furthermore, hWJMSCs possess unique properties of both adult mesenchymal stromal cells and embryonic stromal cells. The human umbilical cord (UC) is approximately 50-60 cm long and the existing studies in the literature have not provided information on which segment of the UC was studied. In this study, hWJMSCs derived from three anatomical segments of the UC are compared. Three segments of the whole UC, each 3 cm in length, were identified anatomically as the maternal, middle and fetal segments. The hWJMSCs from the different segments were analyzed via trypan blue exclusion assay to determine the growth kinetics and cell viability, flow cytometry for immunophenotyping and immunofluorescence and reverse transcriptase polymerase chain reaction (RT-PCR) for expression of stromal cell transcriptional factors. Furthermore, the trilineage differentiation potential (osteogenic, adipogenic and chondrogenic) of these cells was also assessed. hWJMSCs isolated from the maternal and fetal segments displayed greater viability and possessed a significantly higher proliferation rate compared with cells from the middle segment. Immunophenotyping revealed that hWJMSCs derived from all three segments expressed the MSC markers CD105, CD73, CD90, CD44, CD13 and CD29, as well as HLA-ABC and HLA-DR, but were negative for hematopoietic markers CD14, CD34 and CD45. Analysis of the embryonic markers showed that all three segments expressed Nanog and Oct 3/4, but only the maternal and fetal segments expressed SSEA 4 and TRA-160. Cells from all three segments were able to differentiate into chondrogenic, osteogenic and adipogenic lineages with the middle segments showing much lower differentiation

  20. Cellular and Molecular Effect of MEHP Involving LXRα in Human Fetal Testis and Ovary

    OpenAIRE

    Muczynski, Vincent; Lecureuil, Charlotte; Messiaen, Sébastien; Guerquin, Marie-Justine; N’Tumba-Byn, Thierry; Moison, Delphine; Hodroj, Wassim; Benjelloun, Hinde; Baijer, Jan; Livera, Gabriel; Frydman, René; Benachi, Alexandra; Habert, René; Rouiller-Fabre, Virginie

    2012-01-01

    Background Phthalates have been shown to have reprotoxic effects in rodents and human during fetal life. Previous studies indicate that some members of the nuclear receptor (NR) superfamilly potentially mediate phthalate effects. This study aimed to assess if expression of these nuclear receptors are modulated in the response to MEHP exposure on the human fetal gonads in vitro. Methodology/Principal Findings Testes and ovaries from 7 to 12 gestational weeks human fetuses were exposed to 10−4M...

  1. Locally derived traffic-related air pollution and fetal growth restriction: a retrospective cohort study.

    Science.gov (United States)

    Pereira, Gavin; Cook, Angus G; Haggar, Fatima; Bower, Carol; Nassar, Natasha

    2012-11-01

    Fetal growth restriction has been inconsistently associated with maternal exposure to elevated levels of traffic-related air pollution. We investigated the relationship between an individualised measure of fetal growth and maternal exposure to a specific marker for traffic-related air pollution. We estimated maternal residential exposure to a marker for traffic-related air pollution (nitrogen dioxide, NO2) during pregnancy for 23,452 births using temporally adjusted land-use regression. Logistic regression was used to investigate associations with small for gestational age and sex (SGA) and fetal growth restriction, defined as proportion of optimal birth weight (POBW) below the 10th percentile. Sub-populations investigated were: women who spent most time at home, women who did not move house, women with respiratory or circulatory morbidity, women living in low/middle/high socio-economic areas, women who delivered before 37 weeks gestation, and women who delivered from 37 weeks gestation. An IQR increase in traffic-related air pollution in the second trimester across all women was associated with an OR of 1.31 (95% CI 1.07 to 1.60) for fetal growth restriction. Effects on fetal growth restriction (low POBW) were highest among women who subsequently delivered before 37 weeks of gestation. Effects on SGA were highest among women who did not move house: OR 1.35 (95% CI 1.08 to 1.69). Larger effect sizes were observed for low POBW than for SGA. Exposure to traffic-related air pollution in mid to late pregnancy was associated with risk of SGA and low POBW in this study.

  2. Maternal serum copeptin as a marker for fetal growth restriction

    Directory of Open Access Journals (Sweden)

    Ashraf A. Foda

    2013-09-01

    Conclusion: Maternal serum copeptin level can differentiate between the normal sized and small for gestational age fetuses. Also, it can differentiate between constitutionally small and growth restricted fetuses.

  3. Myocardial bridges of the coronary arteries in the human fetal heart.

    Science.gov (United States)

    Cakmak, Yusuf Ozgür; Cavdar, Safiye; Yalin, Aymelek; Yener, Nuran; Ozdogmus, Omer

    2010-09-01

    During the last century, many investigators reported on myocardial bridges in the adult human heart. In the present study, 39 human fetal hearts (the mean gestastional age was 30 weeks) were studied for myocardial bridging, and the results were correlated with adult data. Among the 39 (27 male and 12 female) fetal hearts studied, 26 bridges were observed on 18 fetal hearts (46.2%). Ten of the bridges had one myocardial bridge, whereas double myocardial bridges were observed in eight fetal hearts. The most frequent myocardial bridges were observed on the left anterior descending artery (LAD), which had 13 bridges (50%). Eight (30.7%) myocardial bridges were on the diagonal artery, and on the posterior descending artery there were five (19.3%). Myocardial bridges were not observed on the circumflex artery. The data presented in this study may provide potentially useful information for the preoperative evaluation of the newborn and may have a clinical implication for sudden fetal death.

  4. Fetal, neonatal, infant, and child international growth standards: an unprecedented opportunity for an integrated approach to assess growth and development.

    Science.gov (United States)

    Garza, Cutberto

    2015-07-01

    The recent publication of fetal growth and gestational age-specific growth standards by the International Fetal and Newborn Growth Consortium for the 21st Century Project and the previous publication by the WHO of infant and young child growth standards based on the WHO Multicentre Growth Reference Study enable evaluations of growth from ∼9 wk gestation to 5 y. The most important features of these projects are the prescriptive approach used for subject selection and the rigorous testing of the assertion that growth is very similar among geographically and ethnically diverse nonisolated populations when health, nutrition, and other care needs are met and the environment imposes minimal constraints on growth. Both studies documented that with adequate controls, the principal source of variability in growth during gestation and early childhood resides among individuals. Study sites contributed much less to observed variability. The agreement between anthropometric measurements common to both studies also is noteworthy. Jointly, these studies provide for the first time, to my knowledge, a conceptually consistent basis for worldwide and localized assessments and comparisons of growth performance in early life. This is an important contribution to improving the health care of children across key periods of growth and development, especially given the appropriate interest in pursuing "optimal" health in the "first 1000 d," i.e., the period covering fertilization/implantation, gestation, and postnatal life to 2 y of age. © 2015 American Society for Nutrition.

  5. Recognizing different tissues in human fetal femur cartilage by label-free Raman microspectroscopy

    Science.gov (United States)

    Kunstar, Aliz; Leijten, Jeroen; van Leuveren, Stefan; Hilderink, Janneke; Otto, Cees; van Blitterswijk, Clemens A.; Karperien, Marcel; van Apeldoorn, Aart A.

    2012-11-01

    Traditionally, the composition of bone and cartilage is determined by standard histological methods. We used Raman microscopy, which provides a molecular "fingerprint" of the investigated sample, to detect differences between the zones in human fetal femur cartilage without the need for additional staining or labeling. Raman area scans were made from the (pre)articular cartilage, resting, proliferative, and hypertrophic zones of growth plate and endochondral bone within human fetal femora. Multivariate data analysis was performed on Raman spectral datasets to construct cluster images with corresponding cluster averages. Cluster analysis resulted in detection of individual chondrocyte spectra that could be separated from cartilage extracellular matrix (ECM) spectra and was verified by comparing cluster images with intensity-based Raman images for the deoxyribonucleic acid/ribonucleic acid (DNA/RNA) band. Specific dendrograms were created using Ward's clustering method, and principal component analysis (PCA) was performed with the separated and averaged Raman spectra of cells and ECM of all measured zones. Overall (dis)similarities between measured zones were effectively visualized on the dendrograms and main spectral differences were revealed by PCA allowing for label-free detection of individual cartilaginous zones and for label-free evaluation of proper cartilaginous matrix formation for future tissue engineering and clinical purposes.

  6. Prenatal exposure to traffic pollution: associations with reduced fetal growth and rapid infant weight gain.

    Science.gov (United States)

    Fleisch, Abby F; Rifas-Shiman, Sheryl L; Koutrakis, Petros; Schwartz, Joel D; Kloog, Itai; Melly, Steven; Coull, Brent A; Zanobetti, Antonella; Gillman, Matthew W; Gold, Diane R; Oken, Emily

    2015-01-01

    Prenatal air pollution exposure inhibits fetal growth, but implications for postnatal growth are unknown. We assessed weights and lengths of US infants in the Project Viva cohort at birth and 6 months. We estimated 3rd-trimester residential air pollution exposures using spatiotemporal models. We estimated neighborhood traffic density and roadway proximity at birth address using geographic information systems. We performed linear and logistic regression adjusted for sociodemographic variables, fetal growth, and gestational age at birth. Mean birth weight-for-gestational age z-score (fetal growth) was 0.17 (standard deviation [SD] = 0.97; n = 2,114), 0- to 6-month weight-for-length gain was 0.23 z-units (SD = 1.11; n = 689), and 17% had weight-for-length ≥95th percentile at 6 months of age. Infants exposed to the highest (vs. lowest) quartile of neighborhood traffic density had lower fetal growth (-0.13 units [95% confidence interval (CI) = -0.25 to -0.01]), more rapid 0- to 6-month weight-for-length gain (0.25 units [95% CI = 0.01 to 0.49]), and higher odds of weight-for-length ≥95th percentile at 6 months (1.84 [95% CI = 1.11 to 3.05]). Neighborhood traffic density was additionally associated with an infant being in both the lowest quartile of fetal growth and the highest quartile of 0- to 6-month weight-for-length gain (Q4 vs. Q1, odds ratio = 3.01 [95% CI = 1.08 to 8.44]). Roadway proximity and 3rd-trimester black carbon exposure were similarly associated with growth outcomes. For 3rd-trimester particulate matter (PM2.5), effect estimates were in the same direction, but smaller and imprecise. Infants exposed to higher traffic-related pollution in early life may exhibit more rapid postnatal weight gain in addition to reduced fetal growth.

  7. Maternal exercise, season and sex modify the human fetal circadian rhythm.

    Science.gov (United States)

    Sletten, Julie; Cornelissen, Germaine; Assmus, Jørg; Kiserud, Torvid; Albrechtsen, Susanne; Kessler, Jörg

    2018-05-13

    The knowledge on circadian rhythmicity is rapidly expanding. We aimed to define the longitudinal development of the circadian heart rate rhythm in the human fetus in an unrestricted, out-of-hospital setting, and to examine the effects of maternal physical activity, season and fetal sex. We recruited 48 women with low-risk singleton pregnancies. Using a portable monitor for continuous fetal electrocardiography, fetal heart rate recordings were obtained around gestational weeks 24, 28, 32 and 36. Circadian rhythmicity in fetal heart rate and fetal heart rate variation was detected by cosinor analysis; developmental trends were calculated by population-mean cosinor and multilevel analysis. For the fetal heart rate and fetal heart rate variation, a significant circadian rhythm was present in 122/123 (99.2%) and 116/121 (95.9%) of the individual recordings, respectively. The rhythms were best described by combining cosine waves with periods of 24 and 8 hours. With increasing gestational age, the magnitude of the fetal heart rate rhythm increased, and the peak of the fetal heart rate variation rhythm shifted from a mean of 14:25 (24 weeks) to 20:52 (36 weeks). With advancing gestation, the rhythm-adjusted mean value of the fetal heart rate decreased linearly in females (prhythm diversity was found in male fetuses, during higher maternal physical activity and during the summer season. The dynamic development of the fetal circadian heart rate rhythm during the second half of pregnancy is modified by fetal sex, maternal physical activity and season. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  8. Lung-derived growth factors: possible paracrine effectors of fetal lung development

    International Nuclear Information System (INIS)

    Montes, A.M.

    1985-01-01

    A potential role for paracrine secretions in lung organogenesis has been hypothesized (Alescio and Piperno, 1957). These studies present direct support for the paracrine model by demonstrating the presence of locally produced mitogenic/maturational factors in fetal rat lung tissue. Conditioned serum free medium (CSFM) from nineteen-day fetal rat lung cultures was shown to contain several bioactive peptides as detected by 3 H-Thymidine incorporation into chick embryo and rat lung fibroblasts, as well as 14 C-choline incorporation into surfactant in mixed cell cultures. Using ion-exchange chromatography and Sephadex gel filtration, a partially purified mitogen, 11-III, was obtained. The partially purified 11-III stimulates mitosis in chick embryo fibroblasts and post-natal rat lung fibroblasts. Multiplication in fetal rat lung fibroblasts cultures is stimulated only when these are pre-incubated with a competence factor or unprocessed CSFM. This suggests the existence of an endogenously produced competence factor important in the regulation of fetal lung growth. Preparation 11-III does not possess surfactant stimulating activity as assessed by 3 H-choline incorporation into lipids in predominantly type-II cell cultures. These data demonstrate the presence of a maturational/mitogenic factor, influencing type-II mixed cell cultures. In addition, 11-III had been shown to play an autocrine role stimulating the proliferation of fetal lung fibroblasts. Finally, these data suggest the existence of a local produced competence factor

  9. Fetal growth retardation and lack of hypotaurine in ezrin knockout mice.

    Directory of Open Access Journals (Sweden)

    Tomohiro Nishimura

    Full Text Available Ezrin is a membrane-associated cytoplasmic protein that serves to link cell-membrane proteins with the actin-based cytoskeleton, and also plays a role in regulation of the functional activities of some transmembrane proteins. It is expressed in placental trophoblasts. We hypothesized that placental ezrin is involved in the supply of nutrients from mother to fetus, thereby influencing fetal growth. The aim of this study was firstly to clarify the effect of ezrin on fetal growth and secondly to determine whether knockout of ezrin is associated with decreased concentrations of serum and placental nutrients. Ezrin knockout mice (Ez(-/- were confirmed to exhibit fetal growth retardation. Metabolome analysis of fetal serum and placental extract of ezrin knockout mice by means of capillary electrophoresis-time-of-flight mass spectrometry revealed a markedly decreased concentration of hypotaurine, a precursor of taurine. However, placental levels of cysteine and cysteine sulfinic acid (precursors of hypotaurine and taurine were not affected. Lack of hypotaurine in Ez(-/- mice was confirmed by liquid chromatography with tandem mass spectrometry. Administration of hypotaurine to heterogenous dams significantly decreased the placenta-to-maternal plasma ratio of hypotaurine in wild-type fetuses but only slightly decreased it in ezrin knockout fetuses, indicating that the uptake of hypotaurine from mother to placenta is saturable and that disruption of ezrin impairs the uptake of hypotaurine by placental trophoblasts. These results indicate that ezrin is required for uptake of hypotaurine from maternal serum by placental trophoblasts, and plays an important role in fetal growth.

  10. Femur-sparing pattern of abnormal fetal growth in pregnant women from New York City after maternal Zika virus infection.

    Science.gov (United States)

    Walker, Christie L; Merriam, Audrey A; Ohuma, Eric O; Dighe, Manjiri K; Gale, Michael; Rajagopal, Lakshmi; Papageorghiou, Aris T; Gyamfi-Bannerman, Cynthia; Adams Waldorf, Kristina M

    2018-05-05

    Zika virus is a mosquito-transmitted flavivirus, which can induce fetal brain injury and growth restriction following maternal infection during pregnancy. Prenatal diagnosis of Zika virus-associated fetal injury in the absence of microcephaly is challenging due to an incomplete understanding of how maternal Zika virus infection affects fetal growth and the use of different sonographic reference standards around the world. We hypothesized that skeletal growth is unaffected by Zika virus infection and that the femur length can represent an internal standard to detect growth deceleration of the fetal head and/or abdomen by ultrasound. We sought to determine if maternal Zika virus infection is associated with a femur-sparing pattern of intrauterine growth restriction through analysis of fetal biometric measures and/or body ratios using the 2014 International Fetal and Newborn Growth Consortium for the 21st Century Project and World Health Organization Fetal Growth Chart sonographic references. Pregnant women diagnosed with a possible recent Zika virus infection at Columbia University Medical Center after traveling to an endemic area were retrospectively identified and included if a fetal ultrasound was performed. Data were collected regarding Zika virus testing, fetal biometry, pregnancy, and neonatal outcomes. The 2014 International Fetal and Newborn Growth Consortium for the 21st Century Project and World Health Organization Fetal Growth Chart sonographic standards were applied to obtain Z-scores and/or percentiles for fetal head circumference, abdominal circumference, and femur length specific for each gestational week. A novel 2014 International Fetal and Newborn Growth Consortium for the 21st Century Project standard was also developed to generate Z-scores for fetal body ratios with respect to femur length (head circumference:femur length, abdominal circumference:femur length). Data were then grouped within clinically relevant gestational age strata (34 weeks) to

  11. Human Platelet Lysate as a Replacement for Fetal Bovine Serum in Limbal Stem Cell Therapy.

    Science.gov (United States)

    Suri, Kunal; Gong, Hwee K; Yuan, Ching; Kaufman, Stephen C

    2016-10-01

    To evaluate the use of human platelet lysate (HPL) as an alternative supplement for limbal explant culture. Culture media were prepared using either 10% pooled HPL (PHPL), single donor HPL, or fetal bovine serum (FBS). Limbal tissues, obtained from the Minnesota Lions Eye Bank, were cultured in each medium on plastic plates or on denuded amniotic membrane (AM). Immunofluorescence staining was performed for ABCG2, tumor protein p63α, and cytokeratin 3 (K3). Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to evaluate the expression of ABCG2 and p63. Limbal explants grown in each medium were labeled with bromodeoxyuridine (BrdU) to assess the proliferative capacity in each medium. Concentration of growth factors including epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), and platelet derived growth factor (PDGF) in HPL and PHPL was compared to that in human serum (HS). Immunofluorescence staining on AM showed prominent expression of ABCG2, p63α but sparse expression of K3 in HPL and PHPL supplemented medium. Real time-PCR showed 1.7 fold higher expression of ABCG2 in PHPL supplemented medium (p = 0.03), and similar expression of p63 in HPL and PHPL supplemented medium compared to FBS medium. The proliferation assay showed that LSCs retained their proliferative potential in HPL supplemented medium. Higher concentration of growth factors were found in HPL, compared to HS. Human platelet lysate has higher concentration of grown factors and is effective in maintaining growth and stem cell phenotype of corneal limbal explant cultures.

  12. Human autologous serum as a substitute for fetal bovine serum in human Schwann cell culture.

    Directory of Open Access Journals (Sweden)

    Parisa Goodarzi

    2014-04-01

    Full Text Available Nowadays, cell -based and tissue engineered products have opened new horizons in treatment of incurable nervous system disorders. The number of studies on the role of Schwann cells (SC in treating nervous disorders is higher than other cell types. Different protocols have been suggested for isolation and expansion of SC which most of them have used multiple growth factors, mitogens and fetal bovine sera (FBS in culture medium. Because of potential hazards of animal-derived reagents, this study was designed to evaluate the effect of replacing FBS with human autologous serum (HAS on SC's yield and culture parameters. Samples from 10 peripheral nerve biopsies were retrieved and processed under aseptic condition. The isolated cells cultured in FBS (1st group or autologous serum (2nd group. After primary culture the cells were seeded at 10000 cell/cm2 in a 12 wells cell culture plate for each group. At 100% confluency, the cell culture parameters (count, viability, purity and culture duration of 2 groups were compared using paired t-test. The average donors' age was 35.80 (SD=13.35 and except for 1 sample the others cultured successfully. In first group, the averages of cell purity, viability and culture duration were 97% (SD=1.32, 97/33% (SD=1.22 and 11.77 (SD=2.58 days respectively. This parameters were 97.33% (SD=1.00, 97.55% (SD=1.33 and 10.33 days (SD=1.65 in second group. The difference of cell count, purity and viability were not significant between 2 groups (P>0.05. The cells of second group reached to 100% confluency in shorter period of time (P=0.03. The results of this study showed that autologous serum can be a good substitute for FBS in human SC culture. This can reduce the costs and improve the safety of cell product for clinical application.

  13. IL-27 induces a pro-inflammatory response in human fetal membranes mediating preterm birth.

    Science.gov (United States)

    Yin, Nanlin; Wang, Hanbing; Zhang, Hua; Ge, Huisheng; Tan, Bing; Yuan, Yu; Luo, Xiaofang; Olson, David M; Baker, Philip N; Qi, Hongbo

    2017-09-01

    Inflammation at the maternal-fetal interface has been shown to be involved in the pathogenesis of preterm birth. Interleukin 27 (IL-27), a heterodimeric cytokine, is known to mediate an inflammatory response in some pregnancy complications. In this study, we aimed to determine whether IL-27 could induce an inflammatory reaction at the maternal-fetal interface that would mediate the onset of preterm birth. We found elevated expression of IL-27 in human peripheral serum and elevated expression of its specific receptor (wsx-1) on fetal membranes in cases of preterm birth. Moreover, the release of inflammatory markers (CXCL10, IFN-γ, MCP-1, IL-6, IL-1β and TNF-α), especially CXCL10, was markedly augmented upon stimulation of IL-27 in the fetal membranes. Additionally, IL-27 and IFN-γ cooperated to amplify the expression of CXCL10 in the fetal membranes. Moreover, the production of CXCL10 was increased in IL-27-treated fetal membrane through JNK, PI3K or Erk signaling pathways. Finally, MMP2 and MMP9 were activated by IL-27 in human fetal membranes, which may be related to the onset of preterm premature rupture of membranes (pPROM). In conclusion, for the first time, we reported that the aberrant expression of IL-27 could mediate an excessive inflammatory response in fetal membranes through the JNK, PI3K or Erk signaling pathways, which contributes to preterm birth. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Fetal growth and risk of stillbirth: a population-based case-control study.

    Science.gov (United States)

    Bukowski, Radek; Hansen, Nellie I; Willinger, Marian; Reddy, Uma M; Parker, Corette B; Pinar, Halit; Silver, Robert M; Dudley, Donald J; Stoll, Barbara J; Saade, George R; Koch, Matthew A; Rowland Hogue, Carol J; Varner, Michael W; Conway, Deborah L; Coustan, Donald; Goldenberg, Robert L

    2014-04-01

    Stillbirth is strongly related to impaired fetal growth. However, the relationship between fetal growth and stillbirth is difficult to determine because of uncertainty in the timing of death and confounding characteristics affecting normal fetal growth. We conducted a population-based case-control study of all stillbirths and a representative sample of live births in 59 hospitals in five geographic areas in the US. Fetal growth abnormalities were categorized as small for gestational age (SGA) (90th percentile) at death (stillbirth) or delivery (live birth) using population, ultrasound, and individualized norms. Gestational age at death was determined using an algorithm that considered the time-of-death interval, postmortem examination, and reliability of the gestational age estimate. Data were weighted to account for the sampling design and differential participation rates in various subgroups. Among 527 singleton stillbirths and 1,821 singleton live births studied, stillbirth was associated with SGA based on population, ultrasound, and individualized norms (odds ratio [OR] [95% CI]: 3.0 [2.2 to 4.0]; 4.7 [3.7 to 5.9]; 4.6 [3.6 to 5.9], respectively). LGA was also associated with increased risk of stillbirth using ultrasound and individualized norms (OR [95% CI]: 3.5 [2.4 to 5.0]; 2.3 [1.7 to 3.1], respectively), but not population norms (OR [95% CI]: 0.6 [0.4 to 1.0]). The associations were stronger with more severe SGA and LGA (95th percentile). Analyses adjusted for stillbirth risk factors, subset analyses excluding potential confounders, and analyses in preterm and term pregnancies showed similar patterns of association. In this study 70% of cases and 63% of controls agreed to participate. Analysis weights accounted for differences between consenting and non-consenting women. Some of the characteristics used for individualized fetal growth estimates were missing and were replaced with reference values. However, a sensitivity analysis using individualized norms

  15. Proteolytic processing of anti-Müllerian hormone differs between human fetal testes and adult ovaries

    DEFF Research Database (Denmark)

    Mamsen, L S; Petersen, T S; Jeppesen, J V

    2015-01-01

    and specificity of a panel of five novel high-affinity AMH monoclonal antibodies. Two recognize the mature C-terminal form of AMH, whereas three recognize the active pro-mature form of AMH in human tissue. The antibodies were tested on fetal male testicular and mesonephric tissue aged 8-19 weeks post conception...... (pc), fetal male serum aged 16-26 weeks pc and human immature GCs by immunofluorescence, immunohistochemistry, ELISA and western blotting. The active pro-mature forms of AMH were expressed in both Sertoli cells from human fetal testis and human immature GCs. In contrast, the mature C-terminal form...... of AMH was hardly detected in Sertoli cells, but was readily detected in GCs. This particular form was also located to the nucleus in GCs, whereas the other investigated AMH forms remained in the cytoplasm. Interestingly, the distribution of the AMH forms in the fetal serum of boys showed...

  16. Evaluation of human platelet lysate versus fetal bovine serum for culture of mesenchymal stromal cells.

    Science.gov (United States)

    Hemeda, Hatim; Giebel, Bernd; Wagner, Wolfgang

    2014-02-01

    Culture media for therapeutic cell preparations-such as mesenchymal stromal cells (MSCs)-usually comprise serum additives. Traditionally, fetal bovine serum is supplemented in basic research and in most clinical trials. Within the past years, many laboratories adapted their culture conditions to human platelet lysate (hPL), which further stimulates proliferation and expansion of MSCs. Particularly with regard to clinical application, human alternatives for fetal bovine serum are clearly to be preferred. hPL is generated from human platelet units by disruption of the platelet membrane, which is commonly performed by repeated freeze and thaw cycles. Such culture supplements are notoriously ill-defined, and many parameters contribute to batch-to-batch variation in hPL such as different amounts of plasma, a broad range of growth factors and donor-specific effects. The plasma components of hPL necessitate addition of anticoagulants such as heparins to prevent gelatinization of hPL medium, and their concentration must be standardized. Labels for description of hPL-such as "xenogen-free," "animal-free" and "serum free"-are not used consistently in the literature and may be misleading if not critically assessed. Further analysis of the precise composition of relevant growth factors, attachment factors, microRNAs and exosomes will pave the way for optimized and defined culture conditions. The use of hPL has several advantages and disadvantages: they must be taken into account because the choice of cell culture additive has major impact on cell preparations. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  17. Fetal hyperglycemia changes human preadipocyte function in adult life

    DEFF Research Database (Denmark)

    Hansen, Ninna Schiøler; Strasko, Klaudia Stanislawa; Hjort, Line

    2017-01-01

    Context: Offspring of women with gestational diabetes (O-GDM) or type 1 diabetes mellitus (O-T1DM) have been exposed to hyperglycemia in utero and have an increased risk of developing metabolic disease in adulthood. Design: In total, we recruited 206 adult offspring comprising the two fetal...... acid supply. Conclusions: Taken together, these findings show that intrinsic epigenetic and functional changes exist in preadipocyte cultures from individuals exposed to fetal hyperglycemia who are at increased risk of developing metabolic disease....

  18. 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.

  19. Overexpression of transforming growth factor-β1 in fetal monkey lung results in prenatal pulmonary fibrosis

    Science.gov (United States)

    Tarantal, A.F.; Chen, H.; Shi, T.T.; Lu, C-H.; Fang, A.B.; Buckley, S.; Kolb, M.; Gauldie, J.; Warburton, D.; Shi, W.

    2011-01-01

    Altered transforming growth factor (TGF)-β expression levels have been linked to a variety of human respiratory diseases, including bronchopulmonary dysplasia and pulmonary fibrosis. However, a causative role for aberrant TGF-β in neonatal lung diseases has not been defined in primates. Exogenous and transient TGF-β1 overexpression in fetal monkey lung was achieved by transabdominal ultrasound-guided fetal intrapulmonary injection of adenoviral vector expressing TGF-β1 at the second or third trimester of pregnancy. The lungs were then harvested near term, and fixed for histology and immunohistochemistry. Lung hypoplasia was observed where TGF-β1 was overexpressed during the second trimester. The most clearly marked phenotype consisted of severe pulmonary and pleural fibrosis, which was independent of the gestational time point when TGF-β1 was overexpressed. Increased cell proliferation, particularly in α-smooth muscle actin-positive myofibroblasts, was detected within the fibrotic foci. But epithelium to mesenchyme transdifferentiation was not detected. Massive collagen fibres were deposited on the inner and outer sides of the pleural membrane, with an intact elastin layer in the middle. This induced fibrotic pathology persisted even after adenoviral-mediated TGF-β1 overexpression was no longer evident. Therefore, overexpression of TGF-β1 within developing fetal monkey lung results in severe and progressive fibrosis in lung parenchyma and pleural membrane, in addition to pulmonary hypoplasia. PMID:20351039

  20. Variation in ovarian follicle density during human fetal development.

    Science.gov (United States)

    Geber, Selmo; Megale, Rodrigo; Vale, Fabiene; Lanna, Ana Maria Arruda; Cabral, Antônio Carlos Vieira

    2012-09-01

    To obtain a precise estimate of ovarian follicle density and variation in the number of follicles at several gestational ages during human fetal development. Twelve necropsied ovaries from 9 fetuses (gestational age: 24 to 36 weeks) and 3 neonates (who died within the first hours of life) were studied. Ovaries were fixed with 4 % formaldehyde and embedded in paraffin. Serial, 7 mm thick sections of the ovaries were cut and evaluated at every 50 cuts. Follicles were counted in 10 regions (each measuring 625 μm(2)) of the ovarian cortex and the number of follicles per mm³ was calculated. The number of follicles per 0.25 mm² ranged from 10.9 (± 4.8) in a neonate to 34.7 (± 10.6) also in a neonate. Among fetuses, follicle density was lowest at 36 weeks of gestation (11.1 ± 6.2) and highest at 26 weeks (32 ± 8.9). The total number of follicles ranged from 500,000 at the age of 22 weeks to > 1,000,000 at the age of 39 weeks. Our results show a peak in the number of follicles during intrauterine life at approximately 26 weeks, followed by a rapid reduction in this number before birth, providing a step forward towards the understanding of primordial follicular assembly in humans and, ultimately, the identification of the determinants of reproductive capacity.

  1. The relationship between umbilical and maternal blood leptin and it's effect in fetal growth

    International Nuclear Information System (INIS)

    Chen Linqi; Guo Sheng; Yu Xin; Feng Xing

    2005-01-01

    Objective: To study the correlation of leptin between maternal serum and cord blood and to know relationship between leptin and fetal growth, and the origin of leptin. Methods: The concentration of leptin in 55 cases of maternal serum and cord arterial and venous blood were measured by ELISA assay. According to the neonatal weight and gestational age, three groups were divided into small gestational age (SGA), appropriate gestational age (AGA) and large gestational age (LGA). The nutrition status of neonatal was evaluated by index of Pondernal. The comparision was made in these groups. Results: The concentration of leptin in the cord artery, venous and maternal serum among 55 cases was 16.58 ± 8.13 ng/ml, 12.05 ± 9.87 ng/ml, 13.24 ± 10.58 ng/ml respectively; The concentration of maternal serum leptin was higher than that of cord artery. The concentration of maternal serum leptin was higher than that of venous serum leptin slightly. There was significant difference between cord artery and venous in different gestational age groups. Serum leptin levels of cord artery and venous were well correlated with the one of the weight and gestational age of neonatal. Maternal serum leptin level was not correlated with birth weight, placental weight and gestational age. Conclusions: The leptin from placenta is concerned with the adjustment of fetal growth. Cord leptin can reflect the status of fetal growth. Cord venous leptin indicate that the leptin be from placenta. Cord artery leptin demonstrates a part of placenta leptin, which acts on the fetus and then induces the fetal fat tissue to produce leptin. The maternal leptin does not adjust fetal weight directly. It only adjusts fat content itself and energy metabolism. (authors)

  2. Gender mix in twins and fetal growth, length of gestation and adult cancer risk.

    Science.gov (United States)

    Luke, Barbara; Hediger, Mary; Min, Sung-Joon; Brown, Morton B; Misiunas, Ruta B; Gonzalez-Quintero, Victor Hugo; Nugent, Clark; Witter, Frank R; Newman, Roger B; Hankins, Gary D V; Grainger, David A; Macones, George A

    2005-01-01

    This study evaluated the effect of gender mix (the gender combinations of twin pairs) on fetal growth and length of gestation, and reviewed the literature on the long-term effects of this altered fetal milieu on cancer risk. In singletons, it is well established that females weigh less than males at all gestations, averaging 125-135 g less at full term. This gender difference is generally believed to be the result of the effect of androgens on fetal growth. The gender difference in fetal growth is greater before the third trimester and less towards term, with males growing not only more, but also earlier than females. Plurality is a known risk factor for reduced fetal growth and birthweight. Compared with singletons, the mean birthweight percentiles of twins fall substantially (by 10% or more) below the singleton 10th percentile by 28 weeks, below the singleton 50th percentile by 30 weeks, and below the singleton 90th percentile by 34 weeks. In unlike-gender twin pairs, it has been reported that the female prolongs gestation for her brother, resulting in a higher birthweight for the male twin than that of like-gender male twins. Other researchers have demonstrated that females in unlike-gender pairs had higher birthweights than females in like-gender pairs. Analyses from our consortium on 2491 twin pregnancies with known chorionicity showed longer gestations and faster rates of fetal growth in both males and females in unlike-gender pairs compared with like-gender male or female pairs, although these differences were not statistically significant. The post-natal effects for females growing in an androgenic-anabolic environment include increased sensation-seeking behaviour and aggression, lowered visual acuity, more masculine attitudes and masculinising effects of the auditory system and craniofacial growth. In contrast, there is no evidence to suggest that there might be a similar feminising effect on males from unlike-gender pairs. This hormonal exposure in utero

  3. 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE) : A randomised trial

    NARCIS (Netherlands)

    Lees, Christoph C.; Marlow, Neil; Van Wassenaer-Leemhuis, Aleid; Arabin, Birgit; Bilardo, Caterina M.; Brezinka, Christoph; Calvert, Sandra; Derks, Jan B.; Diemert, Anke; Duvekot, Johannes J.; Ferrazzi, Enrico; Frusca, Tiziana; Ganzevoort, Wessel; Hecher, Kurt; Martinelli, Pasquale; Ostermayer, Eva; Papageorghiou, Aris T.; Schlembach, Dietmar; Schneider, K. T M; Thilaganathan, Baskaran; Todros, Tullia; Valcamonico, Adriana; Visser, Gerard H A; Wolf, Hans; Aktas, Ayse; Borgione, Silvia; Chaoui, Rabih; Cornette, Jerome M J; Diehl, Thilo; Van Eyck, Jim; Fratelli, Nicola; Van Haastert, Inge Lot; Lobmaier, Silvia; Lopriore, Enrico; Missfelder-Lobos, Hannah; Mansi, Giuseppina; Martelli, Paola; Maso, Gianpaolo; Maurer-Fellbaum, Ute; Van Charante, Nico Mensing; De Tollenaer, Susanne Mulder; Napolitano, Raffaele; Oberto, Manuela; Oepkes, Dick; Ogge, Giovanna; Van Der Post, Joris; Prefumo, Federico; Preston, Lucy; Raimondi, Francesco; Reiss, Irwin K M; Scheepers, H. C J; Schuit, Ewoud; Skabar, Aldo; Spaanderman, Marc; Weisglas-Kuperus, Nynke; Zimmermann, Andrea; Moore, Tamanna; Johnson, Samantha; Rigano, Serena

    2015-01-01

    Background: No consensus exists for the best way to monitor and when to trigger delivery in mothers of babies with fetal growth restriction. We aimed to assess whether changes in the fetal ductus venosus Doppler waveform (DV) could be used as indications for delivery instead of cardiotocography

  4. 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE) : a randomised trial

    NARCIS (Netherlands)

    Lees, Christoph C.; Marlow, Neil; van Wassenaer-Leemhuis, Aleid; Arabin, Birgit; Bilardo, Caterina M.; Brezinka, Christoph; Calvert, Sandra; Derks, Jan B.; Diemert, Anke; Duvekot, Johannes J.; Ferrazzi, Enrico; Frusca, Tiziana; Ganzevoort, Wessel; Hecher, Kurt; Martinelli, Pasquale; Ostermayer, Eva; Papageorghiou, Aris T.; Schlembach, Dietmar; Schneider, K. T. M.; Thilaganathan, Baskaran; Todros, Tullia; Valcamonico, Adriana; Visser, G. H. A.; Wolf, Hans

    2015-01-01

    Background No consensus exists for the best way to monitor and when to trigger delivery in mothers of babies with fetal growth restriction. We aimed to assess whether changes in the fetal ductus venosus Doppler waveform (DV) could be used as indications for delivery instead of cardiotocography

  5. Maternal L-glutamine supplementation prevents prenatal alcohol exposure-induced fetal growth restriction in an ovine model.

    Science.gov (United States)

    Sawant, Onkar B; Wu, Guoyao; Washburn, Shannon E

    2015-06-01

    Prenatal alcohol exposure is known to cause fetal growth restriction and disturbances in amino acid bioavailability. Alterations in these parameters can persist into adulthood and low birth weight can lead to altered fetal programming. Glutamine has been associated with the synthesis of other amino acids, an increase in protein synthesis and it is used clinically as a nutrient supplement for low birth weight infants. The aim of this study was to explore the effect of repeated maternal alcohol exposure and L-glutamine supplementation on fetal growth and amino acid bioavailability during the third trimester-equivalent period in an ovine model. Pregnant sheep were randomly assigned to four groups, saline control, alcohol (1.75-2.5 g/kg), glutamine (100 mg/kg, three times daily) or alcohol + glutamine. In this study, a weekend binge drinking model was followed where treatment was done 3 days per week in succession from gestational day (GD) 109-132 (normal term ~147). Maternal alcohol exposure significantly reduced fetal body weight, height, length, thoracic girth and brain weight, and resulted in decreased amino acid bioavailability in fetal plasma and placental fluids. Maternal glutamine supplementation successfully mitigated alcohol-induced fetal growth restriction and improved the bioavailability of glutamine and glutamine-related amino acids such as glycine, arginine, and asparagine in the fetal compartment. All together, these findings show that L-glutamine supplementation enhances amino acid availability in the fetus and prevents alcohol-induced fetal growth restriction.

  6. The effect of superovulation prior to mating on fetal growth in Iambs from Javanese thin-tail ewes

    Directory of Open Access Journals (Sweden)

    W Manalu

    1999-12-01

    Full Text Available Twenty-nine fetuses (11 fetuses from 9 non-superovulated ewes and 18 fetuses from 8 superovulated ewes were used to study the effect of superovulation of ewes prior to mating on fetal weight, fetal length, the length of the body and limbs, chest circumference, weights of the body, head, neck, limb, and viscera. Superovulated ewes, though with a higher litter size, had a greater fetal growth as was indicated by the greater fetal weight and length, the length and weight of the body and limb on day 49 of pregnancy. On day 105 of pregnancy, superovulated ewes with multiple fetuses (≥3 had similar fetal growth than nonsuperovulated ewes with single and twin fetuses. However, superovulated ewes with a single fetus had greater fetal growth as was shown by the greater fetal weight and length, the length of the body and limbs, chest circumference, and weight of the body, limb, and viscera when compared to those non-superovulated ewes with a single or twin fetuses. The results of the experiment suggested that superovulation of ewes prior to mating could be used to improve fetal prenatal growth during pregnancy

  7. Predictors of Cord Blood Leptin Level in Pregnancies Complicated With Preeclampsia, Fetal Growth Restriction and in Normal Pregnancies

    Directory of Open Access Journals (Sweden)

    Nilgün Öztürk Doğan

    2007-04-01

    CONCLUSION: Regulation of cord blood leptin level is a complex process involving fetal gender and fetal anthropometric variables as well as cord blood cortisol, intrauterine growth and hypoxia. Leptin level is decreased in cases of placental insufficiency like IUGR but not in uncomplicated preeclampsia alone.

  8. EG-VEGF controls placental growth and survival in normal and pathological pregnancies: case of fetal growth restriction (FGR).

    Science.gov (United States)

    Brouillet, S; Murthi, P; Hoffmann, P; Salomon, A; Sergent, F; De Mazancourt, P; Dakouane-Giudicelli, M; Dieudonné, M N; Rozenberg, P; Vaiman, D; Barbaux, S; Benharouga, M; Feige, J-J; Alfaidy, N

    2013-02-01

    Identifiable causes of fetal growth restriction (FGR) account for 30 % of cases, but the remainders are idiopathic and are frequently associated with placental dysfunction. We have shown that the angiogenic factor endocrine gland-derived VEGF (EG-VEGF) and its receptors, prokineticin receptor 1 (PROKR1) and 2, (1) are abundantly expressed in human placenta, (2) are up-regulated by hypoxia, (3) control trophoblast invasion, and that EG-VEGF circulating levels are the highest during the first trimester of pregnancy, the period of important placental growth. These findings suggest that EG-VEGF/PROKR1 and 2 might be involved in normal and FGR placental development. To test this hypothesis, we used placental explants, primary trophoblast cultures, and placental and serum samples collected from FGR and age-matched control women. Our results show that (1) EG-VEGF increases trophoblast proliferation ([(3)H]-thymidine incorporation and Ki67-staining) via the homeobox-gene, HLX (2) the proliferative effect involves PROKR1 but not PROKR2, (3) EG-VEGF does not affect syncytium formation (measurement of syncytin 1 and 2 and β hCG production) (4) EG-VEGF increases the vascularization of the placental villi and insures their survival, (5) EG-VEGF, PROKR1, and PROKR2 mRNA and protein levels are significantly elevated in FGR placentas, and (6) EG-VEGF circulating levels are significantly higher in FGR patients. Altogether, our results identify EG-VEGF as a new placental growth factor acting during the first trimester of pregnancy, established its mechanism of action, and provide evidence for its deregulation in FGR. We propose that EG-VEGF/PROKR1 and 2 increases occur in FGR as a compensatory mechanism to insure proper pregnancy progress.

  9. The effect of superovulation prior to mating on fetal growth in Iambs from Javanese thin-tail ewes

    OpenAIRE

    W Manalu

    1999-01-01

    Twenty-nine fetuses (11 fetuses from 9 non-superovulated ewes and 18 fetuses from 8 superovulated ewes) were used to study the effect of superovulation of ewes prior to mating on fetal weight, fetal length, the length of the body and limbs, chest circumference, weights of the body, head, neck, limb, and viscera. Superovulated ewes, though with a higher litter size, had a greater fetal growth as was indicated by the greater fetal weight and length, the length and weight of the body and limb on...

  10. A prospective study of fetal head growth, autistic traits and autism spectrum disorder

    Science.gov (United States)

    Blanken, Laura M. E.; Dass, Alena; Alvares, Gail; van der Ende, Jan; Schoemaker, Nikita K.; El Marroun, Hanan; Hickey, Martha; Pennell, Craig; White, Scott; Maybery, Murray T.; Dissanayake, Cheryl; Jaddoe, Vincent W. V.; Verhulst, Frank C.; Tiemeier, Henning; McIntosh, Will; Whitehouse, Andrew

    2018-01-01

    Altered trajectories of brain growth are often reported in Autism Spectrum Disorder (ASD), particularly during the first year of life. However, less is known about prenatal head growth trajectories, and no study has examined the relation with postnatal autistic symptom severity. The current study prospectively examined the association between fetal head growth and the spectrum of autistic symptom severity in two large population‐based cohorts, including a sample of individuals with clinically diagnosed ASD. This study included 3,820 children from two longitudinal prenatal cohorts in The Netherlands and Australia, comprising 60 individuals with a confirmed diagnosis of ASD. Latent growth curve models were used to examine the relationship between fetal head circumference measured at three different time points and autistic traits measured in postnatal life using either the Social Responsiveness Scale or the Autism‐Spectrum Quotient. While lower initial prenatal HC was weakly associated with increasing autistic traits in the Dutch cohort, this relationship was not observed in the Australian cohort, nor when the two cohorts were analysed together. No differences in prenatal head growth were found between individuals with ASD and controls. This large population‐based study identified no consistent association across two cohorts between prenatal head growth and postnatal autistic traits. Our mixed findings suggest that further research in this area is needed. Autism Res 2018, 11: 602–612. © 2018 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. Lay Summary It is not known whether different patterns of postnatal brain growth in Autism Spectrum Disorder (ASD) also occurs prenatally. We examined fetal head growth and autistic symptoms in two large groups from The Netherlands and Australia. Lower initial prenatal head circumference was associated with autistic traits in the Dutch, but not the Australian

  11. Fetal Growth Restriction at the Limits of Viability

    NARCIS (Netherlands)

    Visser, G. H. A.; Bilardo, Caterina M.; Lees, Christopher

    2014-01-01

    The outcome of early small-for-gestational age and/or intrauterine growth-restricted fetuses is reviewed. In these fetuses the outcome appears to be considerably poorer than that of appropriately grown fetuses and this seems mainly to be caused by intrauterine malnutrition rather than by hypoxemia.

