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Sample records for spectrometry newborn screening

  1. Expanded newborn screening by mass spectrometry: New tests, future perspectives.

    Science.gov (United States)

    Ombrone, Daniela; Giocaliere, Elisa; Forni, Giulia; Malvagia, Sabrina; la Marca, Giancarlo

    2016-01-01

    Tandem mass spectrometry (MS/MS) has become a leading technology used in clinical chemistry and has shown to be particularly sensitive and specific when used in newborn screening (NBS) tests. The success of tandem mass spectrometry is due to important advances in hardware, software and clinical applications during the last 25 years. MS/MS permits a very rapid measurement of many metabolites in different biological specimens by using filter paper spots or directly on biological fluids. Its use in NBS give us the chance to identify possible treatable metabolic disorders even when asymptomatic and the benefits gained by this type of screening is now recognized worldwide. Today the use of MS/MS for second-tier tests and confirmatory testing is promising especially in the early detection of new disorders such as some lysosomal storage disorders, ADA and PNP SCIDs, X-adrenoleucodistrophy (X-ALD), Wilson disease, guanidinoacetate methyltransferase deficiency (GAMT), and Duchenne muscular dystrophy. The new challenge for the future will be reducing the false positive rate by using second-tier tests, avoiding false negative results by using new specific biomarkers and introducing new treatable disorders in NBS programs. © 2015 Wiley Periodicals, Inc.

  2. Newborn screening by tandem mass spectrometry: ethical and social issues.

    Science.gov (United States)

    Avard, Denise; Vallance, Hilary; Greenberg, Cheryl; Potter, Beth

    2007-01-01

    Emerging technologies like Tandem Mass Spectrometry (TMS) enable multiple tests on a single blood sample and allow the expansion of Newborn Screening (NBS) to include various metabolic diseases. Introducing TMS for NBS raises important social and ethical questions: what are the criteria for adding disorders to screening panels? What evidence justifies expansion of screening? How can equity in NBS access and standards be ensured? How can policy standards be set, given the multiplicity of stakeholders? To address emerging issues, policy-makers, patient advocates, clinicians and researchers had a workshop during the 2005 Garrod Symposium. The participants received a summary of the discussion and understood the workshop's goal was to provide a basis for further discussion. This article contributes to this ongoing discussion. Several proposed recommendations assert the centrality of including social and ethical issues in the assessment of whether or not to introduce TMS. The article outlines five key recommendations for advancing the NBS agenda: national public health leadership; transparency; increased national consistency in NBS strategy, including minimum standards; collaboration between the federal and provincial/territorial governments and diverse stakeholders; and supporting research and/or programs based on effectiveness, which integrate ethical and social issues into assessment.

  3. Mass spectrometry in clinical chemistry: the case of newborn screening.

    Science.gov (United States)

    la Marca, Giancarlo

    2014-12-01

    Newborn screening (NBS) program is a complex and organized system consisting of family and personnel education, biochemical tests, confirmatory biochemical and genetic tests, diagnosis, therapy, and patient follow up. The program identifies treatable metabolic disorders possibly when asymptomatic by using dried blood spot (DBS). During the last 20 years tandem mass spectrometry (TMS) has become the leading technology in NBS programs demonstrating to be versatile, sensitive and specific. There is consistent evidence of benefits from NBS for many disorders detected by TMS as well as for congenital hypothyroidism, cystic fibrosis, congenital adrenal hyperplasia by immune-enzymatic methods. Real time PCR tests have more recently been proposed for the detection of some severe combined immunodeficiences (SCID) along with the use of TMS for ADA and PNP SCID; a first evaluation of their cost-benefit ratio is still ongoing. Avoiding false negative results by using specific biomarkers and reducing the false positive rate by using second tier tests, is fundamental for a successful NBS program. The fully integration of NBS and diagnostic laboratories with clinical service is crucial to have the best effectiveness in a comprehensive NBS system. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Nationwide survey of extended newborn screening by tandem mass spectrometry in Taiwan.

    Science.gov (United States)

    Niu, Dau-Ming; Chien, Yin-Hsiu; Chiang, Chuan-Chi; Ho, Hui-Chen; Hwu, Wuh-Liang; Kao, Shu-Min; Chiang, Szu-Hui; Kao, Chuan-Hong; Liu, Tze-Tze; Chiang, Hung; Hsiao, Kwang-Jen

    2010-10-01

    In Taiwan, during the period March 2000 to June 2009, 1,495,132 neonates were screened for phenylketonuria (PKU) and homocystinuria (HCU), and 1,321,123 neonates were screened for maple syrup urine disease (MSUD), methylmalonic academia (MMA), medium-chain acyl-coenzyme A (CoA) dehydrogenase (MCAD) deficiency, isovaleric academia (IVA), and glutaric aciduria type 1 (GA-1) using tandem mass spectrometry (MS/MS). In a pilot study, 592,717 neonates were screened for citrullinemia, 3-methylcrotonyl-CoA carboxylase deficiency (3-MCC) and other fatty acid oxidation defects in the MS/MS newborn screening. A total of 170 newborns and four mothers were confirmed to have inborn errors of metabolism. The overall incidence was approximately 1/5,882 (1/6,219 without mothers). The most common inborn errors were defects of phenylalanine metabolism [five classic PKU, 20 mild PKU, 40 mild hyperphenylalaninemia (HPA), and 13 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency]. MSUD was the second most common amino acidopathy and, significantly, most MSUD patients (10/13) belonged to the Austronesian aboriginal tribes of southern Taiwan. The most frequently detected among organic acid disorders was 3-MCC deficiency (14 newborns and four mothers). GA-1 and MMA were the second most common organic acid disorders (13 and 13 newborns, respectively). In fatty acid disorders, five carnitine transport defect (CTD), five short-chain acyl-CoA dehydrogenase deficiency (SCAD), and two medium-chain acyl-CoA dehydrogenase (MCAD) deficiency were confirmed. This is the largest case of MS/MS newborn screening in an East-Asian population to date. We hereby report the incidences and outcomes of metabolic inborn error diseases found in our nationwide MS/MS newborn screening program.

  5. Screening newborns for metabolic disorders based on targeted metabolomics using tandem mass spectrometry

    OpenAIRE

    Yoon, Hye-Ran

    2015-01-01

    The main purpose of newborn screening is to diagnose genetic, metabolic, and other inherited disorders, at their earliest to start treatment before the clinical manifestations become evident. Understanding and tracing the biochemical data obtained from tandem mass spectrometry is vital for early diagnosis of metabolic diseases associated with such disorders. Accordingly, it is important to focus on the entire diagnostic process, including differential and confirmatory diagnostic options, and ...

  6. Screening newborns for metabolic disorders based on targeted metabolomics using tandem mass spectrometry

    Directory of Open Access Journals (Sweden)

    Hye-Ran Yoon

    2015-09-01

    Full Text Available The main purpose of newborn screening is to diagnose genetic, metabolic, and other inherited disorders, at their earliest to start treatment before the clinical manifestations become evident. Understanding and tracing the biochemical data obtained from tandem mass spectrometry is vital for early diagnosis of metabolic diseases associated with such disorders. Accordingly, it is important to focus on the entire diagnostic process, including differential and confirmatory diagnostic options, and the major factors that influence the results of biochemical analysis. Compared to regular biochemical testing, this is a complex process carried out by a medical physician specialist. It is comprised of an integrated program requiring multidisciplinary approach such as, pediatric specialist, expert scientist, clinical laboratory technician, and nutritionist. Tandem mass spectrometry is a powerful tool to improve screening of newborns for diverse metabolic diseases. It is likely to be used to analyze other treatable disorders or significantly improve existing newborn tests to allow broad scale and precise testing. This new era of various screening programs, new treatments, and the availability of detection technology will prove to be beneficial for the future generations.

  7. Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry : A worldwide collaborative project

    NARCIS (Netherlands)

    McHugh, David M. S.; Cameron, Cynthia A.; Abdenur, Jose E.; Abdulrahman, Mahera; Adair, Ona; Al Nuaimi, Shahira Ahmed; Ahlman, Henrik; Allen, Jennifer J.; Antonozzi, Italo; Archer, Shaina; Au, Sylvia; Auray-Blais, Christiane; Baker, Mei; Bamforth, Fiona; Beckmann, Kinga; Pino, Gessi Bentz; Berberich, Stanton L.; Binard, Robert; Boemer, Francois; Bonham, Jim; Breen, Nancy N.; Bryant, Sandra C.; Caggana, Michele; Caldwell, S. Graham; Camilot, Marta; Campbell, Carlene; Carducci, Claudia; Cariappa, Rohit; Carlisle, Clover; Caruso, Ubaldo; Cassanello, Michela; Miren Castilla, Ane; Castineiras Ramos, Daisy E.; Chakraborty, Pranesh; Chandrasekar, Ram; Ramos, Alfredo Chardon; Cheillan, David; Chien, Yin-Hsiu; Childs, Thomas A.; Chrastina, Petr; Sica, Yuri Cleverthon; Cocho de Juan, Jose Angel; Elena Colandre, Maria; Cornejo Espinoza, Veronica; Corso, Gaetano; Currier, Robert; Cyr, Denis; Czuczy, Noemi; D'Apolito, Oceania; Davis, Tim; de Sain-Van der Velden, Monique G.; Delgado Pecellin, Carmen; Di Gangi, Iole Maria; Di Stefano, Cristina Maria; Dotsikas, Yannis; Downing, Melanie; Downs, Stephen M.; Dy, Bonifacio; Dymerski, Mark; Rueda, Inmaculada; Elvers, Bert; Eaton, Roger; Eckerd, Barbara M.; El Mougy, Fatma; Eroh, Sarah; Espada, Mercedes; Evans, Catherine; Fawbush, Sandy; Fijolek, Kristel F.; Fisher, Lawrence; Franzson, Leifur; Frazier, Dianne M.; Garcia, Luciana R. C.; Garcia-Valdecasas Bermejo, Maria Sierra; Gavrilov, Dimitar; Gerace, Rosemarie; Giordano, Giuseppe; Irazabal, Yolanda Gonzalez; Greed, Lawrence C.; Grier, Robert; Grycki, Elyse; Gu, Xuefan; Gulamali-Majid, Fizza; Hagar, Arthur F.; Han, Lianshu; Hannon, W. Harry; Haslip, Christa; Hassan, Fayza Abdelhamid; He, Miao; Hietala, Amy; Himstedt, Leslie; Hoffman, Gary L.; Hoffman, William; Hoggatt, Philis; Hopkins, Patrick V.; Hougaard, David M.; Hughes, Kerie; Hunt, Patricia R.; Hwu, Wuh-Liang; Hynes, June; Ibarra-Gonzalez, Isabel; Ingham, Cindy A.; Ivanova, Maria; Jacox, Ward B.; John, Catharine; Johnson, John P.; Jonsson, Jon J.; Karg, Eszter; Kasper, David; Klopper, Brenda; Katakouzinos, Dimitris; Khneisser, Issam; Knoll, Detlef; Kobayashi, Hirinori; Koneski, Ronald; Kozich, Viktor; Kouapei, Rasoul; Kohlmueller, Dirk; Kremensky, Ivo; la Marca, Giancarlo; Lavochkin, Marcia; Lee, Soo-Youn; Lehotay, Denis C.; Lemes, Aida; Lepage, Joyce; Lesko, Barbara; Lewis, Barry; Lim, Carol; Linard, Sharon; Lindner, Martin; Lloyd-Puryear, Michele A.; Lorey, Fred; Loukas, Yannis L.; Luedtke, Julie; Maffitt, Neil; Magee, J. Fergall; Manning, Adrienne; Manos, Shawn; Marie, Sandrine; Hadachi, Sonia Marchezi; Marquardt, Gregg; Martin, Stephen J.; Matern, Dietrich; Gibson, Stephanie K. Mayfield; Mayne, Philip; McCallister, Tonya D.; McCann, Mark; McClure, Julie; McGill, James J.; McKeever, Christine D.; McNeilly, Barbara; Morrissey, Mark A.; Moutsatsou, Paraskevi; Mulcahy, Eleanor A.; Nikoloudis, Dimitris; Norgaard-Pedersen, Bent; Oglesbee, Devin; Oltarzewski, Mariusz; Ombrone, Daniela; Ojodu, Jelili; Papakonstantinou, Vagelis; Reoyo, Sherly Pardo; Park, Hyung-Doo; Pasquali, Marzia; Pasquini, Elisabetta; Patel, Pallavi; Pass, Kenneth A.; Peterson, Colleen; Pettersen, Rolf D.; Pitt, James J.; Poh, Sherry; Pollak, Arnold; Porter, Cory; Poston, Philip A.; Price, Ricky W.; Queijo, Cecilia; Quesada, Jonessy; Randell, Edward; Ranieri, Enzo; Raymond, Kimiyo; Reddic, John E.; Reuben, Alejandra; Ricciardi, Charla; Rinaldo, Piero; Rivera, Jeff D.; Roberts, Alicia; Rocha, Hugo; Roche, Geraldine; Greenberg, Cheryl Rochman; Egea Mellado, Jose Maria; Jess Juan-Fita, Maria; Ruiz, Consuelo; Ruoppolo, Margherita; Rutledge, S. Lane; Ryu, Euijung; Saban, Christine; Sahai, Inderneel; Salazar Garcia-Blanco, Maria Isabel; Santiago-Borrero, Pedro; Schenone, Andrea; Schoos, Roland; Schweitzer, Barb; Scott, Patricia; Seashore, Margretta R.; Seeterlin, Mary A.; Sesser, David E.; Sevier, Darrin W.; Shone, Scott M.; Sinclair, Graham; Skrinska, Victor A.; Stanley, Eleanor L.; Strovel, Erin T.; Jones, April L. Studinski; Sunny, Sherlykutty; Takats, Zoltan; Tanyalcin, Tijen; Teofoli, Francesca; Thompson, J. Robert; Tomashitis, Kathy; Domingos, Mouseline Torquado; Torres, Jasmin; Torres, Rosario; Tortorelli, Silvia; Turi, Sandor; Turner, Kimberley; Tzanakos, Nick; Valiente, Alf G.; Vallance, Hillary; Vela-Amieva, Marcela; Vilarinho, Laura; von Doebeln, Ulrika; Vincent, Marie-Francoise; Vorster, B. Chris; Watson, Michael S.; Webster, Dianne; Weiss, Sheila; Wilcken, Bridget; Wiley, Veronica; Williams, Sharon K.; Willis, Sharon A.; Woontner, Michael; Wright, Katherine; Yahyaoui, Raquel; Yamaguchi, Seiji; Yssel, Melissa; Zakowicz, Wendy M.

    Purpose: To achieve clinical validation of cutoff values for newborn screening by tandem mass spectrometry through a worldwide collaborative effort. Methods: Cumulative percentiles of amino acids and acylcarnitines in dried blood spots of approximately 25-30 million normal newborns and 10,742

  8. The inclusion of ADA-SCID in expanded newborn screening by tandem mass spectrometry.

    Science.gov (United States)

    la Marca, Giancarlo; Giocaliere, Elisa; Malvagia, Sabrina; Funghini, Silvia; Ombrone, Daniela; Della Bona, Maria Luisa; Canessa, Clementina; Lippi, Francesca; Romano, Francesca; Guerrini, Renzo; Resti, Massimo; Azzari, Chiara

    2014-01-01

    Severe combined immunodeficiency due to adenosine-deaminase defect (ADA-SCID) is usually deadly in childhood because of severe recurrent infections. When clinical diagnosis is done, permanent damages due to infections or metabolite accumulation are often present. Gene therapy, bone marrow transplantation or enzyme replacement therapy may be effective if started early. The aim of this study was to set-up a robust method suitable for screening with a minimized preparation process and with inexpensive running costs, for diagnosing ADA-SCID by tandem mass spectrometry. ADA-SCID satisfies all the criteria for inclusion in a newborn screening program. We describe a protocol revised to incorporate adenosine and 2-deoxyadenosine testing into an expanded newborn screening program. We assessed the effectiveness of this approach testing dried blood spots from 4 genetically confirmed early-onset and 5 delayed-onset ADA-SCID patients. Reference values were established on 50,000 healthy newborns (deoxyadenosine ADA) gene. The results show that the method having great simplicity, low cost and low process preparations can be fully applicable to a mass screening program. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Variations in IBD (ACAD8) in children with elevated C4-carnitine detected by tandem mass spectrometry newborn screening

    DEFF Research Database (Denmark)

    Pedersen, Christina B; Bischoff, Claus; Christensen, Ernst

    2006-01-01

    or compound heterozygous for variations in the IBD gene have been reported. We present IBD deficiency in an additional four newborns with elevated C(4)-carnitine identified by tandem mass spectrometry (MS/MS) screening in Denmark and the United States. Three showed urinary excretions of isobutyryl...

  10. Dataset and standard operating procedure for newborn screening of six lysosomal storage diseases: By tandem mass spectrometry

    Directory of Open Access Journals (Sweden)

    Susan Elliott

    2016-09-01

    Full Text Available In this data article we provide a detailed standard operating procedure for performing a tandem mass spectrometry, multiplex assay of 6 lysosomal enzymes for newborn screening of the lysosomal storage diseases Mucopolysaccharidosis-I, Pompe, Fabry, Niemann-Pick-A/B, Gaucher, and Krabbe, (Elliott, et al., 2016 [1]. We also provide the mass spectrometry peak areas for the product and internal standard ions typically observed with a dried blood spot punch from a random newborn, and we provide the daily variation of the daily mean activities for all 6 enzymes.

  11. Hearing Loss: Screening Newborns

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Hearing Loss Screening Newborns Past Issues / Spring 2015 Table ... deafness, which account for most cases. Screening Newborns' Hearing Now Standard In 1993, children born in the ...

  12. Reference values of amino acids, acylcarnitines and succinylacetone by tandem mass spectrometry for use in newborn screening in southwest Colombia.

    Science.gov (United States)

    Céspedes, Nora; Valencia, Angela; Echeverry, Carlos Alberto; Arce-Plata, Maria Isabel; Colón, Cristóbal; Castiñeiras, Daisy E; Hurtado, Paula Margarita; Cocho, Jose Angel; Herrera, Sócrates; Arévalo-Herrera, Myriam

    2017-09-30

    Inborn errors of metabolism (IEM) represent an important public health problem due to current diagnosis and treatment limitations, poor life quality of affected patients, and consequent untimely child death. In contrast to classical methods, tandem mass spectrometry (MS/MS) has allowed simultaneous evaluation of multiple metabolites associated with IEM offering higher sensitivity, low false positive rates and high throughput. Determine concentration levels for amino acids and acylcarnitines in blood of newborns from Colombia, to establish reference values for further use in diagnosis of IEM. Implementation of a method to determine amino acids, acylcarnitines and succinylacetone in newborn dried blood spots using MS/MS, and its application in a cross-sectional study conducted in 891 healthy neonates from Cali and Quibdo cities is described. fifty-seven analytes that allow the diagnosis of more than 40 different pathologies were tested. The method showed to be linear, precise and accurate. Healthy neonates 1-18 days of age were included, 523 from Cali and 368 from Quibdo; 52% male and 48% female. Age-related differences on the concentration levels of amino acids and acylcarnitines were observed whereas no significant differences by gender were found. The study has contributed to reveal the usual concentration levels of amino acids, acylcarnitines and succinylacetone that could be used as reference for the establishment of a newborn metabolic screening program in Colombia.