  12. Altered decorin leads to disrupted endothelial cell function: a possible mechanism in the pathogenesis of fetal growth restriction?

    Science.gov (United States)

    Chui, A; Murthi, P; Gunatillake, T; Brennecke, S P; Ignjatovic, V; Monagle, P T; Whitelock, J M; Said, J M

    2014-08-01

    Fetal growth restriction (FGR) is a key cause of adverse pregnancy outcome where maternal and fetal factors are identified as contributing to this condition. Idiopathic FGR is associated with altered vascular endothelial cell functions. Decorin (DCN) has important roles in the regulation of endothelial cell functions in vascular environments. DCN expression is reduced in FGR. The objectives were to determine the functional consequences of reduced DCN in a human microvascular endothelial cell line model (HMVEC), and to determine downstream targets of DCN and their expression in primary placental microvascular endothelial cells (PLECs) from control and FGR-affected placentae. Short-interference RNA was used to reduce DCN expression in HMVECs and the effect on proliferation, angiogenesis and thrombin generation was determined. A Growth Factor PCR Array was used to identify downstream targets of DCN. The expression of target genes in control and FGR PLECs was performed. DCN reduction decreased proliferation and angiogenesis but increased thrombin generation with no effect on apoptosis. The array identified three targets of DCN: FGF17, IL18 and MSTN. Validation of target genes confirmed decreased expression of VEGFA, MMP9, EGFR1, IGFR1 and PLGF in HMVECs and PLECs from control and FGR pregnancies. Reduction of DCN in vascular endothelial cells leads to disrupted cell functions. The targets of DCN include genes that play important roles in angiogenesis and cellular growth. Therefore, differential expression of these may contribute to the pathogenesis of FGR and disease states in other microvascular circulations. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Vitamin D: Effects on human reproduction, pregnancy, and fetal well-being.

    Science.gov (United States)

    Heyden, E L; Wimalawansa, S J

    2018-06-01

    Pregnancy places exceptional demands on vitamin D and calcium availability; thus, their deficiencies during pregnancy threaten the woman and her fetus. Globally, vitamin D and other micronutrient deficiencies are common during pregnancy, especially in developing countries where pregnant women have less access to nutritional supplements. Vitamin D deficiency has been reported to be as high as 40% among pregnant women. As a pregnancy progresses, the requirements for vitamin D increase and thus, can worsen preexisting hypovitaminosis D. Consequently, hypovitaminosis D is increasingly associated with a higher incidence of fetal miscarriage, preeclampsia, gestational diabetes, bacterial vaginosis, and impaired fetal and childhood growth and development. This review explores the recent advances in the understanding of vitamin D and the pivotal role it plays in human reproduction, with an emphasis on pregnancy and its outcomes. Given the seriousness of the issue, there is a pressing need for clinicians to become aware of the risks associated with not identifying and correcting vitamin D deficiency. Identifying and correcting vitamin D deficiency, including safe exposure to sunlight, is particularly relevant for those who seek assistance with fertility issues or prenatal counseling, and those in the beginning of their pregnancy. The data point to a significant protective effects of vitamin D during pregnancy when the 25(OH)D serum level exceeds 30 ng/mL before pregnancy and during the first trimester and, sufficient levels are maintained throughout the pregnancy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Prediction of fetal growth restriction using estimated fetal weight vs a combined screening model in the third trimester.

    Science.gov (United States)

    Miranda, J; Rodriguez-Lopez, M; Triunfo, S; Sairanen, M; Kouru, H; Parra-Saavedra, M; Crovetto, F; Figueras, F; Crispi, F; Gratacós, E

    2017-11-01

    To compare the performance of third-trimester screening, based on estimated fetal weight centile (EFWc) vs a combined model including maternal baseline characteristics, fetoplacental ultrasound and maternal biochemical markers, for the prediction of small-for-gestational-age (SGA) neonates and late-onset fetal growth restriction (FGR). This was a nested case-control study within a prospective cohort of 1590 singleton gestations undergoing third-trimester (32 + 0 to 36 + 6 weeks' gestation) evaluation. Maternal baseline characteristics, mean arterial pressure, fetoplacental ultrasound and circulating biochemical markers (placental growth factor (PlGF), lipocalin-2, unconjugated estriol and inhibin A) were assessed in all women who subsequently delivered a SGA neonate (n = 175), defined as birth weight < 10 th centile according to customized standards, and in a control group (n = 875). Among SGA cases, those with birth weight < 3 rd centile and/or abnormal uterine artery pulsatility index (UtA-PI) and/or abnormal cerebroplacental ratio (CPR) were classified as FGR. Logistic regression predictive models were developed for SGA and FGR, and their performance was compared with that obtained using EFWc alone. In SGA cases, EFWc, CPR Z-score and maternal serum concentrations of unconjugated estriol and PlGF were significantly lower, while mean UtA-PI Z-score and lipocalin-2 and inhibin A concentrations were significantly higher, compared with controls. Using EFWc alone, 52% (area under receiver-operating characteristics curve (AUC), 0.82 (95% CI, 0.77-0.85)) of SGA and 64% (AUC, 0.86 (95% CI, 0.81-0.91)) of FGR cases were predicted at a 10% false-positive rate. A combined screening model including a-priori risk (maternal characteristics), EFWc, UtA-PI, PlGF and estriol (with lipocalin-2 for SGA) achieved a detection rate of 61% (AUC, 0.86 (95% CI, 0.83-0.89)) for SGA cases and 77% (AUC, 0.92 (95% CI, 0.88-0.95)) for FGR. The combined model for the

  15. A Comparative Analysis of Prenatal Care and Fetal Growth in Eight South American Countries

    Science.gov (United States)

    Woodhouse, Cristina; Lopez Camelo, Jorge; Wehby, George L.

    2014-01-01

    There has been little work that comprehensively compared the relationship between prenatal care and infant health across multiple countries using similar data sources and analytical models. Such comparative analyses are useful for understanding the background of differences in infant health between populations. We evaluated the association between prenatal care visits and fetal growth measured by birth weight (BW) in grams or low birth weight (Prenatal care visits were significantly (at pprenatal care and fetal growth are population-specific and may not be generalizable to other populations. Furthermore, as one of the indicators for a country’s healthcare system for maternal and child health, prenatal care is a highly variable indicator between countries in South America. PMID:24625630

  16. Indicators of fetal growth and bipolar disorder: a Danish national register-based study

    DEFF Research Database (Denmark)

    Øgendahl, Bettina; Agerbo, Esben; Byrne, Majella

    2006-01-01

    contradictory. The aim of this study was to investigate whether the risk of bipolar disorder is associated with exposure to indicators of fetal growth.Method. A national population nested case-control study based on Danish longitudinal register databases was carried out. Conditional logistic regression was used......, controlling for potential confounding factors such as parental age at birth, socio-economic indicators and psychiatric history. We identified 196 cases, and each case was time-, age- and sex-matched with 25 normal population-based controls. All cases were between the ages of 12 and 26 years at the time......Background. Several studies have found an association between indicators of fetal growth and/or obstetric complications and schizophrenia but only a few studies have investigated the possible association between these factors and bipolar disorder. Furthermore, the results of these studies have been...

  17. Non-occupational exposure to paint fumes during pregnancy and fetal growth in a general population

    DEFF Research Database (Denmark)

    Sørensen, Mette; Andersen, Anne-Marie N; Raaschou-Nielsen, Ole

    2010-01-01

    in their residence during pregnancy. The mothers were also asked about smoking habits and alcohol consumption during pregnancy, pre-pregnancy weight, height, parity and occupation. Information on birth weight and gestational age was obtained from national registers. We found that 45% of the mothers had been exposed......Occupational exposure to organic solvents during pregnancy has been associated with reduced fetal growth. Though organic solvents in the form of paint fumes are also found in the home environment, no studies have investigated the effect of such exposure in a general population. We studied...... associations between residential exposure to paint fumes during pregnancy and fetal growth within the Danish National Birth Cohort which consecutively recruited pregnant women from 1996 to 2002 from all over Denmark. Around the 30th pregnancy week, 19,000 mothers were interviewed about use of paint...

  18. STRIDER (Sildenafil TheRapy in dismal prognosis early onset fetal growth restriction)

    DEFF Research Database (Denmark)

    Pels, A; Kenny, L C; Alfirevic, Z

    2017-01-01

    randomised placebo-controlled trials have been launched. Women with a singleton pregnancy between 18 and 30 weeks with severe fetal growth restriction of likely placental origin, and where the likelihood of perinatal death/severe morbidity is estimated to be significant are included. Participants......BACKGROUND: Severe, early-onset fetal growth restriction due to placental insufficiency is associated with a high risk of perinatal mortality and morbidity with long-lasting sequelae. Placental insufficiency is the result of abnormal formation and function of the placenta with inadequate...... Restriction (STRIDER) collaboration is to evaluate the effectiveness of sildenafil versus placebo in achieving healthy perinatal survival through the conduct of randomised clinical trials and systematic review including individual patient data meta-analysis. METHODS: Five national/bi-national multicentre...

  19. Malaria in pregnancy: ultrasound studies of fetal growth

    NARCIS (Netherlands)

    Rijken, M.J.

    2012-01-01

    Malaria has been a plague for human mankind. Each year roughly 125 million pregnancies are at risk for malaria infection. This thesis demonstrates the detrimental effects of malaria in pregnancy on the mother and the baby. To determine the effects of malaria in pregnancy on birth outcomes, accurate

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

    Science.gov (United States)

    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.

  1. Maternal Exposure to Bisphenol-A and Fetal Growth Restriction: A Case-Referent Study

    Science.gov (United States)

    Burstyn, Igor; Martin, Jonathan W.; Beesoon, Sanjay; Bamforth, Fiona; Li, Qiaozhi; Yasui, Yutaka; Cherry, Nicola M.

    2013-01-01

    We conducted a case-referent study of the effect of exposure to bisphenol-A on fetal growth in utero in full-term, live-born singletons in Alberta, Canada. Newborns bisphenol-A was estimated from maternal serum collected at 15–16 weeks of gestation. We pooled sera across subjects for exposure assessment, stratified on case-referent status and sex. Individual 1:1 matching was maintained in assembling 69 case and 69 referent pools created from 550 case-referent pairs. Matched pools had an equal number of aliquots from individual women. We used an analytical strategy conditioning on matched set and total pool-level values of covariates to estimate individual-level effects. Pools of cases and referents had identical geometric mean bisphenol-A concentrations (0.5 ng/mL) and similar geometric standard deviations (2.3–2.5). Mean difference in concentration between matched pools was 0 ng/mL, standard deviation: 1 ng/mL. Stratification by sex and control for confounding did not suggest bisphenol-A increased fetal growth restriction. Our analysis does not provide evidence to support the hypothesis that bisphenol-A contributes to fetal growth restriction in full-term singletons. PMID:24336026

  2. Maternal Exposure to Bisphenol-A and Fetal Growth Restriction: A Case-Referent Study

    Directory of Open Access Journals (Sweden)

    Igor Burstyn

    2013-12-01

    Full Text Available We conducted a case-referent study of the effect of exposure to bisphenol-A on fetal growth in utero in full-term, live-born singletons in Alberta, Canada. Newborns <10 percentile of expected weight for gestational age and sex were individually matched on sex, maternal smoking and maternal age to referents with weight appropriate to gestational age. Exposure of the fetus to bisphenol-A was estimated from maternal serum collected at 15–16 weeks of gestation. We pooled sera across subjects for exposure assessment, stratified on case-referent status and sex. Individual 1:1 matching was maintained in assembling 69 case and 69 referent pools created from 550 case-referent pairs. Matched pools had an equal number of aliquots from individual women. We used an analytical strategy conditioning on matched set and total pool-level values of covariates to estimate individual-level effects. Pools of cases and referents had identical geometric mean bisphenol-A concentrations (0.5 ng/mL and similar geometric standard deviations (2.3–2.5. Mean difference in concentration between matched pools was 0 ng/mL, standard deviation: 1 ng/mL. Stratification by sex and control for confounding did not suggest bisphenol-A increased fetal growth restriction. Our analysis does not provide evidence to support the hypothesis that bisphenol-A contributes to fetal growth restriction in full-term singletons.

  3. A Brief Account of the Discovery of the Fetal/Placental Unit for Estrogen Production in Equine and Human Pregnancies: Relation to Human Medicine.

    Science.gov (United States)

    Raeside, James I

    2017-09-01

    The role of steroids in human medicine is well recognized, but the major contributions made by the large domestic animals as a source of material in the discovery, isolation, and determination of the structure of the steroid hormones is less well appreciated. After a brief reminder of the early efforts to obtain a reliable source of steroids for clinical use, the narrative here is to outline one example where success was ultimately achieved for estrogen replacement therapy. Whereas knowledge of the high concentrations of estrogens in urine of pregnant women and mares dates from the late 1920s, it was not until the 1940s that the latter was shown to be a practical source. Initially, the placenta was held to be responsible, but the involvement of the fetus in each case was eventually established. The remarkable enlargement of the human fetal adrenal glands and the fetal gonads in the horse, with characteristic features of steroid secreting tissues, suggested their participation. Ultimately, it was 16-hydroxylation by the fetal liver that resulted in estriol being the major estrogen type, by far, in late human pregnancy. In the mare, the pattern of estrogen production reflected that of the growth and later regression of the fetal gonads. The characteristic production ring-B, unsaturated estrogens in the mare is derived from an alternative pathway involving retention of the additional double bond in the biosynthesis of equilin.

  4. Effects of exposure to radiation during the fetal period on behavior and growth in baby mice

    Energy Technology Data Exchange (ETDEWEB)

    Naruse, I; Kameyama, Y [Nagoya Univ. (Japan). Research Inst. of Environmental Medicine

    1979-03-01

    In order to study the effects of exposure to a small dose of radiation during the fetal period upon behavior and growth, 2 groups of 13-day-old fetal mice were irradiated. One group consisted of 18 fetal mice given 25 R and the other of 15 given 100 R. The control group consisted of 18 fetal mice 13 days old. After birth they were all placed in the center of an open area (50 x 50 x 25 cm) for 3 minutes so as to determine the number of squares traversed ad lib. (the number which their extremities traversed for 3 minutes) and the time day when they began walking and grooming. After they were observed for 3 minutes, the time at which reflex actions such as speedy righting and auditory startle were observed was confirmed. There were no differnces between the 25 R-irradiated group and the control group. In the 100 R-irradiated group, walking was observed earlier than in the control group, and the number of squares traversed increased.

  5. Effects of exposure to radiation during the fetal period on behavior and growth in baby mice

    International Nuclear Information System (INIS)

    Naruse, Ichiro; Kameyama, Yoshiro

    1979-01-01

    In order to study the effects of exposure to a small dose of radiation during the fetal period upon behavior and growth, 2 groups of 13-day-old fetal mice were irradiated. One group consisted of 18 fetal mice given 25 R and the other of 15 given 100 R. The control group consisted of 18 fetal mice 13 days old. After birth they were all placed in the center of an open area (50 x 50 x 25 cm) for 3 minutes so as to determine the number of squares traversed ad lib. (the number which their extremities traversed for 3 minutes) and the time day when they began walking and grooming. After they were observed for 3 minutes, the time at which reflex actions such as speedy righting and auditory startle were observed was confirmed. There were no differnces between the 25 R-irradiated group and the control group. In the 100 R-irradiated group, walking was observed earlier than in the control group, and the number of squares traversed increased. (Ichikawa, K.)

  6. Perinatal morbidity and mortality in early-onset fetal growth restriction : cohort outcomes of the trial of randomized umbilical and fetal flow in Europe (TRUFFLE)

    NARCIS (Netherlands)

    Lees, C.; Marlow, N.; Arabin, B.; Bilardo, C. M.; Brezinka, C.; Derks, J. B.; Duvekot, J.; Frusca, T.; Diemert, A.; Ferrazzi, E.; Ganzevoort, W.; Hecher, K.; Martinelli, P.; Ostermayer, E.; Papageorghiou, A. T.; Schlembach, D.; Schneider, K. T. M.; Thilaganathan, B.; Todros, T.; van Wassenaer-Leemhuis, A.; Valcamonico, A.; Visser, G. H. A.; Wolf, H.

    2013-01-01

    ObjectivesFew data exist for counseling and perinatal management of women after an antenatal diagnosis of early-onset fetal growth restriction. Yet, the consequences of preterm delivery and its attendant morbidity for both mother and baby are far reaching. The objective of this study was to describe

  7. Expression of stem cell markers in the human fetal kidney.

    Directory of Open Access Journals (Sweden)

    Sally Metsuyanim

    Full Text Available In the human fetal kidney (HFK self-renewing stem cells residing in the metanephric mesenchyme (MM/blastema are induced to form all cell types of the nephron till 34(th week of gestation. Definition of useful markers is crucial for the identification of HFK stem cells. Because wilms' tumor, a pediatric renal cancer, initiates from retention of renal stem cells, we hypothesized that surface antigens previously up-regulated in microarrays of both HFK and blastema-enriched stem-like wilms' tumor xenografts (NCAM, ACVRIIB, DLK1/PREF, GPR39, FZD7, FZD2, NTRK2 are likely to be relevant markers. Comprehensive profiling of these putative and of additional stem cell markers (CD34, CD133, c-Kit, CD90, CD105, CD24 in mid-gestation HFK was performed using immunostaining and FACS in conjunction with EpCAM, an epithelial surface marker that is absent from the MM and increases along nephron differentiation and hence can be separated into negative, dim or bright fractions. No marker was specifically localized to the MM. Nevertheless, FZD7 and NTRK2 were preferentially localized to the MM and emerging tubules (50% of HFK cells and predominantly co-express EpCAM(bright, indicating they are mostly markers of differentiation. Furthermore, localization of NCAM exclusively in the MM and in its nephron progenitor derivatives but also in stroma and the expression pattern of significantly elevated renal stem/progenitor genes Six2, Wt1, Cited1, and Sall1 in NCAM(+EpCAM(- and to a lesser extent in NCAM(+EpCAM(+ fractions confirmed regional identity of cells and assisted us in pinpointing the presence of subpopulations that are putative MM-derived progenitor cells (NCAM(+EpCAM(+FZD7(+, MM stem cells (NCAM(+EpCAM(-FZD7(+ or both (NCAM(+FZD7(+. These results and concepts provide a framework for developing cell selection strategies for human renal cell-based therapies.

  8. Influence of Echinacea purpurea intake during pregnancy on fetal growth and tissue angiogenic activity.

    Directory of Open Access Journals (Sweden)

    Ewa Sommer

    2008-04-01

    Full Text Available The process of angiogenesis and control of blood vessels sprouting are fundamental to human health, as they play key roles in many physiological and pathological conditions. Intake of different pharmaceuticals with antiangiogenic activity by pregnant women may lead to severe developmental disturbances as it was described in case of thalidomide. It may also cause immunomodulatory effects as it was shown for antibiotics, theobromine, caffeic acid or catechins on the pregnant mice model. At present, Echinacea purpurea-based phytoceuticals are among the most popular herbals in the marketplace. Many compounds of Echinacea extracts (polysaccharides, alkamides, polyphenols, glycoproteins exert immunomodulatory, anti-oxidative and anti-inflammatory activity. Echinacea is one of the most powerful and effective remedies against many kinds of bacterial and viral infections. In previous studies we shown significant inhibitory effect of the Echinacea purpurea based remedy on tumour angiogenic activity using cutaneous angiogenesis test, and an inhibitory effect on L-1 sarcoma growth was observed . The aim of the present study was to establish whether pharmaceuticals containing alcoholic extracts of Echinacea purpurea given to pregnant mice influence angiogenic activity and tissue VEGF and bFGF production of their fetuses. We showed that angiogenic activity of tissue homogenates was increased in Esberitox group and diminished in case of Immunal forte as compared to standard diet group. In case of Echinapur group we did not find significant differences in angiogenic activity. VEGF and bFGF concentration were lower in all groups compared to the control. In the case of Echinapur and Esberitox number of fetuses in one litter were slightly lower as compared to control group, but the difference is on the border of statistical significance. In conclusion, there is some possibility that pharmaceuticals containing Echinacea purpurea might influence fetal development in

  9. Fetal liver blood flow distribution: role in human developmental strategy to prioritize fat deposition versus brain development.

    Directory of Open Access Journals (Sweden)

    Keith M Godfrey

    Full Text Available Among primates, human neonates have the largest brains but also the highest proportion of body fat. If placental nutrient supply is limited, the fetus faces a dilemma: should resources be allocated to brain growth, or to fat deposition for use as a potential postnatal energy reserve? We hypothesised that resolving this dilemma operates at the level of umbilical blood distribution entering the fetal liver. In 381 uncomplicated pregnancies in third trimester, we measured blood flow perfusing the fetal liver, or bypassing it via the ductus venosus to supply the brain and heart using ultrasound techniques. Across the range of fetal growth and independent of the mother's adiposity and parity, greater liver blood flow was associated with greater offspring fat mass measured by dual-energy X-ray absorptiometry, both in the infant at birth (r = 0.43, P<0.001 and at age 4 years (r = 0.16, P = 0.02. In contrast, smaller placentas less able to meet fetal demand for essential nutrients were associated with a brain-sparing flow pattern (r = 0.17, p = 0.02. This flow pattern was also associated with a higher degree of shunting through ductus venosus (P = 0.04. We propose that humans evolved a developmental strategy to prioritize nutrient allocation for prenatal fat deposition when the supply of conditionally essential nutrients requiring hepatic inter-conversion is limited, switching resource allocation to favour the brain if the supply of essential nutrients is limited. Facilitated placental transfer mechanisms for glucose and other nutrients evolved in environments less affluent than those now prevalent in developed populations, and we propose that in circumstances of maternal adiposity and nutrient excess these mechanisms now also lead to prenatal fat deposition. Prenatal developmental influences play important roles in the human propensity to deposit fat.

  10. Maturation of the human fetal startle response: Evidence for sex-specific maturation of the human fetus1

    Science.gov (United States)

    Buss, Claudia; Davis, Elysia Poggi; Class, Quetzal A.; Gierczak, Matt; Pattillo, Carol; Glynn, Laura M.; Sandman, Curt A.

    2009-01-01

    Despite the evidence for early fetal experience exerting programming influences on later neurological development and health risk, very few prospective studies of human fetal behavior have been reported. In a prospective longitudinal study, fetal nervous system maturation was serially assessed by monitoring fetal heart rate (FHR) responses to vibroacoustic stimulation (VAS) in 191 maternal/fetal dyads. Responses were not detected at 26 weeks gestational age (GA). Sex-specific, age-characteristic changes in the FHR response to VAS were observed by 31 weeks’ GA. Males showed larger responses and continued to exhibit maturational changes until 37 weeks’ GA, females however, presented with a mature FHR startle response by 31 weeks’ GA. The results indicate that there are different rates of maturation in the male and female fetus that may have implications for sex-specific programming influences. PMID:19726143

  11. Maturation of the human fetal startle response: evidence for sex-specific maturation of the human fetus.

    Science.gov (United States)

    Buss, Claudia; Davis, Elysia Poggi; Class, Quetzal A; Gierczak, Matt; Pattillo, Carol; Glynn, Laura M; Sandman, Curt A

    2009-10-01

    Despite the evidence for early fetal experience exerting programming influences on later neurological development and health risk, very few prospective studies of human fetal behavior have been reported. In a prospective longitudinal study, fetal nervous system maturation was serially assessed by monitoring fetal heart rate (FHR) responses to vibroacoustic stimulation (VAS) in 191 maternal/fetal dyads. Responses were not detected at 26 weeks gestational age (GA). Sex-specific, age-characteristic changes in the FHR response to VAS were observed by 31 weeks' GA. Males showed larger responses and continued to exhibit maturational changes until 37 weeks' GA, females however, presented with a mature FHR startle response by 31 weeks' GA. The results indicate that there are different rates of maturation in the male and female fetuses that may have implications for sex-specific programming influences.

  12. Radiation absorbed dose to the human fetal thyroid

    International Nuclear Information System (INIS)

    Watson, E.E.

    1992-01-01

    The embryo/fetus is recognized to be particularly susceptible to damage from exposure to radiation. Many advisory groups have studied available information concerning radiation doses and radiation effects with the goal of reducing the risk to the embryo/fetus. Of particular interest are radioactive isotopes of iodine. Radioiodine taken into the body of a pregnant woman presents a possible hazard for the embryo/fetus. The fetal thyroid begins to concentrate iodine at about 13 weeks after conception and continues to do so throughout gestation. At term, the organic iodine concentration in the fetal blood is about 75% of that in the mother's blood. This paper presents a review the models that have been proposed for the calculation of the dose to the fetal thyroid from radioisotopes of iodine taken into the body of the pregnant woman as sodium iodide. A somewhat different model has been proposed, and estimates of the radiation dose to the fetal thyroid calculated from this model are given for each month of pregnancy from 123 I , 124 I , 125 I , and 131 I

  13. Placental growth factor concentration in maternal circulation decreases after fetal death: lessons from a case series study.

    Science.gov (United States)

    Beharier, Ofer; Shusterman, Eden; Szaingurten-Solodkin, Irit; Weintraub, Adi Y; Sheiner, Eyal; Swissa, Shani S; Gitler, Daniel; Hershkovitz, Reli

    2015-11-01

    Placental growth factor (PlGF) has been suggested as a possible biomarker for major placenta-related disorders such as preeclampsia and intrauterine growth restriction. However, experimental findings suggest that PlGF concentrations may be influenced by other factors besides the placenta. In the present study, we examined how acute fetal injury affects PlGF concentrations in maternal circulation. We therefore monitored PlGF concentrations in maternal circulation before and after feticide. A prospective comparative study was performed. Blood samples were drawn prospectively between January and July 2012, before and after feticide at predetermined time points in relation to the procedure (0, 30, 60, and 120 min). The levels of lactate dehydrogenase (LDH) in the maternal circulation were measured to detect acute tissue damage. PlGF concentrations were measured by standard human ELISA. Following feticide (60 and 120 min), PlGF concentrations decreased significantly compared to the concentrations before feticide. LDH concentrations did not change before and after feticide. Our finding, along with the detailed review of the literature described in our work, supports a new concept in which primary fetal distress can affect PlGF concentration in maternal circulation. A large-scale study is required to strengthen our finding.

  14. Effect of Maternal Obesity on Fetal Growth and Expression of Placental Fatty Acid Transporters.

    Science.gov (United States)

    Ye, Kui; Li, Li; Zhang, Dan; Li, Yi; Wang, Hai Qing; Lai, Han Lin; Hu, Chuan Lai

    2017-12-15

    To explore the effects of maternal high-fat (HF) diet-induced obesity on fetal growth and the expression of placental nutrient transporters. Maternal obesity was established in rats by 8 weeks of pre-pregnancy fed HF diet, while rats in the control group were fed normal (CON) diet. Diet-induced obesity (DIO) rats and diet-induced obesity-resistant (DIR) rats were selected according to body weight gain over this period. After copulation, the CON rats were divided into two groups: switched to HF diet (CON-HF group) or maintained on the CON diet (CON-CON group). The DIO rats and DIR rats were maintained on the HF diet throughout pregnancy. Pregnant rats were euthanized at day 21 gestation, fetal and placental weights were recorded, and placental tissue was collected. Reverse transcription-polymerase chain reaction was used to determine mRNA expression of placental nutrient transporters. Protein expression was determined by Western blot. Average fetal weight of DIO dams was reduced by 6.9%, and the placentas of CON-HF and DIO dams were significantly heavier than the placentas of CON-CON and DIR dams at day 21 of gestation (pobesity induced by a HF diet led to intrauterine growth retardation and down-regulated the expression of placental fatty acid transporters.

  15. Aortic isthmus Doppler velocimetry: role in assessment of preterm fetal growth restriction.

    LENUS (Irish Health Repository)

    Kennelly, M M

    2012-02-01

    Intrauterine fetal growth restriction (IUGR) is an important pregnancy complication associated with significant adverse clinical outcome, stillbirth, perinatal morbidity and cerebral palsy. To date, no uniformly accepted management protocol of Doppler surveillance that reduces mortality and cognitive morbidity has emerged. Aortic isthmus (AoI) evaluation has been proposed as a potential monitoring tool for IUGR fetuses. In this review, the current knowledge of the relationship between AoI Doppler velocimetry and preterm fetal growth restriction is reviewed. Relevant technical aspects and reproducibility data are reviewed as we discuss AoI Doppler and its place within the existing repertoire of Doppler assessments in placental insufficiency. The AoI is a link between the right and left ventricles which perfuse the lower and upper body, respectively. The clinical use of AoI waveforms for monitoring fetal deterioration in IUGR has been limited, but preliminary work suggests that abnormal AoI impedance indices are an intermediate step between placental insufficiency-hypoxemia and cardiac decompensation. Further prospective studies correlating AoI indices with arterial and venous Doppler indices and perinatal outcome are required before encorporating this index into clinical practice.

  16. FA1 immunoreactivity in endocrine tumours and during development of the human fetal pancreas; negative correlation with glucagon expression

    DEFF Research Database (Denmark)

    Tornehave, D; Jensen, Charlotte Harken; Teisner, B

    1996-01-01

    Fetal antigen 1 (FA1) is a glycoprotein containing six epidermal growth factor (EGF)-like repeats. It is closely similar to the protein translated from the human delta-like (dlk) cDNA and probably constitutes a proteolytically processed form of dlk. dlk is homologous to the Drosophila homeotic...... proteins delta and notch and to the murine preadipocyte differentiation factor Pref-1. These proteins participate in determining cell fate choices during differentiation. We now report that FA1 immunoreactivity is present in a number of neuroectodermally derived tumours as well as in pancreatic endocrine...... tumours. A negative correlation between FA1 and glucagon immunoreactants in these tumours prompted a reexamination of FA1 immunoreactants during fetal pancreatic development. At the earliest stages of development, FA1 was expressed by most of the non-endocrine parenchymal cells and, with ensuing...

  17. Increasing fetal ovine number per gestation alters fetal plasma clinical chemistry values.

    Science.gov (United States)

    Zywicki, Micaela; Blohowiak, Sharon E; Magness, Ronald R; Segar, Jeffrey L; Kling, Pamela J

    2016-08-01

    Intrauterine growth restriction (IUGR) is interconnected with developmental programming of lifelong pathophysiology. IUGR is seen in human multifetal pregnancies, with stepwise rises in fetal numbers interfering with placental nutrient delivery. It remains unknown whether fetal blood analyses would reflect fetal nutrition, liver, and excretory function in the last trimester of human or ovine IUGR In an ovine model, we hypothesized that fetal plasma biochemical values would reflect progressive placental, fetal liver, and fetal kidney dysfunction as the number of fetuses per gestation rose. To determine fetal plasma biochemical values in singleton, twin, triplet, and quadruplet/quintuplet ovine gestation, we investigated morphometric measures and comprehensive metabolic panels with nutritional measures, liver enzymes, and placental and fetal kidney excretory measures at gestational day (GD) 130 (90% gestation). As anticipated, placental dysfunction was supported by a stepwise fall in fetal weight, fetal plasma glucose, and triglyceride levels as fetal number per ewe rose. Fetal glucose and triglycerides were directly related to fetal weight. Plasma creatinine, reflecting fetal renal excretory function, and plasma cholesterol, reflecting placental excretory function, were inversely correlated with fetal weight. Progressive biochemical disturbances and growth restriction accompanied the rise in fetal number. Understanding the compensatory and adaptive responses of growth-restricted fetuses at the biochemical level may help explain how metabolic pathways in growth restriction can be predetermined at birth. This physiological understanding is important for clinical care and generating interventional strategies to prevent altered developmental programming in multifetal gestation. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  18. Impact of gestational weight gain on fetal growth in obese normoglycemic mothers: a comparative study.

    Science.gov (United States)

    Elhddad, Agzail S; Fairlie, Fiona; Lashen, Hany

    2014-08-01

    To assess the pattern of gestational weight gain (GWG) and its effect on fetal growth among normogylycemic obese and lean mothers. Prospective longitudinal study. Teaching hospitals, Sheffield, UK. Forty-six euglycemic obese and 30 lean mothers and their offspring. The contrast slope of GWG was calculated and its impact on fetal growth trajectory and birth anthropometry examined in both groups. The GWG contrast slope trended significantly upward in both groups but it was steeper among lean mothers (p = 0.003), particularly in second trimester. Lean mothers had a biphasic GWG pattern with a higher early weight gain (p = 0.02), whereas obese mothers had a monophasic GWG. Both groups had similar third trimester GWG. The GWG contrast slope was influenced by early pregnancy maternal anthropometry in the obese group only. Nonetheless, the obese mothers' glucose and insulin indices had no significant relationship to GWG. GWG had a significant positive relationship with intrauterine femur length (r = 0.32, p = 0.04) and abdominal circumference (r = 0.42, p = 0.006) growth trajectories, as well as birthweight standard deviation scores (r = 0.32, p = 0.036) and the ponderal index (r = 0.45, p = 0.003) in the obese mothers. Gestational weight gain among lean mothers is biphasic and significantly higher than their obese counterparts, but without effect on fetal growth. The obese mothers' monophasic weight gain was influenced by their anthropometry, but not by their insulin or glucose indices, and impacted on the growth of their babies. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

  19. Fetal and infant growth patterns associated with total and abdominal fat distribution in school-age children.

    Science.gov (United States)

    Gishti, Olta; Gaillard, Romy; Manniesing, Rashindra; Abrahamse-Berkeveld, Marieke; van der Beek, Eline M; Heppe, Denise H M; Steegers, Eric A P; Hofman, Albert; Duijts, Liesbeth; Durmuş, Büşra; Jaddoe, Vincent W V

    2014-07-01

    Higher infant growth rates are associated with an increased risk of obesity in later life. We examined the associations of longitudinally measured fetal and infant growth patterns with total and abdominal fat distribution in childhood. We performed a population-based prospective cohort study among 6464 children. We measured growth characteristics in the second and third trimesters of pregnancy, at birth, and at 6, 12, and 24 months. Body mass index, fat mass index (body fat mass/height(2)), lean mass index (body lean mass/height(2)), android/gynoid fat ratio measured by dual-energy x-ray absorptiometry, and sc and preperitoneal abdominal fat measured by ultrasound at the median age of 6.0 years (90% range, 5.7-7.4). We observed that weight gain in the second and third trimesters of fetal life and in early, mid, and late infancy were independently and positively associated with childhood body mass index (P fat mass index, android/gynoid fat ratio, and abdominal fat in childhood (P Children with both fetal and infant growth acceleration had the highest childhood body mass index, fat mass index, and sc abdominal fat, whereas children with fetal growth deceleration and infant growth acceleration had the highest value for android/gynoid fat ratio and the lowest value for lean mass index (P fat. Fetal growth deceleration followed by infant growth acceleration may lead to an adverse body fat distribution in childhood.

  20. Creation of an in vitro microenvironment to enhance human fetal synovium-derived stem cell chondrogenesis.

    Science.gov (United States)

    Li, Jingting; He, Fan; Pei, Ming

    2011-09-01

    Our aim was to assess the feasibility of the sequential application of extracellular matrix (ECM) and low oxygen to enhance chondrogenesis in human fetal synovium-derived stem cells (hfSDSCs). Human fetal synovial fibroblasts (hfSFs) were characterized and found to include hfSDSCs, as evidenced by their multi-differentiation capacity and the surface phenotype markers typical of mesenchymal stem cells. Passage-7 hfSFs were plated on either conventional plastic flasks (P) or ECM deposited by hfSFs (E) for one passage. Passage-8 hfSFs were then reseeded for an additional passage on either P or E. The pellets from expanded hfSFs were incubated in a serum-free chondrogenic medium supplemented with 10 ng/ml transforming growth factor-β3 under either normoxia (21% O(2); 21) or hypoxia (5% O(2); 5) for 14 days. Pellets were collected for evaluation of the treatments (EE21, EE5, EP21, EP5, PE21, PE5, PP21, and PP5) on expanded hfSF chondrogenesis by using histology, immunostaining, biochemistry, and real-time polymerase chain reaction. Our data suggest that, compared with seeding on conventional plastic flasks, hfSFs expanded on ECM exhibit a lower expression of senescence-associated β-galactosidase and an enhanced level of stage-specific embryonic antigen-4. ECM-expanded hfSFs also show increased cell numbers and an enhanced chondrogenic potential. Low oxygen (5% O(2)) during pellet culture enhances hfSF chondrogenesis. Thus, we demonstrate, for the first time, the presence of stem cells in hfSFs, and that modulation of the in vitro microenvironment can enhance hfSDSC chondrogenesis. hfSDSCs might represent a promising cell source for cartilage tissue engineering and regeneration.

  1. Regulation of caspase-3 expression to maintain fetal growth in Porphyromonas gingivalis-infected pregnant rats

    Directory of Open Access Journals (Sweden)

    Banun Kusumawardani

    2016-04-01

    Full Text Available Periodontal disease has been involved in a variety of systemic disorders and suspected as a potential risk factor for fetal growth restriction. Periodontal pathogenic bacteria may actively regulate embryonic development, implantation and placental trophoblast cell invasion. This study aimed to analyze the role of TNF-α, IL-10 and caspase-3 to maintain fetal growth in Porphyromonasgingivalis-infected pregnant rats. Female rats were infected with live-Porphyromonas gingivalis at concentration of 2x109 cells/ml into subgingival sulcus area of the maxillary first molar before and during pregnancy. They were sacrificed on gestational day (GD-14 and GD20. The weight and length of placentas and fetuses were evaluated. The expression of TNF-α, IL-10 and caspase-3 in macrophages and trophoblast cells were detected by immunohistochemistry. On GD14, TNF-α (R2=0.416;P=0.000 and IL-10 (R2=0.187;P=0.012 had an important role to increase expression of caspase-3 in the placenta, but only TNF-α (R2=0.393;P=0.000 was able to increase the expression of caspase-3 on GD20. TNF-α and caspase-3 also had an important role (P0.000. The increasing expressions of TNF-α and IL-10 did not only enhance immune protection, but also maintained the trophoblast cells survival by regulating expression of caspase-3. Porphyromonas gingivalis infection in maternal periodontal tissue can lead to decrease in placental weight, fetal weight and fetal length which mediated by increasing expression of TNF-α, IL-10 and caspase-3 in the placenta.

  2. Symphysis-fundal height curve in the diagnosis of fetal growth deviations

    Directory of Open Access Journals (Sweden)

    Djacyr Magna Cabral Freire

    2010-12-01

    Full Text Available OBJECTIVE: To validate a new symphysis-fundal curve for screening fetal growth deviations and to compare its performance with the standard curve adopted by the Brazilian Ministry of Health. METHODS: Observational study including a total of 753 low-risk pregnant women with gestational age above 27 weeks between March to October 2006 in the city of João Pessoa, Northeastern Brazil. Symphisys-fundal was measured using a standard technique recommended by the Brazilian Ministry of Health. Estimated fetal weight assessed through ultrasound using the Brazilian fetal weight chart for gestational age was the gold standard. A subsample of 122 women with neonatal weight measurements was taken up to seven days after estimated fetal weight measurements and symphisys-fundal classification was compared with Lubchenco growth reference curve as gold standard. Sensitivity, specificity, positive and negative predictive values were calculated. The McNemar χ2 test was used for comparing sensitivity of both symphisys-fundal curves studied. RESULTS: The sensitivity of the new curve for detecting small for gestational age fetuses was 51.6% while that of the Brazilian Ministry of Health reference curve was significantly lower (12.5%. In the subsample using neonatal weight as gold standard, the sensitivity of the new reference curve was 85.7% while that of the Brazilian Ministry of Health was 42.9% for detecting small for gestational age. CONCLUSIONS: The diagnostic performance of the new curve for detecting small for gestational age fetuses was significantly higher than that of the Brazilian Ministry of Health reference curve.

  3. Human Development and Economic Growth

    OpenAIRE

    Ranis, Gustav

    2004-01-01

    Recent literature has contrasted Human Development, described as the ultimate goal of the development process, with economic growth, described as an imperfect proxy for more general welfare, or as a means toward enhanced human development. This debate has broadened the definitions and goals of development but still needs to define the important interrelations between human development (HD) and economic growth (EG). To the extent that greater freedom and capabilities improve economic performan...

  4. Lack of Thromboxane Synthase Prevents Hypertension and Fetal Growth Restriction after High Salt Treatment during Pregnancy.

    Directory of Open Access Journals (Sweden)

    Chen-Hsueh Pai

    Full Text Available Preeclampsia (PE is a potentially fatal pregnancy-related hypertensive disorder characterized by poor placenta development that can cause fetal growth restriction. PE-associated pathologies, including thrombosis, hypertension, and impaired placental development, may result from imbalances between thromboxane A2 (TXA2 and prostacyclin. Low-dose aspirin, which selectively inhibits TXA2 production, is used to prevent high-risk PE. However, the role of TXA2 in aspirin-mediated protective effects in women with PE is not understood fully. In this study, we examined the role of prostanoids in PE using human samples and an induced PE mouse model. We demonstrated that the administration of salted drinking water (2.7% NaCl to wild-type mice resulted in elevated placental TXA2 synthase (TXAS and plasma TXA2, but not prostacyclin, levels, which was also found in our clinical PE placenta samples. The high salt-treated wild-type pregnant mice had shown unchanged maternal body weight, hypertension (MAP increase 15 mmHg, and decreased pup weight (~50% and size (~24%, but these adverse effects were ameliorated in TXAS knockout (KO mice. Moreover, increased expression of interleukin-1β and downstream phosphorylated-p38-mitogen-activated protein kinase were concordant with apoptosis induction in the placentas of salt water-treated wild-type mice. These alterations were not observed in TXAS KO mice. Together, our data suggest that TXA2 depletion has anti-PE effects due to the prevention of hypertension and placental damage through downregulation of the interleukin-1β pathway.

  5. DNA repair and induction of plasminogen activator in human fetal cells treated with ultraviolet light

    International Nuclear Information System (INIS)

    Ben-Ishai, R.; Sharon, R.; Rothman, M.; Miskin, R.

    1984-01-01

    We have tested human fetal fibroblasts for development associated changes in DNA repair by utilizing nucleoid sedimentation as an assay for excision repair. Among skin fibroblasts the rate of excision repair was significantly higher in non-fetal cells than in fibroblasts derived from an 8 week fetus; this was evident by a delay in both the relaxation and the restoration of DNA supercoiling in nucleoids after irradiation. Skin fibroblasts derived at 12 week gestation were more repair proficient than those derived at 8 week gestation. However, they exhibited a somewhat lower rate of repair than non-fetal cells. The same fetal and non-fetal cells were also tested for induction of the protease plasminogen activator (PA) after u.v. irradiation. Enhancement of PA was higher in skin fibroblasts derived at 8 week than in those derived at 12 week gestation and was absent in non-fetal skin fibroblasts. These results are consistent with our previous findings that in human cells u.v. light-induced PA synthesis is correlated with reduced DNA repair capacity. Excision repair and PA inducibility were found to depend on tissue of origin in addition to gestational stage, as shown for skin and lung fibroblasts from the same 12 week fetus. Lung compared to skin fibroblasts exhibited lower repair rates and produced higher levels of PA after irradiation. The sedimentation velocity of nucleoids, prepared from unirradiated fibroblasts, in neutral sucrose gradients with or without ethidium bromide, indicated the presence of DNA strand breaks in fetal cells. It is proposed that reduced DNA repair in fetal cells may result from alterations in DNA supercoiling, and that persistent DNA strand breaks enhance transcription of PA gene(s)

  6. 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)

  7. Fetal Growth and Childhood Acute Lymphoblastic Leukemia: Findings from the Childhood Leukemia International Consortium (CLIC)

    Science.gov (United States)

    Milne, Elizabeth; Greenop, Kathryn R.; Metayer, Catherine; Schüz, Joachim; Petridou, Eleni; Pombo-de-Oliveira, Maria S.; Infante-Rivard, Claire; Roman, Eve; Dockerty, John D.; Spector, Logan G.; Koifman, Sérgio; Orsi, Laurent; Rudant, Jérémie; Dessypris, Nick; Simpson, Jill; Lightfoot, Tracy; Kaatsch, Peter; Baka, Margarita; Faro, Alessandra; Armstrong, Bruce K.; Clavel, Jacqueline; Buffler, Patricia A.

    2013-01-01

    Positive associations have been reported between measures of accelerated fetal growth and risk of childhood acute lymphoblastic leukemia (ALL). We investigated this association by pooling individual-level data from 12 case-control studies participating in the Childhood Leukemia International Consortium. Two measures of fetal growth – weight-for-gestational-age and proportion of optimal birth weight (POBW) – were analysed. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression, and combined in fixed effects meta-analyses. Pooled analyses of all data were also undertaken using multivariable logistic regression. Subgroup analyses were undertaken when possible. Data on weight for gestational age were available for 7,348 cases and 12,489 controls from all 12 studies and POBW data were available for 1,680 cases and 3,139 controls from three studies. The summary ORs from the meta-analyses were 1.24 (95% CI 1.13, 1.36) for children who were large for gestational age relative to appropriate for gestational age, and 1.16 (95% CI: 1.09, 1.24) for a one standard deviation increase in POBW. The pooled analyses produced similar results. The summary and pooled ORs for small-for-gestational-age children were 0.83 (95% CI: 0.75, 0.92) and 0.86 (95% CI 0.77, 0.95) respectively. Results were consistent across subgroups defined by sex, ethnicity and immunophenotype, and when the analysis was restricted to children who did not have high birth weight. The evidence that accelerated fetal growth is associated with a modest increased risk of childhood ALL is strong and consistent with known biological mechanisms involving insulin like growth factors. PMID:23754574

  8. Populations of subplate and interstitial neurons in fetal and adult human telencephalon.

    Science.gov (United States)

    Judaš, Miloš; Sedmak, Goran; Pletikos, Mihovil; Jovanov-Milošević, Nataša

    2010-10-01

    In the adult human telencephalon, subcortical (gyral) white matter contains a special population of interstitial neurons considered to be surviving descendants of fetal subplate neurons [Kostovic & Rakic (1980) Cytology and the time of origin of interstitial neurons in the white matter in infant and adult human and monkey telencephalon. J Neurocytol9, 219]. We designate this population of cells as superficial (gyral) interstitial neurons and describe their morphology and distribution in the postnatal and adult human cerebrum. Human fetal subplate neurons cannot be regarded as interstitial, because the subplate zone is an essential part of the fetal cortex, the major site of synaptogenesis and the 'waiting' compartment for growing cortical afferents, and contains both projection neurons and interneurons with distinct input-output connectivity. However, although the subplate zone is a transient fetal structure, many subplate neurons survive postnatally as superficial (gyral) interstitial neurons. The fetal white matter is represented by the intermediate zone and well-defined deep periventricular tracts of growing axons, such as the corpus callosum, anterior commissure, internal and external capsule, and the fountainhead of the corona radiata. These tracts gradually occupy the territory of transient fetal subventricular and ventricular zones.The human fetal white matter also contains distinct populations of deep fetal interstitial neurons, which, by virtue of their location, morphology, molecular phenotypes and advanced level of dendritic maturation, remain distinct from subplate neurons and neurons in adjacent structures (e.g. basal ganglia, basal forebrain). We describe the morphological, histochemical (nicotinamide-adenine dinucleotide phosphate-diaphorase) and immunocytochemical (neuron-specific nuclear protein, microtubule-associated protein-2, calbindin, calretinin, neuropeptide Y) features of both deep fetal interstitial neurons and deep (periventricular

  9. Endocrine regulation of fetal skeletal muscle growth: impact on future metabolic health

    Science.gov (United States)

    Brown, Laura D.

    2014-01-01

    Establishing sufficient skeletal muscle mass is essential for lifelong metabolic health. The intrauterine environment is a major determinant of the muscle mass that is present for the life course of an individual, because muscle fiber number is set at the time of birth. Thus, a compromised intrauterine environment from maternal nutrient restriction or placental insufficiency that restricts development of muscle fiber number can have permanent effects on the amount of muscle an individual will live with. Reduced muscle mass due to fewer muscle fibers persists even after compensatory or “catch up” postnatal growth occurs. Furthermore, muscle hypertrophy can only partially compensate for this limitation in fiber number. Compelling associations link low birth weight and decreased muscle mass to future insulin resistance, which can drive the development of the metabolic syndrome and type 2 diabetes, and risk for cardiovascular events later in life. There are gaps in knowledge about the origins of reduced muscle growth at the cellular level and how these patterns are set during fetal development. By understanding the nutrient and endocrine regulation of fetal skeletal muscle growth and development, we can direct research efforts towards improving muscle growth early in life in order to prevent the development of chronic metabolic disease later in life. PMID:24532817

  10. KeyGenes, a Tool to Probe Tissue Differentiation Using a Human Fetal Transcriptional Atlas

    NARCIS (Netherlands)

    Roost, Matthias S; van Iperen, Liesbeth; Ariyurek, Yavuz; Buermans, Henk P; Arindrarto, Wibowo; Devalla, Harsha D; Passier, Robert; Mummery, Christine L; Carlotti, Françoise; de Koning, Eelco J P; van Zwet, Erik W; Goeman, Jelle J; Chuva de Sousa Lopes, Susana M

    2015-01-01

    Differentiated derivatives of human pluripotent stem cells in culture are generally phenotypically immature compared to their adult counterparts. Their identity is often difficult to determine with certainty because little is known about their human fetal equivalents in vivo. Cellular identity and

  11. Epicardial excitation pattern as observed in the isolated revived and perfused fetal human heart

    NARCIS (Netherlands)

    Durrer, D.; Büller, J.; Graaff, P.; Lo, G.I.; Meijler, F.L.

    1961-01-01

    The resuscitated fetal human heart can be used as an experimental tooI for the investigation of the excitatory process in the human heart. During perfusion the configuration of the epicardial electrocardiograms does not change appreciably. For accurate recording permitting a detailed analysis, the

  12. 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.

  13. A prospective study of fetal head growth, autistic traits and autism spectrum disorder.

    Science.gov (United States)

    Blanken, Laura M E; Dass, Alena; Alvares, Gail; van der Ende, Jan; Schoemaker, Nikita K; El Marroun, Hanan; Hickey, Martha; Pennell, Craig; White, Scott; Maybery, Murray T; Dissanayake, Cheryl; Jaddoe, Vincent W V; Verhulst, Frank C; Tiemeier, Henning; McIntosh, Will; White, Tonya; Whitehouse, Andrew

    2018-04-01

    Altered trajectories of brain growth are often reported in Autism Spectrum Disorder (ASD), particularly during the first year of life. However, less is known about prenatal head growth trajectories, and no study has examined the relation with postnatal autistic symptom severity. The current study prospectively examined the association between fetal head growth and the spectrum of autistic symptom severity in two large population-based cohorts, including a sample of individuals with clinically diagnosed ASD. This study included 3,820 children from two longitudinal prenatal cohorts in The Netherlands and Australia, comprising 60 individuals with a confirmed diagnosis of ASD. Latent growth curve models were used to examine the relationship between fetal head circumference measured at three different time points and autistic traits measured in postnatal life using either the Social Responsiveness Scale or the Autism-Spectrum Quotient. While lower initial prenatal HC was weakly associated with increasing autistic traits in the Dutch cohort, this relationship was not observed in the Australian cohort, nor when the two cohorts were analysed together. No differences in prenatal head growth were found between individuals with ASD and controls. This large population-based study identified no consistent association across two cohorts between prenatal head growth and postnatal autistic traits. Our mixed findings suggest that further research in this area is needed. Autism Res 2018, 11: 602-612. © 2018 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. It is not known whether different patterns of postnatal brain growth in Autism Spectrum Disorder (ASD) also occurs prenatally. We examined fetal head growth and autistic symptoms in two large groups from The Netherlands and Australia. Lower initial prenatal head circumference was associated with autistic traits in the Dutch, but not the Australian, group. No differences

  14. Catch-up growth following fetal growth restriction promotes rapid restoration of fat mass but without metabolic consequences at one year of age.

    Directory of Open Access Journals (Sweden)

    Jacques Beltrand

    Full Text Available BACKGROUND: Fetal growth restriction (FGR followed by rapid weight gain during early life has been suggested to be the initial sequence promoting central adiposity and insulin resistance. However, the link between fetal and early postnatal growth and the associated anthropometric and metabolic changes have been poorly studied. METHODOLOGY/PRINCIPAL FINDINGS: Over the first year of post-natal life, changes in body mass index, skinfold thickness and hormonal concentrations were prospectively monitored in 94 infants in whom the fetal growth velocity had previously been measured using a repeated standardized procedure of ultrasound fetal measurements. 45 infants, thinner at birth, had experienced previous FGR (FGR+ regardless of birth weight. Growth pattern in the first four months of life was characterized by greater change in BMI z-score in FGR+ (+1.26+/-1.2 vs +0.58 +/-1.17 SD in FGR- resulting in the restoration of BMI and of fat mass to values similar to FGR-, independently of caloric intakes. Growth velocity after 4 months was similar and BMI z-score and fat mass remained similar at 12 months of age. At both time-points, fetal growth velocity was an independent predictor of fat mass in FGR+. At one year, fasting insulin levels were not different but leptin was significantly higher in the FGR+ (4.43+/-1.41 vs 2.63+/-1 ng/ml in FGR-. CONCLUSION: Early catch-up growth is related to the fetal growth pattern itself, irrespective of birth weight, and is associated with higher insulin sensitivity and lower leptin levels after birth. Catch-up growth promotes the restoration of body size and fat stores without detrimental consequences at one year of age on body composition or metabolic profile. The higher leptin concentration at one year may reflect a positive energy balance in children who previously faced fetal growth restriction.

  15. Effects of Prenatal Multiple Micronutrient Supplementation on Fetal Growth Factors: A Cluster-Randomized, Controlled Trial in Rural Bangladesh.

    Directory of Open Access Journals (Sweden)

    Alison D Gernand

    Full Text Available Prenatal multiple micronutrient (MM supplementation improves birth weight through increased fetal growth and gestational age, but whether maternal or fetal growth factors are involved is unclear. Our objective was to examine the effect of prenatal MM supplementation on intrauterine growth factors and the associations between growth factors and birth outcomes in a rural setting in Bangladesh. In a double-blind, cluster-randomized, controlled trial of MM vs. iron and folic acid (IFA supplementation, we measured placental growth hormone (PGH at 10 weeks and PGH and human placental lactogen (hPL at 32 weeks gestation in maternal plasma (n = 396 and insulin, insulin-like growth factor-1 (IGF-1, and IGF binding protein-1 (IGFBP-1 in cord plasma (n = 325. Birth size and gestational age were also assessed. Early pregnancy mean (SD BMI was 19.5 (2.4 kg/m2 and birth weight was 2.68 (0.41 kg. There was no effect of MM on concentrations of maternal hPL or PGH, or cord insulin, IGF-1, or IGFBP-1. However, among pregnancies of female offspring, hPL concentration was higher by 1.1 mg/L in the third trimester (95% CI: 0.2, 2.0 mg/L; p = 0.09 for interaction; and among women with height <145 cm, insulin was higher by 59% (95% CI: 3, 115%; p = 0.05 for interaction in the MM vs. IFA group. Maternal hPL and cord blood insulin and IGF-1 were positively, and IGFBP-1 was negatively, associated with birth weight z score and other measures of birth size (all p<0.05. IGF-1 was inversely associated with gestational age (p<0.05, but other growth factors were not associated with gestational age or preterm birth. Prenatal MM supplementation had no overall impact on intrauterine growth factors. MM supplementation altered some growth factors differentially by maternal early pregnancy nutritional status and sex of the offspring, but this should be examined in other studies.ClinicalTrials.gov NCT00860470.

  16. Effect of fetal growth on maternal protein metabolism in postabsorptive rat

    International Nuclear Information System (INIS)

    Ling, P.R.; Bistrian, B.R.; Blackburn, G.L.; Istfan, N.

    1987-01-01

    Rates of protein synthesis were measured in whole fetuses and maternal tissues at 17 and 20 days of gestation in postabsorptive rats using continuous infusion of L-[1- 14 C]leucine. Fetal protein degradation rates were derived from the fractional rates of synthesis and growth. Whole-body (plasma) leucine kinetics in the mother showed a significant reduction of the fraction of plasma leucine oxidized in the mothers bearing older fetuses, a slight increase in the plasma flux, with total leucine oxidation and incorporation into protein remaining similar at the two gestational ages. Estimates of fractional protein synthesis in maternal tissues revealed an increase in placental and hepatic rates at 20 days of gestation, whereas the fractional synthetic rate in muscle remained unchanged. A model for estimation of the redistribution of leucine between plasma and tissues is described in detail. This model revealed a more efficient utilization of leucine in fetal protein synthesis in comparison with other maternal tissues, a greater dependency of the fetus on plasma supply of leucine, and a significant increase (2-fold) in the release of leucine from maternal muscle as the fetal requirements increased proportionately with its size. The latter conclusion, supported by nitrogen analysis and the ratio of bound-to-free leucine in maternal tissues, confirms the importance of maternal stores in maintaining the homeostasis of essential amino acids during late pregnancy

  17. Invited commentary: the incremental value of customization in defining abnormal fetal growth status.

    Science.gov (United States)

    Zhang, Jun; Sun, Kun

    2013-10-15

    Reference tools based on birth weight percentiles at a given gestational week have long been used to define fetuses or infants that are small or large for their gestational ages. However, important deficiencies of the birth weight reference are being increasingly recognized. Overwhelming evidence indicates that an ultrasonography-based fetal weight reference should be used to classify fetal and newborn sizes during pregnancy and at birth, respectively. Questions have been raised as to whether further adjustments for race/ethnicity, parity, sex, and maternal height and weight are helpful to improve the accuracy of the classification. In this issue of the Journal, Carberry et al. (Am J Epidemiol. 2013;178(8):1301-1308) show that adjustment for race/ethnicity is useful, but that additional fine tuning for other factors (i.e., full customization) in the classification may not further improve the ability to predict infant morbidity, mortality, and other fetal growth indicators. Thus, the theoretical advantage of full customization may have limited incremental value for pediatric outcomes, particularly in term births. Literature on the prediction of short-term maternal outcomes and very long-term outcomes (adult diseases) is too scarce to draw any conclusions. Given that each additional variable being incorporated in the classification scheme increases complexity and costs in practice, the clinical utility of full customization in obstetric practice requires further testing.

  18. The effect of androgen excess on maternal metabolism, placental function and fetal growth in obese dams.

    Science.gov (United States)

    Fornes, Romina; Maliqueo, Manuel; Hu, Min; Hadi, Laila; Jimenez-Andrade, Juan M; Ebefors, Kerstin; Nyström, Jenny; Labrie, Fernand; Jansson, Thomas; Benrick, Anna; Stener-Victorin, Elisabet

    2017-08-14

    Pregnant women with polycystic ovary syndrome (PCOS) are often overweight or obese. To study the effects of maternal androgen excess in obese dams on metabolism, placental function and fetal growth, female C57Bl6J mice were fed a control (CD) or a high fat/high sucrose (HF/HS) diet for 4-10 weeks, and then mated. On gestational day (GD) 15.5-17.5, dams were injected with dihydrotestosterone (CD-DHT, HF/HS-DHT) or a vehicle (CD-Veh, HF/HS-Veh). HF/HS dams had higher fat content, both before mating and on GD18.5, with no difference in glucose homeostasis, whereas the insulin sensitivity was higher in DHT-exposed dams. Compared to the CD groups, the livers from HF/HS dams weighed more on GD18.5, the triglyceride content was higher, and there was a dysregulation of liver enzymes related to lipogenesis and higher mRNA expression of Fitm1. Fetuses from HF/HS-Veh dams had lower liver triglyceride content and mRNA expression of Srebf1c. Maternal DHT exposure, regardless of diet, decreased fetal liver Pparg mRNA expression and increased placental androgen receptor protein expression. Maternal diet-induced obesity, together with androgen excess, affects maternal and fetal liver function as demonstrated by increased triglyceride content and dysfunctional expression of enzymes and transcription factors involved in de novo lipogenesis and fat storage.

  19. Generation of human cortical neurons from a new immortal fetal neural stem cell line

    International Nuclear Information System (INIS)

    Cacci, E.; Villa, A.; Parmar, M.; Cavallaro, M.; Mandahl, N.; Lindvall, O.; Martinez-Serrano, A.; Kokaia, Z.

    2007-01-01

    Isolation and expansion of neural stem cells (NSCs) of human origin are crucial for successful development of cell therapy approaches in neurodegenerative diseases. Different epigenetic and genetic immortalization strategies have been established for long-term maintenance and expansion of these cells in vitro. Here we report the generation of a new, clonal NSC (hc-NSC) line, derived from human fetal cortical tissue, based on v-myc immortalization. Using immunocytochemistry, we show that these cells retain the characteristics of NSCs after more than 50 passages. Under proliferation conditions, when supplemented with epidermal and basic fibroblast growth factors, the hc-NSCs expressed neural stem/progenitor cell markers like nestin, vimentin and Sox2. When growth factors were withdrawn, proliferation and expression of v-myc and telomerase were dramatically reduced, and the hc-NSCs differentiated into glia and neurons (mostly glutamatergic and GABAergic, as well as tyrosine hydroxylase-positive, presumably dopaminergic neurons). RT-PCR analysis showed that the hc-NSCs retained expression of Pax6, Emx2 and Neurogenin2, which are genes associated with regionalization and cell commitment in cortical precursors during brain development. Our data indicate that this hc-NSC line could be useful for exploring the potential of human NSCs to replace dead or damaged cortical cells in animal models of acute and chronic neurodegenerative diseases. Taking advantage of its clonality and homogeneity, this cell line will also be a valuable experimental tool to study the regulatory role of intrinsic and extrinsic factors in human NSC biology

  20. Cognitive ability in adolescents born small for gestational age: Associations with fetal growth velocity, head circumference and postnatal growth.

    Science.gov (United States)

    Jensen, Rikke Beck; Juul, Anders; Larsen, Torben; Mortensen, Erik Lykke; Greisen, Gorm

    2015-12-01

    Small size at birth may be associated with impaired cognitive ability later in life. The aim of this study was to examine the effect of being born small for gestational age (SGA), with or without intrauterine growth restriction (IUGR) on cognitive ability in late adolescence. A follow-up study of a former cohort included 123 participants (52 males); 47 born SGA and 76 born appropriate for gestational age (AGA). Fetal growth velocity (FGV) was determined by serial ultrasound measurements during the third trimester. A control group matched for age and birthplace was included. The original Wechsler Adult Intelligence Scale (WAIS) was administered, and verbal, performance and full-scale Intelligence Quotient (IQ) scores were calculated. There was no difference in IQ between adolescents born SGA and AGA. FGV or IUGR during the third trimester did not influence cognitive ability in late adolescence. Full-scale IQ was positively related to head circumference (HC) in adolescence (B: 1.30, 95% CI: 0.32-2.28, p=0.01). HC at birth and three months was positively associated with full-scale IQ. Catch-up growth in the group of SGA children was associated with a significantly increased height, larger HC, increased levels of insulin-like growth factor-I (IGF-I) and increased full-scale IQ compared to those born SGA without catch-up growth. SGA and IUGR may not be harmful for adult cognitive ability, at least not in individuals born at near-term. However, known risk factors of impaired fetal growth may explain the link between early growth and cognitive ability in adulthood. Copyright © 2015. Published by Elsevier Ireland Ltd.

  1. 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.

  2. 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

  3. Sex-hormone binding globulin (SHBG) levels during pregnancy as predictors for pre-eclampsia and fetal growth restriction

    OpenAIRE

    Valdés R, Enrique; Lattes A, Karina; Muñoz S, Hernán; Ángel Cumsille, Miguel

    2012-01-01

    Background: Sex-Hormone Binding Globulin (SHBG) may be associated to Pre-eclampsia (PE) and Fetal Growth Restriction (RCIU). Aim: To determine if maternal serum SHBG concentrations during the first and second trimesters are predictive biomarkers of Pre-eclampsia and RCIU. Patients and Methods: Prospective cohort study carried out in the Fetal Medicine Unit, Universidad de Chile Clinical Hospital between January, 2005 and December, 2006. Blood samples were obtained from unselectedpregnant wome...

  4. Fetal growth profiles of macrosomic and non-macrosomic infants of women with pregestational or gestational diabetes.

    Science.gov (United States)

    Hammoud, N M; Visser, G H A; Peters, S A E; Graatsma, E M; Pistorius, L; de Valk, H W

    2013-04-01

    To assess fetal growth profiles in an unselected group of pregnant women with either type-1 diabetes (DM1), type-2 diabetes (DM2) or gestational diabetes (GDM), with emphasis on intergroup differences and development of disproportionate fetal growth and macrosomia. Second- and third-trimester longitudinal ultrasound measurements of fetal growth were made in 77 women with DM1, 68 women with DM2 and in 99 women with GDM. Altogether 897 ultrasound examinations were performed and 145 uncomplicated pregnancies with 843 ultrasound examinations were included as controls. Ultrasound data included head circumference (HC), abdominal circumference (AC), femur length (FL) and HC/AC ratio. The AC, but not HC and FL, evolved differently in diabetic pregnancies, with a smaller AC in early pregnancy and larger AC at term (significant for DM1 and DM2). The most striking differences were found for the HC/AC ratio, especially in DM1 pregnancies. HC/AC growth trajectories of both macrosomic and non-macrosomic fetuses differed from that of the controls, and the HC/AC ratio at term was lower in all diabetic subgroups except in non-macrosomic DM2 cases. We found altered (disproportionate) fetal growth in macrosomic and non-macrosomic fetuses of women with DM1, DM2 and GDM. This indicates that the abnormal intrauterine environment affects the majority of these infants. Growth profiles differed among these groups, the most prominent growth deviations being found in the fetuses of women with DM1. The latter was most probably caused by poor glucose control. In monitoring fetal growth in diabetic pregnancies the HC/AC ratio should be used to assess altered fetal growth. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.

  5. 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.

  6. Differential correlations between maternal hair levels of tobacco and alcohol with fetal growth restriction clinical subtypes.

    Science.gov (United States)

    Sabra, Sally; Malmqvist, Ebba; Almeida, Laura; Gratacos, Eduard; Gomez Roig, Maria Dolores

    2018-08-01

    Maternal exposure to tobacco and alcohol is a known cause, among others, for fetal growth restriction (FGR). Clinically, FGR can be subclassified into two forms: intrauterine growth restriction (IUGR) and small for gestational age (SGA), based on the severity of the growth retardation, and abnormal uterine artery Doppler or cerebro-placental ratio. This study aimed at investigating any differential correlation between maternal exposures to these toxins with the two clinical forms of FGR. Therefore, a case-control study was conducted in Barcelona, Spain. Sixty-four FGR subjects, who were further subclassified into IUGR (n = 36) and SGA (n = 28), and 89 subjects matched appropriate-for-gestational age (AGA), were included. The levels of nicotine (NIC) and ethyl glucuronide (EtG), biomarkers of tobacco and alcohol exposure, respectively, were assessed in the maternal hair in the third trimester. Our analysis showed 65% of the pregnant women consumed alcohol, 25% smoked, and 19% did both. The odds ratios (ORs) of IUGR were 21 times versus 14 times for being SGA with maternal heavy smoking, while with alcohol consumption the ORs for IUGR were 22 times versus 37 times for the SGA group. The differential correlations between these toxins with the two subtypes of FGR suggest different mechanisms influencing fetal weight. Our alarming data of alcohol consumption during pregnancy should be considered for further confirmation among Spanish women. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Fetal growth in relation to gestational weight gain in women with Type 2 diabetes

    DEFF Research Database (Denmark)

    Parellada, C B; Asbjörnsdóttir, Björg; Ringholm, Lene

    2014-01-01

    AIMS: To evaluate fetal growth in relation to gestational weight gain in women with Type 2 diabetes. METHODS: A retrospective cohort study of 142 consecutive pregnancies in 28 women of normal weight, 39 overweight women and 75 obese women with Type 2 diabetes (pre-pregnancy BMI .../week, respectively. In multiple linear regression analysis, gestational weight gain was associated with a higher infant birth weight z-score independent of pre-pregnancy BMI, smoking, HbA1c and insulin dose at last visit, ethnicity and parity [β=0.1 (95% CI 0.06-0.14), P

  8. Fetal growth and adverse birth outcomes in women receiving prescriptions for acetaminophen during pregnancy

    DEFF Research Database (Denmark)

    Thulstrup, Ane Marie; Sørensen, Henrik Toft; Nielsen, Gunnar Lauge

    1999-01-01

    not receive any prescription at all. We found more malformations among those who received a prescription with an odds ratio of 2.3 (95% CI 1.0-5.4), but the type of malformations did not indicate a causal link. When restricting the study to first time pregnancies, we identified 58 women who received......We studied the association between acetaminophen exposure during pregnancy and the prevalence of congenital abnormalities and fetal growth. Our study included 123 women who had received a prescription of acetaminophen during pregnancy and/or 30 days before conception and 13,329 controls who did...

  9. Fetal growth and perinatal outcome of pregnancies continuing after threatened abortion.

    Science.gov (United States)

    Das, A G; Gopalan, S; Dhaliwal, L K

    1996-05-01

    The present study was conducted with the aim to find out the effect of threatened abortion in the current pregnancy on the subsequent perinatal outcome and follow the growth pattern of the fetuses of such complicated pregnancies. The study group consisted of 55 women with threatened abortion and 55 women with normal pregnancies formed the control group. Most of the patients presented at 6-12 weeks' gestation. The fetal growth was monitored by both clinical as well as ultrasound (USG) parameters. The mean growth rates were almost identical throughout gestation. The mean values of each parameter of the study group were found lying with 95% confidence limit values of their control group. The apparent increased incidence of low lying placenta in early pregnancy probably contributed to threatened abortion. There was no significant difference in preterm delivery, low birth-weight and overall perinatal outcome.

  10. Fetal- and uterine-specific antigens in human amniotic fluid.

    Science.gov (United States)

    Sutcliffe, R G; Brock, D J; Nicholson, L V; Dunn, E

    1978-09-01

    Removal of the major maternal serum proteins from second trimester amniotic fluid by antibody affinity chromatography revealed various soluble tissue antigens, of which two were fetal-specific skin proteins and another, of alpha2-mobility, was specific to the uterus, and was therefore designated alpha-uterine protein (AUP). These proteins could not be detected in maternal serum by antibody-antigen crossed electrophoresis. The concentration of AUP in amniotic fluid reached a maximum between 10 and 20 weeks of gestation, suggesting that there is an influx of uterine protein into the amniotic fluid at this stage of pregnancy.

  11. Monitoring human growth and development : a continuum from the womb to the classroom

    NARCIS (Netherlands)

    Villar, Jose; Papageorghiou, Aris T.; Pang, Ruyan; Salomon, Laurent J.; Langer, Ana; Victora, Cesar; Purwar, Manorama; Chumlea, Cameron; Wu Qingqing, [Unknown; Scherjon, Sicco A.; Barros, Fernando C.; Carvalho, Maria; Altman, Douglas G.; Giuliani, Francesca; Bertino, Enrico; Jaffer, Yasmin A.; Ismail, Leila Cheikh; Ohuma, Eric O.; Lambert, Ann; Noble, J. Alison; Gravett, Michael G.; Bhutta, Zulfiqar A.; Kennedy, Stephen H.

    2015-01-01

    A comprehensive set of fully integrated anthropometric measures is needed to evaluate human growth from conception to infancy so that consistent judgments can be made about the appropriateness of fetal and infant growth. At present, there are 2 barriers to this strategy. First, descriptive reference

  12. Social inequality in fetal growth: a comparative study of Denmark, Finland, Norway and Sweden in the period 1981-2000

    DEFF Research Database (Denmark)

    Mortensen, Laust Hvas; Diderichsen, F; Arntzen, A

    2008-01-01

    ,077,584; Finland n = 400,442; Norway n = 929,458; Sweden n = 1,761,562). MAIN OUTCOME MEASURE: Slope index of inequality (SII) and mean differences in birthweight for gestational age, SII and risk differences in small-for-gestational-age (SGA) and large-for-gestational-age (LGA) infants. RESULTS: In all countries....... CONCLUSION: The economic recession in Denmark in the 1980s was concurrent with an increase in disparities in fetal growth, whereas the economic recession in Finland and Sweden in the early 1990s did not substantially increase the socioeconomic inequality in fetal growth. The economic growth in the later part...... of the 1990s may have diminished the socioeconomic inequality in fetal growth in Finland, Norway, and Sweden....

  13. Altered Decorin and Smad Expression in Human Fetal Membranes in PPROM1

    Science.gov (United States)

    Horgan, Casie E.; Roumimper, Hailey; Tucker, Richard; Lechner, Beatrice E.

    2014-01-01

    ABSTRACT Humans with Ehlers-Danlos syndrome, a subtype of which is caused by abnormal decorin expression, are at increased risk of preterm birth due to preterm premature rupture of fetal membranes (PPROM). In the mouse model, the absence of decorin leads to fetal membrane abnormalities, preterm birth, and dysregulation of decorin's downstream pathway components, including the transcription factor p-Smad-2. However, the role of decorin and p-Smad-2 in idiopathic human PPROM is unknown. Fetal membranes from 20–25 pregnancies per group were obtained as a cross-sectional sample of births at one institution between January 2010 and December 2012. The groups were term, preterm without PPROM, and preterm with PPROM. Immunohistochemical analysis of fetal membranes was performed for decorin and p-Smad-2 using localization and quantification assessment. Decorin expression is developmentally regulated in fetal membranes and is decreased in preterm birth with PPROM compared to preterm birth without PPROM. In preterm with PPROM samples, the presence of infection is associated with significant decorin downregulation compared to preterm with PPROM samples without infection. The preterm with PPROM group exhibited decreased p-Smad-2 staining compared to both the term controls and the preterm-without-PPROM group. Our findings suggest that dysregulation of decorin and its downstream pathway component p-Smad-2 occurs in fetal membranes during the second trimester in pathological pregnancies, thus supporting a role for decorin and p-Smad-2 in the pathophysiology of fetal membranes and adverse pregnancy outcomes. These findings may lead to the discovery of new targets for the diagnosis and treatment of PPROM. PMID:25232019

  14. From head to heart; : the effects of fetal growth restriction and preterm birth on the cerebral and systemic circulation

    NARCIS (Netherlands)

    Cohen, Emily

    2017-01-01

    Fetal growth restriction (FGR) is the condition where a fetus does not grow according to its genetic growth potential. It is estimated that 3-7% of pregnancies are complicated by FGR. FGR has been associated with many adverse outcomes, including an increased risk of perinatal and neonatal morbidity

  15. Fetal and infant growth patterns associated with total and abdominal fat distribution in school-age children

    NARCIS (Netherlands)

    Gishti, O.; Gaillard, R.; Manniesing, R.; Abrahamse-Berkeveld, M.; Beek, E.M. van der; Heppe, D.H.M.; Steegers, E.A.P.; Hofman, A.; Duijts, L.; Durmus, B.u.; Jaddoe, V.W.

    2014-01-01

    Context: Higher infant growth rates are associated with an increased risk of obesity in later life. Objective: We examined the associations of longitudinally measured fetal and infant growth patterns with total and abdominal fat distribution in childhood. Design, Settings and participants:We

  16. Is There Hope for Renal Growth on Imaging Studies Following Ureteral Reimplant for Boys With Fetal Hydronephrosis and Urinary Reflux?

    Directory of Open Access Journals (Sweden)

    Ming-Hsien Wang

    2015-07-01

    Full Text Available Reflux nephropathy is thought to be the etiology for renal maldevelopment. We present two boys with fetal hydronephrosis and sterile vesicoureteral reflux (VUR. There was lack of renal growth of the refluxing renal units on surveillance renal ultrasound. Parents elected to undergo open ureteral reimplants. Post-surgical ultrasounds demonstrated improved renal growth.

  17. Fetal growth and psychiatric and socioeconomic problems: population-based sibling comparison.

    Science.gov (United States)

    Class, Quetzal A; Rickert, Martin E; Larsson, Henrik; Lichtenstein, Paul; D'Onofrio, Brian M

    2014-11-01

    It is unclear whether associations between fetal growth and psychiatric and socioeconomic problems are consistent with causal mechanisms. To estimate the extent to which associations are a result of unmeasured confounding factors using a sibling-comparison approach. We predicted outcomes from continuously measured birth weight in a Swedish population cohort (n = 3 291 773), while controlling for measured and unmeasured confounding. In the population, lower birth weight (⩽ 2500 g) increased the risk of all outcomes. Sibling-comparison models indicated that lower birth weight independently predicted increased risk for autism spectrum disorder (hazard ratio for low birth weight = 2.44, 95% CI 1.99-2.97) and attention-deficit hyperactivity disorder. Although attenuated, associations remained for psychotic or bipolar disorder and educational problems. Associations with suicide attempt, substance use problems and social welfare receipt, however, were fully attenuated in sibling comparisons. Results suggest that fetal growth, and factors that influence it, contribute to psychiatric and socioeconomic problems. Royal College of Psychiatrists.

  18. Social variations in fetal growth in a Russian setting: an analysis of medical records.

    Science.gov (United States)

    Grjibovski, Andrej M; Bygren, Lars O; Svartbo, Boo; Magnus, Per

    2003-10-01

    The study examines variations in fetal growth by maternal social circumstances in a Russian town. All pregnant women registered at the antenatal clinics in 1999 in Severodvinsk (north-west Russia) and their live born infants comprised the study base (n=1399). Multivariate linear regression analysis was applied to quantify the effect of socio-demographic factors on birthweight and the ponderal index (PI). A clear gradient of birthweight in relation to mothers' education was revealed. Babies of the most educated mothers were 207 g (95% CI, 55, 358) heavier than babies of mothers with basic education. The average weight of those born to mothers with secondary and vocational levels of education was 172 g (95% CI, 91, 253) and 83 g (95% CI, 9, 163) lower compared with infants born to mothers with a university level of education after adjustment for age, parity, pre-pregnancy weight, marital status, maternal occupation, length of gestation, and sex of the baby. Maternal education also influenced the PI. Further studies should focus on the mechanisms of the coherence of maternal education and fetal growth. To ensure that all parts of the society benefit equally from economic and social reforms, social variations in pregnancy outcomes should be monitored during the time of transition.

  19. 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.

  20. Birth weight and fetal growth in infants born to female hairdressers and their sisters.

    Science.gov (United States)

    Axmon, A; Rylander, L

    2009-03-01

    To investigate birth weight and fetal growth in female hairdressers, while controlling for intergenerational effects and effects related to childhood exposures. A cohort of women who had attended vocational schools for hairdressers were compared to their sisters with respect to birth weight and fetal growth (measured as small for gestational age (SGA) or large for gestational age (LGA), respectively) in their infants. In total, 6223 infants born to 3137 hairdressers and 8388 infants born to 3952 hairdressers' sisters were studied. Among the infants born to the hairdressers' sisters, the distribution of birth weights were wider than that among the infants born to the hairdressers. This was also reflected in that hairdresser cohort affiliation tended to be protective against both SGA (odds ratio 0.80; 95% confidence interval 0.49 to 1.31) and LGA (0.77; 0.54 to 1.09). For LGA, this effect was even more pronounced among women who had actually worked as hairdressers during at least one pregnancy (0.60; 0.39 to 0.92). The infants born to these women also had a significantly lower mean birth weight (3387 g vs 3419 g; p = 0.033). The results from the present study suggest that infants born to hairdressers have a decreased risk of being LGA. This is most likely not caused by a shift in birth weight distribution or abnormal glucose metabolism.

  1. Platelet-rich plasma can replace fetal bovine serum in human meniscus cell cultures

    NARCIS (Netherlands)

    Gonzales, V.K.; Mulder, E.L.W. de; Boer, T. den; Hannink, G.; Tienen, T.G. van; Heerde, W.L. van; Buma, P.

    2013-01-01

    Concerns over fetal bovine serum (FBS) limit the clinical application of cultured tissue-engineered constructs. Therefore, we investigated if platelet-rich plasma (PRP) can fully replace FBS for meniscus tissue engineering purposes. Human PRP and platelet-poor plasma (PPP) were isolated from three

  2. Dissecting human cerebral organoids and fetal neocortex using single-cell RNAseq

    Science.gov (United States)

    Treutlein, Barbara

    Cerebral organoids - three-dimensional cultures of human cerebral tissue derived from pluripotent stem cells - have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex. Covariation network analysis using the fetal neocortex data reveals known and novel interactions among genes central to neural progenitor proliferation and neuronal differentiation. In the organoid, we detect diverse progenitors and differentiated cell types of neuronal and mesenchymal lineages, and identify cells that derived from regions resembling the fetal neocortex. We find that these organoid cortical cells use gene expression programs remarkably similar to those of the fetal tissue in order to organize into cerebral cortex-like regions. Our comparison of in vivo and in vitro cortical single cell transcriptomes illuminates the genetic features underlying human cortical development that can be studied in organoid cultures.

  3. Reduced cell number in the neocortical part of the human fetal brain in Down syndrome

    DEFF Research Database (Denmark)

    Larsen, K.B.; Laursen, H.; Graem, N.

    2008-01-01

    Mental retardation is seen in all individuals with Down syndrome (DS) and different brain abnormalities are reported. The aim of this study was to investigate if mental retardation at least in part is a result of a lower cell number in the neocortical part of the human fetal forebrain. We therefore...

  4. Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth.

    Science.gov (United States)

    Aye, Irving L M H; Rosario, Fredrick J; Powell, Theresa L; Jansson, Thomas

    2015-10-13

    Mothers with obesity or gestational diabetes mellitus have low circulating levels of adiponectin (ADN) and frequently deliver large babies with increased fat mass, who are susceptible to perinatal complications and to development of metabolic syndrome later in life. It is currently unknown if the inverse correlation between maternal ADN and fetal growth reflects a cause-and-effect relationship. We tested the hypothesis that ADN supplementation in obese pregnant dams improves maternal insulin sensitivity, restores normal placental insulin/mechanistic target of rapamycin complex 1 (mTORC1) signaling and nutrient transport, and prevents fetal overgrowth. Compared with dams on a control diet, female C57BL/6J mice fed an obesogenic diet before mating and throughout gestation had increased fasting serum leptin, insulin, and C-peptide, and reduced high-molecular-weight ADN at embryonic day (E) 18.5. Placental insulin and mTORC1 signaling was activated, peroxisome proliferator-activated receptor-α (PPARα) phosphorylation was reduced, placental transport of glucose and amino acids in vivo was increased, and fetal weights were 29% higher in obese dams. Maternal ADN infusion in obese dams from E14.5 to E18.5 normalized maternal insulin sensitivity, placental insulin/mTORC1 and PPARα signaling, nutrient transport, and fetal growth without affecting maternal fat mass. Using a mouse model with striking similarities to obese pregnant women, we demonstrate that ADN functions as an endocrine link between maternal adipose tissue and fetal growth by regulating placental function. Importantly, maternal ADN supplementation reversed the adverse effects of maternal obesity on placental function and fetal growth. Improving maternal ADN levels may serve as an effective intervention strategy to prevent fetal overgrowth caused by maternal obesity.

  5. A review of the literature on the effects of ambient air pollution on fetal growth

    International Nuclear Information System (INIS)

    Maisonet, Mildred; Correa, Adolfo; Misra, Dawn; Jaakkola, J.J.K.

    2004-01-01

    A systematic review of the literature on the effects of air pollution on low birth weight (LBW) and its determinants, preterm delivery (PTD) and intrauterine growth restriction (IUGR), was conducted. Twelve epidemiologic investigations that addressed the impact of air pollution on four pregnancy outcomes were identified. Results were analyzed separately for each perinatal outcome because of differences in pathogenic mechanisms. Effects of air pollution were apparent on PTD and IUGR, but not on LBW. Most of the associations reported were rather small. The estimation of summary effects was not meaningful because of the heterogeneity of the effect estimates arising from differences in the measurements of outcome, exposure, and confounders and the small number of studies per outcome (four studies for PTD and six for IUGR). Current scientific knowledge on the impact of air pollution on fetal growth is still limited; thus, several issues should be examined further

  6. Assessment of Fetal Kidney Growth and Birth Weight in an Indigenous Australian Cohort

    Directory of Open Access Journals (Sweden)

    Christopher J. Diehm

    2018-01-01

    Full Text Available Introduction: Indigenous Australians experience higher rates of renal disease and hypertension than non-Indigenous Australians. Low birth weight is recognized as a contributing factor in chronic disease and has been shown to increase the risk of renal failure in adulthood. A smaller kidney volume with fewer nephrons places an individual at risk of hypertension and renal failure. Indigenous Australians have fewer nephrons than non-Indigenous Australians. In this study, intrauterine fetal and kidney growth were evaluated in 174 Indigenous Australian babies throughout gestation in order to record and evaluate fetal growth and kidney size, within a population that is at high risk for chronic illness.Methods: Pregnant women that identified as Indigenous, or non-Indigenous women that were pregnant with a partner who identified as an Indigenous Australian were eligible to participate. Maternal history, smoking status, blood and urine samples and fetal ultrasounds were collected throughout pregnancy. Fetal kidney measurements were collected using ultrasound. Statistical analysis was performed using the Stata 14.1 software package.Results: 15.2% of babies were born prematurely. 44% of the mothers reported smoking in pregnancy. The median birth weight of this cohort was 3,240 g. Male fetuses had higher kidney to body weight ratios than female fetuses (P = 0.02. The birth weights of term neonates whose mothers smoked during pregnancy were lower (327 g, P < 0.001 than the birth weights of term babies from non-smoking mothers. The kidney volumes of babies whose mothers smoked were also smaller (P = 0.02, but were in proportion to body weight.Conclusion: In this cohort of Indigenous women smoking was associated with both increased number of preterm births and with a reduction in birth weights, even of term infants. Since kidney volume is a surrogate measure of nephron number and nephrogenesis is complete at birth, babies whose mothers smoked during pregnancy

  7. Chondrocyte heterogeneity: immunohistologically defined variation of integrin expression at different sites in human fetal knees.

    Science.gov (United States)

    Salter, D M; Godolphin, J L; Gourlay, M S

    1995-04-01

    During development and at maturity different forms of cartilage vary in morphology and macromolecular content. This reflects heterogeneity of chondrocyte activity, in part involving differential interactions with the adjacent extracellular matrix via specialized cell surface receptors such as integrins. We undertook an immunohistological study on a series of human fetal knee joints to assess variation in the expression of integrins by chondrocytes and potential matrix ligands in articular, epiphyseal, growth plate, and meniscal cartilage. The results show that articular chondrocytes (beta 1+, beta 5 alpha V+, alpha 1+, alpha 2+/-, alpha 5+, weakly alpha 6+, alpha V+) differed from epiphyseal (beta 1+, beta 5 alpha V+, alpha 1+/-, alpha 2+/-, alpha 5+, alpha 6+, alpha V+) growth plate (beta 1+, beta 5 alpha V+, alpha 1-, alpha 2-, alpha 5+, alpha 6+, alpha V+), and meniscal cells (beta 1+, beta 5 alpha V+, alpha 1+, strongly alpha 2+, alpha 5+, alpha 6+, alpha V+ in expression of integrin subunits. There was no expression of beta 3, beta 4, beta 6, or alpha 3 by chondrocytes. These results differ from previous reports on the expression of integrins by adult articular cartilage, where alpha 2 and alpha 6 are not seen. Variation in distribution of matrix ligands was also seen. Fibronectin, laminin and Type VI collagen were expressed in all cartilages but there was restricted expression of tenascin, ED-A and ED-B fibronectin isoforms (articular cartilage and meniscus), and vitronectin (absent from growth plate cartilage). Regulated expression of integrins by chondrocytes, associated with changes in the pericellular matrix composition, is of potential importance in control of cartilage differentiation and function in health and disease.