  13. Tandem mass spectrometry-based newborn screening strategy could be used to facilitate rapid and sensitive lung cancer diagnosis

    Directory of Open Access Journals (Sweden)

    Huang T

    2016-04-01

    Full Text Available Ting Huang,1,* Yunfeng Cao,1,* Jia Zeng,1 Jun Dong,2 Xiaoyu Sun,2 Jianxing Chen,1 Peng Gao2,3 1Key Laboratory of Contraceptives and Devices Research (NPFPC, Shanghai Engineer and Technology Research Center of Reproductive Health Drug and Devices, Shanghai Institute of Planned Parenthood Research, Shanghai, 2Clinical Laboratory, Dalian Sixth People’s Hospital, 3CASKey Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, People’s Republic of China *These authors contributed equally to this work Objective: Newborn screening (NBS helps in the early detection of inborn errors of metabolism (IEM. The most effective NBS strategy prevailing in clinics is tandem mass spectrometry (MS/MS analysis using dried blood spot (DBS samples. Taking lung cancer (LC as an example, this study tried to explore if this technique could be of any assistance for the discovery of tumor metabolite markers.Materials and methods: Twenty-six acylcarnitines and 23 amino acids, which are commonly used in IEM screening, were quantified using DBS samples from 222 LC patients, 118 benign lung disease (LD patients, and 96 healthy volunteers (CONT. Forty-four calculated ratios based on the abovementioned metabolites were also included using MS/MS quantification results.Results: This pilot study led to the findings of 65 significantly changed amino acids, acylcarnitines, and some of their ratios for the LC, LD, and CONT groups. Among the differential parameters, 12 items showed reverse changing trends between the LC and LD groups compared to the CONT group. Regression analysis demonstrated that six of them – Arg, Pro, C10:1, Arg/Orn, Cit/Arg, and C5-OH/C0 – could be used to diagnose LC with a sensitivity of 91.3% and a specificity of 92.7%.Conclusion: This study demonstrated the DBS-based MS/MS strategy was a promising tool for the discovery of tumor metabolite markers. Remarkably, this MS

  14. Newborn screening for galactosaemia.

    Science.gov (United States)

    Lak, Rohollah; Yazdizadeh, Bahareh; Davari, Majid; Nouhi, Mojtaba; Kelishadi, Roya

    2017-12-23

    Classical galactosaemia is an autosomal recessive inborn error of metabolism caused by a deficiency of the enzyme galactose-1-phosphate uridyltransferase. This is a rare and potentially lethal condition that classically presents in the first week of life once milk feeds have commenced. Affected babies may present with any or all of the following: cataracts; fulminant liver failure; prolonged jaundice; or Escherichia coli sepsis. Once the diagnosis is suspected, feeds containing galactose must be stopped immediately and replaced with a soya-based formula. The majority of babies will recover, however a number will not survive. There are long-term complications of galactosaemia, despite treatment, including learning disabilities and female infertility. It has been postulated that galactosaemia could be detected on newborn screening and this would prevent the immediate severe liver dysfunction and sepsis. To assess whether there is evidence that newborn screening for galactosaemia prevents or reduces mortality and morbidity and improves clinical outcomes in affected neonates and the quality of life in older children. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from electronic database searches, handsearches of relevant journals and conference abstract books. We also searched online trials registries and the reference lists of relevant articles and reviews.Date of the most recent search of Cochrane Cystic Fibrosis Group's Trials Register: 18 December 2017.Date of the most recent search of additional resources: 11 October 2017. Randomised controlled studies and controlled clinical studies, published or unpublished comparing the use of any newborn screening test to diagnose infants with galactosaemia and presenting a comparison between a screened population versus a non-screened population. No studies of newborn screening for galactosaemia were found. No studies were identified for inclusion in the

  15. Newborn hearing screening.

    Science.gov (United States)

    Stewart, D L; Pearlman, A

    1994-11-01

    Congenital deafness is a relatively common problem with an incidence of 1/300 to 1/1000. Most states have no mass screening program for hearing loss, but the state of Kentucky compiles a High Risk Registry which is a historical survey of parents relating to risk factors for hearing loss. Unfortunately this survey can miss 50% of those who have a hearing deficit. If not detected prior to discharge, there is often a delay in diagnosis of deafness which prevents early intervention. We report 2 years' experience at Kosair Children's Hospital where 1,987 infants admitted to well baby, intermediate, or intensive care nurseries were screened using the ALGO-1 screener (Natus Medical Inc, Foster City, CA) which is a modified auditory brain stem evoked response (ABR). Our screening of this population led to an 11% incidence of referral for complete audiological evaluation. There were no significant complications. Forty-eight infants were found to have nonspecified, sensorineural, or conductive hearing loss. The positive predictive value of the test was 96%. Therefore, we feel that the use of the modified ABR in the newborn is a timely, cost efficient method of screening for hearing loss and should be used for mass screening of all newborns.

  16. Prospective diagnosis of 2-methylbutyryl-CoA dehydrogenase deficiency in the Hmong population by newborn screening using tandem mass spectrometry

    DEFF Research Database (Denmark)

    Matern, Dietrich; He, Miao; Berry, Susan A

    2003-01-01

    but asymptomatic. METHODS: We report 8 additional patients identified by prospective newborn screening using tandem mass spectrometry. RESULTS: Molecular genetic analysis performed for 3 of these patients revealed that all are homozygous for an 1165A>G mutation that causes skipping of exon 10 of the SBCAD gene....... Although there was no obvious consanguinity, all patients belong to the Hmong, an ancient ethnic group that originated in China and constitutes only 0.8% and 0.6% of the Minnesota and Wisconsin population, respectively. Dietary treatment was initiated in the neonatal period. Except for 1 patient who...... developed mild muscle hypotonia, all patients remain asymptomatic at ages ranging from 3 to 14 months of age. CONCLUSIONS: These cases suggest that SBCAD deficiency is another inborn error of metabolism detectable by newborn screening using tandem mass spectrometry. The continued efficacy of long...

  17. Newborn screening by matrix-assisted laser desorption/ionization mass spectrometry based on parylene-matrix chip.

    Science.gov (United States)

    Kim, Jo-Il; Noh, Joo-Yoon; Kim, Mira; Park, Jong-Min; Song, Hyun-Woo; Kang, Min-Jung; Pyun, Jae-Chul

    2017-08-01

    Newborn screening for diagnosis of phenylketonuria, homocystinuria, and maple syrup urine disease have been conducted by analyzing the concentration of target amino acids using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS) based on parylene-matrix chip. Parylene-matrix chip was applied to MALDI-ToF MS analysis reducing the matrix peaks significantly at low mass-to-charge ratio range (m/z  0.98) and the LODs were ranging from 9.0 to 22.9 μg/mL. Effect of proteins in serum was estimated by comparing MALDI-ToF mass spectra of amino acids-spiked serum before and after the methanol extraction. Interference of other amino acids on analysis of target analyte was determined to be insignificant. From these results, MALDI-ToF MS based on parylene-matrix chip could be applicable to medical diagnosis of neonatal metabolic disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Newborn Screening: MedlinePlus Health Topic

    Science.gov (United States)

    ... more articles Reference Desk Glossary (National Center for Biotechnology Information) Find an Expert Eunice Kennedy Shriver National ... other than English on Newborn Screening NIH MedlinePlus Magazine Hearing Loss: Screening Newborns Screening Newborns' Hearing Now ...

  19. Newborn screening of inherited metabolic disorders by tandem mass spectrometry: past, present and future

    Directory of Open Access Journals (Sweden)

    G. Scaturro

    2013-04-01

    Full Text Available Inborn errors of metabolism are inherited biochemical disorders caused by lack of a functional enzyme, transmembrane transporter, or similar protein, which then results in blockage of the corresponding metabolic pathway. Taken individually, inborn errors of metabolism are rare. However, as a group these diseases are relatively frequent and they may account for most of neonatal mortality and need of health resources. The detection of genetic metabolic disorders should occur in a pre-symptomatic phase. Recently, the introduction of the tandem mass spectrometric methods for metabolite analysis has changed our ability to detect intermediates of metabolism in smaller samples and provides the means to detect a large number of metabolic disorders in a single analytical run. Screening panels now include a large number of disorders that may not meet all the criteria that have been used as a reference for years. The rationale behind inclusion or exclusion of a respective disorder is difficult to understand in most cases and it may impose an ethical dilemma. The current organization is an important tool of secondary preventive medicine, essential for children’s healthcare, but the strong inhomogeneity of the regional models of screening applied today create in the Italian neonatal population macroscopic differences with regards to healthcare, which is in effect mainly diversified by the newborn’s place of birth, in possible violation of the universal criterion of the equality of all citizens. Carefully weighed arguments are urgently needed since patient organizations, opinion leaders and politicians are pressing to proceed with expansion of neonatal population screening.

  20. High-throughput tandem mass spectrometry multiplex analysis for newborn urinary screening of creatine synthesis and transport disorders, Triple H syndrome and OTC deficiency.

    Science.gov (United States)

    Auray-Blais, Christiane; Maranda, Bruno; Lavoie, Pamela

    2014-09-25

    Creatine synthesis and transport disorders, Triple H syndrome and ornithine transcarbamylase deficiency are treatable inborn errors of metabolism. Early screening of patients was found to be beneficial. Mass spectrometry analysis of specific urinary biomarkers might lead to early detection and treatment in the neonatal period. We developed a high-throughput mass spectrometry methodology applicable to newborn screening using dried urine on filter paper for these aforementioned diseases. A high-throughput methodology was devised for the simultaneous analysis of creatine, guanidineacetic acid, orotic acid, uracil, creatinine and respective internal standards, using both positive and negative electrospray ionization modes, depending on the compound. The precision and accuracy varied by screening for inherited disorders by biochemical laboratories. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Newborn Screening for Phenylketonuria

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    Gustavo J. C. Borrajo PhD

    2016-12-01

    Full Text Available Newborn screening (NBS for phenylketonuria in Latin America gave its first step in an organized way 3 decades ago when the first national NBS program was implemented in Cuba. From then onward, it experienced a slow but continuous growing, being currently possible to find from countries where no NBS activity is known to several countries with consolidated NBS programs. This complex scenario gave rise to a great diversity in the criteria used for sample collection, selection of analytical methods, and definition of cutoff values. Considering this context, a consensus meeting was held in order to unify such criteria, focusing the discussion in the following aspects—recommended blood specimens and sample collection time; influence of early discharge, fasting, parenteral nutrition, blood transfusions, extracorporeal life support, and antibiotics; main causes of transient hyperphenylalaninemias; required characteristics for methods used in phenylalanine measurement; and finally, criteria to define the more appropriate cutoff values.

  2. Newborn blood spot screening for sickle cell disease by using tandem mass spectrometry: implementation of a protocol to identify only the disease states of sickle cell disease.

    Science.gov (United States)

    Moat, Stuart J; Rees, Derek; King, Lawrence; Ifederu, Adeboye; Harvey, Katie; Hall, Kate; Lloyd, Geoff; Morrell, Christine; Hillier, Sharon

    2014-02-01

    The currently recommended technologies of HPLC and isoelectric focusing for newborn blood spot screening for sickle cell disease (SCD) identify both the disease and carrier states, resulting in large numbers of infants being followed up unnecessarily. Analysis of blood spot tryptic peptides performed by using tandem mass spectrometry (MS/MS) is an alternative technology to detect hemoglobin (Hb) variant disorders. We analyzed 2154 residual newborn blood spots and 675 newborn blood spots from infants with Hb variants by using MS/MS after trypsin digestion. Screening cutoffs were developed by using the ratio between the variant peptide-to-wild-type peptide abundance for HbS, C, D(Punjab), O(Arab), Lepore, and E peptides. A postanalytical data analysis protocol was developed using these cutoffs to detect only the disease states of SCD and not to identify carrier states. A parallel study of 13 249 newborn blood spots from a high-prevalence SCD area were analyzed by both MS/MS and HPLC. Screening cutoffs developed distinguished the infants with the disease states of SCD, infants who were carriers of SCD, and infants with normal Hb. In the parallel study no false-negative results were identified, and all clinically relevant cases were correctly identified using the MS/MS protocol. Unblinding the data revealed a total of 328 carrier infants that were successfully excluded by the protocol. The screening protocol developed correctly identified infants with the disease states of SCD. Furthermore, large numbers of sickle cell carrier infants were successfully not identified, thereby avoiding unnecessary follow-up testing and referral for genetic counseling.

  3. Improvement in the sensitivity of newborn screening for Fabry disease among females through the use of a high-throughput and cost-effective method, DNA mass spectrometry.

    Science.gov (United States)

    Lu, Yung-Hsiu; Huang, Po-Hsun; Wang, Li-Yun; Hsu, Ting-Rong; Li, Hsing-Yuan; Lee, Pi-Chang; Hsieh, Yu-Ping; Hung, Sheng-Che; Wang, Yu-Chen; Chang, Sheng-Kai; Lee, Ya-Ting; Ho, Ping-Hsun; Ho, Hui-Chen; Niu, Dau-Ming

    2018-01-01

    Many female carriers of Fabry disease are likely to develop severe morbidity and mortality. However, by our own estimation, around 80% of female newborns are missed by our current enzyme-based screening approach. Our team's aim was to develop an improved cost-effective screening method that is able to detect Fabry disease among female newborns. In Taiwan, based on a database of 916,000 newborns, ~98% of Fabry patients carry mutations out of a pool of only 21 pathogenic mutations. An Agena iPLEX platform was designed to detect these 21 pathogenic mutations using only a single-assay panel. A total of 54,791 female infants were screened and 136 female newborns with the IVS4 + 919G > A mutation and one female newborn with the c.656T > C mutation were identified. Using the current enzyme-based newborn screening approach as baseline, around 83% of female newborns are being missed. Through a family study of the IVS4 female newborns, 30 IVS4 adult family members were found to have left ventricular hypertrophy. Ten patients received endomyocardial biopsy and all were found to have significant globotriaosylceramide (Gb3) accumulation in their cardiomyocytes. All of these individuals now receive enzyme replacement therapy. We have demonstrated that the Agena iPLEX assay is a powerful tool for detecting females with Fabry disease. Furthermore, through this screening, we also have been able to identify many disease-onset adult family members who were originally undiagnosed for Fabry disease. This screening helps them to receive treatment in time before severe and irreversible cardiac damage has occurred.

  4. Expanded newborn screening: social and ethical issues.

    Science.gov (United States)

    Dhondt, Jean-Louis

    2010-10-01

    Newborn screening and genetic testing have expanded rapidly in the last decade with the advent of multiplex (e.g., tandem mass spectrometry) and/or DNA technologies. However, screening panels include a large number of disorders, which may not meet all of the traditional screening criteria, established in late 1960s, and used for years to justify screening programs. After a period of expansion driven by technological advances, many reports have reconsidered the justification of expanded programs. Many factors have contributed to test-panel discrepancies between countries. The test-panel review methodology, the way health benefits are weighed against harms, and the socioeconomic-political environment all play a role. Expansion of screening also requires reconsideration of the infrastructure (ideally, in the context of national plans for rare diseases) to support testing, counselling, education, treatment, and follow-up. Consequently, economic aspects cannot be ignored and can be a limitation for expansion. New ethical questions have emerged: risks of discrimination or stigmatization, respect of the autonomy of persons to make decisions, parental anxiety resulting from a false positive test (especially when reporting to parents screening results for untreatable conditions identified as by-products of screening), etc. For disorders where there is not yet confirmation of benefit, it may be prudent to recommend pilot screening and to have a mechanism that can be used to adapt or even to stop a program.

  5. Population newborn screening for inherited metabolic disease: current UK perspectives.

    Science.gov (United States)

    Green, A; Pollitt, R J

    1999-06-01

    Some of the generally accepted criteria for screening programmes are inappropriate for newborn metabolic screening as they ignore the family dimension and the importance of timely genetic information. Uncritical application of such criteria creates special difficulties for screening by tandem mass spectrometry, which can detect a range diseases with widely different natural histories and responsiveness to treatment. Further difficulties arise from increasing demands for direct proof of the effects of screening on long-term morbidity and mortality. The randomized controlled trial is held to be the gold standard, but for ethical and practical reasons it will be impossible to achieve for such relatively rare diseases. This approach also oversimplifies the complex matrix of costs and benefits of newborn metabolic screening. A more workable approach could involve Bayesian synthesis, combining quantitative performance data from carefully designed prospective pilot studies of screening with existing experience of the natural history, diagnosis, and management of the individual disorders concerned.

  6. Attitudes toward newborn screening for cytomegalovirus infection.

    Science.gov (United States)

    Din, Erica S; Brown, Cedric J; Grosse, Scott D; Wang, Chengbin; Bialek, Stephanie R; Ross, Danielle S; Cannon, Michael J

    2011-12-01

    Newborns are not routinely screened for cytomegalovirus (CMV), the leading infectious cause of developmental disability. Congenital CMV satisfies a number of criteria for inclusion in newborn screening, and screening potentially offers benefits. Screening could also introduce harms such as anxiety and unnecessary costs for the families of the substantial proportion of CMV-infected children who never develop CMV-related disabilities. Our objective was to assess attitudes toward newborn screening for CMV. We analyzed responses to 5 statements about CMV and newborn screening from 3922 participants in the 2009 HealthStyles survey, a national mail survey designed to include a group similar to the US population with respect to gender, age, race/ethnicity, income, and household size. Two-step cluster analysis was performed to identify clusters of parental attitudes. The majority of respondents strongly or somewhat agreed that they would want to have their newborn tested for CMV even if it was not performed routinely (84%), they had to pay $20 (87%), or CMV-related problems never developed (84%). Nearly half (47%) of them "would worry that the CMV test would lead to unneeded doctor visits and expenses," and 32% "think CMV problems are too rare to worry about." Three clusters of parent respondents were identified on the basis of their attitudes toward CMV screening: "strongly in favor" (31%), "moderately in favor" (49%), and "weakly opposed" (20%). Among most parents, costs, worry, and anxiety associated with newborn screening for CMV would be acceptable. Although attitudes were generally favorable, a minority of the parents were weakly opposed to newborn screening for CMV.

  7. Biochemical screening of 504,049 newborns in Denmark, the Faroe Islands and Greenland--experience and development of a routine program for expanded newborn screening

    DEFF Research Database (Denmark)

    Lund, Allan Meldgaard; Hougaard, David Michael; Simonsen, Henrik

    2012-01-01

    Expanded newborn screening for selected inborn errors of metabolism (IEM) in Denmark, the Faroe Islands and Greenland was introduced in 2002. We now present clinical, biochemical, and statistical results of expanded screening (excluding PKU) of 504,049 newborns during nine years as well as diagno......Expanded newborn screening for selected inborn errors of metabolism (IEM) in Denmark, the Faroe Islands and Greenland was introduced in 2002. We now present clinical, biochemical, and statistical results of expanded screening (excluding PKU) of 504,049 newborns during nine years as well...... as a pilot study during the first seven years, and the experience obtained during these years was used in the development of the routine neonatal screening program introduced in 2009. Methods for screening included tandem mass spectrometry and an assay for determination of biotinidase activity. A total...

  8. Newborn hearing screening protocol in tuscany region.

    Science.gov (United States)

    Berrettini, Stefano; Ghirri, Paolo; Lazzerini, Francesco; Lenzi, Giovanni; Forli, Francesca

    2017-09-20

    Newborn hearing screening has to be considered the first step of a program for the identification, diagnosis, treatment and habilitation/rehabilitation of children with hearing impairment. In Tuscany Region of Italy, the universal newborn hearing screening is mandatory since november 2007. The first guidelines for the execution of the screening have been released in June 2008; then many other Italian regions partially or totally adopted these guidelines. On the basis of the experience from 2008 and according to the recent evidences in the scientific literature, a new screening protocol was released in Tuscany region. The new protocol is an evolution of the previous one. Some issues reported in the previous protocol and in the Joint Committee on Infant Hearing statement published in 2007 were revised, such as the risk factors for auditory neuropathy and for late onset, progressive or acquired hearing loss. The new updated guidelines were submitted to the Sanitary Regional Council and then they have been approved in August 2016. The updated screening protocol is mainly aimed to identify newborns with a congenital moderate-to-profound hearing loss, but it also provides indications for the audiological follow-up of children with risk's factor for progressive or late onset hearing loss; further it provides indications for the audiological surveillance of children at risk for acquired hearing impairment. Then, in the new guidelines the role of the family paediatrician in the newborn hearing screening and audiological follow-up and surveillance is underscored. Finally the new guidelines provide indications for the treatment with hearing aids and cochlear implant, in accordance with the recent Italian Health Technology Assessment (HTA) guidelines. In the paper we report the modality of execution of the universal newborn hearing screening in the Tuscany Region, according to the recently updated protocol. The main features of the protocol and the critical issues are

  9. Newborn screening for MCAD deficiency

    DEFF Research Database (Denmark)

    Horvath, Gabriella A; Davidson, A G F; Stockler-Ipsiroglu, Sylvia G

    2008-01-01

    . Both C8 and C8/C10 ratios remained abnormal in all confirmed MCAD cases. Positive predictive value of screening was 58% with no false negative results. Seven patients were homozygous for the common c.985A > G MCAD mutation and three others were compound heterozygous for the c.985A > G and a second...

  10. Development and validation of a 2nd tier test for identification of purine nucleoside phosphorylase deficiency patients during expanded newborn screening by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    la Marca, Giancarlo; Giocaliere, Elisa; Malvagia, Sabrina; Villanelli, Fabio; Funghini, Silvia; Ombrone, Daniela; Della Bona, Maria; Forni, Giulia; Canessa, Clementina; Ricci, Silvia; Romano, Francesca; Guerrini, Renzo; Resti, Massimo; Azzari, Chiara

    2016-04-01

    Purine nucleoside phosphorylase (PNP) deficiency has been recently introduced in the newborn screening program in Tuscany. In order to improve the PNP screening efficiency, we developed a 2nd tier test to quantify PNP primary markers deoxyguanosine (dGuo) and deoxyinosine (dIno). Dried blood spots (DBS) samples were extracted with 200 μL of methanol and 100 μL of water (by two steps). Internal standards were added at a final concentration of 10 μmol/L. After extraction, samples were analysed by LC-MS/MS. The chromatographic run was performed in gradient mode by using a Synergi Fusion column. The assay was linear over a concentration range of 0.05-50 μmol/L (R2>0.999) for dGuo and 0.5-50 μmol/L (R2>0.998) for dIno. Intra- and interassay imprecision (mean CVs) for dIno and dGuo ranged from 2.9% to 12%. Limit of quantitaion (LOQ) were found to be 0.05 μmol/L and 0.5 μmol/L for dGuo and dIno, respectively. The reference ranges, obtained by measuring dGuo and dIno concentrations on DBS, were close to zero for both biomarkers. Moreover, DBS samples from seven patients with confirmed PNP were retrospectively evaluated and correctly identified. The LC-MS/MS method can reliably measure dIno and dGuo in DBS for the diagnosis of PNP. Validation data confirm the present method is characterised by good reproducibility, accuracy and imprecision for the quantitation of dIno and dGuo. The assay also appears suitable for use in monitoring treatment of PNP patients.

  11. Screening of the hearing of newborns - Update

    Directory of Open Access Journals (Sweden)

    von Voß, Hubertus

    2006-11-01

    Full Text Available Introduction: Permanent congenital bilateral hearing loss (CHL of moderate or greater degree (≥40 dB HL is a rare disease, with a prevalence of about 1 to 3 per 1000 births. However, it is one of the most frequent congenital diseases. Reliance on physician observation and parental recognition has not been successful in the past in detecting significant hearing loss in the first year of life. With this strategy significant hearing losses have been detected in the second year of life. With two objective technologies based on physiologic response to sound, otoacoustic emissions (OAE and auditory brainstem response (ABR hearing screening in the first days of life is made possible. Objectives: The objective of this health technology assessment report is to update the evaluation on clinical effectiveness and cost-effectiveness of newborn hearing screening programs. Universal newborn hearing screening (UHNS (i, selective screening of high risk newborns (ii, and the absence of a systematic screening program are compared for age at identification and age at hearing aid fitting of children with hearing loss. Secondly the potential benefits of early intervention are analysed. Costs and cost-effectiveness of newborn hearing screening programs are determined. This report is intended to make a contribution to the decision making whether and under which conditions a newborn hearing screening program should be reimbursed by the statutory sickness funds in Germany. Methods: This health technology assessment report updates a former health technology assessment (Kunze et al. 2004 [1]. A systematic review of the literature was conducted, based on a documented search and selection of the literature using predefined inclusion and exclusion criteria and a documented extraction and appraisal of the included studies. To assess the cost-effectiveness of the different screening strategies in Germany the decision analytic Markov state model which had been developed in

  12. Cost-effectiveness analysis of universal newborn screening for medium chain acyl-CoA dehydrogenase deficiency in France

    OpenAIRE

    Hamers, Françoise F; Rumeau-Pichon, Catherine

    2012-01-01

    Abstract Background Five diseases are currently screened on dried blood spots in France through the national newborn screening programme. Tandem mass spectrometry (MS/MS) is a technology that is increasingly used to screen newborns for an increasing number of hereditary metabolic diseases. Medium chain acyl-CoA dehydrogenase deficiency (MCADD) is among these diseases. We sought to evaluate the cost-effectiveness of introducing MCADD screening in France. Methods We developed a decision model t...

  13. 21 CFR 862.1055 - Newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem...

    Science.gov (United States)

    2010-04-01

    ..., free carnitine, and acylcarnitines using tandem mass spectrometry. 862.1055 Section 862.1055 Food and... screening test system for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry. (a) Identification. A newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem...

  14. What Disorders Are Newborns Screened for in the United States?

    Science.gov (United States)

    ... core conditions and 26 secondary conditions. The committee’s recommendations are based on the Newborn Screening: Towards a Uniform Screening Panel and System (PDF - 975 KB) and on current research evidence, ...

  15. Newborn screening for X-linked adrenoleukodystrophy: further evidence high throughput screening is feasible.

    Science.gov (United States)

    Theda, Christiane; Gibbons, Katy; Defor, Todd E; Donohue, Pamela K; Golden, W Christopher; Kline, Antonie D; Gulamali-Majid, Fizza; Panny, Susan R; Hubbard, Walter C; Jones, Richard O; Liu, Anita K; Moser, Ann B; Raymond, Gerald V

    2014-01-01

    X-linked adrenoleukodystrophy (ALD) is characterized by adrenal insufficiency and neurologic involvement with onset at variable ages. Plasma very long chain fatty acids are elevated in ALD; even in asymptomatic patients. We demonstrated previously that liquid chromatography tandem mass spectrometry measuring C26:0 lysophosphatidylcholine reliably identifies affected males. We prospectively applied this method to 4689 newborn blood spot samples; no false positives were observed. We show that high throughput neonatal screening for ALD is methodologically feasible. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Newborn screening: need of the hour in India.

    Science.gov (United States)

    Verma, Ishwar C; Bijarnia-Mahay, Sunita; Jhingan, Geetu; Verma, Jyotsna

    2015-01-01

    After a review of the current health scene in India, the authors suggest that the Government of India should consider seriously, the introduction of new born screening. As a first step, a central advisory committee should be constituted to recommend what is required to be done to strengthen the infrastructure and the manpower to carry out new born screening, and the disorders to be screened. In the urban hospitals newborn screening (NBS) for three disorders can be easily introduced (congenital hypothyroidism, congenital adrenal hyperplasia and G-6-PD deficiency), while in the rural areas this should begin with congenital hypothyroidism, especially in the sub Himalayan areas. Concurrently, logistic issues regarding diets and special therapies for inborn errors of metabolism should be sorted out, laboratories to confirm the diagnosis should be set up, and a cadre of metabolic physicians should be build up to treat those identified to have inborn errors of metabolism. Once these are established on a firm footing, tandem mass spectrometry should be introduced as it allows the identification of a number of disorders in an affordable manner. The recent improvements and current trends in health care in India have created the necessary infrastructure for adopting NBS for the benefit of infants in India.

  17. The Newborn Screening Paradox: Sensitivity vs. Overdiagnosis in VLCAD Deficiency

    NARCIS (Netherlands)

    Diekman, Eugene; de Sain-van der Velden, Monique; Waterham, Hans; Kluijtmans, Leo; Schielen, Peter; van Veen, Evert Ben; Ferdinandusse, Sacha; Wijburg, Frits; Visser, Gepke

    2016-01-01

    To improve the efficacy of newborn screening (NBS) for very long chain acyl-CoA dehydrogenase deficiency (VLCADD). Data on all dried blood spots collected by the Dutch NBS from October 2007 to 2010 (742.728) were included. Based solely on the C14:1 levels (cutoff ≥0.8 μmol/L), six newborns with

  18. Conference on Newborn Hearing Screening; Proceedings Summary and Recommendations.

    Science.gov (United States)

    Alexander Graham Bell Association for the Deaf, Inc., Washington, DC.

    Presented in the conference proceedings are schedule and list of participants, seven major papers, and the newborn hearing screening recommendations of the interdisciplinary conference on newborn hearing and early identification of hearing impairment. Neonatal auditory testing is reviewed by Sanford E. Gerber, and Sheldon B. Korones gives a…

  19. Newborn bloodspot screening policy framework for Australia

    Directory of Open Access Journals (Sweden)

    Peter O'Leary

    2015-09-01

    Full Text Available Background The aim of newborn bloodspot screening (NBS is to identify rare genetic and non-genetic conditions in children soon after birth in order to commence therapies that prevent the development of progressive, serious, and irreversible disabilities. Universal NBS programmes have been implemented in most countries, with minor adaptations to target conditions most relevant to the local healthcare environment. Aims In this article, we describe the initiatives of international and Australian governments to develop policies to address the expansion of NBS in their healthcare systems. Methods We have reviewed published public policies and literature to formulate recommendations based on clinical, social, legal, and ethical principles to inform a national governance and policy framework for Australia. Results Australian policy makers have been slow to develop a coordinated plan. While the experience from other governments can guide our national policy, there are specific areas that require further consideration by Australian health experts. Key reforms involve the separation of policy and operational activities, multidisciplinary decision-making and oversight by the Australian Health Ministers’ Advisory Council for policy direction. Conclusion A formal national policy framework will guide the coordination of NBS services that can adapt to the needs of Australian children and families.

  20. Newborn screening for proximal urea cycle disorders: Current evidence supporting recommendations for newborn screening.

    Science.gov (United States)

    Merritt, J Lawrence; Brody, Linnea L; Pino, Gisele; Rinaldo, Piero

    2018-04-20

    Current newborn screening (NBS) for urea cycle disorders (UCD) is incomplete as only distal UCDs are included in most NBS programs by measuring elevated amino acid concentrations. NBS for the proximal UCDs involves the detection in NBS spots of low citrulline values, a finding which is often overlooked because it is considered to be inadequate. We retrospectively analyzed NBS blood spots from known UCD patients comparing the utility of the Region 4 Stork (R4S) interpretive tools to conventional cutoff based interpretation. This study shows the utility of R4S tools in detecting all UCDs, and provides evidence to support the nomination to add proximal UCDs to the recommended uniform screening panel. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Cost-benefit analysis: newborn screening for inborn errors of metabolism in Lebanon.

    Science.gov (United States)

    Khneisser, I; Adib, S; Assaad, S; Megarbane, A; Karam, P

    2015-12-01

    Few countries in the Middle East-North Africa region have adopted national newborn screening for inborn errors of metabolism by tandem mass spectrometry (MS/MS). We aimed to evaluate the cost-benefit of newborn screening for such disorders in Lebanon, as a model for other developing countries in the region. Average costs of expected care for inborn errors of metabolism cases as a group, between ages 0 and 18, early and late diagnosed, were calculated from 2007 to 2013. The monetary value of early detection using MS/MS was compared with that of clinical "late detection", including cost of diagnosis and hospitalizations. During this period, 126000 newborns were screened. Incidence of detected cases was 1/1482, which can be explained by high consanguinity rates in Lebanon. A reduction by half of direct cost of care, reaching on average 31,631 USD per detected case was shown. This difference more than covers the expense of starting a newborn screening programme. Although this model does not take into consideration the indirect benefits of the better quality of life of those screened early, it can be argued that direct and indirect costs saved through early detection of these disorders are important enough to justify universal publicly-funded screening, especially in developing countries with high consanguinity rates, as shown through this data from Lebanon. © The Author(s) 2015.

  2. High-throughput assay of 9 lysosomal enzymes for newborn screening.

    Science.gov (United States)

    Spacil, Zdenek; Tatipaka, Haribabu; Barcenas, Mariana; Scott, C Ronald; Turecek, Frantisek; Gelb, Michael H

    2013-03-01

    There is interest in newborn screening of lysosomal storage diseases (LSDs) because of the availability of treatments. Pilot studies have used tandem mass spectrometry with flow injection of samples to achieve multiplex detection of enzyme products. We report a multiplexing method of 9 enzymatic assays that uses HPLC-tandem mass spectrometry (MS/MS). The assay of 9 enzymes was carried out in 1 or 2 buffers with a cassette of substrates and internal standards and 1 or 2 punches of a dried blood spot (DBS) from a newborn screening card as the source of enzymes. The pre-HPLC-MS/MS sample preparation required only 4 liquid transfers before injection into a dual-column HPLC equipped with switching valves to direct the flow to separation and column equilibration. Product-specific and internal standard-specific ion fragmentations were used for MS/MS quantification in the selected reaction monitoring mode. Analysis of blood spots from 58 random newborns and lysosomal storage disease-affected patients showed that the assay readily distinguished affected from nonaffected individuals. The time per 9-plex analysis (1.8 min) was sufficiently short to be compatible with the workflow of newborn screening laboratories. HPLC-MS/MS provides a viable alternative to flow-injection MS/MS for the quantification of lysosomal enzyme activities. It is possible to assay 9 lysosomal enzymes using 1 or 2 reaction buffers, thus minimizing the number of separate incubations necessary.

  3. Screening for congenital hypothyroidism (CH) among Filipino newborn infants. Philippine Newborn Screening Study Group.

    Science.gov (United States)

    Fagela-Domingo, C; Padilla, C D; Cutiongco, E M

    1999-01-01

    From June 1996 to June 1998 a total of 62.841 newborn infants were screened for congenital hypothyroidism with thyroid stimulating hormone assay as a primary test. The method used was an immunofluorescent assay using the DELFIA TSH Kit on dried blood specimens collected by heelprick on filter paper. All infants with TSH values greater than 20 microU/ml were retested. If the results remained abnormally high, confirmatory testing was done by radioimmunoassay. All infants who were confirmed to be hypothyroid were referred to pediatric endocrinologists for initial management. The overall weighted incidence of congenital hypothyroidism obtained in this study was 0.000277 (95% CI; 0.000122 - 0.000432) or 1:3,610 which may be higher than that reported by most screening programs worldwide. The recall rate was 0.16%. The higher recall rate may be explained by early testing in a number of cases and by the possibility of iodine deficiency in some of the mothers. On the basis of the results of this study, we would recommend (1) screening on a greater number of infants to verify the incidence of CH and (2) establishing normal TSH values at different hours of life to improve our recall rate.

  4. Financing state newborn screening programs: sources and uses of funds.

    Science.gov (United States)

    Johnson, Kay; Lloyd-Puryear, Michele A; Mann, Marie Y; Ramos, Lauren Raskin; Therrell, Bradford L

    2006-05-01

    Financing for newborn screening is different from virtually all other public health programs. All except 5 screening programs collect fees as the primary source of program funding. A fee-based approach to financing newborn screening has been adopted by most states, to ensure consistent funding for this critical public health activity. Two types of data are reported here, ie, primary data from a survey of 37 state public health agencies and findings from exploratory case studies from 7 states. Most of the programs that participated in this survey (73%) reported that their newborn screening funding increased between 2002 and 2005, typically through increased fees and to a lesser extent through Medicaid, Title V Maternal and Child Health Services Block Grant, and state general revenue funding. All of the responding states that collect fees (n = 31) use such funds to support laboratory expenses, and most (70%) finance short-term follow-up services and program management. Nearly one half (47%) finance longer-term follow-up services, case management, or family support beyond diagnosis. Other states (43%) finance genetic or nutritional counseling and formula foods or treatment. Regardless of the source of funds, the available evidence indicates that states are committed to maintaining their programs and securing the necessary financing for the initial screening through diagnosis. Use of federal funding is currently limited; however, pressure to provide dedicated federal funding would likely increase if national recommendations for a uniform newborn screening panel were issued.

  5. Recommendations for newborn screening for galactokinase deficiency: A systematic review and evaluation of Dutch newborn screening data.

    Science.gov (United States)

    Stroek, Kevin; Bouva, Marelle J; Schielen, Peter C J I; Vaz, Frédéric M; Heijboer, Annemieke C; de Jonge, Robert; Boelen, Anita; Bosch, Annet M

    2018-03-21

    Galactokinase (GALK) deficiency causes cataract leading to severe developmental consequences unless treated early. Because of the easy prevention and rapid reversibility of cataract with treatment, the Dutch Health Council advised to include GALK deficiency in the Dutch newborn screening program. The aim of this study is to establish the optimal screening method and cut-off value (COV) for GALK deficiency screening by performing a systematic review of the literature of screening strategies and total galactose (TGAL) values and by evaluating TGAL values in the first week of life in a cohort of screened newborns in the Netherlands. Systematic literature search strategies in OVID MEDLINE and OVID EMBASE were developed and study selection, data collection and analyses were performed by two independent investigators. A range of TGAL values measured by the Quantase Neonatal Total Galactose screening assay in a cohort of Dutch newborns in 2007 was evaluated. Eight publications were included in the systematic review. All four studies describing screening strategies used TGAL as the primary screening marker combined with galactose-1-phosphate uridyltransferase (GALT) measurement that is used for classical galactosemia screening. TGAL COVs of 2200 μmol/L, 1665 μmol/L and 1110 μmol/L blood resulted in positive predictive values (PPV) of 100%, 82% and 10% respectively. TGAL values measured in the newborn period were reported for 39 GALK deficiency patients with individual values ranging from 3963 to 8159 μmol/L blood and 2 group values with mean 8892 μmol/L blood (SD ± 5243) and 4856 μmol/L blood (SD ± 461). Dutch newborn screening data of 72,786 newborns from 2007 provided a median TGAL value of 110 μmol/L blood with a range of 30-2431 μmol/L blood. Based on TGAL values measured in GALK deficiency patients reported in the literature and TGAL measurements in the Dutch cohort by newborn screening we suggest to perform the GALK screening with

  6. The first three years of screening for medium chain acyl-CoA dehydrogenase deficiency (MCADD by newborn screening ontario

    Directory of Open Access Journals (Sweden)

    Fisher Lawrence

    2010-11-01

    Full Text Available Abstract Background Medium chain acyl-CoA dehydrogenase deficiency (MCADD is a disorder of mitochondrial fatty acid oxidation and is one of the most common inborn errors of metabolism. Identification of MCADD via newborn screening permits the introduction of interventions that can significantly reduce associated morbidity and mortality. This study reports on the first three years of newborn screening for MCADD in Ontario, Canada. Methods Newborn Screening Ontario began screening for MCADD in April 2006, by quantification of acylcarnitines (primarily octanoylcarnitine, C8 in dried blood spots using tandem mass spectrometry. Babies with positive screening results were referred to physicians at one of five regional Newborn Screening Treatment Centres, who were responsible for diagnostic evaluation and follow-up care. Results From April 2006 through March 2009, approximately 439 000 infants were screened for MCADD in Ontario. Seventy-four infants screened positive, with a median C8 level of 0.68 uM (range 0.33-30.41 uM. Thirty-one of the screen positive infants have been confirmed to have MCADD, while 36 have been confirmed to be unaffected. Screening C8 levels were higher among infants with MCADD (median 8.93 uM compared to those with false positive results (median 0.47 uM. Molecular testing was available for 29 confirmed cases of MCADD, 15 of whom were homozygous for the common c.985A > G mutation. Infants homozygous for the common mutation tended to have higher C8 levels (median 12.13 uM relative to compound heterozygotes for c.985A > G and a second detectable mutation (median 2.01 uM. Eight confirmed mutation carriers were identified among infants in the false positive group. The positive predictive value of a screen positive for MCADD was 46%. The estimated birth prevalence of MCADD in Ontario is approximately 1 in 14 000. Conclusions The birth prevalence of MCADD and positive predictive value of the screening test were similar to those

  7. Expanded Newborn Screening for Inborn Errors of Metabolism and Genetic Characteristics in a Chinese Population

    Directory of Open Access Journals (Sweden)

    Kejian Guo

    2018-04-01

    Full Text Available The incidence of inborn errors of metabolisms (IEMs varies dramatically in different countries and regions. Expanded newborn screening for IEMs by tandem mass spectrometry (MS/MS is an efficient approach for early diagnosis and presymptomatic treatment to prevent severe permanent sequelae and death. To determine the characteristics of IEMs and IEMs-associated mutations in newborns in Jining area, China, 48,297 healthy neonates were recruited for expanded newborn screening by MS/MS. The incidence of IEMs was 1/1178 in Jining, while methylmalonic acidemia, phenylketonuria, and primary carnitine deficiency ranked the top 3 of all detected IEMs. Thirty mutations in nine IEMs-associated genes were identified in 28 confirmed cases. As 19 cases with the mutations in phenylalanine hydroxylase (PAH, solute carrier family 22 member 5 (SLC22A5, and methylmalonic aciduria (cobalamin deficiency cblC type with homocystinuria (MMACHC genes, respectively, it suggested that mutations in the PAH, SLC22A5, and MMACHC genes are the predominant causes of IEMs, leading to the high incidence of phenylketonuria, primary carnitine deficiency, and methylmalonic acidemia, respectively. Our work indicated that the overall incidence of IEMs is high and the mutations in PAH, SLC22A5, and MMACHC genes are the leading causes of IEMs in Jining area. Therefore, it is critical to increase the coverage of expanded newborn screening by MS/MS and prenatal genetic consulting in Jining area.

  8. Students as Technicians: Screening Newborns for Cystic Fibrosis

    Science.gov (United States)

    Gusky, Sharon

    2014-01-01

    In this activity, freshman college students learn biotechnology techniques while playing the role of a laboratory technician. They perform simulations of three diagnostic tests used to screen newborns for cystic fibrosis. By performing an ELISA, a PCR analysis, and a conductivity test, students learn how biotechnology techniques can be used to…

  9. Newborn screening for classic galactosemia and primary congenital ...

    African Journals Online (AJOL)

    Objectives. The main objective of this work was to establish the incidence of classic galactosaemia and primary congenital hypothyroidism in newborns in the Nkangala district of Mpumalanga. In the process a cost-effective protocol for neonatal screening of both diseases was developed. Study design and setting.

  10. Newborn Hearing Screening: An Analysis of Current Practices

    Science.gov (United States)

    Houston, K. Todd; Bradham, Tamala S.; Munoz, Karen F.; Guignard, Gayla Hutsell

    2011-01-01

    State coordinators of early hearing detection and intervention (EHDI) programs completed a strengths, weaknesses, opportunities, and threats, or SWOT, analysis that consisted of 12 evaluative areas of EHDI programs. For the newborn hearing screening area, a total of 293 items were listed by 49 EHDI coordinators, and themes were identified within…

  11. Lower neonatal screening thyroxine concentrations in Down syndrome newborns

    NARCIS (Netherlands)

    van Trotsenburg, A. S. P.; Vulsma, T.; van Santen, H. M.; Cheung, W.; de Vijlder, J. J. M.

    2003-01-01

    There is an unexplained higher incidence of congenital hypothyroidism (CH) detected by T-4-based neonatal screening programs and a very high prevalence of (mild) plasma TSH elevation in young children with Down syndrome (DS). To determine whether newborns with DS have decreased blood T-4

  12. Screening of newborns for congenital hypothyroidism. Guidance for developing programmes

    International Nuclear Information System (INIS)

    2005-12-01

    Congenital hypothyroidism is a condition that, if left untreated, can cause lifelong human suffering as a result of severe mental retardation and deficiency of growth. With the involvement of the IAEA, screening programmes to detect congenital hypothyroidism in newborn infants have been introduced successfully in a large number of countries. The cornerstone of these programmes is accurate and reliable screening methods involving isotope techniques and simple medical treatment. The suffering - and heavy social and economic burden - caused by congenital hypothyroidism prompted many countries to institute a formalized screening programme directed at newborns, just as a vaccination programme has become an integral part of child health care. In many other countries however, this type of formalized service has not yet been established. For these countries, the implementation of a neonatal screening programme will bring about a considerable improvement in child health care. It is hoped that the guidance in this publication will be especially useful to the signatories of the United Nations Convention on the Rights of the Child. Several factors that prevail in a country - the climate, political environment, economic development, level of health care and the transportation system - have an influence on the overall operational systems, design and implementation of a screening programme. As such, the design of such a programme will differ greatly from country to country. Nevertheless, neonatal screening programmes have many elements in common. This book draws on the IAEA's experience in this area over more than a decade, and on the results of a regional technical cooperation programme on neonatal screening for congenital hypothyroidism in East Asia (IAEA Project RAS6032). This publication provides guidance aimed specifically at implementing and sustaining programmes for the screening of newborn infants

  13. Holocarboxylase synthetase deficiency pre and post newborn screening

    Directory of Open Access Journals (Sweden)

    Taraka R. Donti

    2016-06-01

    Full Text Available Holocarboxylase synthetase deficiency is an autosomal recessive disorder of biotin metabolism resulting in multiple carboxylase deficiency. The typical presentation described in the medical literature is of neonatal onset within hours to weeks of birth with emesis, hypotonia, lethargy, seizures, metabolic ketolactic acidosis, hyperammonemia, developmental delay, skin rash and alopecia. The condition is screened for by newborn screening (NBS tandem mass spectroscopy by elevated hydroxypentanoylcarnitine on dried blood spots. Urine organic acid profile may demonstrate elevated lactic, 3-OH isovaleric, 3-OH propionic, 3-MCC, methylcitric acids, and tiglylglycine consistent with loss of function of the above carboxylases. Here we describe a cohort of patients, 2 diagnosed pre-NBS and 3 post-NBS with broad differences in initial presentation and phenotype. In addition, prior to the advent of NBS, there are isolated reports of late-onset holocarboxylase synthetase deficiency in the medical literature, which describe patients diagnosed between 1 and 8 years of life, however to our knowledge there are no reports of late-onset HCLS being missed by NBS. Also we report two cases, each with novel pathogenic variants HCLS, diagnosed at age 3 years and 21 months respectively. The first patient had a normal newborn screen whilst the second had an abnormal newborn screen but was misdiagnosed as 3-methylcrotonylcarboxylase (3-MCC deficiency and subsequently lost to follow-up until they presented again with severe metabolic acidosis.