  8. Recent advances in the prenatal interrogation of the human fetal genome.

    Science.gov (United States)

    Hui, Lisa; Bianchi, Diana W

    2013-02-01

    The amount of genetic and genomic information obtainable from the human fetus during pregnancy is accelerating at an unprecedented rate. Two themes have dominated recent technological advances in prenatal diagnosis: interrogation of the fetal genome in increasingly high resolution and the development of non-invasive methods of fetal testing using cell-free DNA in maternal plasma. These two areas of advancement have now converged with several recent reports of non-invasive assessment of the entire fetal genome from maternal blood. However, technological progress is outpacing the ability of the healthcare providers and patients to incorporate these new tests into existing clinical care, and further complicates many of the economic and ethical dilemmas in prenatal diagnosis. This review summarizes recent work in this field and discusses the integration of these new technologies into the clinic and society. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Insulin receptors mediate growth effects in cultured fetal neurons. I. Rapid stimulation of protein synthesis

    International Nuclear Information System (INIS)

    Heidenreich, K.A.; Toledo, S.P.

    1989-01-01

    In this study we have examined the effects of insulin on protein synthesis in cultured fetal chick neurons. Protein synthesis was monitored by measuring the incorporation of [3H]leucine (3H-leu) into trichloroacetic acid (TCA)-precipitable protein. Upon addition of 3H-leu, there was a 5-min lag before radioactivity occurred in protein. During this period cell-associated radioactivity reached equilibrium and was totally recovered in the TCA-soluble fraction. After 5 min, the incorporation of 3H-leu into protein was linear for 2 h and was inhibited (98%) by the inclusion of 10 micrograms/ml cycloheximide. After 24 h of serum deprivation, insulin increased 3H-leu incorporation into protein by approximately 2-fold. The stimulation of protein synthesis by insulin was dose dependent (ED50 = 70 pM) and seen within 30 min. Proinsulin was approximately 10-fold less potent than insulin on a molar basis in stimulating neuronal protein synthesis. Insulin had no effect on the TCA-soluble fraction of 3H-leu at any time and did not influence the uptake of [3H]aminoisobutyric acid into neurons. The isotope ratio of 3H-leu/14C-leu in the leucyl tRNA pool was the same in control and insulin-treated neurons. Analysis of newly synthesized proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that insulin uniformly increased the incorporation of 14C-leu into all of the resolved neuronal proteins. We conclude from these data that (1) insulin rapidly stimulates overall protein synthesis in fetal neurons independent of amino acid uptake and aminoacyl tRNA precursor pools; (2) stimulation of protein synthesis is mediated by the brain subtype of insulin receptor; and (3) insulin is potentially an important in vivo growth factor for fetal central nervous system neurons

  10. 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

  11. Gonadotropin-releasing hormone immunoreactivity in the adult and fetal human olfactory system.

    Science.gov (United States)

    Kim, K H; Patel, L; Tobet, S A; King, J C; Rubin, B S; Stopa, E G

    1999-05-01

    Studies in fetal brain tissue of rodents, nonhuman primates and birds have demonstrated that cells containing gonadotropin-releasing hormone (GnRH) migrate from the olfactory placode across the nasal septum into the forebrain. The purpose of this study was to examine GnRH neurons in components of the adult and fetal human olfactory system. In the adult human brain (n=4), immunoreactive GnRH was evident within diffusely scattered cell bodies and processes in the olfactory bulb, olfactory nerve, olfactory cortex, and nervus terminalis located on the anterior surface of the gyrus rectus. GnRH-immunoreactive structures showed a similar distribution in 20-week human fetal brains (n=2), indicating that the migration of GnRH neurons is complete at this time. In 10-11-week fetal brains (n=2), more cells were noted in the nasal cavity than in the brain. Our data are consistent with observations made in other species, confirming olfactory derivation and migration of GnRH neurons into the brain from the olfactory placode. Copyright 1999 Elsevier Science B.V.

  12. Discovery and Characterization of piRNAs in the Human Fetal Ovary

    Directory of Open Access Journals (Sweden)

    Zev Williams

    2015-10-01

    Full Text Available Piwi-interacting RNAs (piRNAs, a class of 26- to 32-nt non-coding RNAs (ncRNAs, function in germline development, transposon silencing, and epigenetic regulation. We performed deep sequencing and annotation of untreated and periodate-treated small RNA cDNA libraries from human fetal and adult germline and reference somatic tissues. This revealed abundant piRNAs originating from 150 piRNA-encoding genes, including some exhibiting gender-specific expression, in fetal ovary and adult testis—developmental periods coinciding with mitotic cell divisions expanding fetal germ cells prior to meiotic divisions. The absence of reads mapping uniquely to annotated piRNA genes demonstrated their paucity in fetal testis and adult ovary and absence in somatic tissues. We curated human piRNA-expressing regions and defined their precise borders and observed piRNA-guided cleavage of transcripts antisense to some piRNA-producing genes. This study provides insights into sex-specific mammalian piRNA expression and function and serves as a reference for human piRNA analysis and annotation.

  13. THE EFFECT OF FETAL CALF SERUM ON HUMAN DENTAL PULP STEM CELLS

    Directory of Open Access Journals (Sweden)

    Jakub Suchánek

    2013-01-01

    Full Text Available Aims: Authors studied potential side effects of fetal calf serum (FCS in cultivation media on human dental pulp stem cells (DPSC during long term cultivation. Methods: Two lines of DPSC obtained healthy donors (male 22 years, female 23 years were used. Both lines were cultivated under standard cultivation conditions in four different media containing 10% or 2% FCS and substituted with growth factors. During long term cultivation proliferation ability, karyotype and phenotype of DPSC were measured. Results: Both lines of DPSC cultivated in a media containing 2% FCS and ITS supplement showed the highest number of population doublings. On the other hand the proliferation rate of DPSC cultivated in a media with 2% FCS without ITS supplement was slowest. Proliferation rate of DPSC cultivated in 10% FCS media with or without FGF-2 was comparable. DPSC cultivated in a media with 10% FCS showed a significantly higher amount of chromosomal aberrations. These chromosomal aberrations do not seem to be clonal but surprisingly we found large amounts of tetraploid cells in the 9th passage in both media containing 10% FCS. Conclusions: Our study proved that cultivation of DPSC in media containing higher concentration of FCS has critical side effects on cell chromosomal stability.

  14. Fetal MRI; Fetales MRT

    Energy Technology Data Exchange (ETDEWEB)

    Blondin, D. [Inst. fuer Diagn. Radiologie, Uniklinikum Duesseldorf (Germany); Turowski, B. [Inst. fuer Diagn. Radiologie, Neuroradiologie, Uniklinikum Duesseldorf (Germany); Schaper, J. [Inst. fuer Diagn. Radiologie, Kinderradiologie, Uniklinikum Duesseldorf (Germany)

    2007-02-15

    Ultrasonography is the method of choice for prenatal malformation screening, but it does not always provide sufficient information for correct diagnosis or adequate abnormality evaluation. Fetal MRI is increasingly being used to complete sonographic findings. It was initially used for evaluation of cerebral abnormalities but is increasingly being applied to other fetal areas. In vivo investigation of fetal brain maturation has been enhanced by MRI. An adequate analysis of fetal chest and abdomen can be achieved with fast T2-, T1-weighted and diffusion-weighted imaging (DWI). The advantages include the great field of view and the excellent soft tissue contrast. This allows correct diagnosis of congenital diaphragmatic hernia and evaluation of the consequences on pulmonary growth. Other pulmonary malformations, such as cystic adenomatoid malformation, sequestration and brochogenic cysts, can also be easily identified. Renal position can be quickly determined using DWI sequences and renal agenesia can be easily diagnosed with only one sequence. Prenatal MRI is virtually as effective as postnatal examination, dispenses with transport of a potentially very ill newborn, and provides logistic advantages. Therefore, prenatal MRI is useful for adequate postnatal treatment of newborns with malformations. (orig.)

  15. Impact of aspirin on fetal growth in diabetic pregnancies according to White classification.

    Science.gov (United States)

    Adkins, Katlynn; Allshouse, Amanda A; Metz, Torri D; Heyborne, Kent D

    2017-10-01

    Current US Preventive Services Task Force and other guidelines recommend low-dose aspirin for all pregnant women with pregestational diabetes mellitus to prevent preeclampsia and small-for-gestational-age birth. The Maternal-Fetal Medicine Units High-Risk Aspirin trial did not show a reduction in either preeclampsia or small-for-gestational-age birth in diabetic women. Our objective was to reassess the impact of aspirin on fetal growth in diabetic pregnancies overall and according to White classification. We hypothesized that aspirin improves fetal growth in pregnancies with vascular complications of diabetes at highest risk for poor fetal growth. We conducted secondary analysis of the cohort of diabetic women enrolled in the Maternal-Fetal Medicine Units High-Risk Aspirin trial. The impact of aspirin prophylaxis on birthweight was assessed in the overall cohort and in 2 groups categorized according to White classification as nonvascular (White class B, C, D) or vascular (White class R, F, RF). Birthweight was converted to Z-score normalized for gestational age at delivery and neonatal sex. Difference in birthweight Z-score between aspirin and placebo was tested with a 2-sample t test. The effect of vascular group, aspirin vs placebo randomization, and the interaction of the 2 on normalized birthweight percentile was estimated with linear regression with a multivariable model including covariates body mass index, tobacco use, race, and parity. The percentage of small and large-for-gestational-age newborns born to aspirin- vs placebo-treated women was compared between groups using Pearson exact χ 2 analysis, and an adjusted model was estimated by logistic regression. All 444 women with pregestational diabetes and complete outcome data were included (53 vascular, 391 nonvascular). Aspirin was significantly associated with a higher birthweight Z-score (0.283; 95% confidence interval, 0.023-0.544) in the overall cohort (P = .03). In the adjusted model, the

  16. Defective trophoblast invasion underlies fetal growth restriction and preeclampsia-like symptoms in the stroke-prone spontaneously hypertensive rat.

    Science.gov (United States)

    Barrientos, G; Pussetto, M; Rose, M; Staff, A C; Blois, S M; Toblli, J E

    2017-07-01

    What is the impact of chronic hypertension on placental development, fetal growth and maternal outcome in the stroke-prone spontaneously hypertensive rat (SHRSP)? SHRSP showed an impaired remodeling of the spiral arteries and abnormal pattern of trophoblast invasion during placentation, which were associated with subsequent maternal glomerular injury and increased baseline hypertension as well as placental insufficiency and asymmetric fetal growth restriction (FGR). A hallmark in the pathogenesis of preeclampsia (PE) is abnormal placentation with defective remodeling of the spiral arteries preceding the onset of the maternal syndrome. Pregnancies affected by chronic hypertension display an increased risk for PE, often associated with poor maternal and fetal outcomes. However, the impact of chronic hypertension on the placentation process as well as the nature of the factors promoting the development of PE in pregnant hypertensive women remain elusive. Timed pregnancies [n = 5] were established by mating 10-12-week-old SHRSP and Wistar Kyoto (WKY, normotensive controls) females with congenic males. Maternal systolic blood pressures (SBPs) were recorded pre-mating, throughout pregnancy (GD1-19) and post-partum by the tail-cuff method. On selected dates, 24 h urine- and blood samples were collected, and animals were euthanized for isolation of implantation sites and kidneys for morphometrical analyses. The 24 h proteinuria and the albumin:creatinine ratio were used for evaluation of maternal renal function. Renal injury was assessed on periodic acid Schiff, Masson's trichrome and Sirius red stainings. Placental and fetal weights were recorded on gestation day (GD)18 and GD20, followed by determination of fetal cephalization indexes and developmental stage, according to the Witschi scale. Morphometric analyses of placental development were conducted on hematoxylin-eosin stained tissue sections collected on GD14 and GD18, and complemented with immunohistochemical

  17. Increased Concentrations of Insulin-Like Growth Factor Binding Protein (IGFBP-2, IGFBP-3, and IGFBP-4 Are Associated With Fetal Mortality in Pregnant Cows

    Directory of Open Access Journals (Sweden)

    Kirsten Mense

    2018-06-01

    Full Text Available Insulin-like growth factors (IGFs play a critical role in fetal growth, and components of the IGF system have been associated with fetal growth restriction in women. In human pregnancy, the proteolytic cleavage of insulin-like growth factor binding proteins (IGFBPs, particularly IGFBP-4, releases free IGF for respective action at the tissue level. The aim of the present study was to determine IGFBP-2, IGFBP-3, and IGFBP-4 concentrations by Western ligand blotting during pregnancy until day 100 in cows and to compare these concentrations with those of non-pregnant cows and cows undergoing embryonic/fetal mortality. Therefore, two study trials (I and II and an in vitro study were conducted. In study I, 43 cows were not pregnant, 34 cows were pregnant, and 4 cows were undergoing fm. In study II, 500 cows were examined, and 7 cases of pregnancy loss between days 24–27 and 34–37 after artificial insemination (AI, late embryonic mortality; em and 8 cases of pregnancy loss between days 34–37 and 54–57 after AI (late embryonic mortality and early fetal mortality; em/fm were defined from the analyses of 30 pregnant and 20 non-pregnant cows randomly selected for insulin-like growth factor 1 and IGFBP analyses. In vitro serum from pregnant (n = 3 and non-pregnant (n = 3 cows spiked after incubation with recombinant human (rh IGFBP-4 for 24 h, and IGFBP-4 levels were analyzed before and after incubation to detect proteolytic degradation. The IGFBP-2, -3, and -4 concentrations did not decline during early pregnancy in cows, while IGFBP-4 concentrations were comparable between pregnant and non-pregnant cows, irrespective of low proteolytic activity, which was also demonstrated in cows. Interestingly, cows with em or fm showed distinct IGFBP patterns. The IGFBP-2 and -3 concentrations were higher (P < 0.05 in cows with fm compared to pregnant. The IGFBP-4 levels were significantly higher in cows developing fm. Thus, distinct differences

  18. Fish intake during pregnancy, fetal growth, and gestational length in 19 European birth cohort studies.

    Science.gov (United States)

    Leventakou, Vasiliki; Roumeliotaki, Theano; Martinez, David; Barros, Henrique; Brantsaeter, Anne-Lise; Casas, Maribel; Charles, Marie-Aline; Cordier, Sylvaine; Eggesbø, Merete; van Eijsden, Manon; Forastiere, Francesco; Gehring, Ulrike; Govarts, Eva; Halldórsson, Thorhallur I; Hanke, Wojciech; Haugen, Margaretha; Heppe, Denise H M; Heude, Barbara; Inskip, Hazel M; Jaddoe, Vincent W V; Jansen, Maria; Kelleher, Cecily; Meltzer, Helle Margrete; Merletti, Franco; Moltó-Puigmartí, Carolina; Mommers, Monique; Murcia, Mario; Oliveira, Andreia; Olsen, Sjúrður F; Pele, Fabienne; Polanska, Kinga; Porta, Daniela; Richiardi, Lorenzo; Robinson, Siân M; Stigum, Hein; Strøm, Marin; Sunyer, Jordi; Thijs, Carel; Viljoen, Karien; Vrijkotte, Tanja G M; Wijga, Alet H; Kogevinas, Manolis; Vrijheid, Martine; Chatzi, Leda

    2014-03-01

    Fish is a rich source of essential nutrients for fetal development, but in contrast, it is also a well-known route of exposure to environmental pollutants. We assessed whether fish intake during pregnancy is associated with fetal growth and the length of gestation in a panel of European birth cohort studies. The study sample of 151,880 mother-child pairs was derived from 19 population-based European birth cohort studies. Individual data from cohorts were pooled and harmonized. Adjusted cohort-specific effect estimates were combined by using a random- and fixed-effects meta-analysis. Women who ate fish >1 time/wk during pregnancy had lower risk of preterm birth than did women who rarely ate fish (≤ 1 time/wk); the adjusted RR of fish intake >1 but 1 but <3 times/wk and 15.2 g (95% CI: 8.9, 21.5 g) for ≥ 3 times/wk independent of gestational age. The association was greater in smokers and in overweight or obese women. Findings were consistent across cohorts. This large, international study indicates that moderate fish intake during pregnancy is associated with lower risk of preterm birth and a small but significant increase in birth weight.

  19. Characterization of insulin-like growth factor I produced by fetal rat pancreatic islets

    International Nuclear Information System (INIS)

    Scharfmann, R.; Corvol, M.; Czernichow, P.

    1989-01-01

    Pancreatic islets were prepared from 22-day-old rat fetuses. After 5 days of culture in dishes allowing cell attachment, neoformed islets were kept free floating in RPMI-1640 medium (16.5 mM glucose, 1% fetal calf serum). The islets were then pulsed with [ 3 H]leucine and [ 35 S]methionine for 24 h. The conditioned medium was acidified with acetic acid (final pH 2.7), desalted, concentrated, and gel filtered on Bio-Gel P100 in acid conditions. The radioactive material that comigrated with immunoreactive insulinlike growth factor I (IGF-I) produced by the islets was pooled, concentrated, and further characterized by reverse-phase high-performance liquid chromatography on a C18 Bondapak column with a linear gradient of acetonitrile (20-80%). The radioactive material that eluted as pure IGF-I (40% acetonitrile) was further studied by chromatofocusing on a Pharmacia PBE 94 column. A sharp radioactive peak containing [ 3 H]leucine and [ 35 S]methionine was eluted at pH 8.55. This material was immunoprecipitated with an antiserum to IGF-I. This study demonstrated that fetal islet cells synthesize molecules that are, by several criteria, equivalent to native IGF-I

  20. Levels of neopterin and C-reactive protein in pregnant women with fetal growth restriction.

    Science.gov (United States)

    Erkenekli, K; Keskin, U; Uysal, B; Kurt, Y G; Sadir, S; Çayci, T; Ergün, A; Erkaya, S; Danişman, N; Uygur, D

    2015-04-01

    The aim of this study was to evaluate whether pregnant women with fetal growth restriction (FGR) have higher plasma neopterin and C-reactive protein (CRP) concentrations compared with those with uncomplicated pregnancy. A total of 34 pregnant women with FGR and 62 patients with uncomplicated pregnancy were included. Neopterin and CRP levels were measured at the time of diagnosis. The primary outcome of this study was to compare the neopterin and CRP levels in pregnant women with FGR and those with uncomplicated pregnancies. The secondary outcome of our study was to evaluate the correlation between fetal birth weight and maternal neopterin levels. The serum neopterin levels were significantly elevated in pregnant women with FGR (22.71 ± 7.70 vs 19.15 ± 8.32). However, CRP was not elevated in pregnant women with FGR (7.47 ± 7.59 vs 5.29 ± 3.58). These findings support the hypothesis that pregnancy with FGR is associated with a marked increase in macrophage activation and the natural immune system.

  1. Management of Very Early-onset Fetal Growth Restriction: Results from 92 Consecutive Cases.

    Science.gov (United States)

    Hoellen, Friederike; Beckmann, Annika; Banz-Jansen, Constanze; Weichert, Jan; Rody, Achim; Bohlmann, Michael K

    2016-01-01

    To evaluate management of early-onset intrauterine growth restriction (IUGR) and to define outcome according to obstetric setting. During an 11-year period (2000-2011), data of patients presenting with IUGR and preterm delivery of less than 30 weeks of gestation at a tertiary perinatal center were retrospectively reviewed. A total of 92 pregnancies were investigated. Delivery was indicated for fetal reasons in 38 out of 92 patients. Sixteen children of our cohort died within one year post partum, out of which eight had suffered from severe early-onset IUGR causing iatrogenic preterm delivery. Concerning the fetal outcome, gestational age at delivery and antenatal exposure to corticosteroids were found to be crucial. In some cases, respiratory distress syndrome prophylaxis and a "wait and see" approach to management in favor of a prolongation of the pregnancy might be favorable. Randomized prospective trials in early-onset IUGR with threatened preterm deliveries are needed in order to define guidelines for an individually tailored management of early-onset preterm infants. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  2. Discarded human fetal tissue and cell cultures for transplantation research

    International Nuclear Information System (INIS)

    Hay, R.J.; Phillips, T.; Thompson, A.; Vilner, L.; Cleland, M.; Tchaw-ren Chen; Zabrenetzky, V.

    1999-01-01

    A feasibility study has been performed to explore the utility of various tissues from discarded human abortuses for transplantation and related research. Specifically, aborted fetuses plus parental blood samples and all relevant clinical data were obtained through a local hospital complex. Whenever possible, pancreas, skin and skeletal muscle, heart, liver, kidney, cartilage and lung tissues were removed, dissociated and subfractionated for cryopreservation, characterization and cultivation trials in vitro. Existing protocols for these manipulations were compared and improved upon as required. Clonal culture, cell aggregate maintenance techniques and use of feeder cell populations have been utilized where appropriate to develop quantitative comparative data. Histological and biochemical assays were applied both to evaluate separation/cultivation methods and to identify optimal culture conditions for maintaining functional cells. Immunochemical and molecular biological procedures were applied to study expression of Major Histocompatibility Vomplex (MHC) class 1 and 11 molecules on cell lines derived. Tissue and cell culture populations were examined for infections with bacteria, ftingi, mycoplasma, HIV, CMV, hepatitis B and other viruses. Only 1% of the abortuses tested were virally infected. Cytogenetic analyses confin-ned the normal diploid status in the vast majority (>98%) of lines tested. A total of over 250 abortuses have been obtained and processed. Only 25 were found to be contaminated with bacteria or fungi and unsuitable for further cultivation trials. A total of over 200 cell populations were isolated, characterized and cryopreserved for further study. Included were kidney, lung, liver and epidermal epithelia: cartilage-derived cells from the spine and epiphyses plus myogenic myoblasts. Selected lines have been immortalized using HPV I 6E6/E7 sequences. Epithelia from the liver and pancreas and cardiac myocytes were the most problematic in that initial

  3. Ultrasonographic fetal growth charts: an informatic approach by quantitative analysis of the impact of ethnicity on diagnoses based on a preliminary report on Salentinian population.

    Science.gov (United States)

    Tinelli, Andrea; Bochicchio, Mario Alessandro; Vaira, Lucia; Malvasi, Antonio

    2014-01-01

    Clear guidance on fetal growth assessment is important because of the strong links between growth restriction or macrosomia and adverse perinatal outcome in order to reduce associated morbidity and mortality. Fetal growth curves are extensively adopted to track fetal sizes from the early phases of pregnancy up to delivery. In the literature, a large variety of reference charts are reported but they are mostly up to five decades old. Furthermore, they do not address several variables and factors (e.g., ethnicity, foods, lifestyle, smoke, and physiological and pathological variables), which are very important for a correct evaluation of the fetal well-being. Therefore, currently adopted fetal growth charts are inadequate to support the melting pot of ethnic groups and lifestyles of our society. Customized fetal growth charts are needed to provide an accurate fetal assessment and to avoid unnecessary obstetric interventions at the time of delivery. Starting from the development of a growth chart purposely built for a specific population, in the paper, authors quantify and analyse the impact of the adoption of wrong growth charts on fetal diagnoses. These results come from a preliminary evaluation of a new open service developed to produce personalized growth charts for specific ethnicity, lifestyle, and other parameters.

  4. Fetal and Neonatal Levels of Omega-3: Effects on Neurodevelopment, Nutrition, and Growth

    Directory of Open Access Journals (Sweden)

    Juliana Rombaldi Bernardi

    2012-01-01

    Full Text Available Nutrition in pregnancy, during lactation, childhood, and later stages has a fundamental influence on overall development. There is a growing research interest on the role of key dietary nutrients in fetal health. Omega-3 polyunsaturated fatty acids (n-3 LCPUFAs play an important role in brain development and function. Evidence from animal models of dietary n-3 LCPUFAs deficiency suggests that these fatty acids promote early brain development and regulate behavioral and neurochemical aspects related to mood disorders (stress responses, depression, and aggression and growth, memory, and cognitive functions. Preclinical and clinical studies suggest the role of n-3 LCPUFAs on neurodevelopment and growth. n-3 LCPUFAs may be an effective adjunctive factor for neural development, growth, and cognitive development, but further large-scale, well-controlled trials and preclinical studies are needed to examine its clinical mechanisms and possible benefits. The present paper discusses the use of n-3 LCPUFAs during different developmental stages and the investigation of different sources of consumption. The paper summarizes the role of n-3 LCPUFAs levels during critical periods and their effects on the children’s neurodevelopment, nutrition, and growth.

  5. Effect of mono-(2-ethylhexyl) phthalate on human and mouse fetal testis: In vitro and in vivo approaches

    Energy Technology Data Exchange (ETDEWEB)

    Muczynski, V. [Univ. Paris Diderot, Sorbonne Paris Cité, Laboratory of Development of the Gonads, Unit of Stem Cells and Radiation, BP 6, 92265 Fontenay-aux-Roses (France); CEA, DSV, iRCM, SCSR, LDRG, 92265 Fontenay-aux-Roses (France); INSERM, Unité 967, F-92265, Fontenay aux Roses (France); Cravedi, J.P. [INRA, INP, Université de Toulouse, UMR1331 TOXALIM, F-31027, Toulouse (France); Lehraiki, A.; Levacher, C.; Moison, D.; Lecureuil, C.; Messiaen, S. [Univ. Paris Diderot, Sorbonne Paris Cité, Laboratory of Development of the Gonads, Unit of Stem Cells and Radiation, BP 6, 92265 Fontenay-aux-Roses (France); CEA, DSV, iRCM, SCSR, LDRG, 92265 Fontenay-aux-Roses (France); INSERM, Unité 967, F-92265, Fontenay aux Roses (France); Perdu, E. [INRA, INP, Université de Toulouse, UMR1331 TOXALIM, F-31027, Toulouse (France); Frydman, R. [Service de Gynécologie-Obstétrique, Hôpital A. Béclère, Université Paris Sud F-92141 Clamart (France); Habert, R. [Univ. Paris Diderot, Sorbonne Paris Cité, Laboratory of Development of the Gonads, Unit of Stem Cells and Radiation, BP 6, 92265 Fontenay-aux-Roses (France); CEA, DSV, iRCM, SCSR, LDRG, 92265 Fontenay-aux-Roses (France); INSERM, Unité 967, F-92265, Fontenay aux Roses (France); and others

    2012-05-15

    The present study was conducted to determine whether exposure to the mono-(2-ethylhexyl) phthalate (MEHP) represents a genuine threat to male human reproductive function. To this aim, we investigated the effects on human male fetal germ cells of a 10{sup −5} M exposure. This dose is slightly above the mean concentrations found in human fetal cord blood samples by biomonitoring studies. The in vitro experimental approach was further validated for phthalate toxicity assessment by comparing the effects of in vitro and in vivo exposure in mouse testes. Human fetal testes were recovered during the first trimester (7–12 weeks) of gestation and cultured in the presence or not of 10{sup −5} M MEHP for three days. Apoptosis was quantified by measuring the percentage of Caspase-3 positive germ cells. The concentration of phthalate reaching the fetal gonads was determined by radioactivity measurements, after incubations with {sup 14}C-MEHP. A 10{sup −5} M exposure significantly increased the rate of apoptosis in human male fetal germ cells. The intratesticular MEHP concentration measured corresponded to the concentration added in vitro to the culture medium. Furthermore, a comparable effect on germ cell apoptosis in mouse fetal testes was induced both in vitro and in vivo. This study suggests that this 10{sup −5} M exposure is sufficient to induce changes to the in vivo development of the human fetal male germ cells. -- Highlights: ► 10{sup −5} M of MEHP impairs germ cell development in the human fetal testis. ► Organotypic culture is a suitable approach to investigate phthalate effects in human. ► MEHP is not metabolized in the human fetal testis. ► In mice, MEHP triggers similar effects both in vivo and in vitro.

  6. MATERNAL HEIGHT AND PRE-PREGNANCY WEIGHT STATUS ARE ASSOCIATED WITH FETAL GROWTH PATTERNS AND NEWBORN SIZE.

    Science.gov (United States)

    Pölzlberger, Eva; Hartmann, Beda; Hafner, Erich; Stümpflein, Ingrid; Kirchengast, Sylvia

    2017-05-01

    The impact of maternal height, pre-pregnancy weight status and gestational weight gain on fetal growth patterns and newborn size was analysed using a dataset of 4261 singleton term births taking place at the Viennese Danube Hospital between 2005 and 2013. Fetal growth patterns were reconstructed from three ultrasound examinations carried out at the 11th/12th, 20th/21th and 32th/33th weeks of gestation. Crown-rump length, biparietal diameter, fronto-occipital diameter, head circumference, abdominal transverse diameter, abdominal anterior-posterior diameter, abdominal circumference and femur length were determined. Birth weight, birth length and head circumference were measured immediately after birth. The vast majority of newborns were of normal weight, i.e. between 2500 and 4000 g. Maternal height showed a just-significant but weak positive association (r=0.03: p=0.039) with crown-rump length at the first trimester and with the majority of fetal parameters at the second trimester (r>0.06; p0.09; p0.08; p0.17; p0.13; p0.13; pnewborn size. Some of these associations were quite weak and the statistical significance was mainly due to the large sample size. The association patterns between maternal height and pre-pregnancy weight status with fetal growth patterns (pnewborn size (p<0.001), were independent of maternal age, nicotine consumption and fetal sex. In general, taller and heavier women gave birth to larger infants. This association between maternal size and fetal growth patterns was detectable from the first trimester onwards.

  7. Growth charts of human development

    NARCIS (Netherlands)

    Van Buuren, Stef

    2014-01-01

    This article reviews and compares two types of growth charts for tracking human development over age. Both charts assume the existence of a continuous latent variable, but relate to the observed data in different ways. The D-score diagram summarizes developmental indicators into a single aggregate

  8. In an in-vitro model using human fetal membranes, 17-α hydroxyprogesterone caproate is not an optimal progestogen for inhibition of fetal membrane weakening.

    Science.gov (United States)

    Kumar, Deepak; Moore, Robert M; Mercer, Brian M; Mansour, Joseph M; Mesiano, Sam; Schatz, Frederick; Lockwood, Charles J; Moore, John J

    2017-12-01

    The progestogen 17-α hydroxyprogesterone caproate (17-OHPC) is 1 of only 2 agents recommended for clinical use in the prevention of spontaneous preterm delivery, and studies of its efficacy have been conflicting. We have developed an in-vitro model to study the fetal membrane weakening process that leads to rupture in preterm premature rupture of the fetal membranes (pPROM). Inflammation/infection associated with tumor necrosis factor-α (TNF-α) induction and decidual bleeding/abruption associated thrombin release are leading causes of preterm premature rupture of the fetal membranes. Both agents (TNF-α and thrombin) cause fetal membrane weakening in the model system. Furthermore, granulocyte-macrophage colony-stimulating factor (GM-CSF) is a critical intermediate for both TNF-α and thrombin-induced fetal membrane weakening. In a previous report, we demonstrated that 3 progestogens, progesterone, 17-alpha hydroxyprogesterone (17-OHP), and medroxyprogesterone acetate (MPA), each inhibit both TNF-α- and thrombin-induced fetal membrane weakening at 2 distinct points of the fetal membrane weakening pathway. Each block both the production of and the downstream action of the critical intermediate granulocyte-macrophage colony-stimulating factor. The objective of the study was to characterize the inhibitory effects of 17-OHPC on TNF-α- and thrombin-induced fetal membrane weakening in vitro. Full-thickness human fetal membrane fragments from uncomplicated term repeat cesarean deliveries were mounted in 2.5 cm Transwell inserts and cultured with/without 17-alpha hydroxyprogesterone caproate (10 -9 to 10 -7 M). After 24 hours, medium (supernatant) was removed and replaced with/without the addition of tumor necrosis factor-alpha (20 ng/mL) or thrombin (10 U/mL) or granulocyte-macrophage colony-stimulating factor (200 ng/mL). After 48 hours of culture, medium from the maternal side compartment of the model was assayed for granulocyte-macrophage colony

  9. [Intelligence level and structure in school age children with fetal growth restriction].

    Science.gov (United States)

    Ma, Jian; Ma, Hong-Wei; Tian, Xiao-Bo; Liu, Fang

    2009-10-01

    To study the intelligence level and structure in school age children with fetal growth restriction (FGR). The intelligence levels were tested by the Wechsler Children Scales of Intelligence (C-WISC) in 54 children with FGR and in 84 normal children. The full intelligence quotient (FIQ), verbal IQ (VIQ) and performance IQ (PIQ) in the FGR group were 105.9+/-10.3, 112.4+/-11.2 and 97.1+/-10.6 respectively, and they all were in a normal range. But the PIQ was significantly lower than that in the control group (104.8+/-10.5; pintelligence level of children with FGR is normal, but there are imbalances in the intelligence structure and dysfunctions in performance ability related to right cerebral hemisphere. Performance trainings should be done from the infancy in children with FGR.

  10. Effect of behavior training on learning and memory of young rats with fetal growth restriction

    Institute of Scientific and Technical Information of China (English)

    Li Xuelan; Gou Wenli; Huang Pu; Li Chunfang; Sun Yunping

    2008-01-01

    Objective: To investigate the effect of behavior training on the learning and memory of young rats with fetal growth restriction (FGR). Methods: The model of FGR was established by passive smoking method to pregnant rats.The new-born rats were divided into FGR group and normal group, and then randomly subdivided into trained and untrained group respectively. Morris water maze behavior training was performed on postnatal months 2 and 4, then learning and memory abilities of young rats were measured by dark-avoidance testing and step-down testing. Results: In the dark-avoidance and step-down testing, the young rats' performance of FGR group was worse than that of control group, and the trained group was better than the untrained group significantly. Conclusion: FGR young rats have descended learning and memory abilities. Behavior training could improve the young rats' learning and memory abilities, especially for the FGR young rats.

  11. Cardiac function and tadalafil used for treating fetal growth restriction in pregnant women without cardiovascular disease.

    Science.gov (United States)

    Tanaka, Kayo; Tanaka, Hiroaki; Maki, Shintaro; Kubo, Michiko; Nii, Masafumi; Magawa, Shoichi; Hatano, Fumi; Tsuji, Makoto; Osato, Kazuhiro; Kamimoto, Yuki; Umekawa, Takashi; Ikeda, Tomoaki

    2018-02-20

    The aim of the present study was to evaluate tadalafil for the treatment of fetal growth restriction (FGR) and the cardiac function in pregnant women without cardiovascular disease who used tadalafil for this reason. We examined nine pregnant women without cardiovascular disease who were using tadalafil to treat FGR. Maternal heart rate, systolic blood pressure (BP), and echocardiographic findings were assessed before and after tadalafil use. Diastolic BP was lower after compared to that before using tadalafil, but the difference was not significant. Echocardiographic findings were not significantly different before and after tadalafil use. Tadalafil did not adversely affect pregnant women without cardiovascular disease and was considered acceptable for use since it did not affect the mother's cardiac function.

  12. Ca uptake and its influence by growth hormone in osteoblasts of fetal rat calvaria

    International Nuclear Information System (INIS)

    Wang Hongfu; Jin Weifang; Sekimoto Haku

    1994-01-01

    Uptake and release of Ca 2+ are important functions of osteoblasts. In the paper we studied the uptake of calcium and influence by Growth Hormone in osteoblasts of fetal rat calvaria by liquid scintillation spectrometry of 45 Ca 2+ . In short-term cultures of the bone derived cells, the uptake of 45 Ca 2+ increased steadily. The activity of 45 Ca 2+ in the cells of 15 minute cultures was 2∼3 times of that in the 0 minute cultures. It continued to increase in the cells of 30 minute cultures. Exposure of the bone cells to GH at 55.3 ng/ml increased the uptake of 45 Ca 2+ by 2.3 times in the 30 minute cultures and 1.5 times in the 60 minute cultures than those of the control

  13. Fetal antigen 1 (FA1), a circulating member of the epidermal growth factor (EGF) superfamily

    DEFF Research Database (Denmark)

    Jensen, Charlotte Harken; Krogh, T N; Støving, René Klinkby

    1997-01-01

    We describe an ELISA technique for quantification of fetal antigen 1 (FA1), a glycoprotein belonging to the EGF-superfamily. The ELISA is based on immunospecifically purified polyclonal antibodies and has a dynamic range of 0.7-5.3 ng/ml, intra- and inter-assay C.V.s of less than 3.2% and an aver......We describe an ELISA technique for quantification of fetal antigen 1 (FA1), a glycoprotein belonging to the EGF-superfamily. The ELISA is based on immunospecifically purified polyclonal antibodies and has a dynamic range of 0.7-5.3 ng/ml, intra- and inter-assay C.V.s of less than 3.......2% and an average recovery of 105% in serum and 98% in urine. Comparison of FA1 in amniotic fluid, serum and urine revealed parallel titration curves, identical elution volumes following size chromatography, immunological identity and similar profiles when analysed by MALDI-MS. The reference interval for serum FA1...... was 12.3-46.6 ng/ml and the levels were 10 times higher in patients with renal failure. FA1 showed no diurnal variation, no variation during the menstrual cycle and was not influenced by the acute phase reaction. In humans (n = 10) the renal clearance of FA1 was 11 ml/min and an identical high renal...

  14. Amnioinfusion before 26 weeks' gestation for severe fetal growth restriction with oligohydramnios: preliminary pilot study.

    Science.gov (United States)

    Takahashi, Yuichiro; Iwagaki, Shigenori; Chiaki, Rika; Iwasa, Tomotake; Takenaka, Motoki; Kawabata, Ichiro; Itoh, Mitsuaki

    2014-03-01

    The prognosis for severe fetal growth restriction (FGR) with severe oligohydramnios before 26 weeks' gestation (WG) is currently poor; furthermore, its management is controversial. We report the innovative new management of FGR, such as therapeutic amnioinfusion and tocolysis. For FGR and severe oligohydramnios before 26 WG complicated with absent or reversed umbilical artery end-diastolic flow velocity and/or deceleration by ultrasonography, we performed transabdominal amnioinfusion with tocolysis. Cases with multiple anomalies were excluded. Survival rate and long-term prognosis were analyzed. Among 570 FGR cases, 18 were included in the study. Mean diagnosis and delivery were at 22.6 ± 2.0 and 28.7 ± 3.3 WG. Median birthweight was 625 g (-4.2 standard deviation). Final survival rate was 11/13 (85%). There were five fetal deaths. In seven cases, oligohydramnios improved. Growth was detected in 10/18 fetuses. Furthermore, 8/8 decelerations, 4/12 cases of reversed umbilical artery end-diastolic flow velocity, 7/14 cases of brain-sparing effect, and 6/13 venous Doppler abnormalities were improved. When we detected umbilical cord compression, 8/10 cases were rescued. Eleven infants were followed up for an average of 5 years; one case of cerebral palsy with normal development and 10 cases with intact motor functions without major neurological handicap were confirmed. In cases of extremely severe FGR before 26 WG with oligohydramnios and circulatory failure, amnioinfusion might be a promising, innovative tool. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

  15. Declines in Birth weight and Fetal Growth Independent of Gestational Length

    Science.gov (United States)

    Morisaki, Naho; Esplin, M. Sean; Varner, Michael W.; Henry, Erick; Oken, Emily

    2014-01-01

    Objective Birth weight is decreasing in the US and elsewhere, even among term singletons, although trends in most maternal characteristics should contribute to increased birth weight. Some studies have attributed this decline to the simultaneous decrease in gestational length. Methods Using data from Intermountain Healthcare, where a successful initiative reduced the number of early term (37–38 week) elective deliveries, we examined trends in birth weight, small-for-gestational-age (SGA), and large-for-gestational-age (LGA) among 219,694 singleton infants born July 2000 to December 2008 at 37–41 weeks gestation. Results Over the 8.5 years, births through scheduled deliveries at 37–38 weeks decreased (9.4% to 4.4%), but overall scheduled deliveries increased (29% to 34%) and mean gestational age at birth (39.1 weeks) did not change. Mean birth weight (3410g to 3383g) and LGA (9.0% to 7.4%) both decreased, whereas SGA increased (7.5% to 8.2%). In multivariable analyses adjusting for maternal and infant characteristics, birth weight decreased (36g; 95% CI: 31, 42), especially among infants born at 37–38 weeks (40g; 30, 49) or that had medical indications for urgent deliveries (48g; 34, 63). Odds of LGA decreased (0.84; 0.80, 0.88) and odds of SGA increased (1.14; 1.08, 1.20). Conclusion Even in a population where gestation length did not change, birth weight and fetal growth declined. Decrease in not only gestational length but in fetal growth as well is likely to be contributing to the widely observed recent decrease in birth weight. PMID:23262927

  16. Fetal Growth and Birth Anthropometrics in Metformin-Exposed Offspring Born to Mothers With PCOS.

    Science.gov (United States)

    Hjorth-Hansen, Anna; Salvesen, Øyvind; Engen Hanem, Liv Guro; Eggebø, Torbjørn; Salvesen, Kjell Å; Vanky, Eszter; Ødegård, Rønnaug

    2018-02-01

    Metformin is used in an attempt to reduce pregnancy complications associated with polycystic ovary syndrome (PCOS). Little is known about the effect of metformin on fetal development and growth. To compare the effect of metformin versus placebo on fetal growth and birth anthropometrics in PCOS offspring compared with a reference population in relation to maternal body mass index (BMI). Post hoc analysis of a randomized controlled trial. Double-blind, placebo-controlled, multicenter study. 258 offspring born to mothers with PCOS. 2000 mg metformin (n = 131) or placebo (n = 121) from first trimester to delivery. Mean abdominal diameter and biparietal diameter (BPD) at gestational weeks 19 and 32. Head circumference (HC), birth length, and weight related to a reference population of healthy offspring, expressed as gestational age- and sex-adjusted z-scores. Metformin- versus placebo-exposed offspring had larger heads at gestational week 32 (BPD, 86.1 mm versus 85.2 mm; P = 0.03) and at birth (HC, 35.6 cm versus 35.1 cm; P mothers. Among normal-weight mothers, the effect of metformin compared with placebo was reduced length (z-score = -0.96 versus -0.42, P = 0.04) and weight (z-score = -0.44 versus 0.02; P = 0.03). Compared with the reference population, offspring born to PCOS mothers (placebo group) had reduced length (z-score = -0.40; 95% confidence interval, -0.60 to -0.40), but similar birth weight and HC. Metformin exposure resulted in larger head size in offspring of overweight mothers, traceable already in utero. Maternal prepregnancy BMI modified the effect of metformin on offspring anthropometrics. Anthropometrics of offspring born to PCOS mothers differed from those of the reference population. Copyright © 2017 Endocrine Society

  17. Placental determinants of fetal growth: identification of key factors in the insulin-like growth factor and cytokine systems using artificial neural networks

    Directory of Open Access Journals (Sweden)

    Faleschini Elena

    2008-06-01

    Full Text Available Abstract Background Changes and relationships of components of the cytokine and IGF systems have been shown in placenta and cord serum of fetal growth restricted (FGR compared with normal newborns (AGA. This study aimed to analyse a data set of clinical and biochemical data in FGR and AGA newborns to assess if a mathematical model existed and was capable of identifying these two different conditions in order to identify the variables which had a mathematically consistent biological relevance to fetal growth. Methods Whole villous tissue was collected at birth from FGR (N = 20 and AGA neonates (N = 28. Total RNA was extracted, reverse transcribed and then real-time quantitative (TaqMan RT-PCR was performed to quantify cDNA for IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IL-6. The corresponding proteins with TNF-α in addition were assayed in placental lysates using specific kits. The data were analysed using Artificial Neural Networks (supervised networks, and principal component analysis and connectivity map. Results The IGF system and IL-6 allowed to predict FGR in approximately 92% of the cases and AGA in 85% of the cases with a low number of errors. IGF-II, IGFBP-2, and IL-6 content in the placental lysates were the most important factors connected with FGR. The condition of being FGR was connected mainly with the IGF-II placental content, and the latter with IL-6 and IGFBP-2 concentrations in placental lysates. Conclusion These results suggest that further research in humans should focus on these biochemical data. Furthermore, this study offered a critical revision of previous studies. The understanding of this system biology is relevant to the development of future therapeutical interventions possibly aiming at reducing IL-6 and IGFBP-2 concentrations preserving IGF bioactivity in both placenta and fetus.