  14. Congenital cytomegalovirus infection: disease burden and screening tools : towards newborn screening

    OpenAIRE

    Vries, Jutte Jacoba Catharina de

    2012-01-01

    Cytomegalovirus (CMV) infection is the most common congenital viral infection worldwide. The symptom of congenital CMV infection encountered most frequently is sensorineural hearing loss, which will affect approximately one out of five congenitally infected newborns. Because of the late-onset nature of the hearing loss, up to half of the children with congenital CMV-related hearing loss may not be detected in the newborn hearing screening. This thesis addresses several aspects of congenital CM...

  15. A Rare Case of Malonic Aciduria Diagnosed by Newborn Screening in Qatar

    Directory of Open Access Journals (Sweden)

    Mamatha Ramaswamy

    2017-03-01

    Full Text Available Malonic aciduria is a rare autosomal recessive organic acid disorder. With the widespread use of tandem mass spectrometry for analysis of the amino acid/acylcarnitine profile on dried blood spots for newborn screening (NBS, this condition can be readily diagnosed and can be included in the organic acid screen in NBS programs. In Qatar, we report the first case of an asymptomatic baby screened and diagnosed with malonic aciduria through NBS. This patient has a genetic variant of malonyl-CoA decarboxylase that has not been previously reported in the literature. This condition should be differentiated from a similar disorder, combined malonic and methylmalonic aciduria. The clinical phenotype of malonic aciduria is variable and the pathophysiology is not fully understood. There is no established guidance or recommendations regarding the appropriate treatment regimen, dietary therapy or regular follow-up of these patients. Most available evidence for treatment is based on a single study or case report.

  16. The Milan Project: a newborn hearing screening programme.

    Science.gov (United States)

    Pastorino, Giancarlo; Sergi, Paola; Mastrangelo, Massimo; Ravazzani, Paolo; Tognola, Gabriella; Parazzini, Marta; Mosca, Fabio; Pugni, Lorenza; Grandori, Ferdinando

    2005-04-01

    Since 1997 a newborn hearing screening programme has been implemented by the U.O. Neurologia-Neurofisiopatologia and Dipartimento di Neonatologia of the Istituti Clinici di Perfezionamento ICP in Milan for both babies with no risk and those at risk of hearing impairment. This programme was named the Milan Project. The protocol for no-risk babies consisted of three stages: in the first two stages, newborns were tested with transient click-evoked otoacoustic emissions (TEOAE), in the third one with conventional auditory brainstem responses (ABR). The first TEOAE test was performed by 36 h of age, before discharge, the second one after 15-30 d in case of referral, and the third one, by ABR, for those babies who failed the second TEOAE stage. Newborns at audiological risk were submitted to conventional ABR before the third month of corrected age. Some of this latter population was also submitted to the TEOAE test. The entire tested population (no-risk babies and newborns at audiological risk) consisted of 19 777 babies: 19 290 without risk ("no risk") and 487 at risk ("at risk"). During the course of the Milan Project, hearing impairment (ABR threshold equal to or greater than 40 dB nHL) was identified in 63 newborns (19 from the no-risk and 44 from the at-risk population), with a prevalence of 0.32%. Bilateral hearing impairment (BHI) was found in 33 newborns (10 from the no-risk and 23 from the at-risk population), corresponding to 0.17%. Among infants with bilateral hearing impairment, 30.3% had no risk factors. The prevalence of hearing impairment was determined on days 15-30 after birth. The results show that the implementation of a hospital-based, universal neonatal hearing screening programme for babies with and without audiological risk is feasible and effective. The effectiveness of the programme has increased as a function of the years since its inception, with a strong decrease in the referral rate. Further improvement is obtained if the TEOAE measurements

  17. Newborn Screening for Severe Combined Immunodeficiency in 11 Screening Programs in the United States

    Science.gov (United States)

    Kwan, Antonia; Abraham, Roshini S.; Currier, Robert; Brower, Amy; Andruszewski, Karen; Abbott, Jordan K.; Baker, Mei; Ballow, Mark; Bartoshesky, Louis E.; Bonagura, Vincent R.; Bonilla, Francisco A.; Brokopp, Charles; Brooks, Edward; Caggana, Michele; Celestin, Jocelyn; Church, Joseph A.; Comeau, Anne Marie; Connelly, James A.; Cowan, Morton J.; Cunningham-Rundles, Charlotte; Dasu, Trivikram; Dave, Nina; De La Morena, Maria T.; Duffner, Ulrich; Fong, Chin-To; Forbes, Lisa; Freedenberg, Debra; Gelfand, Erwin W.; Hale, Jaime E.; Celine Hanson, I.; Hay, Beverly N.; Hu, Diana; Infante, Anthony; Johnson, Daisy; Kapoor, Neena; Kay, Denise M.; Kohn, Donald B.; Lee, Rachel; Lehman, Heather; Lin, Zhili; Lorey, Fred; Abdel-Mageed, Aly; Manning, Adrienne; McGhee, Sean; Moore, Theodore B.; Naides, Stanley J.; Notarangelo, Luigi D.; Orange, Jordan S.; Pai, Sung-Yun; Porteus, Matthew; Rodriguez, Ray; Romberg, Neil; Routes, John; Ruehle, Mary; Rubenstein, Arye; Saavedra-Matiz, Carlos A.; Scott, Ginger; Scott, Patricia M.; Secord, Elizabeth; Seroogy, Christine; Shearer, William T.; Siegel, Subhadra; Silvers, Stacy K.; Stiehm, E. Richard; Sugerman, Robert W.; Sullivan, John L.; Tanksley, Susan; Tierce, Millard L.; Verbsky, James; Vogel, Beth; Walker, Rosalyn; Walkovich, Kelly; Walter, Jolan E.; Wasserman, Richard L.; Watson, Michael S.; Weinberg, Geoffrey A.; Weiner, Leonard B.; Wood, Heather; Yates, Anne B.; Puck, Jennifer M.

    2015-01-01

    IMPORTANCE Newborn screening for severe combined immunodeficiency (SCID) using assays to detect T-cell receptor excision circles (TRECs) began in Wisconsin in 2008, and SCID was added to the national recommended uniform panel for newborn screened disorders in 2010. Currently 23 states, the District of Columbia, and the Navajo Nation conduct population-wide newborn screening for SCID. The incidence of SCID is estimated at 1 in 100 000 births. OBJECTIVES To present data from a spectrum of SCID newborn screening programs, establish population-based incidence for SCID and other conditions with T-cell lymphopenia, and document early institution of effective treatments. DESIGN Epidemiological and retrospective observational study. SETTING Representatives in states conducting SCID newborn screening were invited to submit their SCID screening algorithms, test performance data, and deidentified clinical and laboratory information regarding infants screened and cases with nonnormal results. Infants born from the start of each participating program from January 2008 through the most recent evaluable date prior to July 2013 were included. Representatives from 10 states plus the Navajo Area Indian Health Service contributed data from 3 030 083 newborns screened with a TREC test. MAIN OUTCOMES AND MEASURES Infants with SCID and other diagnoses of T-cell lymphopenia were classified. Incidence and, where possible, etiologies were determined. Interventions and survival were tracked. RESULTS Screening detected 52 cases of typical SCID, leaky SCID, and Omenn syndrome, affecting 1 in 58 000 infants (95%CI, 1/46 000-1/80 000). Survival of SCID-affected infants through their diagnosis and immune reconstitution was 87%(45/52), 92%(45/49) for infants who received transplantation, enzyme replacement, and/or gene therapy. Additional interventions for SCID and non-SCID T-cell lymphopenia included immunoglobulin infusions, preventive antibiotics, and avoidance of live vaccines. Variations in

  18. Newborn Screening in the Era of Precision Medicine.

    Science.gov (United States)

    Yang, Lan; Chen, Jiajia; Shen, Bairong

    2017-01-01

    As newborn screening success stories gained general confirmation during the past 50 years, scientists quickly discovered diagnostic tests for a host of genetic disorders that could be treated at birth. Outstanding progress in sequencing technologies over the last two decades has made it possible to comprehensively profile newborn screening (NBS) and identify clinically relevant genomic alterations. With the rapid developments in whole-genome sequencing (WGS) and whole-exome sequencing (WES) recently, we can detect newborns at the genomic level and be able to direct the appropriate diagnosis to the different individuals at the appropriate time, which is also encompassed in the concept of precision medicine. Besides, we can develop novel interventions directed at the molecular characteristics of genetic diseases in newborns. The implementation of genomics in NBS programs would provide an effective premise for the identification of the majority of genetic aberrations and primarily help in accurate guidance in treatment and better prediction. However, there are some debate correlated with the widespread application of genome sequencing in NBS due to some major concerns such as clinical analysis, result interpretation, storage of sequencing data, and communication of clinically relevant mutations to pediatricians and parents, along with the ethical, legal, and social implications (so-called ELSI). This review is focused on these critical issues and concerns about the expanding role of genomics in NBS for precision medicine. If WGS or WES is to be incorporated into NBS practice, considerations about these challenges should be carefully regarded and tackled properly to adapt the requirement of genome sequencing in the era of precision medicine.

  19. Mass spectrometry for fragment screening.

    Science.gov (United States)

    Chan, Daniel Shiu-Hin; Whitehouse, Andrew J; Coyne, Anthony G; Abell, Chris

    2017-11-08

    Fragment-based approaches in chemical biology and drug discovery have been widely adopted worldwide in both academia and industry. Fragment hits tend to interact weakly with their targets, necessitating the use of sensitive biophysical techniques to detect their binding. Common fragment screening techniques include differential scanning fluorimetry (DSF) and ligand-observed NMR. Validation and characterization of hits is usually performed using a combination of protein-observed NMR, isothermal titration calorimetry (ITC) and X-ray crystallography. In this context, MS is a relatively underutilized technique in fragment screening for drug discovery. MS-based techniques have the advantage of high sensitivity, low sample consumption and being label-free. This review highlights recent examples of the emerging use of MS-based techniques in fragment screening. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  20. False negative newborn screen and neonatal cholestasis in a premature child with cystic fibrosis

    NARCIS (Netherlands)

    Heidendael, J. F.; Tabbers, M. M.; de Vreede, I.

    2014-01-01

    Newborn screening for cystic fibrosis enables early diagnosis and treatment, leading to better outcomes for patients with cystic fibrosis. Although the sensitivity of several screening protocols is high, false negative screening results of the newborn patient still occur, which can lead to a

  1. Maintaining trust in newborn screening: compliance and informed consent in the Netherlands.

    NARCIS (Netherlands)

    Burg, S. van der; Verweij, M.

    2012-01-01

    Newborn screening consists of taking a few drops of blood from a baby's heel in the first week of life and testing it for a list of disorders. In the United States and most countries in Europe, newborn screening programs began in the 1960s and 1970s with screening for phenylketonuria (PKU), a rare

  2. Newborn screening for congenital hypothyroidism in Henan province, China.

    Science.gov (United States)

    Zhao, De-Hua; Shen, Yong; Gong, Jiao-Mei; Meng, Yun; Su, Li; Zhang, Xia

    2016-01-15

    Congenital hypothyroidism is the most common congenital endocrine disorder. The study aimed to determine the congenital hypothyroidism incidence by newborn screening programs in Henan Province, China. The screening programs for congenital hypothyroidism are based on the measurement of TSH in dried blood spots. The TSH concentration was measured in the dry blood spot specimen using a DELFIA fluoroimmunoassay. The TSH cutoff concentration was 8mU/l. The total coverage and the incidence of congenital hypothyroidism were 24.85% (5,142,148/20,694,441) and 0.37‰ (1992/5,142,148), respectively. The coverage and the incidence of CH were only 0.58% (4526/784,580) and 0.22‰ (1/4526) in 1997, respectively. However, the coverage and the incidence of CH were increased to 74.67% (1,203,278/1,611,582) and 0.32‰ (389/1,203,278). There were no significant differences in the number of congenital hypothyroidism between males and females (P>0.05). The number of congenital hypothyroidism was increased year after year. The newborn screening program for CH is successful and quite effective. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Incidence of severe combined immunodeficiency through newborn screening in a Chinese population

    Directory of Open Access Journals (Sweden)

    Yin-Hsiu Chien

    2015-01-01

    Conclusion: Newborn screening to measure the number of TREC copies successfully identifies newborns with T-cell lymphopenia, 22q11.2 microdeletion syndrome, and other high-risk conditions. Taken together, the incidence of T-cell lymphopenia in apparently healthy newborns is more than 1 in 11,821, and further attention to their immune functions is warranted.

  4. Newborn Screening for Severe Combined Immunodeficiency in Israel

    Directory of Open Access Journals (Sweden)

    Erez Rechavi

    2017-06-01

    Full Text Available Newborn screening (NBS programs for severe combined immunodeficiency (SCID, the most severe type of primary immunodeficiency, are being implemented in more and more countries with every passing year. Since October 2015, SCID screening via T cell receptor excision circle (TREC quantification in dried blood spots (DBS has been part of the Israeli NBS program. As an NBS program in its infancy, SCID screening is still evolving, making gathering input from the various programs crucial for compiling an ideal screening algorithm. The relatively high rate of consanguineous marriages in Israel, especially among non-Jews, correlates with an increased incidence of SCID. The Israeli algorithm uses a commercial kit and consists of a two-Guthrie card confirmation system prior to referral to a national immunology center. Preliminary data from the first year and a half of SCID screening in Israel has identified a surprisingly high prevalence of DNA cross-link repair protein 1c (DCLRE1C; ARTEMIS mutations as the cause of SCID in Israel. The clinically unbiased nature of SCID screening helps unearth mild/leaky SCID phenotypes, resulting in a better understanding of true SCID prevalence and etiology.

  5. A Targeted Approach for Congenital Cytomegalovirus Screening Within Newborn Hearing Screening.

    Science.gov (United States)

    Fowler, Karen B; McCollister, Faye P; Sabo, Diane L; Shoup, Angela G; Owen, Kris E; Woodruff, Julie L; Cox, Edith; Mohamed, Lisa S; Choo, Daniel I; Boppana, Suresh B

    2017-02-01

    Congenital cytomegalovirus (cCMV) infection remains a leading cause of childhood hearing loss. Currently universal CMV screening at birth does not exist in the United States. An alternative approach could be testing infants who do not pass their newborn hearing screening (NHS) for cCMV. This study was undertaken to evaluate whether a targeted approach will identify infants with CMV-related sensorineural hearing loss (SNHL). Infants born at 7 US medical centers received NHS and were also screened for cCMV while in the newborn nursery. Infants who tested positive for CMV received further diagnostic audiologic evaluations to identify or confirm hearing loss. Between 2007 and 2012, 99 945 newborns were screened for both hearing impairment and cCMV. Overall, 7.0% of CMV-positive infants did not pass NHS compared with 0.9% of CMV-negative infants (P CMV-infected infants who passed their NHS had SNHL confirmed by further evaluation during early infancy. NHS in this cohort identified 57% of all CMV-related SNHL that occurred in the neonatal period. A targeted CMV approach that tests newborns who fail their NHS identified the majority of infants with CMV-related SNHL at birth. However, 43% of the infants with CMV-related SNHL in the neonatal period and cCMV infants who are at risk for late onset SNHL were not identified by NHS. Copyright © 2017 by the American Academy of Pediatrics.

  6. Screening for C3 deficiency in newborns using microarrays.

    Directory of Open Access Journals (Sweden)

    Magdalena Janzi

    Full Text Available BACKGROUND: Dried blood spot samples (DBSS from newborns are widely used in neonatal screening for selected metabolic diseases and diagnostic possibilities for additional disorders are continuously being evaluated. Primary immunodeficiency disorders comprise a group of more than one hundred diseases, several of which are fatal early in life. Yet, a majority of the patients are not diagnosed due to lack of high-throughput screening methods. METHODOLOGY/PRINCIPAL FINDINGS: We have previously developed a system using reverse phase protein microarrays for analysis of IgA levels in serum samples. In this study, we extended the applicability of the method to include determination of complement component C3 levels in eluates from DBSS collected at birth. Normal levels of C3 were readily detected in 269 DBSS from healthy newborns, while no C3 was detected in sera and DBSS from C3 deficient patients. CONCLUSIONS/SIGNIFICANCE: The findings suggest that patients with deficiencies of specific serum proteins can be identified by analysis of DBSS using reverse phase protein microarrays.

  7. Assessing the Fragile X Syndrome Newborn Screening Landscape.

    Science.gov (United States)

    Riley, Catharine; Wheeler, Anne

    2017-06-01

    Fragile X syndrome (FXS) is the most common known inherited form of intellectual disability. Early identification is an important step in linking FXS individuals with appropriate and timely medical and social services. Newborn screening (NBS) is 1 approach that has been used for other conditions to facilitate early identification. A literature review was conducted to identify issues, barriers, challenges, and approaches to addressing challenges related to NBS for FXS. Search terms included: fragile X syndrome, FMR1, newborn screening, screening, and genetic testing. To supplement the literature review, 9 key informant interviews were conducted. Information gathered through these interviews supplemented what was identified in the literature. Information from both the literature review and supplemental interviews was reviewed by 3 researchers who discussed and came to consensus on thematic areas and categorization of issues. The barriers and challenges related to NBS for FXS identified in the literature and by experts and stakeholders are categorized into 5 thematic areas: public health burden, treatment, timing, screening/testing methodologies, and translating results. Summaries of these issues and barriers are provided, along with potential approaches to addressing them. The issues and barriers described in this article highlight limited areas of knowledge that need be addressed to improve our understanding of FXS and the potential benefit of NBS. The landscape of NBS for FXS could be influenced by a series of research findings over time or a larger breakthrough that demonstrates an effective targeted treatment that has to be implemented early in life. Copyright © 2017 by the American Academy of Pediatrics.

  8. Expanded Newborn Screening Program in Saudi Arabia: Incidence of screened disorders.

    Science.gov (United States)

    Alfadhel, Majid; Al Othaim, Ali; Al Saif, Saif; Al Mutairi, Fuad; Alsayed, Moeenaldeen; Rahbeeni, Zuhair; Alzaidan, Hamad; Alowain, Mohammed; Al-Hassnan, Zuhair; Saeedi, Mohamad; Aljohery, Saeed; Alasmari, Ali; Faqeih, Eissa; Alwakeel, Mansour; AlMashary, Maher; Almohameed, Sulaiman; Alzahrani, Mohammed; Migdad, Abeer; Al-Dirbashi, Osama Y; Rashed, Mohamed; Alamoudi, Mohamed; Jacob, Minnie; Alahaidib, Lujane; El-Badaoui, Fahd; Saadallah, Amal; Alsulaiman, Ayman; Eyaid, Wafaa; Al-Odaib, Ali

    2017-06-01

    To address the implementation of the National Newborn Screening Program (NBS) in Saudi Arabia and stratify the incidence of the screened disorders. A retrospective study conducted between 1 August 2005 and 31 December 2012, total of 775 000 newborns were screened from 139 hospitals distributed among all regions of Saudi Arabia. The NBS Program screens for 16 disorders from a selective list of inborn errors of metabolism (IEM) and endocrine disorders. Heel prick dry blood spot samples were obtained from all newborns for biochemical and immunoassay testing. Recall screening testing was performed for Initial positive results and confirmed by specific biochemical assays. A total of 743 cases were identified giving an overall incidence of 1:1043. Frequently detected disorders nationwide were congenital hypothyroidism and congenital adrenal hyperplasia with an incidence of 1:7175 and 1:7908 correspondingly. The highest incidence among the IEM was propionic acidaemia with an incidence rate of 1:14 000. The article highlights the experience of the NBS Program in Saudi Arabia and providing data on specific regional incidences of all the screened disorders included in the programme; and showed that the incidence of these disorders is one of the highest reported so far world-wide. © 2017 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

  9. Abnormal Newborn Screening in a Healthy Infant of a Mother with Undiagnosed Medium-Chain Acyl-CoA Dehydrogenase Deficiency

    DEFF Research Database (Denmark)

    Aksglaede, Lise; Christensen, Mette; Olesen, Jes

    2015-01-01

    A neonate with low blood free carnitine level on newborn tandem mass spectrometry screening was evaluated for possible carnitine transporter defect (CTD). The plasma concentration of free carnitine was marginally reduced, and the concentrations of acylcarnitines (including C6, C8, and C10:1) were...