  18. Consensus definition and essential reporting parameters of selective fetal growth restriction in twin pregnancy: a Delphi procedure

    NARCIS (Netherlands)

    Khalil, Asma; Beune, Irene; Hecher, Kurt; Wynia, Klaske; Ganzevoort, Wessel; Reed, Keith; Lewi, Liesbeth; Oepkes, Dick; Gratacos, Eduardo; Thilaganathan, Basky; Gordijn, Sanne J.

    2018-01-01

    Twin pregnancies complicated by selective fetal growth restriction (sFGR) are associated with increased perinatal mortality and morbidity. Inconsistences in the diagnostic criteria for sFGR employed in existing studies hinder the ability to compare or combine their findings. It is therefore

  19. Supplements in human islet culture: human serum albumin is inferior to fetal bovine serum.

    Science.gov (United States)

    Avgoustiniatos, Efstathios S; Scott, William E; Suszynski, Thomas M; Schuurman, Henk-Jan; Nelson, Rebecca A; Rozak, Phillip R; Mueller, Kate R; Balamurugan, A N; Ansite, Jeffrey D; Fraga, Daniel W; Friberg, Andrew S; Wildey, Gina M; Tanaka, Tomohiro; Lyons, Connor A; Sutherland, David E R; Hering, Bernhard J; Papas, Klearchos K

    2012-01-01

    Culture of human islets before clinical transplantation or distribution for research purposes is standard practice. At the time the Edmonton protocol was introduced, clinical islet manufacturing did not include culture, and human serum albumin (HSA), instead of fetal bovine serum (FBS), was used during other steps of the process to avoid the introduction of xenogeneic material. When culture was subsequently introduced, HSA was also used for medium supplementation instead of FBS, which was typically used for research islet culture. The use of HSA as culture supplement was not evaluated before this implementation. We performed a retrospective analysis of 103 high-purity islet preparations (76 research preparations, all with FBS culture supplementation, and 27 clinical preparations, all with HSA supplementation) for oxygen consumption rate per DNA content (OCR/DNA; a measure of viability) and diabetes reversal rate in diabetic nude mice (a measure of potency). After 2-day culture, research preparations exhibited an average OCR/DNA 51% higher (p < 0.001) and an average diabetes reversal rate 54% higher (p < 0.05) than clinical preparations, despite 87% of the research islet preparations having been derived from research-grade pancreata that are considered of lower quality. In a prospective paired study on islets from eight research preparations, OCR/DNA was, on average, 27% higher with FBS supplementation than that with HSA supplementation (p < 0.05). We conclude that the quality of clinical islet preparations can be improved when culture is performed in media supplemented with serum instead of albumin.

  20. Antenatal antioxidant treatment with melatonin to decrease newborn neurodevelopmental deficits and brain injury caused by fetal growth restriction.

    Science.gov (United States)

    Miller, Suzanne L; Yawno, Tamara; Alers, Nicole O; Castillo-Melendez, Margie; Supramaniam, Veena G; VanZyl, Niel; Sabaretnam, Tharani; Loose, Jan M; Drummond, Grant R; Walker, David W; Jenkin, Graham; Wallace, Euan M

    2014-04-01

    Fetal intrauterine growth restriction (IUGR) is a serious pregnancy complication associated with increased rates of perinatal morbidity and mortality, and ultimately with long-term neurodevelopmental impairments. No intervention currently exists that can improve the structure and function of the IUGR brain before birth. Here, we investigated whether maternal antenatal melatonin administration reduced brain injury in ovine IUGR. IUGR was induced in pregnant sheep at 0.7 gestation and a subset of ewes received melatonin via intravenous infusion until term. IUGR, IUGR + melatonin (IUGR + MLT) and control lambs were born naturally, neonatal behavioral assessment was used to examine neurological function and at 24 hr after birth the brain was collected for the examination of neuropathology. Compared to control lambs, IUGR lambs took significantly longer to achieve normal neonatal lamb behaviors, such as standing and suckling. IUGR brains showed widespread cellular and axonal lipid peroxidation, and white matter hypomyelination and axonal damage. Maternal melatonin administration ameliorated oxidative stress, normalized myelination and rescued axonopathy within IUGR lamb brains, and IUGR + MLT lambs demonstrated significant functional improvements including a reduced time taken to attach to and suckle at the udder after birth. Based on these observations, we began a pilot clinical trial of oral melatonin administration to women with an IUGR fetus. Maternal melatonin was not associated with adverse maternal or fetal effects and it significantly reduced oxidative stress, as evidenced by reduced malondialdehyde levels, in the IUGR + MLT placenta compared to IUGR alone. Melatonin should be considered for antenatal neuroprotective therapy in human IUGR. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Ultrasonographic measurement of fetal growth parameters over three successive pregnancies in a captive Malayan tapir (Tapirus indicus).

    Science.gov (United States)

    Hoyer, M J; van Engeldorp Gastelaars, H M D

    2014-01-01

    This study was conducted to establish representative curves that allow evaluation of fetal growth and estimation of gestational age from measurement of fetal structures by ultrasound in Malayan tapirs (Tapirus indicus). Three pregnancies (i.e. 3 fetuses) were examined in one female Malayan tapir. Transabdominal ultrasonographic examination was performed without anesthesia from 79 ± 8 days to 281 ± 48 days (mean ± S.D.) post mating. To assess fetal growth attempts were made to measure biparietal diameter (BPD), head length (HL), thorax diameter A (TDA), thorax height A (THA), thorax diameter B (TDB), thorax height B (THB), abdomen diameter (AD), abdomen height (AH), humerus length (HUL) and Crown rump length (CRL). The value of each parameter as an estimator of gestational age was assessed by ease of observation and the length of time the parameter was measurable throughout gestation. The most precise predictors for gestational age in this study were BPD and CRL (weeks 10-20 of gestation), as well as AD and AH (weeks 14-43 of gestation). The parameters TDB, THB and HUL (weeks 15-41 of gestation) gave almost as good predictions. Fetal viability was assessed by identifying a fetal heartbeat and movement. All pregnancies resulted in normal deliveries and healthy offspring. The ultrasound examination was well tolerated by the female. The gestation lengths (399 ± 3 days) were within reported ranges. The serial transabdominal ultrasound, without the need for anesthesia, was an effective method to evaluate fetal growth, development and well being in a Malayan tapir. © 2014 Wiley Periodicals, Inc.

  2. 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.

  3. Fetal and neonatal programming of postnatal growth and feed efficiency in swine.

    Science.gov (United States)

    Ji, Yun; Wu, Zhenlong; Dai, Zhaolai; Wang, Xiaolong; Li, Ju; Wang, Binggen; Wu, Guoyao

    2017-01-01

    Maternal undernutrition or overnutrition during pregnancy alters organ structure, impairs prenatal and neonatal growth and development, and reduces feed efficiency for lean tissue gains in pigs. These adverse effects may be carried over to the next generation or beyond. This phenomenon of the transgenerational impacts is known as fetal programming, which is mediated by stable and heritable alterations of gene expression through covalent modifications of DNA and histones without changes in DNA sequences (namely, epigenetics). The mechanisms responsible for the epigenetic regulation of protein expression and functions include chromatin remodeling; DNA methylation (occurring at the 5´-position of cytosine residues within CpG dinucleotides); and histone modifications (acetylation, methylation, phosphorylation, and ubiquitination). Like maternal malnutrition, undernutrition during the neonatal period also reduces growth performance and feed efficiency (weight gain:feed intake; also known as weight-gain efficiency) in postweaning pigs by 5-10%, thereby increasing the days necessary to reach the market body-weight. Supplementing functional amino acids (e.g., arginine and glutamine) and vitamins (e.g., folate) play a key role in activating the mammalian target of rapamycin signaling and regulating the provision of methyl donors for DNA and protein methylation. Therefore, these nutrients are beneficial for the dietary treatment of metabolic disorders in offspring with intrauterine growth restriction or neonatal malnutrition. The mechanism-based strategies hold great promise for the improvement of the efficiency of pork production and the sustainability of the global swine industry.

  4. Fetal growth in pregnancies conceived after gastric bypass surgery in relation to surgery-to-conception interval: a Danish national cohort study.

    Directory of Open Access Journals (Sweden)

    Lone Nikoline Nørgaard

    Full Text Available OBJECTIVE: To describe early and late fetal growth in pregnancies conceived after gastric bypass surgery in relation to time from surgery to conception of pregnancy. METHODS: National cohort study on 387 Danish women, who had laparoscopic or open gastric bypass surgery prior to a singleton pregnancy in which first trimester screening was performed between January 2008 and June 2011. Data were derived from national registers (Danish National Registry of Patients and Danish National Birth Registry, Pregnancy Complications and Abortion-clinical quality database (PreCAb and the Danish Fetal Medicine Database. Main outcome measures were early and late fetal growth in relation to time from bariatric surgery to conception of the pregnancy. Early fetal growth was expressed as "Fetal Growth Index": the ratio between the estimated number of days from first trimester ultrasound to second trimester ultrasound biometries and the actual calender time elapsed in days. Late fetal growth was expressed as the observed versus expected birthweight according to gestational age (GA. RESULTS: The surgery-to-conception interval ranged from 3 to 1851 days with a mean value of 502 (SD, 351 days. The mean "fetal growth index" was 0.99 (SD, 0.02 days/day and thus significantly lower than in the background population (mean, 1.04 (SD, 0.09 days/day, p<0.0001. The proportion of infants being small for gestational age was 18.8% and the proportion of large for gestational age infants was 6.7%. The correlation coefficients between surgery-to-conception time and "fetal growth index" and birthweight according to GA were 0.01 (p = 0.8 and 0.04 (p = 0.4, respectively. CONCLUSION: Fetal growth index was lower than reported in the background population. No correlation was found between the surgery-to-conception interval and early or late fetal growth in pregnancies conceived after gastric bypass surgery.

  5. The human protooncogene product p33pim is expressed during fetal hematopoiesis and in diverse leukemias

    International Nuclear Information System (INIS)

    Amson, R.; Przedborski, S.; Telerman, A.; Sigaux, F.; Flandrin, G.; Givol, D.

    1989-01-01

    The authors measured the human pim-1 protooncogene (PIM) expression during fetal development and in hematopoietic malignancies. The data indicate that during human fetal hematopoiesis the 33-kDa pim product, p33pim, is highly expressed in the liver and the spleen. In contrast, a the adult stage it is only slightly expressed in circulating granulocytes. Out of 70 hematopoietic malignancies analyzed, 51 patients and 19 cell lines, p33pim was overexpressed in ∼ 30% of the samples, particularly in myeloid and lymphoid acute leukemias. This overexpression was unrelated to any stage of cellular differentiation and was not due to gene rearrangement or amplification. These results imply a physiological role of the pim-1 protooncogene during hematopoietic development and a deregulation in various leukemias

  6. Resveratrol inhibits steroidogenesis in human fetal adrenocortical cells at the end of first trimester

    DEFF Research Database (Denmark)

    Savchuk, Iuliia; Morvan, Marie-Line; Søeborg, Tue

    2017-01-01

    SCOPE: Resveratrol has a diverse array of healthful effects on metabolic parameters in different experimental paradigms but has also potential to inhibit steroidogenesis in rodent adrenals. The aim of the present study was to characterize the effects of resveratrol on human fetal adrenal...... steroidogenesis at gestational weeks (GW) 9-12. METHODS AND RESULTS: Adrenals from aborted fetuses (GW10-12) were used to prepare primary cultures of human fetal adrenocortical cells (HFAC). HFAC were treated in the presence or absence of ACTH (10 ng/ml) with or without resveratrol (10 μM) for 24 hours....... The production of steroids by HFAC was analyzed by gas and liquid chromatography coupled to tandem/mass spectrometry. The expression of steroidogenic enzymes at GW 9-12 was quantified by automated Western blotting. We observed that resveratrol significantly suppressed synthesis of dehydroepiandrosterone (DHEA...

  7. Cellular and molecular effect of MEHP Involving LXRα in human fetal testis and ovary.

    Science.gov (United States)

    Muczynski, Vincent; Lecureuil, Charlotte; Messiaen, Sébastien; Guerquin, Marie-Justine; N'tumba-Byn, Thierry; Moison, Delphine; Hodroj, Wassim; Benjelloun, Hinde; Baijer, Jan; Livera, Gabriel; Frydman, René; Benachi, Alexandra; Habert, René; Rouiller-Fabre, Virginie

    2012-01-01

    Phthalates have been shown to have reprotoxic effects in rodents and human during fetal life. Previous studies indicate that some members of the nuclear receptor (NR) superfamilly potentially mediate phthalate effects. This study aimed to assess if expression of these nuclear receptors are modulated in the response to MEHP exposure on the human fetal gonads in vitro. Testes and ovaries from 7 to 12 gestational weeks human fetuses were exposed to 10(-4)M MEHP for 72 h in vitro. Transcriptional level of NRs and of downstream genes was then investigated using TLDA (TaqMan Low Density Array) and qPCR approaches. To determine whether somatic or germ cells of the testis are involved in the response to MEHP exposure, we developed a highly efficient cytometric germ cell sorting approach. In vitro exposure of fetal testes and ovaries to MEHP up-regulated the expression of LXRα, SREBP members and of downstream genes involved in the lipid and cholesterol synthesis in the whole gonad. In sorted testicular cells, this effect is only observable in somatic cells but not in the gonocytes. Moreover, the germ cell loss induced by MEHP exposure, that we previously described, is restricted to the male gonad as oogonia density is not affected in vitro. We evidenced for the first time that phthalate increases the levels of mRNA for LXRα, and SREBP members potentially deregulating lipids/cholesterol synthesis in human fetal gonads. Interestingly, this novel effect is observable in both male and female whereas the germ cell apoptosis is restricted to the male gonad. Furthermore, we presented here a novel and potentially very useful flow cytometric cell sorting method to analyse molecular changes in germ cells versus somatic cells.

  8. Cellular and molecular effect of MEHP Involving LXRα in human fetal testis and ovary.

    Directory of Open Access Journals (Sweden)

    Vincent Muczynski

    Full Text Available Phthalates have been shown to have reprotoxic effects in rodents and human during fetal life. Previous studies indicate that some members of the nuclear receptor (NR superfamilly potentially mediate phthalate effects. This study aimed to assess if expression of these nuclear receptors are modulated in the response to MEHP exposure on the human fetal gonads in vitro.Testes and ovaries from 7 to 12 gestational weeks human fetuses were exposed to 10(-4M MEHP for 72 h in vitro. Transcriptional level of NRs and of downstream genes was then investigated using TLDA (TaqMan Low Density Array and qPCR approaches. To determine whether somatic or germ cells of the testis are involved in the response to MEHP exposure, we developed a highly efficient cytometric germ cell sorting approach. In vitro exposure of fetal testes and ovaries to MEHP up-regulated the expression of LXRα, SREBP members and of downstream genes involved in the lipid and cholesterol synthesis in the whole gonad. In sorted testicular cells, this effect is only observable in somatic cells but not in the gonocytes. Moreover, the germ cell loss induced by MEHP exposure, that we previously described, is restricted to the male gonad as oogonia density is not affected in vitro.We evidenced for the first time that phthalate increases the levels of mRNA for LXRα, and SREBP members potentially deregulating lipids/cholesterol synthesis in human fetal gonads. Interestingly, this novel effect is observable in both male and female whereas the germ cell apoptosis is restricted to the male gonad. Furthermore, we presented here a novel and potentially very useful flow cytometric cell sorting method to analyse molecular changes in germ cells versus somatic cells.

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

    Science.gov (United States)

    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

  10. Nutritional intra-amniotic therapy increases survival in a rabbit model of fetal growth restriction

    Science.gov (United States)

    Illa, Miriam; Pla, Laura; Zamora, Monica; Crispi, Fatima; Gratacos, Eduard

    2018-01-01

    Objective To evaluate the perinatal effects of a prenatal therapy based on intra-amniotic nutritional supplementation in a rabbit model of intrauterine growth restriction (IUGR). Methods IUGR was surgically induced in pregnant rabbits at gestational day 25 by ligating 40–50% of uteroplacental vessels of each gestational sac. At the same time, modified-parenteral nutrition solution (containing glucose, amino acids and electrolytes) was injected into the amniotic sac of nearly half of the IUGR fetuses (IUGR-T group n = 106), whereas sham injections were performed in the rest of fetuses (IUGR group n = 118). A control group without IUGR induction but sham injection was also included (n = 115). Five days after the ligation procedure, a cesarean section was performed to evaluate fetal cardiac function, survival and birth weight. Results Survival was significantly improved in the IUGR fetuses that were treated with intra-amniotic nutritional supplementation as compared to non-treated IUGR animals (survival rate: controls 71% vs. IUGR 44% p = 0.003 and IUGR-T 63% vs. IUGR 44% p = 0.02), whereas, birth weight (controls mean 43g ± SD 9 vs. IUGR 36g ± SD 9 vs. IUGR-T 35g ± SD 8, p = 0.001) and fetal cardiac function were similar among the IUGR groups. Conclusion Intra-amniotic injection of a modified-parenteral nutrient solution appears to be a promising therapy for reducing mortality among IUGR. These results provide an opportunity to develop new intra-amniotic nutritional strategies to reach the fetus by bypassing the placental insufficiency. PMID:29466434

  11. In vivo placental MRI shape and textural features predict fetal growth restriction and postnatal outcome.

    Science.gov (United States)

    Dahdouh, Sonia; Andescavage, Nickie; Yewale, Sayali; Yarish, Alexa; Lanham, Diane; Bulas, Dorothy; du Plessis, Adre J; Limperopoulos, Catherine

    2018-02-01

    To investigate the ability of three-dimensional (3D) MRI placental shape and textural features to predict fetal growth restriction (FGR) and birth weight (BW) for both healthy and FGR fetuses. We recruited two groups of pregnant volunteers between 18 and 39 weeks of gestation; 46 healthy subjects and 34 FGR. Both groups underwent fetal MR imaging on a 1.5 Tesla GE scanner using an eight-channel receiver coil. We acquired T2-weighted images on either the coronal or the axial plane to obtain MR volumes with a slice thickness of either 4 or 8 mm covering the full placenta. Placental shape features (volume, thickness, elongation) were combined with textural features; first order textural features (mean, variance, kurtosis, and skewness of placental gray levels), as well as, textural features computed on the gray level co-occurrence and run-length matrices characterizing placental homogeneity, symmetry, and coarseness. The features were used in two machine learning frameworks to predict FGR and BW. The proposed machine-learning based method using shape and textural features identified FGR pregnancies with 86% accuracy, 77% precision and 86% recall. BW estimations were 0.3 ± 13.4% (mean percentage error ± standard error) for healthy fetuses and -2.6 ± 15.9% for FGR. The proposed FGR identification and BW estimation methods using in utero placental shape and textural features computed on 3D MR images demonstrated high accuracy in our healthy and high-risk cohorts. Future studies to assess the evolution of each feature with regard to placental development are currently underway. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:449-458. © 2017 International Society for Magnetic Resonance in Medicine.

  12. Fetal effects of epidermal growth factor deficiency induced in rats by autoantibodies against epidermal growth factor

    DEFF Research Database (Denmark)

    Raaberg, Lasse; Nexø, Ebba; Jørgensen, P E

    1995-01-01

    , the amount of surfactant protein-A was decreased, suggesting a delayed lung maturation. The offspring of EGF-immunized rats had dry and wrinkled skin. The skin was thin and the hair follicles were immature. This suggests a role for EGF in the growth and development of the skin. The liver/body weight ratio...

  13. Fetal growth restriction and the programming of heart growth and cardiac insulin-like growth factor 2 expression in the lamb.

    Science.gov (United States)

    Wang, Kimberley C W; Zhang, Lei; McMillen, I Caroline; Botting, Kimberley J; Duffield, Jaime A; Zhang, Song; Suter, Catherine M; Brooks, Doug A; Morrison, Janna L

    2011-10-01

    Reduced growth in fetal life together with accelerated growth in childhood, results in a ~50% greater risk of coronary heart disease in adult life. It is unclear why changes in patterns of body and heart growth in early life can lead to an increased risk of cardiovascular disease in adulthood. We aimed to investigate the role of the insulin-like growth factors in heart growth in the growth-restricted fetus and lamb. Hearts were collected from control and placentally restricted (PR) fetuses at 137-144 days gestation and from average (ABW) and low (LBW) birth weight lambs at 21 days of age. We quantified cardiac mRNA expression of IGF-1, IGF-2 and their receptors, IGF-1R and IGF-2R, using real-time RT-PCR and protein expression of IGF-1R and IGF-2R using Western blotting. Combined bisulphite restriction analysis was used to assess DNA methylation in the differentially methylated region (DMR) of the IGF-2/H19 locus and of the IGF-2R gene. In PR fetal sheep, IGF-2, IGF-1R and IGF-2R mRNA expression was increased in the heart compared to controls. LBW lambs had a greater left ventricle weight relative to body weight as well as increased IGF-2 and IGF-2R mRNA expression in the heart, when compared to ABW lambs. No changes in the percentage of methylation of the DMRs of IGF-2/H19 or IGF-2R were found between PR and LBW when compared to their respective controls. In conclusion, a programmed increased in cardiac gene expression of IGF-2 and IGF-2R may represent an adaptive response to reduced substrate supply (e.g. glucose and/or oxygen) in order to maintain heart growth and may be the underlying cause for increased ventricular hypertrophy and the associated susceptibility of cardiomyocytes to ischaemic damage later in life.

  14. Perfluoroalkyl and polyfluoroalkyl substances and human fetal growth

    DEFF Research Database (Denmark)

    Bach, Cathrine Carlsen; Bech, Bodil Hammer; Brix, Nis

    2015-01-01

    original studies on pregnant women with measurements of PFOA or PFOS in maternal blood during pregnancy or the umbilical cord and associations with birth weight or related outcomes according to the PFAS level. Citations and references from the included articles were investigated to locate more relevant...... articles. Study characteristics and results were extracted to structured tables. The completeness of reporting as well as the risk of bias and confounding were assessed. Results: Fourteen studies were eligible. In utero PFOA exposure was associated with decreased measures of continuous birth weight in all...

  15. Prenatal exposure to mercury and longitudinally assessed fetal growth: Relation and effect modifiers.

    Science.gov (United States)

    Ballester, Ferran; Iñiguez, Carmen; Murcia, Mario; Guxens, Mònica; Basterretxea, Mikel; Rebagliato, Marisa; Vioque, Jesús; Lertxundi, Aitana; Fernandez-Somoano, Ana; Tardon, Adonina; Sunyer, Jordi; Llop, Sabrina

    2018-01-01

    Prenatal mercury exposure has been related to reductions in anthropometry at birth. Levels of mercury have been reported as being relatively elevated in the Spanish population. To investigate the relation between prenatal exposure to mercury and fetal growth. Study subjects were pregnant women and their newborns (n:1867) participating in a population-based birth cohort study set up in four Spanish regions from the INMA Project. Biparietal diameter (BPD), femur length (FL), abdominal circumference (AC), and estimated fetal weight (EFW) were measured by ultrasounds at 12, 20, and 34 weeks of gestation. Size at and growth between these points were assessed by standard deviation (SD) scores adjusted for constitutional characteristics. Total mercury (T-Hg) was determined in cord blood. Associations were investigated by linear regression models, adjusted by sociodemographic, environmental, nutritional - including four seafood groups - and lifestyle-related variables in each sub-cohort. Final estimates were obtained using meta-analysis. Effect modification by sex, seafood intake and polychlorinated biphenyl (PCB) congener 153 concentration was assessed. Geometric mean of cord blood T-Hg was 8.2μg/L. All the estimates of the association between prenatal Hg and growth from 0 to 12 weeks showed reductions in SD-scores, which were only statistically significant for BPD. A doubling of cord blood T-Hg was associated with a 0.58% reduction in size of BPD at week 12 (95% confidence interval -CI-: - 1.10, - 0.07). Size at week 34 showed estimates suggestive of a small reduction in EFW, i.e., a doubling of T-Hg levels was associated with a reduction of 0.38% (95% CI: - 0.91, 0.15). An interaction between PCB153 and T-Hg was found, with statistically significant negative associations of T-Hg with AC and EFW in late pregnancy among participants with PCB153 below the median. Exposure to mercury during pregnancy was associated with early reductions in BPD. Moreover, an antagonism with

  16. Mapping directionality specific volume changes using tensor based morphometry: an application to the study of gyrogenesis and lateralization of the human fetal brain.

    Science.gov (United States)

    Rajagopalan, Vidya; Scott, Julia; Habas, Piotr A; Kim, Kio; Rousseau, Francois; Glenn, Orit A; Barkovich, A James; Studholme, Colin

    2012-11-01

    Tensor based morphometry (TBM) is a powerful approach to analyze local structural changes in brain anatomy. However, conventional scalar TBM methods do not completely capture all direction specific volume changes required to model complex changes such as those during brain growth. In this paper, we describe novel TBM descriptors for studying direction-specific changes in a subject population which can be used in conjunction with scalar TBM to analyze local patterns in directionality of volume change during brain development. We also extend the methodology to provide a new approach to mapping directional asymmetry in deformation tensors associated with the emergence of structural asymmetry in the developing brain. We illustrate the use of these methods by studying developmental patterns in the human fetal brain, in vivo. Results show that fetal brain development exhibits a distinct spatial pattern of anisotropic growth. The most significant changes in the directionality of growth occur in the cortical plate at major sulci. Our analysis also detected directional growth asymmetry in the peri-Sylvian region and the medial frontal lobe of the fetal brain. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. The satisfactory growth and development at 2 years of age of the INTERGROWTH-21st Fetal Growth Standards cohort support its appropriateness for constructing international standards.

    Science.gov (United States)

    Villar, José; Cheikh Ismail, Leila; Staines Urias, Eleonora; Giuliani, Francesca; Ohuma, Eric O; Victora, Cesar G; Papageorghiou, Aris T; Altman, Douglas G; Garza, Cutberto; Barros, Fernando C; Puglia, Fabien; Ochieng, Roseline; Jaffer, Yasmin A; Noble, Julia A; Bertino, Enrico; Purwar, Manorama; Pang, Ruyan; Lambert, Ann; Chumlea, Cameron; Stein, Alan; Fernandes, Michelle; Bhutta, Zulfiqar A; Kennedy, Stephen H

    2018-02-01

    The World Health Organization recommends that human growth should be monitored with the use of international standards. However, in obstetric practice, we continue to monitor fetal growth using numerous local charts or equations that are based on different populations for each body structure. Consistent with World Health Organization recommendations, the INTERGROWTH-21 st Project has produced the first set of international standards to date pregnancies; to monitor fetal growth, estimated fetal weight, Doppler measures, and brain structures; to measure uterine growth, maternal nutrition, newborn infant size, and body composition; and to assess the postnatal growth of preterm babies. All these standards are based on the same healthy pregnancy cohort. Recognizing the importance of demonstrating that, postnatally, this cohort still adhered to the World Health Organization prescriptive approach, we followed their growth and development to the key milestone of 2 years of age. The purpose of this study was to determine whether the babies in the INTERGROWTH-21 st Project maintained optimal growth and development in childhood. In the Infant Follow-up Study of the INTERGROWTH-21 st Project, we evaluated postnatal growth, nutrition, morbidity, and motor development up to 2 years of age in the children who contributed data to the construction of the international fetal growth, newborn infant size and body composition at birth, and preterm postnatal growth standards. Clinical care, feeding practices, anthropometric measures, and assessment of morbidity were standardized across study sites and documented at 1 and 2 years of age. Weight, length, and head circumference age- and sex-specific z-scores and percentiles and motor development milestones were estimated with the use of the World Health Organization Child Growth Standards and World Health Organization milestone distributions, respectively. For the preterm infants, corrected age was used. Variance components analysis was

  18. Towards a new era in fetal medicine in the Nordic countries

    DEFF Research Database (Denmark)

    Sitras, Vasilis; Brodszki, Jana; Carlsson, Ylva

    2016-01-01

    Fetal medicine is a subspecialty of obstetrics investigating the development, growth and disease of the human fetus. The advances in fetal imaging (ultrasonography, MRI) and molecular diagnostic techniques, together with the possibility of intervention in utero, make fetal medicine an important, ...

  19. Epigenetic regulation and fetal programming.

    Science.gov (United States)

    Gicquel, Christine; El-Osta, Assam; Le Bouc, Yves

    2008-02-01

    Fetal programming encompasses the role of developmental plasticity in response to environmental and nutritional signals during early life and its potential adverse consequences (risk of cardiovascular, metabolic and behavioural diseases) in later life. The first studies in this field highlighted an association between poor fetal growth and chronic adult diseases. However, environmental signals during early life may lead to adverse long-term effects independently of obvious effects on fetal growth. Adverse long-term effects reflect a mismatch between early (fetal and neonatal) environmental conditions and the conditions that the individual will confront later in life. The mechanisms underlying this risk remain unclear. However, experimental data in rodents and recent observations in humans suggest that epigenetic changes in regulatory genes and growth-related genes play a significant role in fetal programming. Improvements in our understanding of the biochemical and molecular mechanisms at play in fetal programming would make it possible to identify biomarkers for detecting infants at high risk of adult-onset diseases. Such improvements should also lead to the development of preventive and therapeutic strategies.

  20. Fetal human airway smooth muscle cell production of leukocyte chemoattractants is differentially regulated by fluticasone.

    Science.gov (United States)

    Pearson, Helen; Britt, Rodney D; Pabelick, Christine M; Prakash, Y S; Amrani, Yassine; Pandya, Hitesh C

    2015-12-01

    Adult human airway smooth muscle (ASM) produce cytokines involved in recruitment and survival of leukocytes within airway walls. Cytokine generation by adult ASM is glucocorticoid-sensitive. Whether developing lung ASM produces cytokines in a glucocorticoid-sensitive fashion is unknown. Cultured fetal human ASM cells stimulated with TNF-α (0-20 ng/ml) were incubated with TNF-α receptor-blocking antibodies, fluticasone (1 and 100 nm), or vehicle. Supernatants and cells were assayed for the production of CCL5, CXCL10, and CXCL8 mRNA and protein and glucocorticoid receptor phosphorylation. CCL5, CXCL10, and CXCL8 mRNA and protein production by fetal ASM cell was significantly and dose-dependently following TNF-α treatment. Cytokine mRNA and protein production were effectively blocked by TNF-α R1 and R2 receptor neutralizing antibodies but variably inhibited by fluticasone. TNF-α-induced TNF-R1 and R2 receptor mRNA expression was only partially attenuated by fluticasone. Glucocorticoid receptor phosphorylation at serine (Ser) 211 but not at Ser 226 was enhanced by fluticasone. Production of CCL5, CXCL10, and CXCL8 by fetal ASM appears to involve pathways that are both qualitatively and mechanistically distinct to those described for adult ASM. The findings imply developing ASM has potential to recruit leukocyte into airways and, therefore, of relevance to childhood airway diseases.

  1. Are gestational age, birth weight, and birth length indicators of favorable fetal growth conditions? A structural equation analysis of Filipino infants.

    Science.gov (United States)

    Bollen, Kenneth A; Noble, Mark D; Adair, Linda S

    2013-07-30

    The fetal origins hypothesis emphasizes the life-long health impacts of prenatal conditions. Birth weight, birth length, and gestational age are indicators of the fetal environment. However, these variables often have missing data and are subject to random and systematic errors caused by delays in measurement, differences in measurement instruments, and human error. With data from the Cebu (Philippines) Longitudinal Health and Nutrition Survey, we use structural equation models, to explore random and systematic errors in these birth outcome measures, to analyze how maternal characteristics relate to birth outcomes, and to take account of missing data. We assess whether birth weight, birth length, and gestational age are influenced by a single latent variable that we call favorable fetal growth conditions (FFGC) and if so, which variable is most closely related to FFGC. We find that a model with FFGC as a latent variable fits as well as a less parsimonious model that has birth weight, birth length, and gestational age as distinct individual variables. We also demonstrate that birth weight is more reliably measured than is gestational age. FFGCs were significantly influenced by taller maternal stature, better nutritional stores indexed by maternal arm fat and muscle area during pregnancy, higher birth order, avoidance of smoking, and maternal age 20-35 years. Effects of maternal characteristics on newborn weight, length, and gestational age were largely indirect, operating through FFGC. Copyright © 2013 John Wiley & Sons, Ltd.

  2. Diagnostic accuracy of fundal height and handheld ultrasound-measured abdominal circumference to screen for fetal growth abnormalities

    Science.gov (United States)

    Haragan, Adriane F.; Hulsey, Thomas C.; Hawk, Angela F.; Newman, Roger B.; Chang, Eugene Y.

    2015-01-01

    OBJECTIVE We sought to compare fundal height and handheld ultrasound–measured fetal abdominal circumference (HHAC) for the prediction of fetal growth restriction (FGR) or large for gestational age. STUDY DESIGN This was a diagnostic accuracy study in nonanomalous singleton pregnancies between 24 and 40 weeks’ gestation. Patients underwent HHAC and fundal height measurement prior to formal growth ultrasound. FGR was defined as estimated fetal weight less than 10%, whereas large for gestational age was defined as estimated fetal weight greater than 90%. Sensitivity and specificity were calculated and compared using methods described elsewhere. RESULTS There were 251 patients included in this study. HHAC had superior sensitivity and specificity for the detection of FGR (sensitivity, 100% vs 42.86%) and (specificity, 92.62% vs 85.24%). HHAC had higher specificity but lower sensitivity when screening for LGA (specificity, 85.66% vs 66.39%) and (sensitivity, 57.14% vs 71.43%). CONCLUSION HHAC could prove to be a valuable screening tool in the detection of FGR. Further studies are needed in a larger population. PMID:25818672

  3. Induced pluripotent stem (iPS) cells from human fetal stem cells.

    Science.gov (United States)

    Guillot, Pascale V

    2016-02-01

    Pluripotency defines the ability of stem cells to differentiate into all the lineages of the three germ layers and self-renew indefinitely. Somatic cells can regain the developmental potential of embryonic stem cells following ectopic expression of a set of transcription factors or, in certain circumstances, via modulation of culture conditions and supplementation with small molecule, that is, induced pluripotent stem (iPS) cells. Here, we discuss the use of fetal tissues for reprogramming, focusing in particular on stem cells derived from human amniotic fluid, and the development of chemical reprogramming. We next address the advantages and disadvantages of deriving pluripotent cells from fetal tissues and the potential clinical applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. 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

  5. Research ethics in Canada: experience of a group operating a human embryo and fetal tissue bank.

    Science.gov (United States)

    Milos, N; Bamforth, S; Bagnall, K

    1999-04-01

    A Canadian research group is establishing a human embryo and fetal tissue bank. Its purpose is to provide researchers with frozen or fixed tissue specimens for use in protein and gene expression studies. Several legal and ethical issues have arisen, including questions about consent, use of these rare tissues, cost recovery, and profit-making. These issues are discussed here in light of the present lack of legislation in Canada. We make recommendations in these areas, and suggest that the bank's operations could legally fall under the jurisdiction of the Human Tissue Gift Act.

  6. Permeability of human placenta and fetal membranes to thyrotropin-stimulating hormone in vitro.

    Science.gov (United States)

    Bajoria, R; Fisk, N M

    1998-05-01

    We determined the placental transfer of TSH in an in vitro model of dually perfused isolated lobule in 28 human term placentas by adding varying concentrations (5-60 microIU mL(-1)) of TSH as a single bolus dose to the closed maternal circulation. Transmembrane transfer of TSH was also studied by adding 45 microIU mL(-1) to the maternal or fetal compartment of a dual chamber of fetal membranes in culture. Passage of freely diffusible markers creatinine and antipyrine were also studied in this model. TSH concentration was measured by third generation chemiluminescence assay with a sensitivity of 10 mIU mL(-1). In the perfusion experiments, at physiologic concentrations the slow decline of TSH in the maternal circulation was associated with a small linear increase in fetal levels to 0.11 +/- 0.04% of initial dose at 2 h. The placental transfer rate was 0.08 microIU min(-1). Increasing maternal concentrations of TSH were associated with proportional increases in transfer rate (y = 0.002x; R2 = 0.99) and placental uptake (y = 0.01x; R2 = 0.97). The placental permeability of TSH was 2.4 x 10(-4) mL min(-1) g(-1) and was proportional to its coefficients of diffusion in water and molecular size. The transmembrane transfer and permeability of TSH was comparable to those of the placenta. We conclude that TSH crosses the human term placenta and fetal membranes sparingly.

  7. Placental restriction of fetal growth reduces cutaneous responses to antigen after sensitization in sheep.

    Science.gov (United States)

    Wooldridge, Amy L; Bischof, Robert J; Meeusen, Els N; Liu, Hong; Heinemann, Gary K; Hunter, Damien S; Giles, Lynne C; Kind, Karen L; Owens, Julie A; Clifton, Vicki L; Gatford, Kathryn L

    2014-04-01

    Prenatal and early childhood exposures are implicated as causes of allergy, but the effects of intrauterine growth restriction on immune function and allergy are poorly defined. We therefore evaluated effects of experimental restriction of fetal growth on immune function and allergic sensitization in adolescent sheep. Immune function (circulating total red and white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, and basophils, and the antibody response to Clostridial vaccination) and responses to house dust mite (HDM) allergen and ovalbumin (OVA) antigen sensitization (specific total Ig, IgG1, and IgE antibodies, and cutaneous hypersensitivity) were investigated in adolescent sheep from placentally restricted (PR, n = 23) and control (n = 40) pregnancies. Increases in circulating HDM-specific IgE (P = 0.007) and OVA-specific IgE (P = 0.038) were greater in PR than control progeny. PR did not alter total Ig, IgG1, or IgM responses to either antigen. PR increased OVA-specific but not HDM-specific IgA responses in females only (P = 0.023). Multiple birth increased Ig responses to OVA in a sex-specific manner. PR decreased the proportion of positive cutaneous hypersensitivity responders to OVA at 24 h (P = 0.030) but had no effect on cutaneous responses to HDM. Acute wheal responses to intradermal histamine correlated positively with birth weight in singletons (P = 0.023). Intrauterine growth restriction may suppress inflammatory responses in skin downstream of IgE induction, without impairment in antibody responses to a nonpolysaccharide vaccine. Discord between cutaneous and IgE responses following sensitization suggests new mechanisms for prenatal allergy programming.

  8. Nicotine-induced retardation of chondrogenesis through down-regulation of IGF-1 signaling pathway to inhibit matrix synthesis of growth plate chondrocytes in fetal rats

    International Nuclear Information System (INIS)

    Deng, Yu; Cao, Hong; Cu, Fenglong; Xu, Dan; Lei, Youying; Tan, Yang; Magdalou, Jacques; Wang, Hui; Chen, Liaobin

    2013-01-01

    Previous studies have confirmed that maternal tobacco smoking causes intrauterine growth retardation (IUGR) and skeletal growth retardation. Among a multitude of chemicals associated with cigarette smoking, nicotine is one of the leading candidates for causing low birth weights. However, the possible mechanism of delayed chondrogenesis by prenatal nicotine exposure remains unclear. We investigated the effects of nicotine on fetal growth plate chondrocytes in vivo and in vitro. Rats were given 2.0 mg/kg·d of nicotine subcutaneously from gestational days 11 to 20. Prenatal nicotine exposure increased the levels of fetal blood corticosterone and resulted in fetal skeletal growth retardation. Moreover, nicotine exposure induced the inhibition of matrix synthesis and down-regulation of insulin-like growth factor 1 (IGF-1) signaling in fetal growth plates. The effects of nicotine on growth plates were studied in vitro by exposing fetal growth plate chondrocytes to 0, 1, 10, or 100 μM of nicotine for 10 days. Nicotine inhibited matrix synthesis and down-regulated IGF-1 signaling in chondrocytes in a concentration-dependent manner. These results suggest that prenatal nicotine exposure induces delayed chondrogenesis and that the mechanism may involve the down-regulation of IGF-1 signaling and the inhibition of matrix synthesis by growth plate chondrocytes. The present study aids in the characterization of delayed chondrogenesis caused by prenatal nicotine exposure, which might suggest a candidate mechanism for intrauterine origins of osteoporosis and osteoarthritis. - Highlights: ► Prenatal nicotine-exposure could induce delayed chondrogenesis in fetal rats. ► Nicotine inhibits matrix synthesis of fetal growth plate chondrocytes. ► Nicotine inhibits IGF-1 signaling pathway in fetal growth plate chondrocytes

  9. Nicotine-induced retardation of chondrogenesis through down-regulation of IGF-1 signaling pathway to inhibit matrix synthesis of growth plate chondrocytes in fetal rats

    Energy Technology Data Exchange (ETDEWEB)

    Deng, Yu; Cao, Hong; Cu, Fenglong [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Xu, Dan [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Lei, Youying [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Tan, Yang [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Magdalou, Jacques [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Wang, Hui [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Chen, Liaobin, E-mail: lbchen@whu.edu.cn [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China)

    2013-05-15

    Previous studies have confirmed that maternal tobacco smoking causes intrauterine growth retardation (IUGR) and skeletal growth retardation. Among a multitude of chemicals associated with cigarette smoking, nicotine is one of the leading candidates for causing low birth weights. However, the possible mechanism of delayed chondrogenesis by prenatal nicotine exposure remains unclear. We investigated the effects of nicotine on fetal growth plate chondrocytes in vivo and in vitro. Rats were given 2.0 mg/kg·d of nicotine subcutaneously from gestational days 11 to 20. Prenatal nicotine exposure increased the levels of fetal blood corticosterone and resulted in fetal skeletal growth retardation. Moreover, nicotine exposure induced the inhibition of matrix synthesis and down-regulation of insulin-like growth factor 1 (IGF-1) signaling in fetal growth plates. The effects of nicotine on growth plates were studied in vitro by exposing fetal growth plate chondrocytes to 0, 1, 10, or 100 μM of nicotine for 10 days. Nicotine inhibited matrix synthesis and down-regulated IGF-1 signaling in chondrocytes in a concentration-dependent manner. These results suggest that prenatal nicotine exposure induces delayed chondrogenesis and that the mechanism may involve the down-regulation of IGF-1 signaling and the inhibition of matrix synthesis by growth plate chondrocytes. The present study aids in the characterization of delayed chondrogenesis caused by prenatal nicotine exposure, which might suggest a candidate mechanism for intrauterine origins of osteoporosis and osteoarthritis. - Highlights: ► Prenatal nicotine-exposure could induce delayed chondrogenesis in fetal rats. ► Nicotine inhibits matrix synthesis of fetal growth plate chondrocytes. ► Nicotine inhibits IGF-1 signaling pathway in fetal growth plate chondrocytes.

  10. Do miRNAs Play a Role in Fetal Growth Restriction? A Fresh Look to a Busy Corner

    Directory of Open Access Journals (Sweden)

    Benito Chiofalo

    2017-01-01

    Full Text Available Placenta is the crucial organ for embryo and fetus development and plays a critical role in the development of fetal growth restriction (FGR. There are increasing evidences on the role of microRNAs (miRNAs in a variety of pregnancy-related complications such as preeclampsia and FGR. More than 1880 miRNAs have been reported in humans and most of them are expressed in placenta. In this paper, we aimed to review the current evidence about the topic. According to retrieved data, controversial results about placental expression of miRNAs could be due (at least in part to the different experimental methods used by different groups. Despite the fact that several authors have demonstrated a relatively easy and feasible detection of some miRNAs in maternal whole peripheral blood, costs of these tests should be reduced in order to increase cohorts and have stronger evidence. In this regard, we take the opportunity to solicit future studies on large cohort and adequate statistical power, in order to identify a panel of biomarkers on maternal peripheral blood for early diagnosis of FGR.

  11. The effects of food and maternal conditions in fetal growth and size in wild reindeer

    Directory of Open Access Journals (Sweden)

    Terje Skogland

    1984-05-01

    Full Text Available Fetal growth rates and birth weights were studied in four wild reindeer areas in Southern Norway (Hardangervidda, Hallingskarvet, Knutshø, Forelhogna, representing high and low density populations, with a 5-fold difference in mean lichen winter-food availability. Fetal growth was depressed by 42% in the high-densitv Hardangervidda population, and mean birth weights were 3.7 vs. 6.2 kg, with a 10 days difference in mean birth dates. Fetal size was better correlated with maternal weight, than age. Maternal weights increased until 5 yrs. of age and then decreased in the high-density Hardangervidda population (but not so in the low density Knutshø-Forclhogna populations. 55% of the offspring died before weaning in the Hardangervidda herd, but no significant calf losses were found amont the large-sized does in the food-abundant areas.Effekter av ernæring og simlas kondisjon på vekst og størrelse av foster hos villrein.Abstract in Norwegian / Sammendrag: Fostervekst og fødselsvekter ble undersøkt i fire villreinområder i Sør-Norge (Hardangervidda, Hallingskarvet, Knutshø og Forelhogna som representerer høg- og lågtetthetsstammer, med en 5-foldig forskjell i gjennomsnittlig lavbeite-tilgang om vinteren. Fosterveksten ble nedsatt med 42% i høgtetthetsstammen på Hardangervidda og fødselsvektene var i gjennomsnitt 3,7 kg, mot 6,2 kg i det beste området, og med en 10 dagers forsinkelse i midlere fødselsdato. Fosterets størrelse var korrelert med morens vekt, som igjen var avhengig av hennes alder. Hos de minste simlene i det dårligste området økte vektene til 5-års alder, for deretter å avta for hvert gjenlevende år. Hos simlene i det beste området økte vektene til 10-års alder, og var da dobbelt så tunge som fra det dårligste området. 55% av avkommet døde før de var avvent med diing hos Hardangervidda-simlene, mens det ikke var noen statistisk målbar dødelighet hos kalvene i Knutshø-Forelhogna.Ravinnon vaikutus ja

  12. Maternal weight gain and associations with longitudinal fetal growth in dichorionic twin pregnancies: a prospective cohort study.

    Science.gov (United States)

    Hinkle, Stefanie N; Hediger, Mary L; Kim, Sungduk; Albert, Paul S; Grobman, William; Newman, Roger B; Wing, Deborah A; Grewal, Jagteshwar; Zhang, Cuilin; Buck Louis, Germaine M; Grantz, Katherine L

    2017-12-01

    Background: Maternal metabolic demands are much greater with twin gestations; however, there are no accepted recommendations for maternal weight gain in twin pregnancies. Objective: We assessed the association of maternal weight gain and fetal growth in dichorionic twins throughout pregnancy. Design: This was a prospective US cohort study ( n = 143, 2012-2013) of dichorionic twin pregnancies with known birth outcomes followed from enrollment (11-13 wk) and for ≤6 research visits throughout gestation. Maternal prepregnancy weight was self-reported, and current weight was measured at each research visit and abstracted from prenatal records. Fetal biometry was assessed by ultrasound at each research visit. Maternal weight and twin-pair fetal size trajectories across gestation were modeled. The adjusted associations between maternal weight gain from 0 to 13, 14 to 20, 21 to 27, and 28 to 34 wk and fetal growth at the subsequent week (i.e., 14, 21, 28, and 35 wk, respectively) were estimated with the use of linear regression. Results: The mean ± SD maternal weight gain from 0 to 13, 14 to 20, 21 to 27, and 28 to 34 wk was 2.8 ± 3.0 kg, 3.9 ± 1.2 kg, 3.8 ± 1.4 kg, and 4.4 ± 2.2 kg, respectively, with a total gain of 17.7 ± 7.4 kg. Maternal weight gain from 0 to 13 wk (first trimester) was not associated with fetal size at 14 wk. Maternal weight gain from 14 to 20 and 21 to 27 wk (second trimester) was significantly associated with increased fetal weight at 21 wk [increase of 10.5 g/kg maternal weight gain (95% CI: 1.2, 19.8 g)] and 28 wk [increase of 21.3 g/kg maternal weight gain (95% CI: 0.6, 42.0 g)]. Maternal weight gain from 14 to 20 wk was associated with increased twin abdominal circumference (AC) and biparietal diameter at 21 wk. Maternal weight gain from 21 to 27 wk was associated with increased femur and humerus lengths at 28 wk. Conclusion: Maternal weight gain was associated with dichorionic twin fetal growth in the second trimester only, driven by an

  13. Transport and Biodistribution of Dendrimers Across Human Fetal Membranes: Implications for Intravaginal Administration of Dendrimers

    Science.gov (United States)

    Menjoge, Anupa R.; Navath, Raghavendra S.; Asad, Abbas; Kannan, Sujatha; Kim, Chong Jai; Romero, Roberto; Kannan, Rangaramanujam M.

    2010-01-01

    Dendrimers are emerging as promising topical antimicrobial agents, and as targeted nanoscale drug delivery vehicles. Topical intravaginal antimicrobial agents are prescribed to treat the ascending genital infections in pregnant women. The fetal membranes separate the extra-amniotic space and fetus. The purpose of the study is to determine if the dendrimers can be selectively used for local intravaginal application to pregnant women without crossing the membranes into the fetus. In the present study, the transport and permeability of PAMAM (poly(amidoamine)) dendrimers, across human fetal membrane (using a side-by-side diffusion chamber), and its biodistribution (using immunofluorescence) are evaluated ex-vivo. Transport across human fetal membranes (from the maternal side) was evaluated using Fluorescein (FITC), an established transplacental marker (positive control, size~ 400 Da) and fluorophore-tagged G4-PAMAM dendrimers (~ 16 kDa). The fluorophore-tagged G4-PAMAM dendrimers were synthesized and characterized using 1H NMR, MALDI TOF-MS and HPLC analysis. Transfer was measured across the intact fetal membrane (chorioamnion), and the separated chorion and amnion layers. Over a five hour period, the dendrimer transport across all the three membranes was less than transport of FITC was relatively fast with as much as 49% transport across the amnion. The permeability of FITC (7.9 × 10-7 cm2/s) through the chorioamnion was 7-fold higher than that of the dendrimer (5.8 × 10-8 cm2/s). The biodistribution showed that the dendrimers were largely present in interstitial spaces in the decidual stromal cells and the chorionic trophoblast cells (in 2.5 to 4 h) and surprisingly, to a smaller extent internalized in nuclei of trophoblast cells and nuclei and cytoplasm of stromal cells. Passive diffusion and paracellular transport appear to be the major route for dendrimer transport. The overall findings further suggest that entry of drugs conjugated to dendrimers would be

  14. 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.

  15. Association of maternal and umbilical cord blood leptin concentrations and abnormal color Doppler indices of umbilical artery with fetal growth restriction

    Directory of Open Access Journals (Sweden)

    Elahe Zareaan

    2017-08-01

    Full Text Available Background: Fetal growth restriction (FGR is a condition with heterogeneous pathophysiology which characterized by fetal weight less than the tenth percentile for gestational age. Several factors have impact on maternal, placental and fetal due to growth restriction. Objective: The aim of this study was to investigate the relationship between levels of leptin in the cord, and serum leptin of mothers also abnormal color Doppler indices of umbilical artery with fetal growth restriction. Materials and Methods: This is a cross sectional study conducted in Isfahan, Iran, 2015-2016. We recruited 40 women with singleton pregnancies complicated by fetal growth restriction (Group I and 40 pregnant women with normal fetal growth (Group II with matched age. Maternal serum and umbilical artery leptin levels were determined with Enzyme-Linked immunosorben method. Also, color Doppler ultrasound of umbilical artery was performed. Results: Mean maternal and fetal leptin levels were lower in the FGR group compared to the normal group (36.58±(20.99 and 7.42 ±(4.08vs. 47.32±(22.50 and 30.49±(14.50 respectively. Also, mean fetal leptin level was lower in the group with abnormal color Doppler sonographic indices compared to the normal group (7. 40 ±(4.10vs 27.06±(15.80, respectively. Conclusion: This study indicated that maternal and fetal leptin levels are correlated with FGR originating from damaged placental function; also fetal leptin level can indicate changes in color Doppler sonographic indices.

  16. Trophoblastic progranulin expression is upregulated in cases of fetal growth restriction and preeclampsia.

    Science.gov (United States)

    Stubert, Johannes; Schattenberg, Florian; Richter, Dagmar-Ulrike; Dieterich, Max; Briese, Volker

    2012-05-13

    The expression of the anti-inflammatory glycoprotein progranulin and the hypoxia-induced transcription factor 1α (HIF-1α) in the villous trophoblast was compared between placentae from patients with preeclampsia (PE), fetal growth restriction (FGR), and normal controls. Matched pairs analysis of third trimester placentae specimens (mean gestational age 36+2) was performed by semiquantitative measurements of the immunohistochemical staining intensities for progranulin and HIF-1α expression (PE n=13, FGR n=9 and controls n=11). Further, placental progranulin mRNA expression was analyzed by qRT-PCR on term placentae (n=3 for each group). Compared to controls, villous trophoblast revealed a significantly higher expression of progranulin in cases of PE (Pprogranulin protein was not accompanied by an increase of the progranulin mRNA in term placentae. Increased expression of progranulin protein in villous trophoblast cells in cases of PE and FGR may result from disturbed placental development and, therefore, may be of pathogenetic importance. The increase was correlated to HIF-1α expression. Further evaluation of this potential mechanism of regulation is required.

  17. Placental oxidative stress and maternal endothelial function in pregnant women with normotensive fetal growth restriction.

    Science.gov (United States)

    Yoshida, Atsumi; Watanabe, Kazushi; Iwasaki, Ai; Kimura, Chiharu; Matsushita, Hiroshi; Wakatsuki, Akihiko

    2018-04-01

    The purpose of this study was to investigate the relationship between placental oxidative stress and maternal endothelial function in pregnant women with normotensive fetal growth restriction (FGR). We examined serum concentrations of oxygen free radicals (d-ROMs), maternal angiogenic factor (PlGF), and sFlt-1, placental oxidative DNA damage, and maternal endothelial function in 17 women with early-onset preeclampsia (PE), 18 with late-onset PE, 14 with normotensive FGR, and 21 controls. Flow-mediated vasodilation (FMD) was assessed as a marker of maternal endothelial function. Immunohistochemical analysis was performed to measure the proportion of placental trophoblast cell nuclei staining positive for 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage. Maternal serum d-ROM, sFlt-1 concentrations, and FMD did not significantly differ between the control and normotensive FGR groups. The proportion of nuclei staining positive for 8-OHdG was significantly higher in the normotensive FGR group relative to the control group. Our findings demonstrate that, despite the presence of placental oxidative DNA damage as observed in PE patients, pregnant women with normotensive FGR show no increase in the concentrations of sFlt-1 and d-ROMs, or a decrease in FMD.

  18. Fetal growth and preterm birth in children exposed to maternal or paternal rheumatoid arthritis. A nationwide cohort study

    DEFF Research Database (Denmark)

    Rom, Ane L; Wu, Chunsen; Olsen, Jørn

    2014-01-01

    OBJECTIVE: To assess indicators of fetal growth and risk of preterm birth in children of parents with rheumatoid arthritis (RA). METHODS: Through linkage of Danish national registries, we identified all children born in Denmark between 1977 and 2008. We used general linear regression models...... to estimate mean differences in indicators of fetal growth among children with a parent with RA compared to unexposed children. Odds ratios (ORs) and 95% confidence intervals (95% CIs) of preterm birth were calculated using a logistic regression model. RESULTS: Of the 1,917,723 children included, a total...... of 13,556 children were exposed to maternal RA or maternal preclinical RA. Children exposed to maternal RA (n = 2,101) had approximately similar length, head circumference, and abdominal circumference at birth compared with children of mothers without RA. Birth weight was 87 gm lower (mean difference...

  19. Region-specific maturation of cerebral cortex in human fetal brain: diffusion tensor imaging and histology

    International Nuclear Information System (INIS)

    Trivedi, Richa; Gupta, Rakesh K.; Saksena, Sona; Husain, Nuzhat; Srivastava, Savita; Rathore, Ram K.S.; Sarma, Manoj K.; Malik, Gyanendra K.; Das, Vinita; Pradhan, Mandakini; Pandey, Chandra M.; Narayana, Ponnada A.

    2009-01-01

    In this study, diffusion tensor imaging (DTI) and glial fibrillary acidic protein (GFAP) immunohistochemical analysis in different cortical regions in fetal brains at different gestational age (GA) were performed. DTI was performed on 50 freshly aborted fetal brains with GA ranging from 12 to 42 weeks to compare age-related fractional anisotropy (FA) changes in different cerebral cortical regions that include frontal, parietal, occipital, and temporal lobes at the level of thalami. GFAP immunostaining was performed and the percentage of GFAP-positive areas was quantified. The cortical FA values in the frontal lobe peaked at around 26 weeks of GA, occipital and temporal lobes at around 20 weeks, and parietal lobe at around 23 weeks. A significant, but modest, positive correlation (r=0.31, p=0.02) was observed between cortical FA values and percentage area of GFAP expression in cortical region around the time period during which the migrational events are at its peak, i.e., GA ≤ 28 weeks for frontal cortical region and GA≤22 weeks for rest of the lobes. The DTI-derived FA quantification with its GFAP immunohistologic correlation in cortical regions of the various lobes of the cerebral hemispheres supports region-specific migrational and maturational events in human fetal brain. (orig.)

  20. Region-specific maturation of cerebral cortex in human fetal brain: diffusion tensor imaging and histology

    Energy Technology Data Exchange (ETDEWEB)

    Trivedi, Richa; Gupta, Rakesh K.; Saksena, Sona [Sanjay Gandhi Post Graduate Institute of Medical Sciences, Department of Radiodiagnosis, Lucknow, UP (India); Husain, Nuzhat; Srivastava, Savita [CSM Medical University, Department of Pathology, Lucknow (India); Rathore, Ram K.S.; Sarma, Manoj K. [Indian Institute of Technology, Department of Mathematics and Statistics, Kanpur (India); Malik, Gyanendra K. [CSM Medical University, Department of Pediatrics, Lucknow (India); Das, Vinita [CSM Medical University, Department of Obstetrics and Gynecology, Lucknow (India); Pradhan, Mandakini [Sanjay Gandhi Postgraduate Institute of Medical Sciences, Department of Medical Genetics, Lucknow (India); Pandey, Chandra M. [Sanjay Gandhi Postgraduate Institute of Medical Sciences, Department of Biostatistics, Lucknow (India); Narayana, Ponnada A. [University of Texas Medical School at Houston, Department of Diagnostic and Interventional Imaging, Houston, TX (United States)

    2009-09-15

    In this study, diffusion tensor imaging (DTI) and glial fibrillary acidic protein (GFAP) immunohistochemical analysis in different cortical regions in fetal brains at different gestational age (GA) were performed. DTI was performed on 50 freshly aborted fetal brains with GA ranging from 12 to 42 weeks to compare age-related fractional anisotropy (FA) changes in different cerebral cortical regions that include frontal, parietal, occipital, and temporal lobes at the level of thalami. GFAP immunostaining was performed and the percentage of GFAP-positive areas was quantified. The cortical FA values in the frontal lobe peaked at around 26 weeks of GA, occipital and temporal lobes at around 20 weeks, and parietal lobe at around 23 weeks. A significant, but modest, positive correlation (r=0.31, p=0.02) was observed between cortical FA values and percentage area of GFAP expression in cortical region around the time period during which the migrational events are at its peak, i.e., GA {<=} 28 weeks for frontal cortical region and GA{<=}22 weeks for rest of the lobes. The DTI-derived FA quantification with its GFAP immunohistologic correlation in cortical regions of the various lobes of the cerebral hemispheres supports region-specific migrational and maturational events in human fetal brain. (orig.)

  1. Time is on whose side? Time trends in the association between maternal social disadvantage and offspring fetal growth. A study of 1,409,339 births in Denmark 1981-2004

    DEFF Research Database (Denmark)

    Mortensen, Laust H; Diderichsen, Finn; Davey-Smith, George

    2009-01-01

    OBJECTIVE: Fetal growth is highly socially patterned and is related to health across the life course, but how the social patterns of fetal growth change over time remains understudied. We examined the time trends in maternal social disadvantage in relation to fetal growth in the context of a univ......OBJECTIVE: Fetal growth is highly socially patterned and is related to health across the life course, but how the social patterns of fetal growth change over time remains understudied. We examined the time trends in maternal social disadvantage in relation to fetal growth in the context...... of a universal welfare state under changing macroeconomic conditions over a 24-year period. Design and settings: All births in Denmark 1981-2004. MAIN OUTCOME MEASURE: The association between maternal social disadvantage in relation to birth weight for gestational age z-scores over time were analysed using...... linear regression. RESULTS: All measures of social disadvantage were associated with decreased fetal growth (p

  2. Zinc supplementation during pregnancy protects against lipopolysaccharide-induced fetal growth restriction and demise through its anti-inflammatory effect.

    Science.gov (United States)

    Chen, Yuan-Hua; Zhao, Mei; Chen, Xue; Zhang, Ying; Wang, Hua; Huang, Ying-Ying; Wang, Zhen; Zhang, Zhi-Hui; Zhang, Cheng; Xu, De-Xiang

    2012-07-01

    LPS is associated with adverse developmental outcomes, including preterm delivery, fetal death, teratogenicity, and intrauterine growth restriction (IUGR). Previous reports showed that zinc protected against LPS-induced teratogenicity. In the current study, we investigated the effects of zinc supplementation during pregnancy on LPS-induced preterm delivery, fetal death and IUGR. All pregnant mice except controls were i.p. injected with LPS (75 μg/kg) daily from gestational day (GD) 15 to GD17. Some pregnant mice were administered zinc sulfate through drinking water (75 mg elemental Zn per liter) throughout the pregnancy. As expected, an i.p. injection with LPS daily from GD15 to GD17 resulted in 36.4% (4/11) of dams delivered before GD18. In dams that completed the pregnancy, 63.2% of fetuses were dead. Moreover, LPS significantly reduced fetal weight and crown-rump length. Of interest, zinc supplementation during pregnancy protected mice from LPS-induced preterm delivery and fetal death. In addition, zinc supplementation significantly alleviated LPS-induced IUGR and skeletal development retardation. Further experiments showed that zinc supplementation significantly attenuated LPS-induced expression of placental inflammatory cytokines and cyclooxygenase-2. Zinc supplementation also significantly attenuated LPS-induced activation of NF-κB and MAPK signaling in mononuclear sinusoidal trophoblast giant cells of the labyrinth zone. It inhibited LPS-induced placental AKT phosphorylation as well. In conclusion, zinc supplementation during pregnancy protects against LPS-induced fetal growth restriction and demise through its anti-inflammatory effect.

  3. The exposure of nonsmoking and smoking mothers to environmental tobacco smoke during different gestational phases and fetal growth

    Czech Academy of Sciences Publication Activity Database

    Dejmek, Jan; Solanský, I.; Peterková, Kateřina; Šrám, Radim

    2002-01-01

    Roč. 110, č. 6 (2002), s. 601-606 ISSN 0091-6765 R&D Projects: GA MŽP SI/340/1/97; GA MŽP SI/340/2/00 Institutional research plan: CEZ:AV0Z5039906 Keywords : active smoking * passive smoking * fetal growth Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 3.452, year: 2002

  4. Fetal growth and subsequent risk of breast cancer: results from long term follow up of Swedish cohort

    OpenAIRE

    McCormack, V A; dos Santos Silva, I; De Stavola, B L; Mohsen, R; Leon, D A; Lithell, H O

    2003-01-01

    OBJECTIVE: To investigate whether size at birth and rate of fetal growth influence the risk of breast cancer in adulthood. DESIGN: Cohort identified from detailed birth records, with 97% follow up. SETTING: Uppsala Academic Hospital, Sweden. PARTICIPANTS: 5358 singleton females born during 1915-29, alive and traced to the 1960 census. MAIN OUTCOME MEASURES: Incidence of breast cancer before (at age <50 years) and after (> or = 50 years) the menopause. RESULTS: Size at birth was positive...

  5. 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.

  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

    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

  7. An outcome-based approach for the creation of fetal growth standards: do singletons and twins need separate standards?

    Science.gov (United States)

    Joseph, K S; Fahey, John; Platt, Robert W; Liston, Robert M; Lee, Shoo K; Sauve, Reg; Liu, Shiliang; Allen, Alexander C; Kramer, Michael S

    2009-03-01

    Contemporary fetal growth standards are created by using theoretical properties (percentiles) of birth weight (for gestational age) distributions. The authors used a clinically relevant, outcome-based methodology to determine if separate fetal growth standards are required for singletons and twins. All singleton and twin livebirths between 36 and 42 weeks' gestation in the United States (1995-2002) were included, after exclusions for missing information and other factors (n = 17,811,922). A birth weight range was identified, at each gestational age, over which serious neonatal morbidity and neonatal mortality rates were lowest. Among singleton males at 40 weeks, serious neonatal morbidity/mortality rates were lowest between 3,012 g (95% confidence interval (CI): 3,008, 3,018) and 3,978 g (95% CI: 3,976, 3,980). The low end of this optimal birth weight range for females was 37 g (95% CI: 21, 53) less. The low optimal birth weight was 152 g (95% CI: 121, 183) less for twins compared with singletons. No differences were observed in low optimal birth weight by period (1999-2002 vs. 1995-1998), but small differences were observed for maternal education, race, parity, age, and smoking status. Patterns of birth weight-specific serious neonatal morbidity/neonatal mortality support the need for plurality-specific fetal growth standards.

  8. Effects of hyperthyroidism on expression of vascular endothelial growth factor (VEGF) and apoptosis in fetal adrenal glands.

    Science.gov (United States)

    Karaca, T; Hulya Uz, Y; Karabacak, R; Karaboga, I; Demirtas, S; Cagatay Cicek, A

    2015-11-26

    This study investigated the expression of vascular endothelial growth factor (VEGF), vascular density, and apoptosis in fetal rat adrenal glands with hyperthyroidism in late gestation. Twelve mature female Wistar albino rats with the same biological and physiological features were used for this study. Rats were divided into two groups: control and hyperthyroidism. Hyperthyroidism was induced by daily subcutaneous injections of L-thyroxine (250 μg/kg) before pregnancy for 21 days and during pregnancy. Rats in the control and hyperthyroidism groups were caged according to the number of male rats. Zero day of pregnancy (Day 0) was indicated when the animals were observed to have microscopic sperm in vaginal smears. Pregnant rats were sacrificed on the 20th day of pregnancy; blood from each animal was collected to determine the concentrations of maternal adrenocorticotropic hormone and thyroxine. Rat fetuses were then quickly removed from the uterus, and the adrenal glands of the fetuses were dissected. VEGF expression, vascular density, and apoptosis were analyzed in fetal rat adrenal glands. Maternal serum levels of the adrenocorticotropic hormone and free thyroxine were significantly higher in the hyperthyroidism group than in the control group. Immunohistochemistry revealed that the number of VEGF positive cells and vessel density significantly increased in the hyperthyroidism rat fetal adrenal group compared with the control group. Hyperthyroidism did not change the fetal and placental weights and the number of fetuses. This study demonstrates that hyperthyroidism may have an effect on the development of rat adrenal glands mediated by VEGF expression, angiogenesis, and apoptosis.

  9. Lactobacillus rhamnosus GG and its SpaC pilus adhesin modulate inflammatory responsiveness and TLR-related gene expression in the fetal human gut

    Science.gov (United States)

    Ganguli, Kriston; Collado, Maria Carmen; Rautava, Jaana; Lu, Lei; Satokari, Reetta; von Ossowski, Ingemar; Reunanen, Justus; de Vos, Willem M.; Palva, Airi; Isolauri, Erika; Salminen, Seppo; Walker, W. Allan; Rautava, Samuli

    2015-01-01

    Background Bacterial contact in utero modulates fetal and neonatal immune responses. Maternal probiotic supplementation reduces the risk of immune-mediated disease in the infant. We investigated the immunomodulatory properties of live Lactobacillus rhamnosus GG and its SpaC pilus adhesin in human fetal intestinal models. Methods TNF-α mRNA expression was measured by qPCR in a human fetal intestinal organ culture model exposed to live L. rhamnosus GG and proinflammatory stimuli. Binding of recombinant SpaC pilus protein to intestinal epithelial cells was assessed in human fetal intestinal organ culture and the human fetal intestinal epithelial cell line H4 by immunohistochemistry and immunofluorescence, respectively. TLR-related gene expression in fetal ileal organ culture after exposure to recombinant SpaC was assessed by qPCR. Results Live L. rhamnosus GG significantly attenuates pathogen-induced TNF-α mRNA expression in the human fetal gut. Recombinant SpaC protein was found to adhere to the fetal gut and to modulate varying levels of TLR-related gene expression. Conclusion The human fetal gut is responsive to luminal microbes. L. rhamnosus GG significantly attenuates fetal intestinal inflammatory responses to pathogenic bacteria. The L. rhamnosus GG pilus adhesin SpaC binds to immature human intestinal epithelial cells and directly modulates intestinal epithelial cell innate immune gene expression. PMID:25580735

  10. Central vagal sensory and motor connections: human embryonic and fetal development.

    Science.gov (United States)

    Cheng, Gang; Zhou, Xiangtian; Qu, Jia; Ashwell, Ken W S; Paxinos, G

    2004-07-30

    The embryonic and fetal development of the nuclear components and pathways of vagal sensorimotor circuits in the human has been studied using Nissl staining and carbocyanine dye tracing techniques. Eight fetal brains ranging from 8 to 28 weeks of development had DiI (1,1'-dioctadecyl-3,3,3',3' tetramethylindocarbocyanine perchlorate) inserted into either the thoracic vagus nerve at the level of the sternal angle (two specimens of 8 and 9 weeks of gestation) or into vagal rootlets at the surface of the medulla (at all other ages), while a further five were used for study of cytoarchitectural development. The first central labeling resulting from peripheral application of DiI to the thoracic vagus nerve was seen at 8 weeks. By 9 weeks, labeled bipolar cells at the ventricular surface around the sulcus limitans (sl) were seen after DiI application to the thoracic vagus nerve. Subnuclear organization as revealed by both Nissl staining and carbocyanine dye tracing was found to be advanced at a relatively early fetal age, with afferent segregation in the medial Sol apparent at 13 weeks and subnuclear organization of efferent magnocellular divisions of dorsal motor nucleus of vagus nerve noticeable at the same stage. The results of the present study also confirm that vagal afferents are distributed to the dorsomedial subnuclei of the human nucleus of the solitary tract, with particular concentrations of afferent axons in the gelatinosus subnucleus. These vagal afferents appeared to have a restricted zone of termination from quite early in development (13 weeks) suggesting that there is no initial exuberance in the termination field of vagal afferents in the developing human nucleus of the solitary tract. On the other hand, the first suggestion of afferents invading 10N from the medial Sol was not seen until 20 weeks and was not well developed until 24 weeks, suggesting that direct monosynaptic connections between the sensory and effector components of the vagal

  11. Rab11 family expression in the human placenta: Localization at the maternal-fetal interface

    Science.gov (United States)

    Artemiuk, Patrycja A.; Hanscom, Sara R.; Lindsay, Andrew J.; Wuebbolt, Danielle; Breathnach, Fionnuala M.; Tully, Elizabeth C.; Khan, Amir R.; McCaffrey, Mary W.

    2017-01-01

    Rab proteins are a family of small GTPases involved in a variety of cellular processes. The Rab11 subfamily in particular directs key steps of intracellular functions involving vesicle trafficking of the endosomal recycling pathway. This Rab subfamily works through a series of effector proteins including the Rab11-FIPs (Rab11 Family-Interacting Proteins). While the Rab11 subfamily has been well characterized at the cellular level, its function within human organ systems is still being explored. In an effort to further study these proteins, we conducted a preliminary investigation of a subgroup of endosomal Rab proteins in a range of human cell lines by Western blotting. The results from this analysis indicated that Rab11a, Rab11c(Rab25) and Rab14 were expressed in a wide range of cell lines, including the human placental trophoblastic BeWo cell line. These findings encouraged us to further analyse the localization of these Rabs and their common effector protein, the Rab Coupling Protein (RCP), by immunofluorescence microscopy and to extend this work to normal human placental tissue. The placenta is a highly active exchange interface, facilitating transfer between mother and fetus during pregnancy. As Rab11 proteins are closely involved in transcytosis we hypothesized that the placenta would be an interesting human tissue model system for Rab investigation. By immunofluorescence microscopy, Rab11a, Rab11c(Rab25), Rab14 as well as their common FIP effector RCP showed prominent expression in the placental cell lines. We also identified the expression of these proteins in human placental lysates by Western blot analysis. Further, via fluorescent immunohistochemistry, we noted abundant localization of these proteins within key functional areas of primary human placental tissues, namely the outer syncytial layer of placental villous tissue and the endothelia of fetal blood vessels. Overall these findings highlight the expression of the Rab11 family within the human

  12. A Case of Alloimmune Thrombocytopenia, Hemorrhagic Anemia-Induced Fetal Hydrops, Maternal Mirror Syndrome, and Human Chorionic Gonadotropin–Induced Thyrotoxicosis

    Directory of Open Access Journals (Sweden)

    Venu Jain

    2013-05-01

    Full Text Available Fetal/neonatal alloimmune thrombocytopenia (FNAIT can be a cause of severe fetal thrombocytopenia, with the common presentation being intracranial hemorrhage in the fetus, usually in the third trimester. A very unusual case of fetal anemia progressed to hydrops. This was further complicated by maternal Mirror syndrome and human chorionic gonadotropin–induced thyrotoxicosis. Without knowledge of etiology, and possibly due to associated cardiac dysfunction, fetal transfusion resulted in fetal demise. Subsequent testing revealed FNAIT as the cause of severe hemorrhagic anemia. In cases with fetal anemia without presence of red blood cell antibodies, FNAIT must be ruled out as a cause prior to performing fetal transfusion. Fetal heart may adapt differently to acute hemorrhagic anemia compared with a more subacute hemolytic anemia.

  13. Organochlorine compounds and ultrasound measurements of fetal growth in the INMA cohort (Spain)

    NARCIS (Netherlands)

    M.-J. Lopez-Espinosa (Maria-Jose); M. Murcia (Mario); A. Iñiguez (Andrés); E. Vizcaino (Esther); O. Costa (Olga); A. Fernández-Somoano (Ana); M. Basterrechea (Mikel); A. Lertxundi (Aitana); M. Guxens Junyent (Mònica); M. Gascon (Mireia); F. Goñi-Irigoyen (Fernando); J.O. Grimalt (Joan O.); A. Tardón (Adonina); F. Ballester (Ferran)

    2016-01-01

    textabstractBackground: Several studies have reported decreases in birth size associated with exposure to organochlorine compounds (OCs), but uncertainties remain regarding the critical windows of prenatal exposure and the effects on fetal body segments. Objective: We examined the relationship

  14. Typing of human fetal organs for the histocompatibility antigens A, B and DR.

    Science.gov (United States)

    Tuch, B E; Doran, T J; Messel, N; Turtle, J R

    1985-01-01

    In the transplantation of human fetal pancreatic explants into diabetic man, the importance of matching the histocompatibility antigens of donor and recipient to decrease the chances of rejection is unknown. Before this question can be answered human fetuses must be tissue typed. We have shown that lymphocytes harvested from fetal liver, thymus, bone marrow and spleen can be successfully HLA DR typed in 64% and A and B typed in 57% of 58 fetuses aged 15 wk or more. Typing should ideally be carried out on unseparated T and B cells. Best results were achieved if all four of the above organs were available and more than one million viable cells were able to be harvested for typing. Whilst the DR antigens could be typed from all tissues, the A and B antigens could be typed, with few exceptions only from thymus, spleen and bone marrow. The efficacy of matching the histocompatibility antigens of recipient and donor fetuses, especially the DR antigens can now be tested in the human diabetic being transplanted with pancreatic explants.

  15. Skin thickness as a potential marker of gestational age at birth despite different fetal growth profiles: A feasibility study.

    Directory of Open Access Journals (Sweden)

    Gabriela Luiza Nogueira Vitral

    Full Text Available New methodologies to estimate gestational age (GA at birth are demanded to face the limited access to obstetric ultrasonography and imprecision of postnatal scores. The study analyzed the correlation between neonatal skin thickness and pregnancy duration. Secondarily, it investigated the influence of fetal growth profiles on tissue layer dimensions.In a feasibility study, 222 infants selected at a term-to-preterm ratio of 1:1 were assessed. Reliable information on GA was based on the early ultrasonography-based reference. The thicknesses of the epidermal and dermal skin layers were examined using high-frequency ultrasonography. We scanned the skin over the forearm and foot plantar surface of the newborns. A multivariate regression model was adjusted to determine the correlation of GA with skin layer dimensions. The best model to correlate skin thickness with GA was fitted using the epidermal layer on the forearm site, adjusted to cofactors, as follows: Gestational age (weeks = -28.0 + 12.8 Ln (Thickness - 4.4 Incubator staying; R2 = 0.604 (P<0.001. In this model, the constant value for the standard of fetal growth was statistically null. The dermal layer thickness on the forearm and plantar surfaces had a negative moderate linear correlation with GA (R = -0.370, P<0.001 and R = -0.421, P<0.001, respectively. The univariate statistical analyses revealed the influence of underweight and overweight profiles on neonatal skin thickness at birth. Of the 222 infants, 53 (23.9% had inappropriate fetal growths expected for their GA. Epidermal thickness was not fetal growth standard dependent as follows: 172.2 (19.8 μm for adequate for GA, 171.4 (20.6 μm for SGA, and 177.7 (15.2 μm for LGA (P = 0.525, mean [SD] on the forearm.The analysis highlights a new opportunity to relate GA at birth to neonatal skin layer thickness. As this parameter was not influenced by the standard of fetal growth, skin maturity can contribute to clinical applications.

  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. 3H-cyclosporine internalization and secretion by human fetal pancreatic islets

    International Nuclear Information System (INIS)

    Formby, B.; Walker, L.; Peterson, C.M.

    1988-01-01

    Human fetal pancreatic islets were isolated from 16- to 20-week-old fetuses by a collagenase technique and cultured 48 hr in RPMI 1640 containing 10% human adult serum and unlabeled 0 to 5 micrograms cyclosporine A (CsA)/ml. Insulin secretory capacity of human fetal islets was expressed as a fractional stimulatory ratio FSR = F2/F1 of the fractional secretion rates during two successive 1 hr static incubations first with 2 mM glucose (F1) to stabilize secretion followed by maximal stimulus, i.e., 25 mM glucose plus 10 mM L-leucine and 10 mM L-arginine (F2). Unlabeled CsA at the above concentrations had no significant effects on the insulin secretory capacity expressed by FSR-values. Studies of net uptake of 3H-CsA by islets cultured for varying periods up to 40 hr and expressed as picomole 3H-CsA per picomole islet insulin content demonstrated that uptake rate was slow and did not reach isotopic equilibrium over the 40 hr of culture. When isolated fetal islets were cultured for 48 hr in the presence of 3H-CsA and varying concentrations of unlabeled CsA it was found during two successive 1 hr static incubations that fetal islets secrete insulin concomitantly with 3H-CsA following maximal stimulus for secretion. An optimal secretory molar ratio of 3H-CsA to insulin of 4.0 +/- 1.3 (n = 7) was found after islets were cultured 48 hr in the presence of a saturating 2.128 micrograms 3H-CsA per milliliter culture medium. In three successive 30-min static incubations of 3H-CsA loaded islets, first with low glucose, followed by high glucose plus L-arginine and L-leucine, and finally with high glucose plus L-arginine and L-leucine and 10 mM theophylline, the proportional fractional secretion rates of insulin and 3H-CsA were of the same magnitude

  18. Changes of the glomerular size during the human fetal kidney development

    Directory of Open Access Journals (Sweden)

    Daković-Bjelaković Marija

    2006-01-01

    Full Text Available Introduction. Newborns adaptation on postnatal conditions includes significant morphological and functional renal changes. Every kidney contains a constant number of nephrons, at the end of the nephrogenesis period, which extends from week 8 to 34 of gestation. Mature juxtamedullary nephrons possess higher filtration capacity than primitive superficial nephrons, which have insufficient vascularization. Objective. The objective of the study was to calculate an average glomerular diameter in cortical zones of the kidney during development, to define periods of their most intensive growth, and to record differences of glomerular size between different cortical zones. METHOD A total of 30 human fetal kidneys aged from IV to X lunar months were analyzed. Stereological methods were used for calculating the average glomerular diameter in superficial, intermediate and juxtamedullary zone of the kidney cortex. Results. Glomeruli in the superficial cortical zone had the lowest average diameter. The average glomerular diameter continually increased from IV lunar month (0.057±0.004 mm to X lunar month (0.082±0.004 mm, with highly significant correlation with gestational age (r=0.755; p<0.01. The average glomerular diameter in the intermediate zone increased from 0.081±0.004 mm (IV lunar month to 0.096±0.004 mm (X lunar month with low linear correlation with gestational age (r=0.161. Juxtamedullary glomeruli were the biggest ones. Their average diameter, during the IV LM ranged from 0.093±0.006 mm to 0.101±0.004 mm. In the newborns (X lunar month, juxtamedullary glomeruli had spherical structures with an average diameter of 0.103±0.004 mm, and low negative correlation (r=-0.032 with gestational age. In the IV and V lunar months of gestation, there was significant difference (p<0.01; p<0.05 between the average glomerular diameter in the different zones of the kidney cortex. Conclusion. Superficial glomeruli had the smallest diameter, while

  19. Energy, economic growth, and human welfare

    International Nuclear Information System (INIS)

    Schurr, S.H.

    1984-01-01

    The subject is covered in sections, entitled: economic growth and human welfare; world-wide economic growth; economic growth and energy consumption; assessing the future; caution advised; energy supply and economic growth; supply as constraint; sound policies needed. (U.K.)

  20. 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.

  1. Maternal Dietary Patterns and Fetal Growth: A Large Prospective Cohort Study in China.

    Science.gov (United States)

    Lu, Min-Shan; Chen, Qiao-Zhu; He, Jian-Rong; Wei, Xue-Ling; Lu, Jin-Hua; Li, Sheng-Hui; Wen, Xing-Xuan; Chan, Fan-Fan; Chen, Nian-Nian; Qiu, Lan; Mai, Wei-Bi; Zhang, Rui-Fang; Hu, Cui-Yue; Xia, Hui-Min; Qiu, Xiu

    2016-04-28

    There was limited evidence revealing the association of Chinese maternal dietary patterns with fetal growth. We aimed to examine the relationship of maternal dietary patterns during pregnancy to neonatal birth weight and birth weight for gestational age in a Chinese population. A total of 6954 mother-child pairs were included from the Born in Guangzhou Cohort Study. Maternal diet during pregnancy was assessed using a self-administered food frequency questionnaire. Cluster analysis was used to identify dietary patterns. The following six dietary patterns were identified: "Cereals, eggs, and Cantonese soups" (n 1026, 14.8%), "Dairy" (n 1020, 14.7%), "Fruits, nuts, and Cantonese desserts" (n 799, 11.5%), "Meats" (n 1066, 15.3%), "Vegetables" (n 1383, 19.9%), and "Varied" (n 1224, 17.6%). The mean neonatal birth weight Z scores of women in the above patterns were 0.02, 0.07, 0.20, 0.01, 0.06, and 0.14, respectively. Women in the "Fruits, nuts, and Cantonese desserts" and "Varied" groups had significantly heavier infants compared with those in the "Cereals, eggs, and Cantonese soups" group. Compared with women in the "Cereals, eggs, and Cantonese soups" group, those in the "Varied" group had marginally significantly lower odds of having a small-for-gestational age (SGA) infant after adjustment for other confounders (OR 0.77, 95% CI 0.57, 1.04, p = 0.08). These findings suggest that compared to a traditional Cantonese diet high in cereals, eggs, and Cantonese soups, a diet high in fruits, nuts, and Cantonese desserts might be associated with a higher birth weight, while a varied diet might be associated with a greater birth weight and also a decreased risk of having a SGA baby.

  2. Circulating C19MC MicroRNAs in Preeclampsia, Gestational Hypertension, and Fetal Growth Restriction

    Directory of Open Access Journals (Sweden)

    Ilona Hromadnikova

    2013-01-01

    Full Text Available The objective of the study was to identify the profile of circulating C19MC microRNAs (miR-516-5p, miR-517*, miR-518b, miR-520a*, miR-520h, miR-525, and miR-526a in patients with established preeclampsia (n=63, fetal growth restriction (n=27, and gestational hypertension (n=23. We examined the correlation between plasmatic concentrations and expression levels of microRNAs and the severity of the disease with respect to clinical signs, requirements for the delivery, and Doppler ultrasound parameters. Using absolute and relative quantification approaches, increased extracellular C19MC microRNA levels (miR-516-5p, P=0.037, P=0.009; miR-517*, P=0.033, P=0.043; miR-520a*, P=0.001, P=0.009; miR-525, P=0.026, P=0.01; miR-526a, P=0.03, P=0.035 were detected in patients with preeclampsia. The association analysis pointed to no relationship between C19MC microRNA plasmatic concentrations and expression profile and identified risk factors for a poorer perinatal outcome. However, the dependence between the levels of plasmatic C19MC microRNAs and the pulsatility index in the middle cerebral artery and the values of cerebroplacental ratio was demonstrated. The study brought the interesting finding that the upregulation of miR-516-5p, miR-517*, miR-520a*, miR-525, and miR-526a is a characteristic phenomenon of established preeclampsia.

  3. Maternal Dietary Patterns and Fetal Growth: A Large Prospective Cohort Study in China

    Directory of Open Access Journals (Sweden)

    Min-Shan Lu

    2016-04-01

    Full Text Available There was limited evidence revealing the association of Chinese maternal dietary patterns with fetal growth. We aimed to examine the relationship of maternal dietary patterns during pregnancy to neonatal birth weight and birth weight for gestational age in a Chinese population. A total of 6954 mother-child pairs were included from the Born in Guangzhou Cohort Study. Maternal diet during pregnancy was assessed using a self-administered food frequency questionnaire. Cluster analysis was used to identify dietary patterns. The following six dietary patterns were identified: “Cereals, eggs, and Cantonese soups” (n 1026, 14.8%, “Dairy” (n 1020, 14.7%, “Fruits, nuts, and Cantonese desserts” (n 799, 11.5%, “Meats” (n 1066, 15.3%, “Vegetables” (n 1383, 19.9%, and “Varied” (n 1224, 17.6%. The mean neonatal birth weight Z scores of women in the above patterns were 0.02, 0.07, 0.20, 0.01, 0.06, and 0.14, respectively. Women in the “Fruits, nuts, and Cantonese desserts” and “Varied” groups had significantly heavier infants compared with those in the “Cereals, eggs, and Cantonese soups” group. Compared with women in the “Cereals, eggs, and Cantonese soups” group, those in the “Varied” group had marginally significantly lower odds of having a small-for-gestational age (SGA infant after adjustment for other confounders (OR 0.77, 95% CI 0.57, 1.04, p = 0.08. These findings suggest that compared to a traditional Cantonese diet high in cereals, eggs, and Cantonese soups, a diet high in fruits, nuts, and Cantonese desserts might be associated with a higher birth weight, while a varied diet might be associated with a greater birth weight and also a decreased risk of having a SGA baby.