  10. The Newborn Screening Paradox: Sensitivity vs. Overdiagnosis in VLCAD Deficiency.

    Science.gov (United States)

    Diekman, Eugene; de Sain-van der Velden, Monique; Waterham, Hans; Kluijtmans, Leo; Schielen, Peter; van Veen, Evert Ben; Ferdinandusse, Sacha; Wijburg, Frits; Visser, Gepke

    2016-01-01

    To improve the efficacy of newborn screening (NBS) for very long chain acyl-CoA dehydrogenase deficiency (VLCADD). Data on all dried blood spots collected by the Dutch NBS from October 2007 to 2010 (742.728) were included. Based solely on the C14:1 levels (cutoff ≥0.8 μmol/L), six newborns with VLCADD had been identified through NBS during this period. The ratio of C14:1 over C2 was calculated. DNA of all blood spots with a C14:1/C2 ratio of ≥0.020 was isolated and sequenced. Children homozygous or compound heterozygous for mutations in the ACADVL gene were traced back and invited for detailed clinical, biochemical, and genetic evaluation. Retrospective analysis based on the C14:1/C2 ratio with a cutoff of ≥0.020 identified an additional five children with known ACADVL mutations and low enzymatic activity. All were still asymptomatic at the time of diagnosis (age 2-5 years). Increasing the cutoff to ≥0.023 resulted in a sensitivity of 93% and a positive predictive value of 37%. The sensitivity of the previously used screening approach (C14:1 ≥0.8) was 50%. This study shows that the ratio C14:1/C2 is a more sensitive marker than C14:1 for identifying VLCADD patients in NBS. However, as these patients were all asymptomatic at the time of diagnosis, this suggests that a more sensitive screening approach may also identify individuals who may never develop clinical disease. Long-term follow-up studies are needed to establish the risk of these VLCADD-deficient individuals for developing clinical signs and symptoms.

  11. Fostering caring relationships: Suggestions to rethink liberal perspectives on the ethics of newborn screening

    NARCIS (Netherlands)

    Burg, S. van der; Oerlemans, A.J.M.

    2018-01-01

    Newborn screening (NBS) involves the collection of blood from the heel of a newborn baby and testing it for a list of rare and inheritable disorders. New biochemical screening technologies led to expansions of NBS programs in the first decade of the 21st century. It is expected that they will in

  12. Cost-effectiveness analysis of universal newborn screening for medium chain acyl-CoA dehydrogenase deficiency in France

    Directory of Open Access Journals (Sweden)

    Hamers Françoise F

    2012-06-01

    Full Text Available Abstract Background Five diseases are currently screened on dried blood spots in France through the national newborn screening programme. Tandem mass spectrometry (MS/MS is a technology that is increasingly used to screen newborns for an increasing number of hereditary metabolic diseases. Medium chain acyl-CoA dehydrogenase deficiency (MCADD is among these diseases. We sought to evaluate the cost-effectiveness of introducing MCADD screening in France. Methods We developed a decision model to evaluate, from a societal perspective and a lifetime horizon, the cost-effectiveness of expanding the French newborn screening programme to include MCADD. Published and, where available, routine data sources were used. Both costs and health consequences were discounted at an annual rate of 4%. The model was applied to a French birth cohort. One-way sensitivity analyses and worst-case scenario simulation were performed. Results We estimate that MCADD newborn screening in France would prevent each year five deaths and the occurrence of neurological sequelae in two children under 5 years, resulting in a gain of 128 life years or 138 quality-adjusted life years (QALY. The incremental cost per year is estimated at €2.5 million, down to €1 million if this expansion is combined with a replacement of the technology currently used for phenylketonuria screening by MS/MS. The resulting incremental cost-effectiveness ratio (ICER is estimated at €7 580/QALY. Sensitivity analyses indicate that while the results are robust to variations in the parameters, the model is most sensitive to the cost of neurological sequelae, MCADD prevalence, screening effectiveness and screening test cost. The worst-case scenario suggests an ICER of €72 000/QALY gained. Conclusions Although France has not defined any threshold for judging whether the implementation of a health intervention is an efficient allocation of public resources, we conclude that the expansion of the French

  13. Cost-effectiveness analysis of universal newborn screening for medium chain acyl-CoA dehydrogenase deficiency in France.

    Science.gov (United States)

    Hamers, Françoise F; Rumeau-Pichon, Catherine

    2012-06-08

    Five diseases are currently screened on dried blood spots in France through the national newborn screening programme. Tandem mass spectrometry (MS/MS) is a technology that is increasingly used to screen newborns for an increasing number of hereditary metabolic diseases. Medium chain acyl-CoA dehydrogenase deficiency (MCADD) is among these diseases. We sought to evaluate the cost-effectiveness of introducing MCADD screening in France. We developed a decision model to evaluate, from a societal perspective and a lifetime horizon, the cost-effectiveness of expanding the French newborn screening programme to include MCADD. Published and, where available, routine data sources were used. Both costs and health consequences were discounted at an annual rate of 4%. The model was applied to a French birth cohort. One-way sensitivity analyses and worst-case scenario simulation were performed. We estimate that MCADD newborn screening in France would prevent each year five deaths and the occurrence of neurological sequelae in two children under 5 years, resulting in a gain of 128 life years or 138 quality-adjusted life years (QALY). The incremental cost per year is estimated at €2.5 million, down to €1 million if this expansion is combined with a replacement of the technology currently used for phenylketonuria screening by MS/MS. The resulting incremental cost-effectiveness ratio (ICER) is estimated at €7 580/QALY. Sensitivity analyses indicate that while the results are robust to variations in the parameters, the model is most sensitive to the cost of neurological sequelae, MCADD prevalence, screening effectiveness and screening test cost. The worst-case scenario suggests an ICER of €72 000/QALY gained. Although France has not defined any threshold for judging whether the implementation of a health intervention is an efficient allocation of public resources, we conclude that the expansion of the French newborn screening programme to MCADD would appear to be cost

  14. Results of a Targeted Screening Program for Congenital Cytomegalovirus Infection in Infants Who Fail Newborn Hearing Screening.

    Science.gov (United States)

    Vancor, Emily; Shapiro, Eugene D; Loyal, Jaspreet

    2018-01-24

    Congenital cytomegalovirus (CMV) infection is a major cause of sensorineural hearing loss. By law, newborns in Connecticut who fail newborn hearing screening are tested for infection with CMV. This targeted screening is controversial, because most children with congenital CMV infection are asymptomatic, and CMV-related hearing loss can have a delayed onset. Our hospital uses a saliva polymerase chain reaction (PCR) assay (confirmed by a urine PCR assay) to detect CMV. Here, we report the results of the first year of our screening program. We reviewed the medical records of newborns in the Yale New Haven Health System who failed the newborn hearing screening test between January 1 and December 31, 2016. Of 10964 newborns, 171 failed newborn hearing screening, and 3 of these newborns had positive saliva CMV PCR test results. Of these 3 newborns, 2 had positive results on the confirmatory test (for 1 of them the confirmatory test was not performed until the infant was 10 weeks old), and 1 had a negative result on the confirmatory test. Three additional newborns with congenital CMV infection were tested because of clinical indications (1 for ventriculomegaly on prenatal ultrasound and 2 for CMV infection of the mother). Results of audiology follow-up were available for 149 (87.1%) of the 171 newborns who failed newborn hearing screening; 127 (85.2%) had normal results. Our targeted screening program for congenital CMV infection had a low yield. Consideration should be given to other strategies for identifying children at risk of hearing loss as a result of congenital CMV infection. © The Author(s) 2018. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Data integration and warehousing: coordination between newborn screening and related public health programs.

    Science.gov (United States)

    Therrell, Bradford L

    2003-01-01

    At birth, patient demographic and health information begin to accumulate in varied databases. There are often multiple sources of the same or similar data. New public health programs are often created without considering data linkages. Recently, newborn hearing screening (NHS) programs and immunization programs have virtually ignored the existence of newborn dried blood spot (DBS) newborn screening databases containing similar demographic data, creating data duplication in their 'new' systems. Some progressive public health departments are developing data warehouses of basic, recurrent patient information, and linking these databases to other health program databases where programs and services can benefit from such linkages. Demographic data warehousing saves time (and money) by eliminating duplicative data entry and reducing the chances of data errors. While newborn screening data are usually the first data available, they should not be the only data source considered for early data linkage or for populating a data warehouse. Birth certificate information should also be considered along with other data sources for infants that may not have received newborn screening or who may have been born outside of the jurisdiction and not have birth certificate information locally available. This newborn screening serial number provides a convenient identification number for use in the DBS program and for linking with other systems. As a minimum, data linkages should exist between newborn dried blood spot screening, newborn hearing screening, immunizations, birth certificates and birth defect registries.

  16. Improving regional universal newborn hearing screening programmes in Italy.

    Science.gov (United States)

    Molini, E; Cristi, M C; Lapenna, R; Calzolaro, L; Muzzi, E; Ciciriello, E; Della Volpe, A; Orzan, E; Ricci, G

    2016-02-01

    The Universal Newborn Hearing Screening (UNHS) programme aims at achieving early detection of hearing impairment. Subsequent diagnosis and intervention should follow promptly. Within the framework of the Ministry of Health project CCM 2013 "Preventing Communication Disorders: a Regional Program for early Identification, Intervention and Care of Hearing Impaired Children", the limitations and strengths of current UNHS programs in Italy have been analysed by a group of professionals working in tertiary centres involved in regional UNHS programmes, using SWOT analysis and a subsequent TOWS matrix. Coverage and lost-to-follow up rates are issues related to UNHS programmes. Recommendations to improve the effectiveness of the UNHS programme have been identified. The need for homogeneous policies, high-quality information and dissemination of knowledge for operators and families of hearing-impaired children emerged from the discussion. © Copyright by Società Italiana di Otorinolaringologia e Chirurgia Cervico-Facciale.

  17. Understanding Midwives’ Preferences for Providing Information About Newborn Bloodspot Screening

    Directory of Open Access Journals (Sweden)

    Stuart James Wright

    2018-01-01

    Full Text Available Background: Understanding preferences for information provision in the context of health care service provision is challenging because of the number of potential attributes that may influence preferences. This study aimed to identify midwives’ preferences for the process and outcomes of information provision in an expanded national newborn bloodspot screening program. Design: A sample of practicing midwives completed a hybrid-stated preference survey including a conjoint analysis (CA and discrete choice experiment to quantify preferences for the types of, and way in which, information should be provided in a newborn bloodspot screening program. Six conjoint analysis questions captured the impact of different types of information on parents’ ability to make a decision, and 10 discrete choice experiment questions identified preferences for four process attributes (including parents’ ability to make a decision. Results: Midwives employed by the UK National Health Service (n = 134 completed the survey. All types of information content were perceived to improve parents’ ability to make a decision except for the possibility of false-positive results. Late pregnancy was seen to be the best time to provide information, followed by day 3 postbirth. Information before 20 weeks of pregnancy was viewed as reducing parents’ ability to make a decision. Midwives preferred information to be provided by an individual discussion and did not think parents should receive information on the Internet. Conclusion: A hybrid stated preference survey design identified that a wide variety of information should be provided to maximize parents’ ability to make a decision ideally provided late in pregnancy or on day 3 postbirth.

  18. Newborn screening for congenital hypothyroidism in a public sector hospital

    International Nuclear Information System (INIS)

    Ghafoor, F.; Mohsin, S.N.; Mukhtar, S.; Hussain, W.

    2013-01-01

    Background: Congenital hypothyroidism if left untreated results in growth failure, irreversible mental retardation, and cretinism. National neonatal screening programs are therefore, launched to diagnose congenital hypothyroidism and manage it timely. Objectives: To screen new borns for congenital hypothyroidism in two public sector hospitals of Lahore. Study type, settings and duration:Cross sectional descriptive study conducted at departments of Gynae/Obs and Pediatric Shaikh Zayed Hospital and Jinnah Hospital, Lahore from February 2010 to November 2011. Subjects and Methods: Awareness brochures for congenital hypothyroidism were developed and attached with the antenatal card of each pregnant case attending antenatal clinic at Gynae/Obs OPD. Newborns who had stayed in hospital for more than 24 hour, and whose parents consented for heal prick were tested for blood spot thyroid-stimulating hormone. Results were reported within four days and thyroid-stimulating hormone >= 20mIU/L was taken as high value. Parents of those neonates who had high value were contacted to give a fresh sample for confirmation. Confirmed results were provided within next 4-5 days to the parents and treating pediatrician for appropriate treatment. Results: A total of 1357 samples were screened using blood spot thyroid-stimulating hormone and out of these 1330 were normal ( =20mIU/L). These 27 neonates were further tested using confirmatory tests For serum thyroid-stimulating hormone, T3 and T4. After confirmatory tests only one case had congenital hypothyroidism who was referred for treatment. Three cases were suspected to have subclinical hypothyroidism and these were retested after six months which, picked another case of confirmed subclinical hypothyroidism who was referred for treatment. The incidence of congenital hypothyroidism was 2 out of 1357 cases. Conclusion: The screening could pick 2 cases of hypothyroidism from a total of 1357 cases which is high when compared to global rates

  19. Screening of carnitine and biotin deficiencies on tandem mass spectrometry.

    Science.gov (United States)

    Hagiwara, Shin-Ichiro; Kubota, Mitsuru; Nambu, Ryusuke; Kagimoto, Seiichi

    2017-04-01

    It is important to assess pediatric patients for nutritional deficiency when they are receiving specific interventions, such as enteral feeding. We focused on measurement of C0 and 3-hydroxyisovalerylcarnitine (C5-OH) with tandem mass spectrometry (MS/MS), which is performed as part of the newborn mass screening. The purpose of this study was to investigate the usefulness of MS/MS for screening carnitine and biotin deficiencies. Forty-two children (24 boys, 18 girls) were enrolled between December 2013 and December 2015. Blood tests, including measurement of serum free carnitine via the enzyme cycling method, and acylcarnitine analysis on MS/MS of dried blood spot (DBS), were performed for the evaluation of nutrition status. Median patient age was 2 years (range, 2 months-14 years). Mean serum free carnitine was 41.8 ± 19.2 μmol/L. In six of the 42 patients, serum free carnitine was 1.00 nmol/L. Therapy-resistant eczema was improved by treatment with additional biotin and a non-hydrolyzed formula. C0 and C5-OH, measured on MS/MS of DBS, were useful for screening carnitine and biotin deficiencies. © 2016 Japan Pediatric Society.

  20. Analysis of MicroRNA Expression in Newborns with Differential Birth Weight Using Newborn Screening Cards

    Directory of Open Access Journals (Sweden)

    Patricia Rodil-Garcia

    2017-11-01

    Full Text Available Birth weight is an early predictor for metabolic diseases and microRNAs (miRNAs are proposed as fetal programming participants. To evaluate the use of dried blood spots (DBS on newborn screening cards (NSC as a source of analyzable miRNAs, we optimized a commercial protocol to recover total miRNA from normal birth weight (NBW, n = 17–20, low birth weight (LBW, n = 17–20 and high birth weight (macrosomia, n = 17–20 newborns and analyzed the relative expression of selected miRNAs by stem-loop RT-qPCR. The possible role of miRNAs on the fetal programming of metabolic diseases was explored by bioinformatic tools. The optimized extraction of RNA resulted in a 1.2-fold enrichment of miRNAs respect to the commercial kit. miR-33b and miR-375 were overexpressed in macrosomia 9.8-fold (p < 0.001 and 1.7-fold, (p < 0.05, respectively and miR-454-3p was overexpressed in both LBW and macrosomia (19.7-fold, p < 0.001 and 10.8-fold, p < 0.001, respectively, as compared to NBW. Potential target genes for these miRNAs are associated to cyclic-guanosine monophosphate (cGMP-dependent protein kinase (PKG, mitogen-activated protein kinase (MAPK, type 2 diabetes, transforming growth factor-β (TGF-βand Forkhead box O protein (FoxO pathways. In summary, we improved a protocol for analyzing miRNAs from NSC and provide the first evidence that birth weight modifies the expression of miRNAs associated to adult metabolic dysfunctions. Our work suggests archived NSC are an invaluable resource in the search for fetal programming biomarkers.

  1. CDC’s Newborn Screening Program - Role of Laboratories

    Centers for Disease Control (CDC) Podcasts

    When newborn screening started in the U.S. 50 years ago, many questioned whether it was even possible to test every baby born in every state. Today, all states screen babies for at least 29 disorders that can be detected through laboratory testing. In this podcast, Dr. Carla Cuthbert talks about CDC’s Newborn Screening Quality Assurance Program and the role laboratories play in keeping babies healthy.

  2. No more tears? Maternal involvement during the newborn screening examination.

    LENUS (Irish Health Repository)

    Ganda, Augustine Josie

    2012-01-31

    BACKGROUND: Babies often show signs of discomfort and distress by crying during the neonatal screening examination (NSE). The authors hypothesized that supporting the baby with maternal participation may reduce infant crying during NSE. The objective of this study was to document incidental infant crying during NSE, before and after training residents, on maternal involvement and infant comfort techniques to help. METHODS: A total of 20 NSEs of normal newborn babies by pediatric residents were observed (video-recorded) following informed consent of the doctor and the baby\\'s mother. The examining doctors were then taught how to use maternal participation and developmental care (MPDC) comfort techniques to support the baby during NSE. Mothers were shown how to focus on their baby\\'s needs by supporting the baby\\'s head (preventing atonic neck reflexes) and, if necessary, providing nonnutritive sucking to the baby and an encouraging, repetitive low-tone voices to sooth the baby. A further 14 NSEs on different babies were video-recorded using these techniques. The video recordings were analyzed by independent observers for total length of crying and duration of crying during specific components of the NSE. Mothers in both groups were given a questionnaire to assess their opinions of the NSE. RESULTS: The median length of crying was significantly longer in the pre-MPDC group (93.5 seconds; range 0-198 seconds) compared with the post-MPDC infants (0 seconds; range 0-123 seconds; P = .001). Only 1 of 20 infants in the pre-MPDC did not cry during NSE compared with 8 of 14 babies in the post-MPDC group. CONCLUSION: Newborn infants cry less and mothers were more satisfied with NSEs when shown simple support and comfort techniques for their babies.

  3. Newborn hearing screening with transient evoked otoacoustic emissions and automatic auditory brainstem response

    OpenAIRE

    Renata Mota Mamede de Carvallo; Carla Gentile Matas; Isabela de Souza Jardim

    2008-01-01

    Objective: The aim of the present investigation was to check Transient Evoked Otoacoustic Emissions and Automatic Auditory Brainstem Response tests applied together in regular nurseries and Newborn Intensive Care Units (NICU), as well as to describe and compare the results obtained in both groups. Methods: We tested 150 newborns from regular nurseries and 70 from NICU. Rresults: The newborn hearing screening results using Transient Evoked Otoacoustic Emissions and Automatic Auditory Brainstem...

  4. Efficacy and outcome of expanded newborn screening for metabolic diseases - Report of 10 years from South-West Germany *

    Directory of Open Access Journals (Sweden)

    Mengel Eugen

    2011-06-01

    Full Text Available Abstract Background National newborn screening programmes based on tandem-mass spectrometry (MS/MS and other newborn screening (NBS technologies show a substantial variation in number and types of disorders included in the screening panel. Once established, these methods offer the opportunity to extend newborn screening panels without significant investment and cost. However, systematic evaluations of newborn screening programmes are rare, most often only describing parts of the whole process from taking blood samples to long-term evaluation of outcome. Methods In a prospective single screening centre observational study 373 cases with confirmed diagnosis of a metabolic disorder from a total cohort of 1,084,195 neonates screened in one newborn screening laboratory between January 1, 1999, and June 30, 2009 and subsequently treated and monitored in five specialised centres for inborn errors of metabolism were examined. Process times for taking screening samples, obtaining results, initiating diagnostic confirmation and starting treatment as well as the outcome variables metabolic decompensations, clinical status, and intellectual development at a mean age of 3.3 years were evaluated. Results Optimal outcome is achieved especially for the large subgroup of patients with medium-chain acyl-CoA dehydrogenase deficiency. Kaplan-Meier-analysis revealed disorder related patterns of decompensation. Urea cycle disorders, organic acid disorders, and amino acid disorders show an early high and continuous risk, medium-chain acyl-CoA dehydrogenase deficiency a continuous but much lower risk for decompensation, other fatty acid oxidation disorders an intermediate risk increasing towards the end of the first year. Clinical symptoms seem inevitable in a small subgroup of patients with very early disease onset. Later decompensation can not be completely prevented despite pre-symptomatic start of treatment. Metabolic decompensation does not necessarily result in

  5. Public health and laboratory considerations regarding newborn screening for congenital cytomegalovirus.

    Science.gov (United States)

    Dollard, Sheila C; Schleiss, Mark R; Grosse, Scott D

    2010-10-01

    Congenital cytomegalovirus (CMV) infection is the most common infection in newborns worldwide and causes hearing loss and other neurological disability in 15-20% of infected infants. Only about half of the hearing loss resulting from congenital CMV infection is currently detected by universal newborn hearing screening because of late-onset hearing loss. Thus, much of the hearing loss and the majority of other CMV-associated disabilities remain undetected for years after birth and are never connected to CMV infection. Congenital CMV may be appropriate to include in national newborn screening (NBS) programs because it is more common than other disorders tested for by NBS programs and is a major cause of disability. Significant obstacles to the implementation of screening for congenital CMV include the lack of a standardized, high-throughput screening test and a protocol for follow-up of CMV-infected children. Nonetheless, screening newborns for congenital CMV infection merits further consideration.