  4. Circulating cell-derived microparticles in severe preeclampsia and in fetal growth restriction.

    Science.gov (United States)

    Alijotas-Reig, Jaume; Palacio-Garcia, Carles; Farran-Codina, Immaculada; Ruiz-Romance, Mar; Llurba, Elisa; Vilardell-Tarres, Miquel

    2012-02-01

    The behavior of the circulating microparticles (cMP) in severe preeclampsia (PE) and fetal growth restriction (FGR) is disputed. METHOD OF STUDY  Non-matched case-control study. Seventy cases of severe PE/HELLP/FGR were compared to 38 healthy pregnant women. Twenty healthy non-pregnant women acted as a control. cMP were analyzed using flow cytometry. Results are given as total (annexin-A5-ANXA5+), platelet (CD41+), leukocyte (CD45+), endothelial (CD144+CD31+//CD41-), and CD41-negative cMP/μL of plasma. Antiphospholipid antibodies (aPL) were analyzed through usual methods. Platelet and endothelial cMP increased in healthy pregnant women. PE whole group (PE±FGR) showed an increase in endothelial and CD41-negative, but not in platelet-derived, cMP. Comparing PE whole group versus healthy pregnant, we found cMP levels of endothelial and CD41- had increased. The cMP results obtained in PE group were similar to those of the PE whole group. Comparing PE group to isolated FGR, significant CD41-negative cMP increase was found in PE. According to its aPL positivity, a trend to decrease in leukocyte and endothelial-derived cMP was found in PE group. Normal pregnancy is accompanied by endothelial and platelet cell activation. Endothelial cell activation has been shown in PE but not in isolated FGR. In PE, aPL may contribute to endothelial and possibly to leukocyte cell activation. © 2011 John Wiley & Sons A/S.

  5. Lifetime racism and blood pressure changes during pregnancy: implications for fetal growth.

    Science.gov (United States)

    Hilmert, Clayton J; Dominguez, Tyan Parker; Schetter, Christine Dunkel; Srinivas, Sindhu K; Glynn, Laura M; Hobel, Calvin J; Sandman, Curt A

    2014-01-01

    Research suggests that exposure to racism partially explains why African American women are 2 to 3 times more likely to deliver low birth weight and preterm infants. However, the physiological pathways by which racism exerts these effects are unclear. This study examined how lifetime exposure to racism, in combination with maternal blood pressure changes during pregnancy, was associated with fetal growth. African American pregnant women (n = 39) reported exposure to childhood and adulthood racism in several life domains (e.g., at school, at work), which were experienced directly or indirectly, meaning vicariously experienced when someone close to them was treated unfairly. A research nurse measured maternal blood pressure at 18 to 20 and 30 to 32 weeks gestation. Standardized questionnaires and trained interviewers assessed maternal demographics. Neonatal length of gestation and birth weight data were collected from medical charts. Childhood racism interacted with diastolic blood pressure to predict birth weight. Specifically, women with two or more domains of indirect exposure to racism in childhood and increases in diastolic blood pressure between 18 and 32 weeks had lower gestational age adjusted birth weight than the other women. A similar pattern was found for direct exposure to racism in childhood. Increases in diastolic blood pressure between the second and third trimesters predicted lower birth weight, but only when racism exposure in childhood (direct or indirect) was relatively high. Understanding pregnant African American women's lifetime direct and indirect experiences with racism in combination with prenatal blood pressure may improve identification of highest risk subgroups within this population. 2014 APA, all rights reserved

  6. Growth Patterns of Fetal Lung Volumes in Healthy Fetuses and Fetuses With Isolated Left-Sided Congenital Diaphragmatic Hernia.

    Science.gov (United States)

    Ruano, Rodrigo; Britto, Ingrid Schwach Werneck; Sananes, Nicolas; Lee, Wesley; Sangi-Haghpeykar, Haleh; Deter, Russell L

    2016-06-01

    To evaluate fetal lung growth using 3-dimensional sonography in healthy fetuses and those with congenital diaphragmatic hernia (CDH). Right and total lung volumes were serially evaluated by 3-dimensional sonography in 66 healthy fetuses and 52 fetuses with left-sided CDH between 20 and 37 weeks' menstrual age. Functions fitted to these parameters were compared for 2 groups: (1) healthy versus those with CDH; and (2) fetuses with CHD who survived versus those who died. Fetal right and total lung volumes as well as fetal observed-to-expected right and total lung volume ratios were significantly lower in fetuses with CDH than healthy fetuses (Pvolume ratios did not vary with menstrual age in healthy fetuses or in those with CDH (independent of outcome). Lung volume rates were lower in fetuses with left-sided CDH compared to healthy fetuses, as well as in fetuses with CDH who died compared to those who survived. The observed-to-expected right and total lung volume ratios were relatively constant throughout menstrual age in fetuses with left-sided CDH, suggesting that the origin of their lung growth abnormalities occurred before 20 weeks and did not progress. The observed-to-expected ratios may be useful in predicting the outcome in fetuses with CDH independent of menstrual age. © 2016 by the American Institute of Ultrasound in Medicine.

  7. Antenatal betamethasone and fetal growth in prematurely born children: implications for temperament traits at the age of 2 years.

    Science.gov (United States)

    Pesonen, Anu-Katriina; Räikkönen, Katri; Lano, Aulikki; Peltoniemi, Outi; Hallman, Mikko; Kari, M Anneli

    2009-01-01

    We explored whether repeated dose of antenatal betamethasone and variation in intrauterine growth of prematurely born children predict temperament characteristics at the age of 2 years. The patients (n = 142) were prematurely born children (mean gestational age: 31.0 weeks; range: 24.6-35.0 weeks) who participated in a randomized and blinded trial testing the effects of a repeated dose of antenatal betamethasone in imminent preterm birth. Fetal growth was estimated as weight, length, and head circumference in SDs according to Finnish growth charts. Parents assessed their toddlers' temperament with 201 items of the Early Childhood Temperament Questionnaire (mean child corrected age: 2.1 years). No significant main effects of repeated betamethasone on toddler temperament existed. However, a significant interaction between study group and duration of exposure to betamethasone emerged; those exposed to a repeated dose for >24 hours before delivery were more impulsive. One-SD increases in weight, length, and head circumference at birth were associated with 0.14- to 0.19-SD lower levels of negative affectivity (fearfulness, anger proneness, and sadness); 1-SD increases in length, weight, and head circumference at birth were associated with 0.14- to 0.18-SD higher levels of effortful control (self-regulation). Repeated antenatal betamethasone did not induce alterations in toddler temperament. The results, however, suggest that a longer duration of exposure is associated with higher impulsivity scores. Regardless of betamethasone exposure, slower fetal growth exerted influences on temperament. Our findings indicate prenatal programming of psychological development and imply that more attention is needed to support the development of infants born at the lower end of the fetal growth distribution.

  8. Mutator/hypermutable fetal/juvenile metakaryotic stem cells and human colorectal carcinogenesis.

    Directory of Open Access Journals (Sweden)

    Lohith G. Kini

    2013-10-01

    Full Text Available Adult age-specific colorectal cancer incidence rates increase exponentially from maturity, reach a maximum, then decline in extreme old age. Armitage and Doll (1957 postulated that the exponential increase resulted from n mutations occurring throughout adult life in normal cells at risk that initiated the growth of a preneoplastic colony in which subsequent m mutations promoted one of the preneoplastic cells at risk to form a lethal neoplasia. We have reported cytologic evidence that these cells at risk are fetal/juvenile organogenic, then preneoplastic metakaryotic stem cells. Metakaryotic cells display stem-like behaviors of both symmetric and asymmetric nuclear divisions and peculiarities such as bell shaped nuclei and amitotic nuclear fission that distinguish them from embryonic, eukaryotic stem cells. Analyses of mutant colony sizes and numbers in adult lung epithelia supported the inferences that the metakaryotic organogenic stem cells are constitutively mutator/hypermutable and that their contributions to cancer initiation are limited to the fetal/juvenile period. We have amended the two-stage model of Armitage and Doll and incorporated these several inferences in a computer program CancerFit v.5.0. We compared the expectations of the amended model to adult (15-104 yr age-specific colon cancer rates for European American males born 1890-99 and observed remarkable concordance. When estimates of normal colonic fetal/juvenile APC and OAT gene mutation rates (~2-5 x 10-5 per stem cell doubling and preneoplastic colonic gene loss rates (~ 8 x 10-3 were applied, the model was in accordance only for the values of n = 2 and m = 4 or 5.

  9. Isolation and characterization of full-length cDNA clones coding for cholinesterase from fetal human tissues

    International Nuclear Information System (INIS)

    Prody, C.A.; Zevin-Sonkin, D.; Gnatt, A.; Goldberg, O.; Soreq, H.

    1987-01-01

    To study the primary structure and regulation of human cholinesterases, oligodeoxynucleotide probes were prepared according to a consensus peptide sequence present in the active site of both human serum pseudocholinesterase and Torpedo electric organ true acetylcholinesterase. Using these probes, the authors isolated several cDNA clones from λgt10 libraries of fetal brain and liver origins. These include 2.4-kilobase cDNA clones that code for a polypeptide containing a putative signal peptide and the N-terminal, active site, and C-terminal peptides of human BtChoEase, suggesting that they code either for BtChoEase itself or for a very similar but distinct fetal form of cholinesterase. In RNA blots of poly(A) + RNA from the cholinesterase-producing fetal brain and liver, these cDNAs hybridized with a single 2.5-kilobase band. Blot hybridization to human genomic DNA revealed that these fetal BtChoEase cDNA clones hybridize with DNA fragments of the total length of 17.5 kilobases, and signal intensities indicated that these sequences are not present in many copies. Both the cDNA-encoded protein and its nucleotide sequence display striking homology to parallel sequences published for Torpedo AcChoEase. These finding demonstrate extensive homologies between the fetal BtChoEase encoded by these clones and other cholinesterases of various forms and species

  10. Fetal Microchimerism in Cancer Protection and Promotion: Current Understanding in Dogs and the Implications for Human Health.

    Science.gov (United States)

    Bryan, Jeffrey N

    2015-05-01

    Fetal microchimerism is the co-existence of small numbers of cells from genetically distinct individuals living within a mother's body following pregnancy. During pregnancy, bi-directional exchange of cells occurs resulting in maternal microchimerism and even sibling microchimerism in offspring. The presence of fetal microchimerism has been identified with lower frequency in patients with cancers such as breast and lymphoma and with higher frequency in patients with colon cancer and autoimmune diseases. Microchimeric cells have been identified in healing and healed tissues as well as normal and tumor tissues. This has led to the hypothesis that fetal microchimerism may play a protective role in some cancers and may provoke other cancers or autoimmune disease. The long periods of risk for these diseases make it a challenge to prospectively study this phenomenon in human populations. Dogs get similar cancers as humans, share our homes and environmental exposures, and live compressed life-spans, allowing easier prospective study of disease development. This review describes the current state of understanding of fetal microchimerism in humans and dogs and highlights the similarities of the common cancers mammary carcinoma, lymphoma, and colon cancer between the two species. Study of fetal microchimerism in dogs might hold the key to characterization of the type and function of microchimeric cells and their role in health and disease. Such an understanding could then be applied to preventing and treating disease in humans.

  11. Serum-converted platelet lysate can substitute for fetal bovine serum in human mesenchymal stromal cell cultures.

    Science.gov (United States)

    Mojica-Henshaw, Mariluz P; Jacobson, Pam; Morris, Julie; Kelley, Linda; Pierce, Jan; Boyer, Michael; Reems, Jo-Anna

    2013-12-01

    Fetal bovine serum (FBS) is commonly used as a serum supplement for culturing human mesenchymal stromal cells (hMSCs). However, human cells grown in FBS, especially for extended periods, risk potential exposure to bovine immunogenic proteins and infectious agents. To address this issue, we investigated the ability of a novel human platelet serum supplement to substitute for FBS in hMSC cultures. Platelet lysate-serum (PL-serum) was converted from platelet lysate-plasma (PL-plasma) that was manufactured from pooled platelet-rich plasma (PRP) apheresis units. Growth factor levels and the number of residual intact platelets in PL-serum and PL-plasma were compared with enzyme-linked immunosorbent assays and flow cytometry, respectively. Proliferation responses of hMSCs cultured in PL-serum, PL-plasma, or FBS were assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, the immunophenotype of harvested hMSCs was evaluated by flow cytometry and tri-lineage differentiation potential was evaluated by assessing adipogenic, osteogenic and chondrogenic development. Selected growth factor levels in PL-serum were not significantly different from PL-plasma (P > 0.05). hMSC cultures supplemented with PL-serum had comparable growth kinetics to PL-plasma, and hMSC yields were consistently greater than with FBS. hMSCs harvested from cultures supplemented with PL-serum, PL-plasma or FBS had similar cell surface phenotypes and maintained tri-lineage differentiation potential. PL-serum, similar to PL-plasma, can substitute for FBS in hMSC cultures. Use of PL-serum, in contrast to PL-plasma, has an added advantage of not requiring addition of a xenogeneic source of heparin, providing a completely xeno-free culture medium. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  12. An implantable vascularized protein gel construct that supports human fetal hepatoblast survival and infection by hepatitis C virus in mice.

    Directory of Open Access Journals (Sweden)

    Martha J Harding

    2010-04-01

    Full Text Available Widely accessible small animal models suitable for the study of hepatitis C virus (HCV in vivo are lacking, primarily because rodent hepatocytes cannot be productively infected and because human hepatocytes are not easily engrafted in immunodeficient mice.We report here on a novel approach for human hepatocyte engraftment that involves subcutaneous implantation of primary human fetal hepatoblasts (HFH within a vascularized rat collagen type I/human fibronectin (rCI/hFN gel containing Bcl-2-transduced human umbilical vein endothelial cells (Bcl-2-HUVEC in severe combined immunodeficient X beige (SCID/bg mice. Maturing hepatic epithelial cells in HFH/Bcl-2-HUVEC co-implants displayed endocytotic activity at the basolateral surface, canalicular microvilli and apical tight junctions between adjacent cells assessed by transmission electron microscopy. Some primary HFH, but not Huh-7.5 hepatoma cells, appeared to differentiate towards a cholangiocyte lineage within the gels, based on histological appearance and cytokeratin 7 (CK7 mRNA and protein expression. Levels of human albumin and hepatic nuclear factor 4alpha (HNF4alpha mRNA expression in gel implants and plasma human albumin levels in mice engrafted with HFH and Bcl-2-HUVEC were somewhat enhanced by including murine liver-like basement membrane (mLBM components and/or hepatocyte growth factor (HGF-HUVEC within the gel matrix. Following ex vivo viral adsorption, both HFH/Bcl-2-HUVEC and Huh-7.5/Bcl-2-HUVEC co-implants sustained HCV Jc1 infection for at least 2 weeks in vivo, based on qRT-PCR and immunoelectron microscopic (IEM analyses of gel tissue.The system described here thus provides the basis for a simple and robust small animal model of HFH engraftment that is applicable to the study of HCV infections in vivo.

  13. Development of steroid signaling pathways during primordial follicle formation in the human fetal ovary.

    Science.gov (United States)

    Fowler, Paul A; Anderson, Richard A; Saunders, Philippa T; Kinnell, Hazel; Mason, J Ian; Evans, Dean B; Bhattacharya, Siladitya; Flannigan, Samantha; Franks, Stephen; Monteiro, Ana; O'Shaughnessy, Peter J

    2011-06-01

    Ovarian primordial follicle formation is critical for subsequent human female fertility. It is likely that steroid, and especially estrogen, signaling is required for this process, but details of the pathways involved are currently lacking. The aim was to identify and characterize key members of the steroid-signaling pathway expressed in the second trimester human fetal ovary. We conducted an observational study of the female fetus, quantifying and localizing steroid-signaling pathway members. The study was conducted at the Universities of Aberdeen, Edinburgh, and Glasgow. Ovaries were collected from 43 morphologically normal human female fetuses from women undergoing elective termination of second trimester pregnancies. We measured mRNA transcript levels and immunolocalized key steroidogenic enzymes and steroid receptors, including those encoded by ESR2, AR, and CYP19A1. Levels of mRNA encoding the steroidogenic apparatus and steroid receptors increased across the second trimester. CYP19A1 transcript increased 4.7-fold during this period with intense immunostaining for CYP19A detected in pregranulosa cells around primordial follicles and somatic cells around oocyte nests. ESR2 was localized primarily to germ cells, but androgen receptor was exclusively expressed in somatic cells. CYP17A1 and HSD3B2 were also localized to oocytes, whereas CYP11A1 was detected in oocytes and some pregranulosa cells. The human fetal ovary expresses the machinery to produce and detect multiple steroid signaling pathways, including estrogenic signaling, with the oocyte acting as a key component. This study provides a step-change in our understanding of local dynamics of steroid hormone signaling during the key period of human primordial follicle formation.

  14. Long chain poly-unsaturated fatty acids attenuate the IL-1?-induced pro-inflammatory response in human fetal intestinal epithelial cells

    OpenAIRE

    Wijendran, Vasuki; Brenna, JT; Wang, Dong Hao; Zhu, Weishu; Meng, Di; Ganguli, Kriston; Kothapalli, Kumar SD; Requena, Pilar; Innis, Sheila; Walker, WA

    2015-01-01

    Background Evidence suggests that excessive inflammation of the immature intestine may predispose premature infants to necrotizing enterocolitis (NEC). We investigated the anti-inflammatory effects of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and arachidonic acid (ARA) in human fetal and adult intestinal epithelial cells (IEC) in primary culture. Methods Human fetal IEC in culture were derived from a healthy fetal small intestine (H4) or resected small intestine of a neonate wit...

  15. Evidence-based national guidelines for the management of suspected fetal growth restriction: comparison, consensus, and controversy.

    Science.gov (United States)

    McCowan, Lesley M; Figueras, Francesc; Anderson, Ngaire H

    2018-02-01

    Small for gestational age is usually defined as an infant with a birthweight restriction refers to a fetus that has failed to reach its biological growth potential because of placental dysfunction. Small-for-gestational-age babies make up 28-45% of nonanomalous stillbirths, and have a higher chance of neurodevelopmental delay, childhood and adult obesity, and metabolic disease. The majority of small-for-gestational-age babies are not recognized before birth. Improved identification, accompanied by surveillance and timely delivery, is associated with reduction in small-for-gestational-age stillbirths. Internationally and regionally, detection of small for gestational age and management of fetal growth problems vary considerably. The aim of this review is to: summarize areas of consensus and controversy between recently published national guidelines on small for gestational age or fetal growth restriction; highlight any recent evidence that should be incorporated into existing guidelines; and identify future research priorities in this field. A search of MEDLINE, Google, and the International Guideline Library identified 6 national guidelines on management of pregnancies complicated by fetal growth restriction/small for gestational age published from 2010 onwards. There is general consensus between guidelines (at least 4 of 6 guidelines in agreement) in early pregnancy risk selection, and use of low-dose aspirin for women with major risk factors for placental insufficiency. All highlight the importance of smoking cessation to prevent small for gestational age. While there is consensus in recommending fundal height measurement in the third trimester, 3 specify the use of a customized growth chart, while 2 recommend McDonald rule. Routine third-trimester scanning is not recommended for small-for-gestational-age screening, while women with major risk factors should have serial scanning in the third trimester. Umbilical artery Doppler studies in suspected small

  16. Development of the Human Placenta and Fetal Heart: Synergic or Independent?

    Directory of Open Access Journals (Sweden)

    Graham J. Burton

    2018-04-01

    Full Text Available The placenta is the largest fetal organ, and toward the end of pregnancy the umbilical circulation receives at least 40% of the biventricular cardiac output. It is not surprising, therefore, that there are likely to be close haemodynamic links between the development of the placenta and the fetal heart. Development of the placenta is precocious, and in advance of that of the fetus. The placenta undergoes considerable remodeling at the end of the first trimester of pregnancy, and its vasculature is capable of adapting to environmental conditions and to variations in the blood supply received from the mother. There are two components to the placental membranes to consider, the secondary yolk sac and the chorioallantoic placenta. The yolk sac is the first of the extraembryonic membranes to be vascularized, and condensations in the mesenchyme at ~17 days post-conception (p.c. give rise to endothelial and erythroid precursors. A network of blood vessels is established ~24 days p.c., with the vitelline vein draining through the region of the developing liver into the sinus venosus. Gestational sacs of early pregnancy failures often display aberrant development of the yolk sac, which is likely to be secondary to abnormal fetal development. Vasculogenesis occurs in the villous mesenchyme of the chorioallantoic placenta at a similarly early stage. Nucleated erythrocytes occupy the lumens of the placental capillaries and end-diastolic flow is absent in the umbilical arterial circulation throughout most of the first trimester, indicating a high resistance to blood flow. Resistance begins to fall in the umbilico-placental circulation around 12–14 weeks. During normal early pregnancy the placental capillary network is plastic, and considerable remodeling occurs in response to the local oxygen concentration, and in particular to oxidative stress. In pregnancies complicated by preeclampsia and/or fetal growth restriction, utero-placental malperfusion induces

  17. Prolonged exposure to acetaminophen reduces testosterone production by the human fetal testis in a xenograft model

    DEFF Research Database (Denmark)

    van den Driesche, Sander; Macdonald, Joni; Anderson, Richard A

    2015-01-01

    Most common male reproductive disorders are linked to lower testosterone exposure in fetal life, although the factors responsible for suppressing fetal testosterone remain largely unknown. Protracted use of acetaminophen during pregnancy is associated with increased risk of cryptorchidism in sons...

  18. Circulating soluble endoglin levels in pregnant women in Cameroon and Malawi--associations with placental malaria and fetal growth restriction.

    Science.gov (United States)

    Silver, Karlee L; Conroy, Andrea L; Leke, Rose G F; Leke, Robert J I; Gwanmesia, Philomina; Molyneux, Malcolm E; Taylor, Diane Wallace; Wallace, Diane Taylor; Rogerson, Stephen J; Kain, Kevin C

    2011-01-01

    Placental infections with Plasmodium falciparum are associated with fetal growth restriction resulting in low birth weight (LBW). The mechanisms that mediate these effects have yet to be completely described; however, they are likely to involve inflammatory processes and dysregulation of angiogenesis. Soluble endoglin (sEng), a soluble receptor of transforming growth factor (TGF)-β previously associated with preeclampsia in pregnant women and with severe malaria in children, regulates the immune system and influences angiogenesis. We hypothesized that sEng may play a role in development of LBW associated with placental malaria (PM). Plasma levels of sEng were measured in women (i) followed prospectively throughout pregnancy in Cameroon (n = 52), and (ii) in a case-control study at delivery in Malawi (n = 479). The relationships between sEng levels and gravidity, peripheral and placental parasitemia, gestational age, and adverse outcomes of PM including maternal anemia and LBW were determined. In the longitudinal cohort from Cameroon, 28 of 52 women (54%) experienced at least one malaria infection during pregnancy. In Malawi we enrolled two aparasitemic gravidity-matched controls for every case with PM. sEng levels varied over the course of gestation and were significantly higher in early and late gestation as compared to delivery (Pwomen and PM in Malawian women were each associated with elevated sEng levels following correction for gestational age and gravidity (p = 0.006 and p = 0.033, respectively). Increased sEng was also associated with the delivery of LBW infants in primigravid Malawian women (p = 0.017); the association was with fetal growth restriction (p = 0.003) but not pre-term delivery (p = 0.286). Increased circulating maternal sEng levels are associated with P. falciparum infection in pregnancy and with fetal growth restriction in primigravidae with PM.

  19. Growth charts of human development.

    Science.gov (United States)

    van Buuren, Stef

    2014-08-01

    This article reviews and compares two types of growth charts for tracking human development over age. Both charts assume the existence of a continuous latent variable, but relate to the observed data in different ways. The D-score diagram summarizes developmental indicators into a single aggregate score measuring global development. The relations between the indicators should be consistent with the Rasch model. If true, the D-score is a measure with interval scale properties, and allows for the calculation of meaningful differences both within and across age. The stage line diagram describes the natural development of ordinal indicators. The method models the transition probabilities between successive stages of the indicator as smoothly varying functions of age. The location of each stage is quantified by the mid-P-value. Both types of diagrams assist in identifying early and delayed development, as well as finding differences in tempo. The relevant techniques are illustrated to track global development during infancy and early childhood (0-2 years) and Tanner pubertal stages (8-21 years). New reference values for both applications are provided. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  20. The value of predicting restriction of fetal growth and compromise of its wellbeing: Systematic quantitative overviews (meta-analysis) of test accuracy literature.

    Science.gov (United States)

    Morris, Rachel K; Khan, Khalid S; Coomarasamy, Aravinthan; Robson, Stephen C; Kleijnen, Jos

    2007-03-08

    Restriction of fetal growth and compromise of fetal wellbeing remain significant causes of perinatal death and childhood disability. At present, there is a lack of scientific consensus about the best strategies for predicting these conditions before birth. Therefore, there is uncertainty about the best management of pregnant women who might have a growth restricted baby. This is likely to be due to a dearth of clear collated information from individual research studies drawn from different sources on this subject. A series of systematic reviews and meta-analyses will be undertaken to determine, among pregnant women, the accuracy of various tests to predict and/or diagnose fetal growth restriction and compromise of fetal wellbeing. We will search Medline, Embase, Cochrane Library, MEDION, citation lists of review articles and eligible primary articles and will contact experts in the field. Independent reviewers will select studies, extract data and assess study quality according to established criteria. Language restrictions will not be applied. Data synthesis will involve meta-analysis (where appropriate), exploration of heterogeneity and publication bias. The project will collate and synthesise the available evidence regarding the value of the tests for predicting restriction of fetal growth and compromise of fetal wellbeing. The systematic overviews will assess the quality of the available evidence, estimate the magnitude of potential benefits, identify those tests with good predictive value and help formulate practice recommendations.

  1. The value of predicting restriction of fetal growth and compromise of its wellbeing: Systematic quantitative overviews (meta-analysis of test accuracy literature

    Directory of Open Access Journals (Sweden)

    Robson Stephen C

    2007-03-01

    Full Text Available Abstract Background Restriction of fetal growth and compromise of fetal wellbeing remain significant causes of perinatal death and childhood disability. At present, there is a lack of scientific consensus about the best strategies for predicting these conditions before birth. Therefore, there is uncertainty about the best management of pregnant women who might have a growth restricted baby. This is likely to be due to a dearth of clear collated information from individual research studies drawn from different sources on this subject. Methods/Design A series of systematic reviews and meta-analyses will be undertaken to determine, among pregnant women, the accuracy of various tests to predict and/or diagnose fetal growth restriction and compromise of fetal wellbeing. We will search Medline, Embase, Cochrane Library, MEDION, citation lists of review articles and eligible primary articles and will contact experts in the field. Independent reviewers will select studies, extract data and assess study quality according to established criteria. Language restrictions will not be applied. Data synthesis will involve meta-analysis (where appropriate, exploration of heterogeneity and publication bias. Discussion The project will collate and synthesise the available evidence regarding the value of the tests for predicting restriction of fetal growth and compromise of fetal wellbeing. The systematic overviews will assess the quality of the available evidence, estimate the magnitude of potential benefits, identify those tests with good predictive value and help formulate practice recommendations.

  2. DNA methylation of IGF2DMR and H19 is associated with fetal and infant growth: the generation R study.

    Directory of Open Access Journals (Sweden)

    Marieke I Bouwland-Both

    Full Text Available Changes in epigenetic programming of embryonic growth genes during pregnancy seem to affect fetal growth. Therefore, in a population-based prospective birth cohort in the Netherlands, we examined associations between fetal and infant growth and DNA methylation of IGF2DMR, H19 and MTHFR. For this study, we selected 69 case children born small-for-gestational age (SGA, birth weight <-2SDS and 471 control children. Fetal growth was assessed with serial ultrasound measurements. Information on birth outcomes was retrieved from medical records. Infant weight was assessed at three and six months. Methylation was assessed in DNA extracted from umbilical cord white blood cells. Analyses were performed using linear mixed models with DNA methylation as dependent variable. The DNA methylation levels of IGF2DMR and H19 in the control group were, median (90% range, 53.6% (44.5-61.6 and 30.0% (25.6-34.2 and in the SGA group 52.0% (43.9-60.9 and 30.5% (23.9-32.9, respectively. The MTHFR region was found to be hypomethylated with limited variability in the control and SGA group, 2.5% (1.4-4.0 and 2.4% (1.5-3.8, respectively. SGA was associated with lower IGF2DMR DNA methylation (β = -1.07, 95% CI -1.93; -0.21, P-value = 0.015, but not with H19 methylation. A weight gain in the first three months after birth was associated with lower IGF2DMR DNA methylation (β = -0.53, 95% CI -0.91; -0.16, P-value = 0.005. Genetic variants in the IGF2/H19 locus were associated with IGF2DMR DNA methylation (P-value<0.05, but not with H19 methylation. Furthermore, our results suggest a possibility of mediation of DNA methylation in the association between the genetic variants and SGA. To conclude, IGF2DMR and H19 DNA methylation is associated with fetal and infant growth.

  3. Human milk composition and infant growth

    DEFF Research Database (Denmark)

    Eriksen, Kamilla Gehrt; Christensen, Sophie Hilario; Lind, Mads Vendelbo

    2018-01-01

    PURPOSE OF REVIEW: This review highlights relevant studies published between 2015 and 2017 on human milk composition and the association with infant growth. RECENT FINDINGS: High-quality studies investigating how human milk composition is related to infant growth are sparse. Recent observational...... studies show that human milk concentrations of protein, fat, and carbohydrate likely have important influence on infant growth and body composition. Furthermore, some observational studies examining human milk oligosaccharides and hormone concentrations suggest functional relevance to infant growth....... For human milk micronutrient concentrations and microbiota content, and other bioactive components in human milk, the association with infant growth is still speculative and needs further investigation. The included studies in this review are all limited in their methodological design and methods but have...

  4. Fetal cardiology

    International Nuclear Information System (INIS)

    Meijboom, E.J.; Rijsterborgh, N.; Bom, N.

    1986-01-01

    Doppler echocardiography makes it possible to diagnose congenital heart disease in early pregnancy. It allows us to study the anatomical configuration of the fetal heart, and additionally, to evaluate the physiological conditions of the fetus. Evaluation of the direction, velocity, wave form pattern, and quantification of blood flow at the various sites in the fetal heart helps us to assess the characteristics of the fetal circulation and condition of the fetal heart. In order to use this technique in pathological situations, an initial study of the developing normal human fetal circulation was necessary. The authors studied 34 uncomplicated pregnancies by serial Doppler echocardiography. The studies were performed every 4 weeks from 16-weeks gestation to term. The pulsed Doppler sector scanner provided cardiac cross-sectional images, mitral and tricuspid blood velocities were obtained from apical four-chamber views. Angle corrected maximal and mean temporal velocities were calculated by digitizing the Doppler frequency shift recording on a graphic tablet computed with a minicomputer. The angle between the Doppler interrogation beam and the direction of blood flow was kept as small as possible in order to minimize the error

  5. Screening for fetal growth restriction with universal third trimester ultrasonography in nulliparous women in the Pregnancy Outcome Prediction (POP) study: a prospective cohort study.

    Science.gov (United States)

    Sovio, Ulla; White, Ian R; Dacey, Alison; Pasupathy, Dharmintra; Smith, Gordon C S

    2015-11-21

    Fetal growth restriction is a major determinant of adverse perinatal outcome. Screening procedures for fetal growth restriction need to identify small babies and then differentiate between those that are healthy and those that are pathologically small. We sought to determine the diagnostic effectiveness of universal ultrasonic fetal biometry in the third trimester as a screening test for small-for-gestational-age (SGA) infants, and whether the risk of morbidity associated with being small differed in the presence or absence of ultrasonic markers of fetal growth restriction. The Pregnancy Outcome Prediction (POP) study was a prospective cohort study of nulliparous women with a viable singleton pregnancy at the time of the dating ultrasound scan. Women participating had clinically indicated ultrasonography in the third trimester as per routine clinical care and these results were reported as usual (selective ultrasonography). Additionally, all participants had research ultrasonography, including fetal biometry at 28 and 36 weeks' gestational age. These results were not made available to participants or treating clinicians (universal ultrasonography). We regarded SGA as a birthweight of less than the 10th percentile for gestational age and screen positive for SGA an ultrasonographic estimated fetal weight of less than the 10th percentile for gestational age. Markers of fetal growth restriction included biometric ratios, utero-placental Doppler, and fetal growth velocity. We assessed outcomes for consenting participants who attended research scans and had a livebirth at the Rosie Hospital (Cambridge, UK) after the 28 weeks' research scan. Between Jan 14, 2008, and July 31, 2012, 4512 women provided written informed consent of whom 3977 (88%) were eligible for analysis. Sensitivity for detection of SGA infants was 20% (95% CI 15-24; 69 of 352 fetuses) for selective ultrasonography and 57% (51-62; 199 of 352 fetuses) for universal ultrasonography (relative sensitivity 2

  6. Growth trajectories of the human embryonic head and periconceptional maternal conditions.

    Science.gov (United States)

    Koning, I V; Baken, L; Groenenberg, I A L; Husen, S C; Dudink, J; Willemsen, S P; Gijtenbeek, M; Koning, A H J; Reiss, I K M; Steegers, E A P; Steegers-Theunissen, R P M

    2016-05-01

    Can growth trajectories of the human embryonic head be created using 3D ultrasound (3D-US) and virtual reality (VR) technology, and be associated with second trimester fetal head size and periconceptional maternal conditions? Serial first trimester head circumference (HC) and head volume (HV) measurements were used to create reliable growth trajectories of the embryonic head, which were significantly associated with fetal head size and periconceptional maternal smoking, age and ITALIC! in vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI) treatment. Fetal growth is influenced by periconceptional maternal conditions. We selected 149 singleton pregnancies with a live born non-malformed fetus from the Rotterdam periconception cohort. Bi-parietal diameter and occipital frontal diameter to calculate HC, HV and crown-rump length (CRL) were measured weekly between 9 + 0 and 12 + 6 weeks gestational age (GA) using 3D-US and VR. Fetal HC was obtained from second trimester structural anomaly scans. Growth trajectories of the embryonic head were created with general additive models and linear mixed models were used to estimate associations with maternal periconceptional conditions as a function of GA and CRL, respectively. A total of 303 3D-US images of 149 pregnancies were eligible for embryonic head measurements (intra-class correlation coefficients >0.99). Associations were found between embryonic HC and fetal HC ( ITALIC! ρ = 0.617, ITALIC! P head measured by HC and HV (All ITALIC! P head may be of benefit in future early antenatal care. This study was funded by the Department of Obstetrics and Gynaecology, Erasmus MC University Medical Centre and Sophia Foundation for Medical Research, Rotterdam, The Netherlands (SSWO grant number 644). No competing interests are declared. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email

  7. Expanding the spectrum of human ganglionic eminence region anomalies on fetal magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Righini, Andrea; Parazzini, Cecilia; Izzo, Giana [Children' s Hospital ' ' V. Buzzi' ' , Department of Radiology and Neuroradiology, Milan (Italy); Cesaretti, Claudia [Children' s Hospital ' ' V. Buzzi' ' , Department of Radiology and Neuroradiology, Milan (Italy); Ospedale Maggiore Policlinico, Medical Genetics Unit, Fondazione I.R.C.C.S. Ca' Granda, Milan (Italy); Conte, Giorgio [Children' s Hospital ' ' V. Buzzi' ' , Department of Radiology and Neuroradiology, Milan (Italy); University of Milan, Department of Health Sciences, Milan (Italy); Frassoni, Carolina; Inverardi, Francesca [Fondazione I.R.C.C.S. Istituto Neurologico ' ' C. Besta' ' , Clinical Epileptology and Experimental Neurophysiology Unit, Milan (Italy); Bulfamante, Gaetano; Avagliano, Laura [San Paolo Hospital, Division of Human Pathology, Milan (Italy); Rustico, Mariangela [Children' s Hospital ' ' V. Buzzi' ' , Department of Obstetrics and Gynaecology, Prenatal Diagnosis, Milan (Italy)

    2016-03-15

    Ganglionic eminence (GE) is a transient fetal brain structure that harvests a significant amount of precursors of cortical GABA-ergic interneurons. Prenatal magnetic resonance (MR) imaging features of GE anomalies (i.e., cavitations) have already been reported associated with severe micro-lissencephaly. The purpose of this report was to illustrate the MR imaging features of GE anomalies in conditions other than severe micro-lissencephalies. Among all the fetuses submitted to prenatal MR imaging at our center from 2005 to 2014, we collected eight cases with GE anomalies and only limited associated brain anomalies. The median gestational age at the time of MR imaging was 21 weeks ranging from 19 to 29 weeks. Two senior pediatric neuroradiologists categorized the anomalies of the GE region in two groups: group one showing cavitation in the GE region and group two showing enlarged GE region. For each fetal case, associated cranial anomalies were also reported. Five out of the eight cases were included in group one and three in group two. Besides the GE region abnormality, all eight cases had additional intracranial anomalies, such as mild partial callosal agenesis, vermian hypoplasia and rotation, cerebellar hypoplasia, ventriculomegaly, enlarged subarachnoid spaces, molar tooth malformation. Ultrasound generally detected most of the associated intracranial anomalies, prompting the MR investigation; on the contrary in none of the cases, GE anomalies had been detected by ultrasound. Our observation expands the spectrum of human GE anomalies, demonstrating that these may take place also without associated severe micro-lissencephalies. (orig.)

  8. Expanding the spectrum of human ganglionic eminence region anomalies on fetal magnetic resonance imaging

    International Nuclear Information System (INIS)

    Righini, Andrea; Parazzini, Cecilia; Izzo, Giana; Cesaretti, Claudia; Conte, Giorgio; Frassoni, Carolina; Inverardi, Francesca; Bulfamante, Gaetano; Avagliano, Laura; Rustico, Mariangela

    2016-01-01

    Ganglionic eminence (GE) is a transient fetal brain structure that harvests a significant amount of precursors of cortical GABA-ergic interneurons. Prenatal magnetic resonance (MR) imaging features of GE anomalies (i.e., cavitations) have already been reported associated with severe micro-lissencephaly. The purpose of this report was to illustrate the MR imaging features of GE anomalies in conditions other than severe micro-lissencephalies. Among all the fetuses submitted to prenatal MR imaging at our center from 2005 to 2014, we collected eight cases with GE anomalies and only limited associated brain anomalies. The median gestational age at the time of MR imaging was 21 weeks ranging from 19 to 29 weeks. Two senior pediatric neuroradiologists categorized the anomalies of the GE region in two groups: group one showing cavitation in the GE region and group two showing enlarged GE region. For each fetal case, associated cranial anomalies were also reported. Five out of the eight cases were included in group one and three in group two. Besides the GE region abnormality, all eight cases had additional intracranial anomalies, such as mild partial callosal agenesis, vermian hypoplasia and rotation, cerebellar hypoplasia, ventriculomegaly, enlarged subarachnoid spaces, molar tooth malformation. Ultrasound generally detected most of the associated intracranial anomalies, prompting the MR investigation; on the contrary in none of the cases, GE anomalies had been detected by ultrasound. Our observation expands the spectrum of human GE anomalies, demonstrating that these may take place also without associated severe micro-lissencephalies. (orig.)

  9. [Influence of maternal nutritional status, weight gain and energy intake on fetal growth in high-risk pregnancies].

    Science.gov (United States)

    Nomura, Roseli Mieko Yamamoto; Paiva, Letícia Vieira; Costa, Verbênia Nunes; Liao, Adolfo Wenjaw; Zugaib, Marcelo

    2012-03-01

    To analyze the influence of maternal nutritional status, weight gain and energy consumption on fetal growth in high-risk pregnancies. A prospective study from August 2009 to August 2010 with the following inclusion criteria: puerperae up to the 5th postpartum day; high-risk singleton pregnancies (characterized by medical or obstetrical complications during pregnancy); live fetus at labor onset; delivery at the institution; maternal weight measured on the day of delivery, and presence of medical and/or obstetrical complications characterizing pregnancy as high-risk. Nutritional status was assessed by pregestational body mass index and body mass index in late pregnancy, and the patients were classified as: underweight, adequate, overweight and obese. A food frequency questionnaire was applied to evaluate energy consumption. We investigated maternal weight gain, delivery data and perinatal outcomes, as well as fetal growth based on the occurrence of small for gestational age and large for gestational age neonates. We included 374 women who were divided into three study groups according to newborn birth weight: adequate for gestational age (270 cases, 72.2%), small for gestational age (91 cases, 24.3%), and large for gestational age (13 cases, 3.5%). Univaried analysis showed that women with small for gestational age neonates had a significantly lower mean pregestational body mass index (23.5 kg/m², ppregnancy (27.7 kg/m², ppregnancy (25.3%, ppregnancy (34.3 kg/m², ppregnancy (53.8%, ppregnancy (OR=0.9; CI95% 0.8-0.9, ppregnancy (OR=3.6; 95%CI 1.1-11.7, p=0.04). The maternal nutritional status at the end of pregnancy in high-risk pregnancies is independently associated with fetal growth, the body mass index during late pregnancy is a protective factor against small for gestational age neonates, and maternal obesity is a risk factor for large for gestational age neonates.

  10. 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

  11. Effects of hyperthyroidism on expression of vascular endothelial growth factor (VEGF and apoptosis in fetal adrenal glands

    Directory of Open Access Journals (Sweden)

    T. Karaca

    2015-11-01

    Full Text Available This study investigated the expression of vascular endothelial growth factor (VEGF, vascular density, and apoptosis in fetal rat adrenal glands with hyperthyroidism in late gestation. Twelve mature female Wistar albino rats with the same biological and physiological features were used for this study. Rats were divided into two groups: control and hyperthyroidism. Hyperthyroidism was induced by daily subcutaneous injections of L-thyroxine (250 μg/kg before pregnancy for 21 days and during pregnancy. Rats in the control and hyperthyroidism groups were caged according to the number of male rats. Zero day of pregnancy (Day 0 was indicated when the animals were observed to have microscopic sperm in vaginal smears. Pregnant rats were sacrificed on the 20th day of pregnancy; blood from each animal was collected to determine the concentrations of maternal adrenocorticotropic hormone and thyroxine. Rat fetuses were then quickly removed from the uterus, and the adrenal glands of the fetuses were dissected. VEGF expression, vascular density, and apoptosis were analyzed in fetal rat adrenal glands. Maternal serum levels of the adrenocorticotropic hormone and free thyroxine were significantly higher in the hyperthyroidism group than in the control group. Immunohistochemistry revealed that the number of VEGF positive cells and vessel density significantly increased in the hyperthyroidism rat fetal adrenal group compared with the control group. Hyperthyroidism did not change the fetal and placental weights and the number of fetuses. This study demonstrates that hyperthyroidism may have an effect on the development of rat adrenal glands mediated by VEGF expression, angiogenesis, and apoptosis. 

  12. Effect of a micronutrient‐rich snack taken preconceptionally and throughout pregnancy on ultrasound measures of fetal growth: The Mumbai Maternal Nutrition Project (MMNP)

    Science.gov (United States)

    Lawande, Ashwin; Di Gravio, Chiara; Potdar, Ramesh D.; Sahariah, Sirazul A.; Gandhi, Meera; Chopra, Harsha; Sane, Harshad; Kehoe, Sarah H.; Marley‐Zagar, Ella; Margetts, Barrie M.; Jackson, Alan A.

    2017-01-01

    Abstract Improving micronutrient intakes of under‐nourished mothers in low‐ and middle‐income countries increases birth weight, but there is little data on the nature and timing during gestation of any effects on fetal growth. Ultrasound measures of fetal size were used to determine whether and when a food‐based supplement affected fetal growth. Non‐pregnant women living in Mumbai slums, India (N = 6,513), were randomly assigned to receive either a daily micronutrient‐rich snack containing green leafy vegetables, fruit, and milk (treatment) or a snack made from lower‐micronutrient vegetables (control) in addition to their usual diet from before pregnancy until delivery. From 2,291 pregnancies, the analysis sample comprised 1,677 fetuses (1,335 fetuses of women supplemented for ≥3 months before conception). First‐trimester (median: 10 weeks, interquartile range: 9–12 weeks) fetal crown‐rump length was measured. Fetal head circumference, biparietal diameter, femur length, and abdominal circumference were measured during the second (19, 19–20 weeks) and third trimesters (29, 28–30 weeks). The intervention had no effect on fetal size or growth at any stage of pregnancy. In the second trimester, there were interactions between parity and allocation group for biparietal diameter (p = .02) and femur length (p = .04) with both being smaller among fetuses of primiparous women and larger among those of multiparous women, in the treatment group compared with the controls. Overall, a micronutrient‐rich supplement did not increase standard ultrasound measures of fetal size and growth at any stage of pregnancy. Additional ultrasound measures of fetal soft tissues (fat and muscle) may be informative. PMID:28251804

  13. Effect of a micronutrient-rich snack taken preconceptionally and throughout pregnancy on ultrasound measures of fetal growth: The Mumbai Maternal Nutrition Project (MMNP).