  6. Newborn hearing screening vs later hearing screening and developmental outcomes in children with permanent childhood hearing impairment

    NARCIS (Netherlands)

    Korver, Anna M. H.; Konings, Saskia; Dekker, Friedo W.; Beers, Mieke; Wever, Capi C.; Frijns, Johan H. M.; Oudesluys-Murphy, Anne M.; de Vries, Jutte; Vossen, Ann; Kant, Sarina; van den Akker-van Marle, Elske; le Cessie, Saskia; Rieffe, Carolien; Ens-Dokkum, Martina; van Straaten, Irma; Uilenburg, Noelle; Elvers, Bert; Loeber, Gerard; Meuwese-Jongejeugd, Anneke; Maré, Marcel; van Zanten, Bert; Goedegebure, André; Coster, Francien; van Dijk, Pim; Goverts, Theo; Admiraal, Ronald; Cremers, Cor; Kunst, Dirk; de Leeuw, Marina; Dijkhuizen, Janette; Scharloo, Marleen; Hoeben, Dirk; Rijpma, Gerti; Graef, Wim; Linschoten, Dik; Kuijper, Jessica; Hof, Nanda; Koldewijn, Reinoud; Pans, Donné; Jorritsma, Frank; van Beurden, Maarten; ter Huurne, Christien; Brienesse, Patrick; Seekles, Lisanne; de Jong, Jantine; Thijssen, Andrea; Lievense, Andrea; van Egdom-van der Wind, Marina; Theunissen, Stephanie; Mooij, Sophie

    2010-01-01

    Newborn hearing screening programs have been implemented in many countries because it was thought that the earlier permanent childhood hearing impairment is detected, the less developmentally disadvantaged children would become. To date, however, no strong evidence exists for universal introduction

  7. The Dried Bloodspot: Newborn Screening Research Saving the Lives of Babies

    Science.gov (United States)

    Levy-Fisch, Jill; Gartzke, Micki; Leight, Kelly

    2010-01-01

    Newborn screening is a test done on every child born in the US shortly after birth to detect diseases where, if not diagnosed and treated in the newborn period, the child will suffer significant trauma, disability or die. A few drops of blood from each baby's heel is put on a card and sent to the state's public health lab for testing. Most states…

  8. Two faces of patient advocacy: the current controversy in newborn screening.

    Science.gov (United States)

    Arnold, Cosby G

    2014-08-01

    Newborn screening programmes began in the 1960s, have traditionally been conducted without parental permission and have grown dramatically in the last decade. Whether these programmes serve patients' best interests has recently become a point of controversy. Privacy advocates, concerned that newborn screening infringes upon individual liberties, are demanding fundamental changes to these programmes. These include parental permission and limiting the research on the blood samples obtained, an agenda at odds with the viewpoints of newborn screening advocates. This essay presents the history of newborn screening in the USA, with attention to factors that have contributed to concerns about these programmes. The essay suggests that the rapid increase in the number of disorders screened for and the addition of research without either public knowledge or informed consent were critical to the development of resistance to mandatory newborn screening and research. Future newborn screening initiatives should include public education and comment to ensure continued support. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  9. Newborn screening for congenital cytomegalovirus: Options for hospital-based and public health programs.

    Science.gov (United States)

    Grosse, Scott D; Dollard, Sheila; Ross, Danielle S; Cannon, Michael

    2009-12-01

    Congenital cytomegalovirus (CMV) infection is a leading cause of sensorineural hearing loss (SNHL) and developmental disability in children. Early identification of infected children through screening could allow for early intervention and improvement in functional outcomes among the subset who develop sequelae. To outline potential options and strategies for screening newborns for congenital CMV infection and to discuss barriers to screening and data needs to inform future policy decisions. Commentary based on the literature and expert opinion on newborn dried blood spot screening, newborn hearing screening/Early Hearing Detection and Intervention (EHDI) programs, and congenital CMV. Although no population-based screening for congenital CMV is underway, pilot newborn screening studies using a variety of assays with urine or dried blood spot specimens are underway. Challenges to screening are both practical-uncertain sensitivity of blood spot assays suitable for large-scale screening and lack of infrastructure for collection of urine specimens; and evidentiary-the need to demonstrate improved outcomes and value of screening to offset the expense and potential adverse psychosocial consequences for children and families whose children require periodic monitoring but never develop sequelae. Screening for congenital CMV infection is a potentially important intervention that merits additional research, including the logistical feasibility of different screening options and psychosocial consequences for families.

  10. Newborn screening for six lysosomal storage disorders in a cohort of Mexican patients: Three-year findings from a screening program in a closed Mexican health system.

    Science.gov (United States)

    Navarrete-Martínez, Juana Inés; Limón-Rojas, Ana Elena; Gaytán-García, Maria de Jesús; Reyna-Figueroa, Jesús; Wakida-Kusunoki, Guillermo; Delgado-Calvillo, Ma Del Rocío; Cantú-Reyna, Consuelo; Cruz-Camino, Héctor; Cervantes-Barragán, David Eduardo

    2017-05-01

    To evaluate the results of a lysosomal newborn screening (NBS) program in a cohort of 20,018 Mexican patients over the course of 3years in a closed Mexican Health System (Petróleos Mexicanos [PEMEX] Health Services). Using dried blood spots (DBS), we performed a multiplex tandem mass spectrometry enzymatic assay for six lysosomal storage disorders (LSDs) including Pompe disease, Fabry disease, Gaucher disease, mucopolysaccharidosis type I (MPS-I), Niemann-Pick type A/B, and Krabbe disease. Screen-positive cases were confirmed using leukocyte enzymatic activity and DNA molecular analysis. From July 2012 to April 2016, 20,018 patients were screened; 20 patients were confirmed to have an LSD phenotype (99.9 in 100,000 newborns). Final distributions include 11 Pompe disease, five Fabry disease, two MPS-I, and two Niemann-Pick type A/B patients. We did not find any Gaucher or Krabbe patients. A final frequency of 1 in 1001 LSD newborn phenotypes was established. NBS is a major public health achievement that has decreased the morbidity and mortality of inborn errors of metabolism. The introduction of NBS for LSD presents new challenges. This is the first multiplex Latin-American study of six LSDs detected through NBS. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Medium-Chain Acyl-CoA Deficiency: Outlines from Newborn Screening, In Silico Predictions, and Molecular Studies

    Science.gov (United States)

    Catarzi, Serena; Caciotti, Anna; Thusberg, Janita; Tonin, Rodolfo; Malvagia, Sabrina; la Marca, Giancarlo; Pasquini, Elisabetta; Cavicchi, Catia; Ferri, Lorenzo; Donati, Maria A.; Baronio, Federico; Guerrini, Renzo; Mooney, Sean D.; Morrone, Amelia

    2013-01-01

    Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a disorder of fatty acid oxidation characterized by hypoglycemic crisis under fasting or during stress conditions, leading to lethargy, seizures, brain damage, or even death. Biochemical acylcarnitines data obtained through newborn screening by liquid chromatography-tandem mass spectrometry (LC-MS/MS) were confirmed by molecular analysis of the medium-chain acyl-CoA dehydrogenase (ACADM) gene. Out of 324.000 newborns screened, we identified 14 MCADD patients, in whom, by molecular analysis, we found a new nonsense c.823G>T (p.Gly275∗) and two new missense mutations: c.253G>C (p.Gly85Arg) and c.356T>A (p.Val119Asp). Bioinformatics predictions based on both phylogenetic conservation and functional/structural software were used to characterize the new identified variants. Our findings confirm the rising incidence of MCADD whose existence is increasingly recognized due to the efficacy of an expanded newborn screening panel by LC-MS/MS making possible early specific therapies that can prevent possible crises in at-risk infants. We noticed that the “common” p.Lys329Glu mutation only accounted for 32% of the defective alleles, while, in clinically diagnosed patients, this mutation accounted for 90% of defective alleles. Unclassified variants (UVs or VUSs) are especially critical when considering screening programs. The functional and pathogenic characterization of genetic variants presented here is required to predict their medical consequences in newborns. PMID:24294134

  12. Medium-Chain Acyl-CoA Deficiency: Outlines from Newborn Screening, In Silico Predictions, and Molecular Studies

    Directory of Open Access Journals (Sweden)

    Serena Catarzi

    2013-01-01

    Full Text Available Medium-chain acyl-CoA dehydrogenase deficiency (MCADD is a disorder of fatty acid oxidation characterized by hypoglycemic crisis under fasting or during stress conditions, leading to lethargy, seizures, brain damage, or even death. Biochemical acylcarnitines data obtained through newborn screening by liquid chromatography-tandem mass spectrometry (LC-MS/MS were confirmed by molecular analysis of the medium-chain acyl-CoA dehydrogenase (ACADM gene. Out of 324.000 newborns screened, we identified 14 MCADD patients, in whom, by molecular analysis, we found a new nonsense c.823G>T (p.Gly275* and two new missense mutations: c.253G>C (p.Gly85Arg and c.356T>A (p.Val119Asp. Bioinformatics predictions based on both phylogenetic conservation and functional/structural software were used to characterize the new identified variants. Our findings confirm the rising incidence of MCADD whose existence is increasingly recognized due to the efficacy of an expanded newborn screening panel by LC-MS/MS making possible early specific therapies that can prevent possible crises in at-risk infants. We noticed that the “common” p.Lys329Glu mutation only accounted for 32% of the defective alleles, while, in clinically diagnosed patients, this mutation accounted for 90% of defective alleles. Unclassified variants (UVs or VUSs are especially critical when considering screening programs. The functional and pathogenic characterization of genetic variants presented here is required to predict their medical consequences in newborns.

  13. Heptadecanoylcarnitine (C17) a novel candidate biomarker for propionic and methylmalonic acidemias during expanded newborn screening

    Science.gov (United States)

    Malvagia, Sabrina; Haynes, Christopher A.; Grisotto, Laura; Ombrone, Daniela; Funghini, Silvia; Moretti, Elisa; McGreevy, Kathleen; Buggeri, Annibale; Guerrini, Renzo; Yahyaoui, Raquel; Garg, Uttam; Seeterlin, Mary; Chace, Donald; De Jesus, Victor; la Marca, Giancarlo

    2017-01-01

    Background 3-hydroxypalmitoleoyl-carnitine (C16:1-OH) was recently reported to be elevated in acylcarnitine profile of propionic acidemia (PA) or methylmalonic acidemia (MMA) patients during expanded newborn screening (NBS). High levels of C16:1-OH, combined with other hydroxylated long chain acylcarnitines are related to long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD). Methods The acylcarnitine profile of two LCHADD patients was evaluated using liquid chromatography-tandem mass spectrometric method. A specific retention time was reported for each hydroxylated long chain acylcarnitine. The same method was applied to some neonatal dried blood spots (DBS) from PA and MMA patients presenting abnormal C16:1-OH concentrations. Results The final retention time of the peak corresponding to C16:1-OH in LCHADD patients differed from those in MMA and PA patients. Heptadecanoylcarnitine (C17) has been identified as the novel biomarker specific for PA and MMA patients through high resolution mass spectrometry (Orbitrap) experiments. We found that 21 out of 23 neonates (22 MMA, and 1PA) diagnosed through the Tuscany region NBS program had significantly higher levels of C17 compared to levels detected in controls. Twenty-three maternal deficiencies (21 vitamin B12 deficiency, 1 homocystinuria and 1 gastrin deficiency) and 82 false positive for propionylcarnitine (C3) results were also analyzed. Conclusions This paper reports on the characterization of a novel biomarker able to detect propionate disorders during expanded newborn screening (NBS). The use of this new biomarker may improve the analytical performances of NBS programs especially in laboratories where second tier tests are not performed. PMID:26368264

  14. Heptadecanoylcarnitine (C17) a novel candidate biomarker for newborn screening of propionic and methylmalonic acidemias.

    Science.gov (United States)

    Malvagia, Sabrina; Haynes, Christopher A; Grisotto, Laura; Ombrone, Daniela; Funghini, Silvia; Moretti, Elisa; McGreevy, Kathleen S; Biggeri, Annibale; Guerrini, Renzo; Yahyaoui, Raquel; Garg, Uttam; Seeterlin, Mary; Chace, Donald; De Jesus, Victor R; la Marca, Giancarlo

    2015-10-23

    3-Hydroxypalmitoleoyl-carnitine (C16:1-OH) has recently been reported to be elevated in acylcarnitine profiles of patients with propionic acidemia (PA) or methylmalonic acidemia (MMA) during expanded newborn screening (NBS). High levels of C16:1-OH, combined with other hydroxylated long chain acylcarnitines are related to long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and trifunctional protein (TFP) deficiency. The acylcarnitine profile of two LCHADD patients was evaluated using liquid chromatography-tandem mass spectrometric method. A specific retention time was determined for each hydroxylated long chain acylcarnitine. The same method was applied to some neonatal dried blood spots (DBSs) from PA and MMA patients presenting abnormal C16:1-OH concentrations. The retention time of the peak corresponding to C16:1-OH in LCHADD patients differed from those in MMA and PA patients. Heptadecanoylcarnitine (C17) has been identified as the novel biomarker specific for PA and MMA patients through high resolution mass spectrometry (Orbitrap) experiments. We found that 21 out of 23 neonates (22 MMA, and 1PA) diagnosed through the Tuscany region NBS program exhibited significantly higher levels of C17 compared to controls. Twenty-three maternal deficiency (21 vitamin B12 deficiency, 1 homocystinuria and 1 gastrin deficiency) samples and 82 false positive for elevated propionylcarnitine (C3) were also analyzed. We have characterized a novel biomarker able to detect propionate disorders during expanded newborn screening (NBS). The use of this new biomarker may improve the analytical performances of NBS programs especially in laboratories where second tier tests are not performed. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Informing parents about expanded newborn screening: influences on provider involvement.

    Science.gov (United States)

    Hayeems, Robin Z; Miller, Fiona A; Little, Julian; Carroll, June C; Allanson, Judith; Chakraborty, Pranesh; Wilson, Brenda J; Bytautas, Jessica P; Christensen, Robert J

    2009-09-01

    Expanded newborn screening (NBS) identifies some disorders for which clinical benefit is uncertain, as well as "incidental" findings (eg, carrier status), thus enhancing the need to inform parents about NBS before sample collection. A self-complete survey was sent to a cross-sectional, stratified, random sample of 5 provider groups in Ontario (obstetricians, midwives, family physicians, pediatricians, and nurses). Univariate and multivariate analyses were used to investigate the effects of core beliefs, perceived barriers, and demographic characteristics on the reported frequency of informing parents about NBS before sample collection. Virtually all of the midwives and almost half of the nurses reported discussing NBS with parents, whereas less than one sixth of the physicians did so. Providers who perceived a responsibility to inform parents were 3 times more likely to report doing so than those who did not perceive this responsibility (odds ratio: 2.9 [95% confidence interval: 2.1-4.1]). Those who lacked confidence to inform parents were 70% less likely to discuss NBS with parents compared with those who did not experience this cognitive barrier (odds ratio: 0.3 [95% confidence interval: 0.2-0.4]). Controlling for these covariates, family physicians and obstetricians were more likely than pediatricians to inform parents. These results provide guidance for capacity building among providers who are positioned to inform parents about NBS before sample collection. Our findings call for targeted educational interventions that consider patterns of provider practice related to prenatal and NBS care, seek to redress confidence limitations, and engage key provider groups in the importance of this professional responsibility.

  16. Triagem neonatal: o que os pediatras deveriam saber Newborn screening: what pediatricians should know

    Directory of Open Access Journals (Sweden)

    Letícia Lima Leão

    2008-08-01

    , PubMed (MeSH and MD Consult, using the keywords newborn screening, neonatal, pediatrics, diagnosis, primary care, ethics and their equivalents in Portuguese, in isolation and in combination, in addition to medical textbooks on genetics and inborn errors of metabolism, published between January 1998 and December 2007, the National Neonatal Screening Program technical standards and routines manual, and Ministry of Health decree 822/2001. SUMMARY OF THE FINDINGS: Published data demonstrate a great diversity in the number of diseases included in the neonatal screening programs of different countries. In Brazil, the National Neonatal Screening Program was set up in 2001, to screen for phenylketonuria, congenital hypothyroidism, sickle-cell anemia and cystic fibrosis. Screening for a wider range of conditions using mass spectrometry is currently the subject of disagreement and discussion of financial and ethical issues. CONCLUSIONS: Neonatal screening is one of the most important advances for the prevention of pediatric diseases. Nevertheless, implementation is complex, multidisciplinary and dependent on public health policies and, to date, there is no consensus on which diseases should be included. A large number of scientific and ethical questions need to be discussed in order to better define the screening panels to be implemented. Pediatricians have important roles to play in all stages of neonatal screening programs.

  17. SUMA Technology and Newborn Screening Tests for Inherited Metabolic Diseases in Cuba

    Directory of Open Access Journals (Sweden)

    Ernesto Carlos González Reyes PhD

    2016-07-01

    Full Text Available The ultramicroanalytic system (SUMA, created in the 1980s, is a complete system of reagents and instrumentation to perform ultramicroassays combining the sensitivity of the micro-enzyme-linked immunosorbent assay (ELISA tests with the use of ultramicrovolumes. This technology permitted establishing large-scale newborn screening programs (NSPs for metabolic and endocrine disorders in Cuba. This article summarizes the main results of the implementation during the 30 years of SUMA technology in NSP for 5 inherited metabolic diseases, using ultramicroassays developed at the Department of Newborn Screening at the Immunoassay Center. Since 1986, SUMA technology has been used in the Cuban NSP for congenital hypothyroidism, initially studying thyroid hormone in cord serum samples. In 2000, a decentralized program for the detection of hyperphenylalaninemias using heel dried blood samples was initiated. These successful experiences permitted including protocols for screening congenital adrenal hyperplasia, galactosemia, and biotinidase deficiency in 2005. A program for the newborn screening of CH using the thyroid-stimulating hormone Neonatal ultramicro-ELISA was fully implemented in 2010. Nowadays, the NSP is supported by a network of 175 SUMA laboratories. After 30 years, more than 3.8 million Cuban newborns have been screened, and 1002 affected children have been detected. Moreover, SUMA technology has been presented in Latin America for over 2 decades and has contributed to screen around 17 million newborns. These results prove that developing countries can develop appropriate diagnostic technologies for making health care accessible to all.

  18. Tamiz metabólico neonatal por espectrometría de masas en tándem: dos años de experiencia en Nuevo León, México Expand newborn screening using tandem mass spectrometry: two years' experience in Nuevo León, Mexico

    Directory of Open Access Journals (Sweden)

    María del Rosario Torres-Sepúlveda

    2008-06-01

    Full Text Available OBJETIVO: Instituir un programa estatal de tamizaje neonatal ampliado para identificar errores innatos del metabolismo y determinar su prevalencia en la población de recién nacidos del estado de Nuevo León. MATERIAL Y MÉTODOS: Entre marzo de 2002 y febrero de 2004 se incluyeron neonatos consecutivos nacidos en hospitales públicos del estado. Se colectaron muestras de sangre en papel filtro entre las 24 y 48 horas de vida y se las sometió a tamiz metabólico mediante espectrometría de masas en tándem. RESULTADOS: Se analizaron 42 264 primeras muestras y se detectaron siete casos, uno de cada padecimiento: homocistinuria, fenilcetonuria, citrulinemia, tirosinemia/transitoria, deficiencia de 3-metilcrotonil-CoA carboxilasa, deficiencia de 3-hidroxi-3-metilglutaril-CoA liasa y galactosemia típica. CONCLUSIONES: La incidencia acumulada de defectos metabólicos en la población fue de 1:5 000 con 0.22% de casos falso-positivos. El programa permitió identificar y tratar con oportunidad los trastornos metabólicos al nacimiento con una efectiva prevención secundaria del retraso mental.OBJECTIVE: To initiate a statewide expanded metabolic screening program in neonates with the purpose of identifying the most common inborn errors of metabolism. MATERIAL AND METHODS: From March 2002 through February 2004, a blood sample was obtained between 24 and 48 hours after delivery from every consecutive child born in public hospitals in Nuevo León. It was spotted on filter paper and analyzed by tandem mass spectrometry for expanded metabolic screening. RESULTS: A total of 42 264 samples were analyzed. Were obtained seven positive results, one for each disorder: homocystinuria, hyperphenylalaninemia, citrulinemia, transient tyrosinemia, 3-methylcrotonyl CoA carboxylase deficiency, 3-hydroxy-3-methylglutaryl CoA deficiency, and classic galactosemia. CONCLUSIONS: The estimated incidence of inborn errors of metabolism is 1:5 000, with a false positive rate

  19. Investigation of newborns with abnormal results in a newborn screening program for four lysosomal storage diseases in Brazil

    Directory of Open Access Journals (Sweden)

    Heydy Bravo

    2017-09-01

    Full Text Available Lysosomal storage diseases (LSDs are genetic disorders, clinically heterogeneous, mainly caused by defects in genes encoding lysosomal enzymes that degrade macromolecules. Several LSDs already have specific therapies that may improve clinical outcomes, especially if introduced early in life. With this aim, screening methods have been established and newborn screening (NBS for some LSDs has been developed. Such programs should include additional procedures for the confirmation (or not of the cases that had an abnormal result in the initial screening. We present here the methods and results of the additional investigation performed in four babies with positive initial screening results in a program of NBS for LSDs performed by a private laboratory in over 10,000 newborns in Brazil. The suspicion in these cases was of Mucopolysaccharidosis I - MPS I (in two babies, Pompe disease and Gaucher disease (one baby each. One case of pseudodeficiency for MPS I, 1 carrier for MPS I, 1 case of pseudodeficiency for Pompe disease and 1 carrier for Gaucher disease were identified. This report illustrates the challenges that may be encountered by NBS programs for LSDs, and the need of a comprehensive protocol for the rapid and precise investigation of the babies who have an abnormal screening result.