    Science.gov (United States)

    Lawande, Ashwin; Di Gravio, Chiara; Potdar, Ramesh D; Sahariah, Sirazul A; Gandhi, Meera; Chopra, Harsha; Sane, Harshad; Kehoe, Sarah H; Marley-Zagar, Ella; Margetts, Barrie M; Jackson, Alan A; Fall, Caroline H D

    2018-01-01

    Improving micronutrient intakes of under-nourished mothers in low- and middle-income countries increases birth weight, but there is little data on the nature and timing during gestation of any effects on fetal growth. Ultrasound measures of fetal size were used to determine whether and when a food-based supplement affected fetal growth. Non-pregnant women living in Mumbai slums, India (N = 6,513), were randomly assigned to receive either a daily micronutrient-rich snack containing green leafy vegetables, fruit, and milk (treatment) or a snack made from lower-micronutrient vegetables (control) in addition to their usual diet from before pregnancy until delivery. From 2,291 pregnancies, the analysis sample comprised 1,677 fetuses (1,335 fetuses of women supplemented for ≥3 months before conception). First-trimester (median: 10 weeks, interquartile range: 9-12 weeks) fetal crown-rump length was measured. Fetal head circumference, biparietal diameter, femur length, and abdominal circumference were measured during the second (19, 19-20 weeks) and third trimesters (29, 28-30 weeks). The intervention had no effect on fetal size or growth at any stage of pregnancy. In the second trimester, there were interactions between parity and allocation group for biparietal diameter (p = .02) and femur length (p = .04) with both being smaller among fetuses of primiparous women and larger among those of multiparous women, in the treatment group compared with the controls. Overall, a micronutrient-rich supplement did not increase standard ultrasound measures of fetal size and growth at any stage of pregnancy. Additional ultrasound measures of fetal soft tissues (fat and muscle) may be informative. © 2017 The Authors. Maternal & Child Nutrition Published by John Wiley & Sons Ltd.

  14. The effect of obesity on early fetal growth and pregnancy duration

    DEFF Research Database (Denmark)

    Thagaard, Ida Näslund; Krebs, Lone; Holm, Jens-Christian

    2017-01-01

    OBJECTIVE: The objective of this study is to investigate the effect of maternal obesity on fetal size in first- and second-trimester pregnancies and to determine duration of pregnancy as estimated by a variety of methods. METHODS: Between 2006 and 2011, a cohort study included (n = 9055) singleto...

  15. Influence of fetal growth velocity and smallness at birth on adrenal function in adolescence

    DEFF Research Database (Denmark)

    Beck Jensen, Rikke; vielwerth, Signe; Larsen, Torben

    2011-01-01

    The hypothalamic-pituitary-adrenal axis is susceptible to programming during fetal development and may be linked to risk of disease later in life. In a former prospective study the cohort was divided into those born appropriate for gestational age (AGA) or small for gestational age (SGA; birth...

  16. Treatment with oral beta-blockers during pregnancy complicated by maternal heart disease increases the risk of fetal growth restriction

    DEFF Research Database (Denmark)

    Ersbøll, A S; Hedegaard, M; Søndergaard, L

    2014-01-01

    OBJECTIVE: To investigate the effect on fetal growth of treatment with oral beta-blockers during pregnancy in women with congenital or acquired heart disease. DESIGN: Historical matched cohort study. SETTING: Centre for Pregnant Women with Heart Disease, Copenhagen University Hospital, Denmark....... POPULATION: A cohort of 175 women with heart disease, grouped according to beta-blocker treatment, and a cohort of 627 women from the overall population matched on seven birthweight-determining factors. METHODS: Differences between groups were tested by simple descriptive statistics and assessed using...

  17. Creatine supplementation during pregnancy: summary of experimental studies suggesting a treatment to improve fetal and neonatal morbidity and reduce mortality in high-risk human pregnancy

    Science.gov (United States)

    2014-01-01

    While the use of creatine in human pregnancy is yet to be fully evaluated, its long-term use in healthy adults appears to be safe, and its well documented neuroprotective properties have recently been extended by demonstrations that creatine improves cognitive function in normal and elderly people, and motor skills in sleep-deprived subjects. Creatine has many actions likely to benefit the fetus and newborn, because pregnancy is a state of heightened metabolic activity, and the placenta is a key source of free radicals of oxygen and nitrogen. The multiple benefits of supplementary creatine arise from the fact that the creatine-phosphocreatine [PCr] system has physiologically important roles that include maintenance of intracellular ATP and acid–base balance, post-ischaemic recovery of protein synthesis, cerebral vasodilation, antioxidant actions, and stabilisation of lipid membranes. In the brain, creatine not only reduces lipid peroxidation and improves cerebral perfusion, its interaction with the benzodiazepine site of the GABAA receptor is likely to counteract the effects of glutamate excitotoxicity – actions that may protect the preterm and term fetal brain from the effects of birth hypoxia. In this review we discuss the development of creatine synthesis during fetal life, the transfer of creatine from mother to fetus, and propose that creatine supplementation during pregnancy may have benefits for the fetus and neonate whenever oxidative stress or feto-placental hypoxia arise, as in cases of fetal growth restriction, premature birth, or when parturition is delayed or complicated by oxygen deprivation of the newborn. PMID:24766646

  18. Differential regional brain growth and rotation of the prenatal human tentorium cerebelli.

    Science.gov (United States)

    Jeffery, Nathan

    2002-02-01

    Folds of dura mater, the falx cerebri and tentorium cerebelli, traverse the vertebrate endocranial cavity and compartmentalize the brain. Previous studies suggest that the tentorial fold has adopted an increasingly important role in supporting the increased load of the cerebrum during human evolution, brought about by encephalization and an adaptation to bipedal posture. Ontogenetic studies of the fetal tentorium suggest that its midline profile rotates inferoposteriorly towards the foramen magnum in response to disproportionate growth of the cerebrum. This study tests the hypothesis that differential growth of the cerebral and cerebellar components of the brain underlies the inferoposterior rotation of the tentorium cerebelli during human fetal development. Brain volumes and tentorial angles were taken from high-resolution magnetic resonance images of 46 human fetuses ranging from 10 to 29 gestational weeks. Apart from the expected increases of both supratentorial and infratentorial brain volumes with age, the results confirm previous studies showing a significant relative enlargement of the supratentorial volume. Correlated with this enlargement was a rotation of the midline section of the tentorium towards the posterior cranial base. These findings support the concept that increases of supratentorial volume relative to infratentorial volume affect an inferoposterior rotation of the human fetal tentorium cerebelli. These results are discussed in the context of the role played by the tentorium cerebelli during human evolution and underline implications for phylogenetic and ontogenetic models of encephalization.

  19. Expression of immunohistochemical markers for testicular carcinoma in situ by normal human fetal germ cells

    DEFF Research Database (Denmark)

    Jørgensen, N; Rajpert-De Meyts, E; Graem, N

    1995-01-01

    study. EXPERIMENTAL DESIGN: Normal human germ cells from 10 first-trimester fetuses and 76 second- and third-trimester testes were investigated for the immunohistochemical expression of the markers of testicular carcinoma in situ. The panel of markers included in the study consisted of placental......-like alkaline phosphatase, the protooncogene c-kit protein product, and the antigens for the monoclonal antibodies TRA-1-60 and M2A. The relative numbers of fetal germ cells that demonstrated positive reaction with the markers were calculated. RESULTS: The vast majority of the germ cells (75-100%) in the first......-trimester gonads were positive for placental-like alkaline phosphatase, TRA-1-60, and M2A. The c-kit protein was detected in three out of the ten first-trimester gonads. The relative number of germ cells positive for all the markers studied declined rapidly during the first part of the second trimester...

  20. Human fetal antehypophysis in vitro. Immunocytological study and radioimmunoassay of LH and FSH

    International Nuclear Information System (INIS)

    Li, J.Y.; Begeot, M.; Dubois, P.M.; Claustrat, B.

    1977-01-01

    Human fetal antehypophysis (16 males, 16 females and 4 unknown sex) were cultivated during several weeks. By immunocytochemistry LH gonadotroph cells were determined with anti-hTSH and anti-pLH serum. The release in vitro of LH and FSH was studied by radioimmunoassay. At the first medium change, the quantity of LH and FSH release was related to the gestational age and sex. A rapid decline of both LH and FSH occured over the 10 first days. There after, a basal release of LH was maintained during several months; the release of FSH was generally maintained at the lower limit of the assay. After 1 month in vitro, the level of LH could not be related to the sex. Release of LH was stimulated by synthetic LRF. A significant increase was observed independently of the sex and age of the fetuses studied [fr

  1. Anatomical relationships between testis and epididymis during the fetal period in humans (10-36 weeks postconception)

    NARCIS (Netherlands)

    Favorito, LA; Sampaio, FJB

    1998-01-01

    Objective: To determine the anatomy of the epididymis and its relationship with the testis during the fetal period in normal individuals. Methods: We studied bilaterally 146 testes and epididymides taken from 73 normal fresh human fetuses ranging in age from 10 to 36 weeks postconception. The

  2. Donor-Specific Anti-HLA Antibodies in Huntington's Disease Recipients of Human Fetal Striatal Grafts.

    Science.gov (United States)

    Porfirio, Berardino; Paganini, Marco; Mazzanti, Benedetta; Bagnoli, Silvia; Bucciantini, Sandra; Ghelli, Elena; Nacmias, Benedetta; Putignano, Anna Laura; Rombolà, Giovanni; Saccardi, Riccardo; Lombardini, Letizia; Di Lorenzo, Nicola; Vannelli, Gabriella B; Gallina, Pasquale

    2015-01-01

    Fetal grafting in a human diseased brain was thought to be less immunogenic than other solid organ transplants, hence the minor impact on the efficacy of the transplant. How much prophylactic immune protection is required for neural allotransplantation is also debated. High-sensitive anti-HLA antibody screening in this field has never been reported. Sixteen patients with Huntington's disease underwent human fetal striatal transplantation in the frame of an open-label observational trial, which is being carried out at Florence University. All patients had both brain hemispheres grafted in two separate robotic-stereotactic procedures. The trial started in February 2006 with the first graft to the first patient (R1). R16 was given his second graft on March 2011. All patients received triple immunosuppressive treatment. Pre- and posttransplant sera were analyzed for the presence of anti-HLA antibodies using the multiplexed microsphere-based suspension array Luminex xMAP technology. Median follow-up was 38.5 months (range 13-85). Six patients developed anti-HLA antibodies, which turned out to be donor specific. Alloimmunization occurred in a time window of 0-49 months after the first neurosurgical procedure. The immunogenic determinants were non-self-epitopes from mismatched HLA antigens. These determinants were both public epitopes shared by two or more HLA molecules and private epitopes unique to individual HLA molecules. One patient had non-donor-specific anti-HLA antibodies in her pretransplant serum sample, possibly due to previous sensitization events. Although the clinical significance of donor-specific antibodies is far from being established, particularly in the setting of neuronal transplantation, these findings underline the need of careful pre- and posttransplant immunogenetic evaluation of patients with intracerebral grafts.

  3. Yeast-2-Hybrid data file showing progranulin interactions in human fetal brain and bone marrow libraries

    Directory of Open Access Journals (Sweden)

    Irmgard Tegeder

    2016-12-01

    Full Text Available Progranulin deficiency in humans is associated with neurodegeneration. Its mechanisms are not yet fully understood. We performed a Yeast-2-Hybrid screen using human full-length progranulin as bait to assess the interactions of progranulin. Progranulin was screened against human fetal brain and human bone marrow libraries using the standard Matchmaker technology (Clontech. This article contains the full Y2H data table, including blast results and sequences, a sorted table according to selection criteria for likely positive, putatively positive, likely false and false preys, and tables showing the gene ontology terms associated with the likely and putative preys of the brain and bone marrow libraries. The interactions with autophagy proteins were confirmed and functionally analyzed in "Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: Role of autophagy" (C. Altmann, S. Hardt, C. Fischer, J. Heidler, H.Y. Lim, A. Haussler, B. Albuquerque, B. Zimmer, C. Moser, C. Behrends, F. Koentgen, I. Wittig, M.H. Schmidt, A.M. Clement, T. Deller, I. Tegeder, 2016 [1].

  4. Yeast-2-Hybrid data file showing progranulin interactions in human fetal brain and bone marrow libraries.

    Science.gov (United States)

    Tegeder, Irmgard

    2016-12-01

    Progranulin deficiency in humans is associated with neurodegeneration. Its mechanisms are not yet fully understood. We performed a Yeast-2-Hybrid screen using human full-length progranulin as bait to assess the interactions of progranulin. Progranulin was screened against human fetal brain and human bone marrow libraries using the standard Matchmaker technology (Clontech). This article contains the full Y2H data table, including blast results and sequences, a sorted table according to selection criteria for likely positive, putatively positive, likely false and false preys, and tables showing the gene ontology terms associated with the likely and putative preys of the brain and bone marrow libraries. The interactions with autophagy proteins were confirmed and functionally analyzed in "Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: Role of autophagy" (C. Altmann, S. Hardt, C. Fischer, J. Heidler, H.Y. Lim, A. Haussler, B. Albuquerque, B. Zimmer, C. Moser, C. Behrends, F. Koentgen, I. Wittig, M.H. Schmidt, A.M. Clement, T. Deller, I. Tegeder, 2016) [1].

  5. Fetal and neo-natal maxillary ontogeny in extant humans and the utility of prenatal maxillary morphology in predicting ancestral affiliation

    Science.gov (United States)

    Nicholas, Christina L.

    2016-01-01

    Objectives The midface of extant H. sapiens is known to undergo shape changes through fetal and neo-natal ontogeny; however, little work has been done to quantify these shape changes. Further, while midfacial traits which vary in frequency between populations of extant humans are presumed to develop prenatally, patterns of population-specific variation maxillary shape across ontogeny are not well documented. Only one study of fetal ontogeny which included specific discussion of the midface has taken a 3D geometric morphometric approach, and that study was limited to one population (Japanese). The present research project seeks to augment our understanding of fetal maxillary growth patterns, most especially in terms of intraspecific variation. Materials and Methods Three-dimensional coordinate landmark data were collected on the right maxillae of 102 fetal and neo-natal individuals from three groups (Euro-American, African-American, “Mixed Ancestry”). Results Shape changes were seen mainly in the lateral wall of the piriform aperture, the anterior nasal spine, and the subnasal alveolar region. The greatest difference across age groups (2nd Trimester, 3rd Trimester, Neonates) was between the second and third trimester. Euro-Americans and African-Americans clustered by population and differences in midfacial morphology related to ancestry could be discerned as early as the second trimester (p=0.002), indicating that population variation in maxillary morphology appears very early in ontogeny. Discussion The midface is a critical region of the skull for assessing ancestry and these results indicate that maxillary morphology may be useful for estimating ancestry for prenatal individuals as young as the second trimester. PMID:27412693

  6. Maternal 25-Hydroxyvitamin D Level and Fetal Growth assessed by Ultrasound

    DEFF Research Database (Denmark)

    Galthen-Sørensen, Mathias; Andersen, Louise Bjørkholt; Sperling, Lene

    2014-01-01

    to femoral and humeral Z-scores when calcium intake was insufficient. The two largest studies found no association between 25(OH)D and FL, but detected a direct association to femoral PMD, and an inverse relation to distal femoral CSA, respectively. CONCLUSIONS: Sparse observational studies suggest that low...... maternal 25(OH)D may affect fetal bone under certain circumstances, especially in case of simultaneous low calcium intake. Further studies are needed.....

  7. Second- to third-trimester longitudinal growth assessment for prediction of small-for-gestational age and late fetal growth restriction.

    Science.gov (United States)

    Caradeux, J; Eixarch, E; Mazarico, E; Basuki, T R; Gratacós, E; Figueras, F

    2018-02-01

    Detection of fetal growth restriction (FGR) remains poor and most screening strategies rely on cross-sectional evaluation of fetal size during the third trimester. A longitudinal and individualized approach has been proposed as an alternative method of evaluation. The aim of this study was to compare second- to third-trimester longitudinal growth assessment to cross-sectional evaluation in the third trimester for the prediction of small-for-gestational age (SGA) and late FGR in low-risk singleton pregnancy. This was a prospective cohort study of 2696 unselected consecutive low-risk singleton pregnancies scanned at 21 ± 2 and 32 ± 2 weeks. For cross-sectional growth assessment, abdominal circumference (AC) measurements were transformed to z-values according the 21st-INTERGROWTH standards. Longitudinal growth assessment was performed by calculating the AC z-velocity and the second- to third-trimester AC conditional growth centile. Longitudinal assessment was compared with cross-sectional assessment at 32 weeks. Association of cross-sectional and longitudinal evaluations with SGA and late FGR was assessed by logistic regression analysis. Predictive performance was determined by receiver-operating characteristics curve analysis. In total, 210 (7.8%) newborns were classified as SGA and 103 (3.8%) as late FGR. Neither longitudinal measurement improved the association with SGA or late FGR provided by cross-sectional evaluation of AC z-score at 32 weeks. Areas under the curves of AC z-velocity and conditional AC growth were significantly smaller than those of cross-sectional AC z-scores (P third trimester has a low predictive capacity for SGA and late FGR in low-risk singleton pregnancy compared with cross-sectional growth evaluation. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

  8. Increased oxidative stress in human fetal membranes overlying the cervix from term non-labouring and post labour deliveries.

    Science.gov (United States)

    Chai, M; Barker, G; Menon, R; Lappas, M

    2012-08-01

    Enzymatic breakdown of the collagen-rich extracellular matrix (ECM) that connects the amnion and chorion layers of the fetal membranes is one of the key events leading to rupture of membranes. Oxidant stress caused by increased formation of reactive oxygen species and/or reduced antioxidant capacity may predispose to membrane rupture, a major cause of preterm birth. The aim of this study was to determine the effect of human labour and supracervical (SC) apposition on antioxidant enzymes and 8-isoprostane (a marker of lipid peroxidation). To determine the effect of human labour on oxidative stress status, fetal membranes from the SC site (SCS) were collected from women at term Caesarean section (no labour), and from the site of membrane rupture (SOR) after spontaneous labour onset and delivery (post labour). To determine the effect of SC apposition on oxidative stress status, amnion was collected from the SCS and a distal site (DS) in women at term Caesarean section in the absence of labour. The release of 8-isoprostane was significantly higher in amnion from the SCS compared to DS, and in fetal membranes from the SOR compared to the SCS. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity were lower in amnion from the SC compared to DS. SOD gene expression and enzyme activity were lower in fetal membranes after labour. There was no difference in expression or activity in catalase, GPx and glutathione reductase (GSR) between no labour and post labour fetal membranes. In primary amnion cells, SOD supplementation significantly augmented IL-1β induced MMP-9 expression and activity. In summary, non-labouring SC fetal membranes are characterised by reduced antioxidant enzyme activity when compared to distal membranes, and, as such, may be more susceptible to oxidative damage and thus membrane rupture. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Are Gestational Age, Birth Weight, and Birth Length Indicators of Favorable Fetal Growth Conditions? A Structural Equation Analysis of Filipino Infants

    OpenAIRE

    Bollen, Kenneth A.; Noble, Mark D.; Adair, Linda S.

    2013-01-01

    The fetal origin hypothesis emphasizes the life-long health impacts of prenatal conditions. Birth weight, birth length, and gestational age are indicators of the fetal environment. However, these variables often have missing data and are subject to random and systematic errors caused by delays in measurement, differences in measurement instruments, and human error. With data from the Cebu (Philippines) Longitudinal Health and Nutrition Survey, we use structural equation models (SEMs), to expl...

  10. Anthropometric protocols for the construction of new international fetal and newborn growth standards: the INTERGROWTH-21st Project.

    Science.gov (United States)

    Cheikh Ismail, L; Knight, H E; Bhutta, Z; Chumlea, W C

    2013-09-01

    The primary aim of the INTERGROWTH-21(st) Project is to construct new, prescriptive standards describing optimal fetal and preterm postnatal growth. The anthropometric measurements include the head circumference, recumbent length and weight of the infants, and the stature and weight of the parents. In such a large, international, multicentre project, it is critical that all study sites follow standardised protocols to ensure maximal validity of the growth and nutrition indicators used. This paper describes, in detail, the selection of anthropometric personnel, equipment, and measurement and calibration protocols used to construct the new standards. Implementing these protocols at each study site ensures that the anthropometric data are of the highest quality to construct the international standards. © 2013 Royal College of Obstetricians and Gynaecologists.

  11. Nonproductive human immunodeficiency virus type 1 infection of human fetal astrocytes: independence from CD4 and major chemokine receptors.

    Science.gov (United States)

    Sabri, F; Tresoldi, E; Di Stefano, M; Polo, S; Monaco, M C; Verani, A; Fiore, J R; Lusso, P; Major, E; Chiodi, F; Scarlatti, G

    1999-11-25

    Human immunodeficiency virus type 1 (HIV-1) infection of the brain is associated with neurological manifestations both in adults and in children. The primary target for HIV-1 infection in the brain is the microglia, but astrocytes can also be infected. We tested 26 primary HIV-1 isolates for their capacity to infect human fetal astrocytes in culture. Eight of these isolates, independent of their biological phenotype and chemokine receptor usage, were able to infect astrocytes. Although no sustained viral replication could be demonstrated, the virus was recovered by coculture with receptive cells such as macrophages or on stimulation with interleukin-1beta. To gain knowledge into the molecular events that regulate attachment and penetration of HIV-1 in astrocytes, we investigated the expression of several chemokine receptors. Fluorocytometry and calcium-mobilization assay did not provide evidence of expression of any of the major HIV-1 coreceptors, including CXCR4, CCR5, CCR3, and CCR2b, as well as the CD4 molecule on the cell surface of human fetal astrocytes. However, mRNA transcripts for CXCR4, CCR5, Bonzo/STRL33/TYMSTR, and APJ were detected by RT-PCR. Furthermore, infection of astrocytes by HIV-1 isolates with different chemokine receptor usage was not inhibited by the chemokines SDF-1beta, RANTES, MIP-1beta, or MCP-1 or by antibodies directed against the third variable region or the CD4 binding site of gp120. These data show that astrocytes can be infected by primary HIV-1 isolates via a mechanism independent of CD4 or major chemokine receptors. Furthermore, astrocytes are potential carriers of latent HIV-1 and on activation may be implicated in spreading the infection to other neighbouring cells, such as microglia or macrophages. Copyright 1999 Academic Press.

  12. Human herpesvirus 6A induces apoptosis of primary human fetal astrocytes via both caspase-dependent and -independent pathways

    Directory of Open Access Journals (Sweden)

    Gu Bin

    2011-12-01

    Full Text Available Abstract Background Human herpesvirus 6 (HHV-6 is a T-lymphtropic and neurotropic virus that can infect various types of cells. Sequential studies reported that apoptosis of glia and neurons induced by HHV-6 might act a potential trigger for some central nervous system (CNS diseases. HHV-6 is involved in the pathogenesis of encephalitis, multiple sclerosis (MS and fatigue syndrome. However, the mechanisms responsible for the apoptosis of infected CNS cells induced by HHV-6 are poorly understood. In this study, we investigated the cell death processes of primary human fetal astrocytes (PHFAs during productive HHV-6A infection and the underlying mechanisms. Results HHV-6A can cause productive infection in primary human fetal astrocytes. Annexin V-PI staining and electron microscopic analysis indicated that HHV-6A was an inducer of apoptosis. The cell death was associated with activation of caspase-3 and cleavage of poly (ADP-ribose polymerase (PARP, which is known to be an important substrate for activated caspase-3. Caspase-8 and -9 were also significantly activated in HHV-6A-infected cells. Moreover, HHV-6A infection led to Bax up-regulation and Bcl-2 down-regulation. HHV-6A infection increased the release of Smac/Diablo, AIF and cytochrome c from mitochondria to cytosol, which induced apoptosis via the caspase-dependent and -independent pathways. In addition, we also found that anti-apoptotic factors such as IAPs and NF-κB decreased in HHV-6A infected PHFAs. Conclusion This is the first demonstration of caspase-dependent and -independent apoptosis in HHV-6A-infected glial cells. These findings would be helpful in understanding the mechanisms of CNS diseases caused by HHV-6.

  13. Fetal topographical anatomy of the female urethra and descending vagina: a histological study of the early human fetal urethra.

    Science.gov (United States)

    Masumoto, Hiroshi; Rodríguez-Vázquez, Jose Francisco; Verdugo-López, Samuel; Murakami, Gen; Matsubara, Akio

    2011-12-20

    Which parts of the male urethra correspond to the female urethra? To resolve this question, we need to understand fetal topographical changes in the urethra, its external sphincter and vagina. The vagina joins the mid-course of the primitive urethra and, later "descends" to the vaginal vestibulum. We examined histological sections of 14 female and 4 male mid-term fetuses. The inferior end of the vagina was consistently embedded in the posterior wall of the urethra at 9-12 weeks. The supero-inferior level of the vaginal merging was lower in larger fetuses. Thus, the sequential variation in levels appeared to reflect the process of vaginal descent. However, in spite of penetration of the vaginal end into the posterior urethral wall, we found no sign of destruction of the urethral wall after vaginal descent in the low-merging types. Before vaginal descent, the female external sphincter extended posterolaterally around the urethra. The vaginal descent is classically regarded as a relative topographical change, but it is likely to be a result of elongation of the proximal urethra in the superior side of the vaginal merging. Conversely, the distal urethra is likely to be incorporated into the vaginal vestibulum by 15 weeks. During these processes, most of the female external sphincter seems to be expelled from the original anterior position into the vestibular wall as the urethrovaginal sphincter. The adult female urethra seems to correspond to the male prostatic urethra superior to the prostatic colliculus. Copyright © 2011 Elsevier GmbH. All rights reserved.

  14. Fetal functional imaging portrays heterogeneous development of emerging human brain networks

    Directory of Open Access Journals (Sweden)

    Andras eJakab

    2014-10-01

    Full Text Available The functional connectivity architecture of the adult human brain enables complex cognitive processes, and exhibits a remarkably complex structure shared across individuals. We are only beginning to understand its heterogeneous structure, ranging from a strongly hierarchical organization in sensorimotor areas to widely distributed networks in areas such as the parieto-frontal cortex. Our study relied on the functional magnetic resonance imaging data of 32 fetuses with no detectable morphological abnormalities. After adapting functional magnetic resonance acquisition, motion correction and nuisance signal reduction procedures of resting-state functional data analysis to fetuses, we extracted neural activity information for major cortical and subcortical structures. Resting fMRI networks were observed for increasing regional functional connectivity from 21st – 38th gestational weeks (GW with a network-based statistical inference approach. The overall connectivity network, short range and interhemispheric connections showed sigmoid expansion curve peaking at the 26-29. GW. In contrast, long-range connections exhibited linear increase with no periods of peaking development. Region-specific increase of functional signal synchrony followed a sequence of occipital (peak: 24.8 GW, temporal (peak: 26 GW, frontal (peak: 26.4 GW and parietal expansion (peak: 27.5 GW. We successfully adapted functional neuroimaging and image post-processing approaches to correlate macroscopical scale activations in the fetal brain with gestational age. This in vivo study reflects the fact that the mid-fetal period hosts events that cause the architecture of the brain circuitry to mature, which presumably manifests in increasing strength of intra- and interhemispheric functional macroconnectivity.

  15. Fetal functional imaging portrays heterogeneous development of emerging human brain networks.

    Science.gov (United States)

    Jakab, András; Schwartz, Ernst; Kasprian, Gregor; Gruber, Gerlinde M; Prayer, Daniela; Schöpf, Veronika; Langs, Georg

    2014-01-01

    The functional connectivity architecture of the adult human brain enables complex cognitive processes, and exhibits a remarkably complex structure shared across individuals. We are only beginning to understand its heterogeneous structure, ranging from a strongly hierarchical organization in sensorimotor areas to widely distributed networks in areas such as the parieto-frontal cortex. Our study relied on the functional magnetic resonance imaging (fMRI) data of 32 fetuses with no detectable morphological abnormalities. After adapting functional magnetic resonance acquisition, motion correction, and nuisance signal reduction procedures of resting-state functional data analysis to fetuses, we extracted neural activity information for major cortical and subcortical structures. Resting fMRI networks were observed for increasing regional functional connectivity from 21st to 38th gestational weeks (GWs) with a network-based statistical inference approach. The overall connectivity network, short range, and interhemispheric connections showed sigmoid expansion curve peaking at the 26-29 GW. In contrast, long-range connections exhibited linear increase with no periods of peaking development. Region-specific increase of functional signal synchrony followed a sequence of occipital (peak: 24.8 GW), temporal (peak: 26 GW), frontal (peak: 26.4 GW), and parietal expansion (peak: 27.5 GW). We successfully adapted functional neuroimaging and image post-processing approaches to correlate macroscopical scale activations in the fetal brain with gestational age. This in vivo study reflects the fact that the mid-fetal period hosts events that cause the architecture of the brain circuitry to mature, which presumably manifests in increasing strength of intra- and interhemispheric functional macro connectivity.

  16. Diet quality in early pregnancy and its effects on fetal growth outcomes: the Infancia y Medio Ambiente (Childhood and Environment) Mother and Child Cohort Study in Spain.

    Science.gov (United States)

    Rodríguez-Bernal, Clara L; Rebagliato, Marisa; Iñiguez, Carmen; Vioque, Jesús; Navarrete-Muñoz, Eva M; Murcia, Mario; Bolumar, Francisco; Marco, Alfredo; Ballester, Ferran

    2010-06-01

    Maternal diet has been associated with fetal growth outcomes; however, evidence is scarce on the role of dietary quality. The objective was to assess the effect of diet quality during the first trimester of pregnancy, as measured by the Alternate Healthy Eating Index (AHEI) adapted for pregnancy, on fetal growth. We studied 787 women and their newborns from a Spanish cohort study. Diet quality was assessed by using a modification of the AHEI. Adjusted birth weight, birth length, and head circumference were used as continuous outcomes. We used a customized model to define fetal growth restriction in weight, length, and head circumference. After adjustment of multivariate models, a positive association was observed between diet quality and adjusted birth weight and adjusted birth length. The greatest differences were found between the fourth and first quintiles of the AHEI. Newborns of women in the fourth quintile were on average 126.3 g (95% CI: 38.5, 213.9 g) heavier and 0.47 cm (95% CI: 0.08, 0.86 cm) longer than those in the lowest quintile (P for trend = 0.009 and 0.013, respectively). Women with the highest AHEI scores had a significantly lower risk of delivering a fetal growth-restricted infant for weight (odds ratio: 0.24; 95% CI: 0.10, 0.55; P for trend = 0.001) than did women in the lowest quintile, but this was not the case for fetal growth restriction in length (P for trend = 0.538) or head circumference (P for trend = 0.070). A high-quality diet in the first trimester of pregnancy is associated with birth size and the risk of fetal growth restriction.

  17. Role of fetal nutrient restriction and postnatal catch-up growth on structural and mechanical alterations of rat aorta.

    Science.gov (United States)

    Gutiérrez-Arzapalo, Perla Y; Rodríguez-Rodríguez, Pilar; Ramiro-Cortijo, David; López de Pablo, Ángel L; López-Giménez, María Rosario; Condezo-Hoyos, Luis; Greenwald, Stephen E; González, Maria Del Carmen; Arribas, Silvia M

    2017-12-26

    Intrauterine growth restriction (IUGR), induced by maternal undernutrition, leads to impaired aortic development. This is followed by hypertrophic remodelling associated with accelerated growth during lactation. Fetal nutrient restriction is associated with increased aortic compliance at birth and at weaning, but not in adult animals. This mechanical alteration may be related to a decreased perinatal collagen deposition. Aortic elastin scaffolds purified from young male and female IUGR animals also exhibit increased compliance, only maintained in adult IUGR females. These mechanical alterations may be related to differences in elastin deposition and remodelling. Fetal undernutrition induces similar aortic structural and mechanical alterations in young male and female rats. Our data argue against an early mechanical cause for the sex differences in hypertension development induced by maternal undernutrition. However, the larger compliance of elastin in adult IUGR females may contribute to the maintenance of a normal blood pressure level. Fetal undernutrition programmes hypertension development, males being more susceptible. Deficient fetal elastogenesis and vascular growth is a possible mechanism. We investigated the role of aortic mechanical alterations in a rat model of hypertension programming, evaluating changes at birth, weaning and adulthood. Dams were fed ad libitum (Control) or 50% of control intake during the second half of gestation (maternal undernutrition, MUN). Offspring aged 3 days, 21 days and 6 months were studied. Blood pressure was evaluated in vivo. In the thoracic aorta we assessed gross structure, mechanical properties (intact and purified elastin), collagen and elastin content and internal elastic lamina (IEL) organization. Only adult MUN males developed hypertension (systolic blood pressure: MUN males  = 176.6 ± 5.6 mmHg; Control males  = 136.1 ± 4.9 mmHg). At birth MUN rats were lighter, with smaller aortic cross-sectional area

  18. The influence of IVF/ICSI treatment on human embryonic growth trajectories.

    Science.gov (United States)

    Eindhoven, S C; van Uitert, E M; Laven, J S E; Willemsen, S P; Koning, A H J; Eilers, P H C; Exalto, N; Steegers, E A P; Steegers-Theunissen, R P M

    2014-12-01

    groups (βIVF/ICSI = 6 g; P = 0.36 and βIVF/ICSI = 80 g; P = 0.24, respectively). Variations in embryonic growth trajectories of spontaneously conceived pregnancies with reliable pregnancy dating may partially be a result of less precise pregnancy dating and differences in endometrium receptivity compared with IVF/ICSI pregnancies. The absence of a significant difference in embryonic and fetal growth trajectories suggests safety of IVF/ICSI treatment with regard to early embryonic growth. However, further research is warranted to ascertain the influence of IVF/ICSI treatments in a larger study population, and to estimate the impact of the underlying causes of the subfertility and other periconceptional exposures on human embryonic and fetal growth trajectories. This study was supported by the Department of Obstetrics and Gynaecology of the Erasmus MC, University Medical Centre. No competing interests are declared. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Cadmium-induced neural tube defects and fetal growth restriction: Association with disturbance of placental folate transport

    International Nuclear Information System (INIS)

    Zhang, Gui-Bin; Wang, Hua; Hu, Jun; Guo, Min-Yin; Wang, Ying; Zhou, Yan; Yu, Zhen; Fu, Lin; Chen, Yuan-Hua; Xu, De-Xiang

    2016-01-01

    Previous studies found that maternal Cd exposure on gestational day (GD)9 caused forelimb ectrodactyly and tail deformity, the characteristic malformations. The aim of the present study was to investigate whether maternal Cd exposure on GD8 induces fetal neural tube defects (NTDs). Pregnant mice were intraperitoneally injected with CdCl 2 (2.5 or 5.0 mg/kg) on GD8. Neither forelimb ectrodactyly nor tail deformity was observed in mice injected with CdCl 2 on GD8. Instead, maternal Cd exposure on GD8 resulted in the incidence of NTDs. Moreover, maternal Cd exposure on GD8 resulted in fetal growth restriction. In addition, maternal Cd exposure on GD8 reduced placental weight and diameter. The internal space of maternal and fetal blood vessels in the labyrinth layer was decreased in the placentas of mice treated with CdCl 2 . Additional experiment showed that placental PCFT protein and mRNA, a critical folate transporter, was persistently decreased when dams were injected with CdCl 2 on GD8. Correspondingly, embryonic folate content was markedly decreased in mice injected with CdCl 2 on GD8, whereas Cd had little effect on folate content in maternal serum. Taken together, these results suggest that maternal Cd exposure during organogenesis disturbs transport of folate from maternal circulation to the fetuses through down-regulating placental folate transporters. - Highlights: • Maternal Cd exposure during organogenesis causes NTDs and FGR. • Maternal Cd exposure during organogenesis impairs placental development. • Cd disturbs transport of folate by down-regulating placental folate transporters.

  20. Cadmium-induced neural tube defects and fetal growth restriction: Association with disturbance of placental folate transport

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Gui-Bin; Wang, Hua, E-mail: wanghuadev@126.com; Hu, Jun; Guo, Min-Yin; Wang, Ying; Zhou, Yan; Yu, Zhen; Fu, Lin; Chen, Yuan-Hua; Xu, De-Xiang, E-mail: xudex@126.com

    2016-09-01

    Previous studies found that maternal Cd exposure on gestational day (GD)9 caused forelimb ectrodactyly and tail deformity, the characteristic malformations. The aim of the present study was to investigate whether maternal Cd exposure on GD8 induces fetal neural tube defects (NTDs). Pregnant mice were intraperitoneally injected with CdCl{sub 2} (2.5 or 5.0 mg/kg) on GD8. Neither forelimb ectrodactyly nor tail deformity was observed in mice injected with CdCl{sub 2} on GD8. Instead, maternal Cd exposure on GD8 resulted in the incidence of NTDs. Moreover, maternal Cd exposure on GD8 resulted in fetal growth restriction. In addition, maternal Cd exposure on GD8 reduced placental weight and diameter. The internal space of maternal and fetal blood vessels in the labyrinth layer was decreased in the placentas of mice treated with CdCl{sub 2}. Additional experiment showed that placental PCFT protein and mRNA, a critical folate transporter, was persistently decreased when dams were injected with CdCl{sub 2} on GD8. Correspondingly, embryonic folate content was markedly decreased in mice injected with CdCl{sub 2} on GD8, whereas Cd had little effect on folate content in maternal serum. Taken together, these results suggest that maternal Cd exposure during organogenesis disturbs transport of folate from maternal circulation to the fetuses through down-regulating placental folate transporters. - Highlights: • Maternal Cd exposure during organogenesis causes NTDs and FGR. • Maternal Cd exposure during organogenesis impairs placental development. • Cd disturbs transport of folate by down-regulating placental folate transporters.

  1. Differential proteomic expression of human placenta and fetal development following e-waste lead and cadmium exposure in utero

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Long; Ge, Jingjing; Huo, Xia; Zhang, Yuling [Laboratory of Environmental Medicine and Developmental Toxicology, Shantou University Medical College, Shantou 515041 (China); Lau, Andy T.Y. [Laboratory of Cancer Biology and Epigenetics, Shantou University Medical College, Shantou 515041 (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou 515041 (China); Xu, Xijin, E-mail: xuxj@stu.edu.cn [Laboratory of Environmental Medicine and Developmental Toxicology, Shantou University Medical College, Shantou 515041 (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou 515041 (China)

    2016-04-15

    ABSTRACT: Prenatal exposure to lead (Pb) and cadmium (Cd) has been associated with a series of physiological problems resulting in fetal growth restriction. We aimed to investigate the effects of Pb and Cd exposure on placental function and the potential mechanisms involved in fetal development. Placental specimens and questionnaires were collected from an e-waste area and a reference area in China. Two-dimensional electrophoresis combined with MALDI-TOF-MS/MS and molecular network relationship were performed to analyze differentially expressed proteins using a compositing sample pool. Compared with the reference group, the exposed group exhibited significantly higher levels of placental Pb and Cd (p < 0.01), shorter body length and higher gestational age (p < 0.01). After bivariate adjustment in a linear regression model, decreases of 205.05 g in weight and 0.44 cm in body length were associated with a 10 ng/g wt increase in placental Cd. Pb showed a negative trend but lacked statistical significance. Proteomic analysis showed 32 differentially-expressed proteins and were predominantly involved in protein translocation, cytoskeletal structure, and energy metabolism. Fumarate hydratase was down-regulated in the exposed placenta tissues and validated by ELISA. Alterations in placental proteome suggest that imbalances in placental mitochondria respiration might be a vital pathway targeting fetal growth restriction induced by exposure to Cd. - Highlights: • The placental Pb and Cd levels were higher in the e-waste polluted area. • Proteome in placenta tissues was performed by two-dimensional gel electrophoresis. • Cd exposure in the placenta was associated with the reduced fetal development. • 32 proteins covered in translocation, energy metabolism and cytoskeletal structure. • Dysregulated mitochondrial respiration may act in the Cd-reduced fetal development.

  2. Differential proteomic expression of human placenta and fetal development following e-waste lead and cadmium exposure in utero

    International Nuclear Information System (INIS)

    Xu, Long; Ge, Jingjing; Huo, Xia; Zhang, Yuling; Lau, Andy T.Y.; Xu, Xijin

    2016-01-01

    ABSTRACT: Prenatal exposure to lead (Pb) and cadmium (Cd) has been associated with a series of physiological problems resulting in fetal growth restriction. We aimed to investigate the effects of Pb and Cd exposure on placental function and the potential mechanisms involved in fetal development. Placental specimens and questionnaires were collected from an e-waste area and a reference area in China. Two-dimensional electrophoresis combined with MALDI-TOF-MS/MS and molecular network relationship were performed to analyze differentially expressed proteins using a compositing sample pool. Compared with the reference group, the exposed group exhibited significantly higher levels of placental Pb and Cd (p < 0.01), shorter body length and higher gestational age (p < 0.01). After bivariate adjustment in a linear regression model, decreases of 205.05 g in weight and 0.44 cm in body length were associated with a 10 ng/g wt increase in placental Cd. Pb showed a negative trend but lacked statistical significance. Proteomic analysis showed 32 differentially-expressed proteins and were predominantly involved in protein translocation, cytoskeletal structure, and energy metabolism. Fumarate hydratase was down-regulated in the exposed placenta tissues and validated by ELISA. Alterations in placental proteome suggest that imbalances in placental mitochondria respiration might be a vital pathway targeting fetal growth restriction induced by exposure to Cd. - Highlights: • The placental Pb and Cd levels were higher in the e-waste polluted area. • Proteome in placenta tissues was performed by two-dimensional gel electrophoresis. • Cd exposure in the placenta was associated with the reduced fetal development. • 32 proteins covered in translocation, energy metabolism and cytoskeletal structure. • Dysregulated mitochondrial respiration may act in the Cd-reduced fetal development.

  3. A developmental stage-specific switch from DAZL to BOLL occurs during fetal oogenesis in humans, but not mice.

    Directory of Open Access Journals (Sweden)

    Jing He

    Full Text Available The Deleted in Azoospermia gene family encodes three germ cell-specific RNA-binding proteins (DAZ, DAZL and BOLL that are essential for gametogenesis in diverse species. Targeted disruption of Boll in mice causes male-specific spermiogenic defects, but females are apparently fertile. Overexpression of human BOLL promotes the derivation of germ cell-like cells from genetically female (XX, but not male (XY human ES cells however, suggesting a functional role for BOLL in regulating female gametogenesis in humans. Whether BOLL is expressed during oogenesis in mammals also remains unclear. We have therefore investigated the expression of BOLL during fetal oogenesis in humans and mice. We demonstrate that BOLL protein is expressed in the germ cells of the human fetal ovary, at a later developmental stage than, and almost mutually-exclusive to, the expression of DAZL. Strikingly, BOLL is downregulated, and DAZL re-expressed, as primordial follicles form, revealing BOLL expression to be restricted to a narrow window during fetal oogenesis. By quantifying the extent of co-expression of DAZL and BOLL with markers of meiosis, we show that this window likely corresponds to the later stages of meiotic prophase I. Finally, we demonstrate that Boll is also transiently expressed during oogenesis in the fetal mouse ovary, but is simultaneously co-expressed within the same germ cells as Dazl. These data reveal significant similarities and differences between the expression of BOLL homologues during oogenesis in humans and mice, and raise questions as to the validity of the Boll(-/- mouse as a model for understanding BOLL function during human oogenesis.

  4. Genes expressed in specific areas of the human fetal cerebral cortex display distinct patterns of evolution.

    Directory of Open Access Journals (Sweden)

    Nelle Lambert

    2011-03-01

    Full Text Available The developmental mechanisms through which the cerebral cortex increased in size and complexity during primate evolution are essentially unknown. To uncover genetic networks active in the developing cerebral cortex, we combined three-dimensional reconstruction of human fetal brains at midgestation and whole genome expression profiling. This novel approach enabled transcriptional characterization of neurons from accurately defined cortical regions containing presumptive