  20. CDC’s Newborn Screening Program - Role of Laboratories

    Centers for Disease Control (CDC) Podcasts

    2013-09-03

    When newborn screening started in the U.S. 50 years ago, many questioned whether it was even possible to test every baby born in every state. Today, all states screen babies for at least 29 disorders that can be detected through laboratory testing. In this podcast, Dr. Carla Cuthbert talks about CDC’s Newborn Screening Quality Assurance Program and the role laboratories play in keeping babies healthy.  Created: 9/3/2013 by National Center for Environmental Health (NCEH).   Date Released: 9/3/2013.

  1. Cost-effectiveness of newborn screening for cystic fibrosis determined with real-life data

    NARCIS (Netherlands)

    van der Ploeg, C. P B; van den Akker-van Marle, M. E.; Vernooij-van Langen, A. M M; Elvers, L. H.; Gille, J. J P; Verkerk, P. H.; Dankert-Roelse, J. E.; Dankert-Roelse, J. E.; Vernooij-van Langen, A. M M; Loeber, J. G.; Elvers, L. H.; Triepels, R. H.; Gille, J. J P; Van der Ploeg, C. P B; van der Pal, S. M.; Dompeling, E.; Pals, G.; van den Akker van Marle, M. E.; Gulmans, V. A M; Oey-Spauwen, M. J W; Wijnands, Y. H H M; Castricum, L. M.; Arets, H. G M; van der Ent, C. K.; Tiddens, H. A W M; de Rijke, Y. B.; Yntema, J. B.

    2015-01-01

    Background: Previous cost-effectiveness studies using data from the literature showed that newborn screening for cystic fibrosis (NBSCF) is a good economic option with positive health effects and longer survival. Methods: We used primary data to compare cost-effectiveness of four screening

  2. Newborn screening healthcare information system based on service-oriented architecture.

    Science.gov (United States)

    Hsieh, Sung-Huai; Hsieh, Sheau-Ling; Chien, Yin-Hsiu; Weng, Yung-Ching; Hsu, Kai-Ping; Chen, Chi-Huang; Tu, Chien-Ming; Wang, Zhenyu; Lai, Feipei

    2010-08-01

    In this paper, we established a newborn screening system under the HL7/Web Services frameworks. We rebuilt the NTUH Newborn Screening Laboratory's original standalone architecture, having various heterogeneous systems operating individually, and restructured it into a Service-Oriented Architecture (SOA), distributed platform for further integrity and enhancements of sample collections, testing, diagnoses, evaluations, treatments or follow-up services, screening database management, as well as collaboration, communication among hospitals; decision supports and improving screening accuracy over the Taiwan neonatal systems are also addressed. In addition, the new system not only integrates the newborn screening procedures among phlebotomy clinics, referral hospitals, as well as the newborn screening center in Taiwan, but also introduces new models of screening procedures for the associated, medical practitioners. Furthermore, it reduces the burden of manual operations, especially the reporting services, those were heavily dependent upon previously. The new system can accelerate the whole procedures effectively and efficiently. It improves the accuracy and the reliability of the screening by ensuring the quality control during the processing as well.

  3. Expanded newborn screening in the Health Services of the Mexican Navy

    Directory of Open Access Journals (Sweden)

    Max Trigo-Madrid

    2014-11-01

    Full Text Available In Mexico the birth prevalence of the metabolic diseases detected by expanded newborn screening is poorly known and there is little information about its performance indicators.Objective. Describe the birth prevalence of the metabolic defects detected by the expanded newborn screening program implemented in the Mexican Navy (Secretaría de Marina Armada de México, SEMAR, and to make known some of its performance indicators. Materials and Methods. A blood sample of 5 205 newborns from 18 Mexican states were taken. The age at blood sampling, the proportion of samples taken between the 3rd and the 5th days of life, and the time of results delivery were analyzed. The number and type of detected metabolic diseases, as well as the maternal age and body mass index, the type of birth, the gestational age and weight of the newborns were analized. Results. The age at blood sampling was 4.7 days and 81.15 percent of the samples were obtained in optimal time. Two cases of congenital hypothyroidism (3.8/10 000 newborns, one of adrenal congenital hyperplasia (1.9/10 000 newborns and five cases of deficiency of glucose- 6-phosphate dehydrogenase (9.6/10 000 newborns were detected. The 85.6% of mothers had pregnancies at an optimal reproductive age (20-35 years, but overweight and obesity occurred in 44.7% of them. Conclusions. In this analyzed population, the birth prevalence of metabolic defects was 15.37/10 000 newborns. The expanded newborn screening program allowed its identification and timely treatment, with the aim of preventing disability and death.

  4. Incidence of Inborn Errors of Metabolism by Expanded Newborn Screening in a Mexican Hospital

    Directory of Open Access Journals (Sweden)

    Consuelo Cantú-Reyna MD

    2016-09-01

    Full Text Available Newborn screening for the detection of inborn errors of metabolism (IEM, endocrinopathies, hemoglobinopathies, and other disorders is a public health initiative aimed at identifying specific diseases in a timely manner. Mexico initiated newborn screening in 1973, but the national incidence of this group of diseases is unknown or uncertain due to the lack of large sample sizes of expanded newborn screening (ENS programs and lack of related publications. The incidence of a specific group of IEM, endocrinopathies, hemoglobinopathies, and other disorders in newborns was obtained from a Mexican hospital. These newborns were part of a comprehensive ENS program at Ginequito (a private hospital in Mexico, from January 2012 to August 2014. The retrospective study included the examination of 10 000 newborns’ results obtained from the ENS program (comprising the possible detection of more than 50 screened disorders. The findings were the following: 34 newborns were confirmed with an IEM, endocrinopathies, hemoglobinopathies, or other disorders and 68 were identified as carriers. Consequently, the estimated global incidence for those disorders was 3.4 in 1000 newborns; and the carrier prevalence was 6.8 in 1000. Moreover, a 0.04% false-positive rate was unveiled as soon as diagnostic testing revealed negative results. The most frequent diagnosis was glucose-6-phosphate dehydrogenase deficiency; and in the case of carriers, it was hemoglobinopathies. The benefit of the ENS is clear as it offers prompt treatment on the basis of an early diagnosis including proper genetic counseling. Furthermore, these results provide a good estimation of the frequencies of different forms of newborn IEM, endocrinopathies, hemoglobinopathies, and other disorders at Ginequito.

  5. Newborn hearing screening and strategy for early detection of hearing loss in infants.

    Science.gov (United States)

    Jakubíková, Janka; Kabátová, Zuzana; Pavlovcinová, Gabriela; Profant, Milan

    2009-04-01

    More than 80% of permanent hearing losses (HL) in children are congenital. Newborn hearing screening (NHS) is the best method for early detection of suspected hearing loss. If the NHS is not universal more than 30% permanent hearing losses are not identified. There are various methods of NHS: otoacoustic emissions (TEOAE, DPOAE) and automatic auditory brainstem response (AABR). After hearing screening, and when hearing loss is suspected, tympanometry and audiological methods then used for determination of hearing threshold; these include ABR, ASSR or/and behavioral methods. The goal of this study is to evaluate the influence of UNHS on the early detection of hearing loss in children before and after the implementation of obligatory universal newborn hearing screening in Slovakia, and also on the etiologic evaluation of hearing impaired infants identified by screening. In Slovakia NHS started in 1998 and was provided in ENT departments. From May 1, 2006 UNHS has been mandatory in Slovakia, using two stages TEOAE in all newborn departments in Slovakia (64 newborn departments). In year 2005--42% of newborns in Slovakia were screened, in 2006--66% newborns and in 2007--94, 99% (three small newborn departments do not yet have equipment for OAE screening). For determination of hearing thresholds ASSR are used in two ENT departments and ABR in the other four ENT departments. Comparing the number of identified cases with bilateral severe permanent HL or deafness before and after UNHS, 22.8% more cases of PHL were identified in the first year of UNHS. Also the average age of diagnosis of PHL was lower. In the year 2007, 94% of newborns were screened. We found 0.947/1000 newborns with bilateral severe PHL (35.9%) more than before UNHS). After audiologic and etiologic assessment of the 76 infants who failed screening, 5 (6.58%) were found to have normal hearing, 16 (22.54%) had unilateral and 55 (77.46%) had bilateral SNHL. A non-syndromic genetic cause was present in 25

  6. The Use of Economic Evaluation to Inform Newborn Screening Policy Decisions: The Washington State Experience.

    Science.gov (United States)

    Grosse, Scott D; Thompson, John D; Ding, Yao; Glass, Michael

    2016-06-01

    Newborn screening not only saves lives but can also yield net societal economic benefit, in addition to benefits such as improved quality of life to affected individuals and families. Calculations of net economic benefit from newborn screening include the monetary equivalent of avoided deaths and reductions in costs of care for complications associated with late-diagnosed individuals minus the additional costs of screening, diagnosis, and treatment associated with prompt diagnosis. Since 2001 the Washington State Department of Health has successfully implemented an approach to conducting evidence-based economic evaluations of disorders proposed for addition to the state-mandated newborn screening panel. Economic evaluations can inform policy decisions on the expansion of newborn screening panels. This article documents the use of cost-benefit models in Washington State as part of the rule-making process that resulted in the implementation of screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and 4 other metabolic disorders in 2004, cystic fibrosis (CF) in 2006, 15 other metabolic disorders in 2008, and severe combined immune deficiency (SCID) in 2014. We reviewed Washington State Department of Health internal reports and spreadsheet models of expected net societal benefit of adding disorders to the state newborn screening panel. We summarize the assumptions and findings for 2 models (MCAD and CF) and discuss them in relation to findings in the peer-reviewed literature. The MCAD model projected a benefit-cost ratio of 3.4 to 1 based on assumptions of a 20.0 percentage point reduction in infant mortality and a 13.9 percentage point reduction in serious developmental disability. The CF model projected a benefit-cost ratio of 4.0-5.4 to 1 for a discount rate of 3%-4% and a plausible range of 1-2 percentage point reductions in deaths up to age 10 years. The Washington State cost-benefit models of newborn screening were broadly consistent with peer

  7. Cost-benefit analysis of hyperphenylalaninemia due to 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency: for consideration of expanded newborn screening in Hong Kong.

    Science.gov (United States)

    Lee, Hencher Han-Chih; Mak, Chloe Miu; Poon, Grace Wing-Kit; Wong, Kar-Yin; Lam, Ching-Wan

    2014-06-01

    To evaluate the cost-benefit of implementing an expanded newborn screening programme for hyperphenylalaninemias due to 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency in Hong Kong. Regional public hospitals in Hong Kong providing care for cases of inborn errors of metabolism. Implementational and operational costs of a new expanded mass spectrometry-based newborn screening programme were estimated. Data on various medical expenditures for the mild and severe phenotypic subtypes were gathered from a case cohort diagnosed with PTPS deficiency from 2001 to 2009. Local incidence from a previously published study was used. Implementation and operational costs of an expanded newborn screening programme in Hong Kong were estimated at HKD 10,473,848 (USD 1,342,801) annually. Assuming a birthrate of 50,000 per year and an incidence of 1 in 29,542 live births, the medical costs and adjusted loss of workforce per year would be HKD 20,773,207 (USD 2,663,232). Overall the annual savings from implementing the programme would be HKD 9,632,750 (USD 1,234,968). Our estimates show that implementation of an expanded newborn screening programme in Hong Kong is cost-effective, with a significant annual saving for public expenditure. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  8. A focus group study of consumer attitudes toward genetic testing and newborn screening for deafness.

    Science.gov (United States)

    Burton, Sarah K; Withrow, Kara; Arnos, Kathleen S; Kalfoglou, Andrea L; Pandya, Arti

    2006-12-01

    Progress in identifying genes for deafness together with implementation of universal audiologic screening of newborns has provided the opportunity for more widespread use of molecular tests to detect genetic forms of hearing loss. Efforts to assess consumer attitudes toward these advances have lagged behind. Consumer focus groups were held to explore attitudes toward genetic advances and technologies for hearing loss, views about newborn hearing screening, and reactions to the idea of adding molecular screening for hearing loss at birth. Focus group discussions were recorded, transcribed and analyzed. Five focus groups with 44 participants including hearing parents of deaf children, deaf parents and young deaf adults were held. Focus group participants supported the use of genetic tests to identify the etiology of hearing loss but were concerned that genetic information might influence reproductive decisions. Molecular newborn screening was advocated by some; however, others expressed concern about its effectiveness. Documenting the attitudes of parents and other consumers toward genetic technologies establishes the framework for discussions on the appropriateness of molecular newborn screening for hearing loss and informs specialists about potential areas of public education necessary prior to the implementation of such screening.

  9. A simple method for the analysis by MS/MS of underivatized amino acids on dry blood spots from newborn screening.

    Science.gov (United States)

    Wang, Chunyan; Zhang, Wenyan; Song, Fengrui; Liu, Zhiqiang; Liu, Shuying

    2012-05-01

    The analysis by electrospray-ionization tandem mass spectrometry of amino acids with butyl esterification and isotopically labeled internal standard is routine in newborn screening laboratories worldwide. In the present study, we established a direct analysis method of higher accuracy that uses a non-deuterated internal standard. The automatic sampler and the pump of an LC apparatus were used to inject sample and mobile phase to MS, but no LC column was needed. The dry blood spot (DBS) material was prepared at levels of low, medium and high concentration; the running time was 1 min. In parallel to the new procedure, we applied the established method to analyze nine amino acids on DBS of healthy newborns and phenylketonuria newborns. The newly proposed method of product ion confirmation scan along with multiple reaction monitoring resulted in a very accurate identification of each amino acid. Our innovative protocol had high sensitivity and specificity in the analysis of cases of suspected metabolic diseases.

  10. [Results from ten years newborn hearing screening in a secondary hospital].

    Science.gov (United States)

    Sequi Canet, José Miguel; Sala Langa, Maria José; Collar Del Castillo, José Ignacio

    2016-10-01

    A critical analysis is performed on the results of a newborn hearing screening program in a regional hospital. Screening results from 14,247 newborns in our maternity ward from 2002 to 2013. Two step recordings of bilateral otoacoustic emissions (initial and repeat, if failed, at about one month of life). Assessment by clinical brainstem responses. The first step was performed on 14,015 newborns (98.3% of the total) reaching the screening objective. The first step pass figures were 93.7%, which implies a good pass rate with a few patients to repeat. The second step is also good because it has a pass rate of 88.9% of newborns examined (only 0.63% of initial group needed brainstem responses assessment), but 10.6% were lost to follow up, and that is a major problem. In newborns, scheduled for brainstem responses, the loss to follow-up is worse, with a figure of 29.5%, despite the high accuracy of this test given that 69.4% of those assessed showed hearing loss. This figure represents a 0.31% of the initial group, and is a similar to that published for congenital hearing loss. Including patients that were lost to follow up this figure could be greater. Newborn hearing screening is useful but needs stronger control to avoid the follow up loss. In order to achieve this, it is crucial to have a good database and a screening coordinator. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Enhancing the quality and efficiency of newborn screening programs through the use of health information technology.

    Science.gov (United States)

    Downing, Gregory J; Zuckerman, Alan E; Coon, Constanze; Lloyd-Puryear, Michele A

    2010-04-01

    A variety of efforts are underway at national, state, regional, and local levels to enhance the performance of programs for early detection of inherited diseases and conditions of newborn infants. Newborn screening programs serve a vital purpose in identifying nonsymptomatic clinical conditions and enabling early intervention strategies that lessen morbidity and mortality. Currently, the programs of most intense focus are early hearing detection and intervention, using physiological techniques for audiology screening and use of newborn dried blood spots for detection of metabolites or proteins representing inherited disorders. One of the primary challenges to effective newborn screening programs to date has been the inability to provide information in a timely and easily accessible way to a variety of users. Other challenging communication issues being faced include the complexity introduced by the diversity of conditions for which testing is conducted and laboratory methods being used by each state's screening programs, lack of an electronic information infrastructure to facilitate information exchange, and variation in policies that enable access to information while protecting patient privacy and confidentiality. In this study, we address steps being taken to understand these challenges, outline progress made to date to overcome them, and provide examples of how electronic health information exchange will enhance the utility of newborn screening. It is likely that future advances in science and technology will bring many more opportunities to prevent and preempt disabilities among children through early detection programs. To take their advantage, effective communication strategies are needed among the public health, primary care practice, referral/specialty service, and consumer advocacy communities to provide continuity of information required for medical decision-making throughout prenatal, newborn, and early childhood periods of patient care. Published by

  12. Mass spectrometry-assisted protease substrate screening

    DEFF Research Database (Denmark)

    Schlüter, Hartmut; Rykl, Jana; Thiemann, Joachim

    2007-01-01

    -phase chromatography they are analyzed by tandem mass spectrometry and the substrates identified by database searching. The proof of principle in this study is demonstrated by incubating immobilized human plasma proteins with thrombin and by identifying by tandem mass spectrometry the fibrinopeptides, released...

  13. Detecting congenital hypothyroidism with newborn screening: the relevance of thyroid-stimulating hormone cutoff values.

    Science.gov (United States)

    Silvestrin, Stela Maris; Leone, Claudio; Leone, Cléa Rodrigues

    To assess the prevalence of congenital hypothyroidism and the ability of various neonatal thyroid-stimulating hormone (TSHneo) cutoff values to detect this disease. This cohort study was based on the retrospective collection of information available from the Reference Service for Newborn Screening database for all live births from January 1, 2010, to December 31, 2012, assessed using the Newborn Screening Program of a Brazilian state, Brazil. The infants were divided into two groups: I - Control: infants with normal newborn screening tests and II - Study: infants with congenital hypothyroidism. Analysis included comparing the TSHneo levels from both groups. A receiver operating characteristic (ROC) curve was constructed to assess the TSHneo cutoff values. Using a TSHneo cutoff value of 5.0μIU/mL, 50 out of 111,705 screened infants had diagnosis of congenital hypothyroidism (prevalence 1:2234 live births). The ROC curve showed that TSHneo value of 5.03μIU/mL had 100% sensitivity and the greatest associated specificity (93.7%). The area under the curve was 0.9898 (pvalue of 5.0μIU/mL adopted by the Newborn Screening Program of a Brazilian state was the most appropriate for detecting congenital hypothyroidism and most likely explains the high prevalence that was found. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  14. Web-based newborn screening system for metabolic diseases: machine learning versus clinicians.

    Science.gov (United States)

    Chen, Wei-Hsin; Hsieh, Sheau-Ling; Hsu, Kai-Ping; Chen, Han-Ping; Su, Xing-Yu; Tseng, Yi-Ju; Chien, Yin-Hsiu; Hwu, Wuh-Liang; Lai, Feipei

    2013-05-23

    A hospital information system (HIS) that integrates screening data and interpretation of the data is routinely requested by hospitals and parents. However, the accuracy of disease classification may be low because of the disease characteristics and the analytes used for classification. The objective of this study is to describe a system that enhanced the neonatal screening system of the Newborn Screening Center at the National Taiwan University Hospital. The system was designed and deployed according to a service-oriented architecture (SOA) framework under the Web services .NET environment. The system consists of sample collection, testing, diagnosis, evaluation, treatment, and follow-up services among collaborating hospitals. To improve the accuracy of newborn screening, machine learning and optimal feature selection mechanisms were investigated for screening newborns for inborn errors of metabolism. The framework of the Newborn Screening Hospital Information System (NSHIS) used the embedded Health Level Seven (HL7) standards for data exchanges among heterogeneous platforms integrated by Web services in the C# language. In this study, machine learning classification was used to predict phenylketonuria (PKU), hypermethioninemia, and 3-methylcrotonyl-CoA-carboxylase (3-MCC) deficiency. The classification methods used 347,312 newborn dried blood samples collected at the Center between 2006 and 2011. Of these, 220 newborns had values over the diagnostic cutoffs (positive cases) and 1557 had values that were over the screening cutoffs but did not meet the diagnostic cutoffs (suspected cases). The original 35 analytes and the manifested features were ranked based on F score, then combinations of the top 20 ranked features were selected as input features to support vector machine (SVM) classifiers to obtain optimal feature sets. These feature sets were tested using 5-fold cross-validation and optimal models were generated. The datasets collected in year 2011 were used as

  15. Retinal and Optic Nerve Hemorrhages in the Newborn Infant: One-Year Results of the Newborn Eye Screen Test Study.

    Science.gov (United States)

    Callaway, Natalia F; Ludwig, Cassie A; Blumenkranz, Mark S; Jones, Jennifer Michelle; Fredrick, Douglas R; Moshfeghi, Darius M

    2016-05-01

    To report the birth prevalence, risk factors, characteristics, and location of fundus hemorrhages (FHs) of the retina and optic nerve present in newborns at birth. Prospective cohort study at Stanford University School of Medicine. All infants who were 37 weeks postmenstrual age or older and stable were eligible for screening. Infants with known or suspected infectious conjunctivitis were excluded. Infants born at Lucile Packard Children's Hospital (LPCH) from July 25, 2013, through July 25, 2014, were offered universal newborn screening via wide-angle digital retinal photography in the Newborn Eye Screen Test study. Maternal, obstetric, and neonatal factors were obtained from hospital records. The location, retinal layer, and laterality of FH were recorded by 1 pediatric vitreoretinal specialist. Birth prevalence of FH. Secondary outcomes included rate of adverse events, risk factors for FH, hemorrhage characteristics, and adverse events. The birth prevalence of FH in this study was 20.3% (41/202 infants). Ninety-five percent of FHs involved the periphery, 83% involved the macula, and 71% involved multiple layers of the retina. The fovea was involved in 15% of FH cases (birth prevalence, 3.0%). No cases of bilateral foveal hemorrhage were found. Fundus hemorrhages were more common in the left eye than the right. Fundus hemorrhages were most commonly optic nerve flame hemorrhages (48%) and white-centered retinal hemorrhages (30%). Retinal hemorrhages were found most frequently in all 4 quadrants (35%) and more often were multiple than solitary. Macular hemorrhages most often were intraretinal (40%). Among the risk factors examined in this study, vaginal delivery compared with cesarean section (odds ratio [OR], 9.34; 95% confidence interval [CI], 2.57-33.97) showed the greatest level of association with FH. Self-identified ethnicity as Hispanic or Latino showed a protective effect (OR, 0.43; 95% CI, 0.20-0.94). Other study factors were not significant. Fundus

  16. Neonatal detection of Aicardi Goutières Syndrome by increased C26:0 lysophosphatidylcholine and interferon signature on newborn screening blood spots.

    Science.gov (United States)

    Armangue, Thais; Orsini, Joseph J; Takanohashi, Asako; Gavazzi, Francesco; Conant, Alex; Ulrick, Nicole; Morrissey, Mark A; Nahhas, Norah; Helman, Guy; Gordish-Dressman, Heather; Orcesi, Simona; Tonduti, Davide; Stutterd, Chloe; van Haren, Keith; Toro, Camilo; Iglesias, Alejandro D; van der Knaap, Marjo S; Goldbach Mansky, Raphaela; Moser, Anne B; Jones, Richard O; Vanderver, Adeline

    2017-11-01

    Aicardi Goutières Syndrome (AGS) is a heritable interferonopathy associated with systemic autoinflammation causing interferon (IFN) elevation, central nervous system calcifications, leukodystrophy and severe neurologic sequelae. An infant with TREX1 mutations was recently found to have abnormal C26:0 lysophosphatidylcholine (C26:0 Lyso-PC) in a newborn screening platform for X-linked adrenoleukodystrophy, prompting analysis of this analyte in retrospectively collected samples from individuals affected by AGS. In this study, we explored C26:0 Lyso-PC levels and IFN signatures in newborn blood spots and post-natal blood samples in 19 children with a molecular and clinical diagnosis of AGS and in the blood spots of 22 healthy newborns. We used Nanostring nCounter™ for IFN-induced gene analysis and a high-performance liquid chromatography with tandem mass spectrometry (HPLC MS/MS) newborn screening platform for C26:0 Lyso-PC analysis. Newborn screening cards from patients across six AGS associated genes were collected, with a median disease presentation of 2months. Thirteen out of 19 (68%) children with AGS had elevations of first tier C26:0 Lyso-PC (>0.4μM), that would have resulted in a second screen being performed in a two tier screening system for X-linked adrenoleukodystrophy (X-ALD). The median (95%CI) of first tier C26:0 Lyso-PC values in AGS individuals (0.43μM [0.37-0.48]) was higher than that seen in controls (0.21μM [0.21-0.21]), but lower than X-ALD individuals (0.72μM [0.59-0.84])(p<0.001). Fourteen of 19 children had elevated expression of IFN signaling on blood cards relative to controls (Sensitivity 73.7%, 95%CI 51-88%, Specificity 95%, 95% CI 78-99%) including an individual with delayed disease presentation (36months of age). All five AGS patients with negative IFN signature at birth had RNASEH2B mutations. Consistency of agreement between IFN signature in neonatal and post-natal samples was high (0.85). This suggests that inflammatory markers

  17. A three-year follow-up of congenital adrenal hyperplasia newborn screening.

    Science.gov (United States)

    Pezzuti, Isabela L; Barra, Cristina B; Mantovani, Rafael M; Januário, José N; Silva, Ivani N

    2014-01-01

    congenital adrenal hyperplasia (CAH) newborn screening can prevent neonatal mortality in children with the salt-wasting form of the disease and prevent incorrect gender assignments, which can occur in females. However, the occurrence of false-positive results in preterm or low-birth-weight newborns creates some diagnostic difficulties, with consequent therapeutic implications. This study aimed to report the results of a pilot project for neonatal CAH screening conducted in the state of Minas Gerais, Brazil from 09/2007 to 05/2008 with a three-year follow-up. dried blood specimens were collected on filter paper cards three to seven days after birth of all newborns in the period. Samples were analyzed for 17-hydroxyprogesterone using an enzyme-linked immunosorbent assay (ELISA). a total of 159,415 children were screened. The apparent incidence of the classic variant of the disease was 1:9,963, based on initial diagnoses following newborn screening. During the follow-up period, eight of 16 children initially diagnosed with CAH were reclassified as unaffected, resulting in a revised incidence of 1:19,927. The false-positive rate was 0.31%, and the positive predictive value was 2.1%. Sensitivity and specificity were 100% and 99.7%, respectively. newborn screening is an important public health policy in developing countries such as Brazil, where CAH remains underdiagnosed. It has great potential to identify children with the disease who otherwise cannot be diagnosed earlier. Long-term follow-up and monitoring of all children with positive screening results are crucial to ensure a correct diagnosis and to calculate a reliable incidence ratio of the disease. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  18. Efficacy of screening immune system function in at-risk newborns

    OpenAIRE

    Pavlovski, Christopher J

    2014-01-01

    This paper explores the introduction of a screening test to highlight impaired immune system status for newborn infants and its efficacy as a preventative clinical measure. Moreover, it is suggested that screening of the infantile immune system has the potential to highlight susceptibility to a range of infant and childhood diseases, bestowing an opportunity to introduce early intervention to reduce the incidence of these diseases. Development of the neonatal immune system is an important hea...

  19. Newborn hearing screening with transient evoked otoacoustic emissions and automatic auditory brainstem response

    Directory of Open Access Journals (Sweden)

    Renata Mota Mamede de Carvallo

    2008-09-01

    Full Text Available Objective: The aim of the present investigation was to check Transient Evoked Otoacoustic Emissions and Automatic Auditory Brainstem Response tests applied together in regular nurseries and Newborn Intensive Care Units (NICU, as well as to describe and compare the results obtained in both groups. Methods: We tested 150 newborns from regular nurseries and 70 from NICU. Rresults: The newborn hearing screening results using Transient Evoked Otoacoustic Emissions and Automatic Auditory Brainstem Response tests could be applied to all babies. The “pass” result for the group of babies from the nursery was 94.7% using Transient Evoked Otoacoustic Emissions and 96% using Automatic Auditory Brainstem Response. The newborn intensive care unit group obtained 87.1% on Transient Evoked Otoacoustic Emissions and 80% on the Automatic Auditory Brainstem Response, and there was no statistical difference between the procedures when the groups were evaluated individually. However, comparing the groups, Transient Evoked Otoacoustic Emissions were presented in 94.7% of the nursery babies and in 87.1% in the group from the newborn intensive care unit. Considering the Automatic Auditory Brainstem Response, we found 96 and 87%, respectively. Cconclusions: Transient Evoked Otoacoustic Emissions and Automatic Auditory Brainstem Response had similar “pass” and “fail” results when the procedures were applied to neonates from the regular nursery, and the combined tests were more precise to detect hearing impairment in the newborn intensive care unit babies.

  20. Screening for seemingly healthy newborns with congenital cytomegalovirus infection by quantitative real-time polymerase chain reaction using newborn urine: an observational study.

    Science.gov (United States)

    Yamaguchi, Akira; Oh-Ishi, Tsutomu; Arai, Takashi; Sakata, Hideaki; Adachi, Nodoka; Asanuma, Satoshi; Oguma, Eiji; Kimoto, Hirofumi; Matsumoto, Jiro; Fujita, Hidetoshi; Uesato, Tadashi; Fujita, Jutaro; Shirato, Ken; Ohno, Hideki; Kizaki, Takako

    2017-01-20

    Approximately 8-10% of newborns with asymptomatic congenital cytomegalovirus (cCMV) infection develop sensorineural hearing loss (SNHL). However, the relationship between CMV load, SNHL and central nervous system (CNS) damage in cCMV infection remains unclear. This study aimed to examine the relationship between urinary CMV load, SNHL and CNS damage in newborns with cCMV infection. The study included 23 368 newborns from two maternity hospitals in Saitama Prefecture, Japan. Urine screening for cCMV infection (quantitative real-time PCR) and newborn hearing screening (automated auditory brainstem response (AABR) testing) were conducted within 5 days of birth to examine the incidence of cCMV infection and SNHL, respectively. CNS damage was assessed by MRI of cCMV-infected newborns. The incidence of cCMV infection was 60/23 368 (0.257%; 95% CI 0.192% to 0.322%). The geometric mean urinary CMV DNA copy number in newborns with cCMV was 1.79×10 6 copies/mL (95% CI 7.97×10 5 to 4.02×10 6 ). AABR testing revealed abnormalities in 171 of the 22 229 (0.769%) newborns whose parents approved hearing screening. Of these 171 newborns, 22 had SNHL (12.9%), and 5 of these 22 were infected with cCMV (22.7%). Newborns with both cCMV and SNHL had a higher urinary CMV DNA copy number than newborns with cCMV without SNHL (p=0.036). MRI revealed CNS damage, including white matter abnormalities, in 83.0% of newborns with cCMV. Moreover, newborns with CNS damage had a significantly greater urinary CMV load than newborns without CNS damage (p=0.013). We determined the incidence of cCMV infection and urinary CMV DNA copy number in seemingly healthy newborns from two hospitals in Saitama Prefecture. SNHL and CNS damage were associated with urinary CMV DNA copy number. Quantification of urinary CMV load may effectively predict the incidence of late-onset SNHL and neurodevelopmental disorders. Published by the BMJ Publishing Group Limited. For permission to use (where not already

  1. Initial results from the newborn hearing screening programme in Ireland.

    LENUS (Irish Health Repository)

    O'Connor, A

    2013-03-02

    INTRODUCTION: Hearing screening programmes aim to detect hearing loss in the neonate. The Health Service Executive (HSE) South was the first phase of a national roll-out of a neonatal hearing screening programme in Ireland, going live on 28 April 2011. RESULTS: Over 11,738 babies have been screened for permanent childhood hearing impairment (PCHI) during the first 12 months. The percentage of eligible babies offered hearing screening was 99.2 %. Only 0.2 % (n = 25) of those offered screening declined. 493 (4 %) were referred for immediate diagnostic audiological assessment. The average time between screen and diagnostic audiology appointment was 2 weeks. 15 (1.3\\/1,000) babies have been identified with a PCHI over the 12-month period. 946 (4 %) babies screened were admitted to the neonatal intensive care unit (NICU) for >48 h. The prevalance of PCHI is 7.3\\/1,000 in the NICU population compared to 0.6\\/1000 in the well baby population. 214 (1.8 % of total babies screened) had a clear response in the screening programmes, but were deemed to be at risk of an acquired childhood hearing impairment. These babies will be reassessed with a diagnostic audiology appointment at 8-9 months of age. To date, there is one case of acquired hearing impairment through this targeted follow-up screen. Of the 15 cases of PCHI identified, 8 (53 %) of these had one or more risk factors for hearing loss and 7 (37 %) were admitted to the NICU for >48 h. Four babies were referred for assessment at the National Cochlear Implant Centre.

  2. Second-tier test for quantification of underivatized amino acids in dry blood spot for metabolic diseases in newborn screening.

    Science.gov (United States)

    Wang, Chunyan; Zhu, Hongbin; Zhang, Wenyan; Song, Fengrui; Liu, Zhiqiang; Liu, Shuying

    2013-02-01

    The quantitative analysis of amino acids (AAs) in single dry blood spot (DBS) samples is an important issue for metabolic diseases as a second-tier test in newborn screening. An analytical method for quantifying underivatized AAs in DBS was developed by using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The sample preparation in this method is simple and ion-pairing agent is not used in the mobile phase that could avoid ion suppression, which happens in mass spectrometry and avoids damage to the column. Through chromatographic separation, some isomeric compounds could be identified and quantified, which cannot be solved through only appropriate multiple reactions monitoring transitions by MS/MS. The concentrations of the different AAs were determined using non-deuterated internal standard. All calibration curves showed excellent linearity within test ranges. For most of the amino acids the accuracy of extraction recovery was between 85.3 and 115 %, and the precision of relative standard deviation was <7.0 %. The 35 AAs could be identified in DBS specimens by the developed LC-MS/MS method in 17-19 min, and eventually 24 AAs in DBS were quantified. The results of the present study prove that this method as a second-tier test in newborn screening for metabolic diseases could be performed by the quantification of free AAs in DBS using the LC-MS/MS method. The assay has advantages of high sensitive, specific, and inexpensive merits because non-deuterated internal standard and acetic acid instead of ion-pairing agent in mobile phase are used in this protocol.

  3. VLCAD deficiency: Pitfalls in newborn screening and confirmation of diagnosis by mutation analysis

    DEFF Research Database (Denmark)

    Boneh, A; Andresen, Brage Storstein; Gregersen, Niels

    2006-01-01

    samples taken at age 48-72 h were diagnostic whereas repeat samples at an older age were normal in 4/6 babies. Urine analysis was normal in 5/5. We conclude that the timing of blood sampling for newborn screening is important and that it is important to perform mutation analysis to avoid false......-negative diagnoses of VLCADD in asymptomatic newborn babies. In view of the emerging genotype-phenotype correlation in this disorder, the information derived from mutational analysis can be helpful in designing the appropriate follow-up and therapeutic regime for these patients....

  4. Newborn screening for congenital adrenal hyperplasia in Cuba: six years of experience.

    Science.gov (United States)

    González, Ernesto Carlos; Carvajal, Frank; Frómeta, Amarilys; Arteaga, Ana Luisa; Castells, Elisa María; Espinosa, Tania; Coto, Remigio; Pérez, Pedro Lucio; Tejeda, Yileidis; Del Río, Lesley; Segura, Mary Triny; Almenares, Pedro; Robaina, René; Fernández, José Luis

    2013-06-05

    Since 2005, a newborn screening program for congenital adrenal hyperplasia (CAH) by measuring 17-alpha-hydroxyprogesterone (17OHP) in dried blood spots was introduced in Cuba. The hormone was measured by the 17OHP Neonatal UMELISA method, in samples collected on the 5th day as average. Confirmatory test was performed to those neonates with 17OHP values above 55 nmol/l. Some perinatal factors that can influence on 17OHP levels were studied. From January 2005 to December 2010, 621,303 newborns were screened and 39 CAH cases were detected. Coverage of the program reached 98%. The incidence of CAH in Cuba was 1:15,931, similar to that reported by other programs. A recall for suspected CAH was performed in 10,799 cases (1.74%). Therapy in classical CAH patients was started at the mean age of 22 days. 17OHP levels were significantly higher in newborns with lower birth-weight (BW) and/or gestational age (GA). In addition, 17OHP values were affected by the gender, twin status or mode of delivery. In Cuba, the nationwide newborn screening program has allowed the early detection of CAH. The use of an optimized cut-off level for BW or GA could lead to a reduction in the percentage of recalled babies. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Temporal trends of polybrominated diphenyl ethers (PBDEs) in the blood of newborns from New York State during 1997 through 2011: analysis of dried blood spots from the newborn screening program.

    Science.gov (United States)

    Ma, Wan-Li; Yun, Sehun; Bell, Erin M; Druschel, Charlotte M; Caggana, Michele; Aldous, Kenneth M; Buck Louis, Germaine M; Kannan, Kurunthachalam

    2013-07-16

    Polybrominated diphenyl ethers (PBDEs) are ubiquitous environmental pollutants, and on a global basis, North American populations are exposed to the highest doses of PBDEs. In response to the exponential increase in human exposure to PBDEs during the late 1990s, some PBDE formulations were phased out from production in the early 2000s. The effectiveness of the phase-out of commercial penta-BDE and octa-BDE mixtures in 2004 in the U.S. on human exposure levels is not known. Dried blood spots (DBSs), collected for the newborn screening program (NSP) in the U.S., are a valuable resource for the elucidation of trends in exposure to environmental pollutants in newborns. In this study, seven PBDE congeners were determined by gas chromatography-high resolution mass spectrometry (GC-HRMS) in archived DBS samples (in total, 51 blood spot composites from 1224 newborns) collected from newborns in New York State (NYS) from 1997 to 2011. The most frequently detected PBDE congener was BDE-47, with a detection rate (DR) of 86%, followed by BDE-99 (DR: 45%) and BDE-100 (DR: 43%). The mean concentrations determined during 1997 through 2011 in the whole blood of newborns were 0.128, 0.040, and 0.012 ng/mL for BDE-47, -99, and -100, respectively. A significant correlation was found among the concentrations of three major congeners (p < 0.001). PBDE concentrations were similar during 1997 through 2002 and, thereafter, decreased significantly, which was similar to the trends observed for perfluorinated compounds (PFCs) in DBS samples. Occurrence of PBDEs in the whole blood of newborns confirms that these compounds do cross the placental barrier.

  6. Inborn errors of metabolism and expanded newborn screening: review and update.

    Science.gov (United States)

    Mak, Chloe Miu; Lee, Han-Chih Hencher; Chan, Albert Yan-Wo; Lam, Ching-Wan

    2013-11-01

    Inborn errors of metabolism (IEM) are a phenotypically and genetically heterogeneous group of disorders caused by a defect in a metabolic pathway, leading to malfunctioning metabolism and/or the accumulation of toxic intermediate metabolites. To date, more than 1000 different IEM have been identified. While individually rare, the cumulative incidence has been shown to be upwards of 1 in 800. Clinical presentations are protean, complicating diagnostic pathways. IEM are present in all ethnic groups and across every age. Some IEM are amenable to treatment, with promising outcomes. However, high clinical suspicion alone is not sufficient to reduce morbidities and mortalities. In the last decade, due to the advent of tandem mass spectrometry, expanded newborn screening (NBS) has become a mandatory public health strategy in most developed and developing countries. The technology allows inexpensive simultaneous detection of more than 30 different metabolic disorders in one single blood spot specimen at a cost of about USD 10 per baby, with commendable analytical accuracy and precision. The sensitivity and specificity of this method can be up to 99% and 99.995%, respectively, for most amino acid disorders, organic acidemias, and fatty acid oxidation defects. Cost-effectiveness studies have confirmed that the savings achieved through the use of expanded NBS programs are significantly greater than the costs of implementation. The adverse effects of false positive results are negligible in view of the economic health benefits generated by expanded NBS and these could be minimized through increased education, better communication, and improved technologies. Local screening agencies should be given the autonomy to develop their screening programs in order to keep pace with international advancements. The development of biochemical genetics is closely linked with expanded NBS. With ongoing advancements in nanotechnology and molecular genomics, the field of biochemical genetics

  7. Elevated phenylalanine on newborn screening: follow-up testing may reveal undiagnosed galactosaemia.

    Science.gov (United States)

    Shakespeare, Lynette; Downing, Melanie; Allen, Joyce; Casbolt, Ann-Marie; Ellin, Sheila; Maloney, Martin; Race, Gillian; Bonham, Jim

    2010-11-01

    Introduction Newborn screening for phenylketonuria (PKU) can reveal other conditions which lead to an increased blood spot phenylalanine (Phe) concentration. We have investigated the proportion of blood spot samples that gave a positive screen due to clinically significant conditions other than PKU, compared the positive predictive value (PPV) of our referral Phe cut-off with that recommended by the UK Newborn Screening Programme Centre (UKNSPC) (>210 and >240 μmol/L, respectively) and evaluated the effectiveness of reflex testing for galactosaemia using a lower blood spot Phe cut-off concentration of 130 μmol/L. All blood spot samples that screened positive, for an increased Phe concentration, between April 2001 and March 2008, were identified from the records of the Sheffield Newborn Screening Laboratory and the diagnoses noted. In addition, all cases of galactosaemia detected in or notified to our screening laboratory within this time were also examined and the screened Phe concentrations compared. Out of 438,674 babies who were screened, 67 had Phe concentration >210 μmol/L (15 per 100,000). Of these, 40 had PKU or persistent hyperphenylalaninaemia with a Phe concentration identified by screening between 270 and 2350 μmol/L. A further 11 were diagnosed with another clinically significant disorder: galactosaemia (n = 8), biopterin defects (n = 2), tyrosinaemia Type 1 (n = 1). In addition, 16 had transient elevations in Phe. In total, nine cases of galactosaemia were identified, of whom, three had Phe concentrations 240 μmol/L) will not affect the detection rate of classical PKU, but will improve the PPV from 76% to 80%. The use of a lower cut-off (130 μmol/L) for reflex galactosaemia testing enables the timely identification of asymptomatic cases that benefit particularly from early treatment, without prompting any unnecessary clinical referrals or delaying any referrals. This intervention may reduce mortality in this vulnerable group.

  8. Screening of a healthy newborn identifies three adult family members with symptomatic glutaric aciduria type I

    Directory of Open Access Journals (Sweden)

    MCH Janssen

    2014-06-01

    Full Text Available We report three adult sibs (one female, two males with symptomatic glutaric acidura type I, who were diagnosed after a low carnitine level was found by newborn screening in a healthy newborn of the women. All three adults had low plasma carnitine, elevated glutaric acid levels and pronounced 3-hydroxyglutaric aciduria. The diagnosis was confirmed by undetectable glutaryl-CoA dehydrogenase activity in lymphocytes and two pathogenic heterozygous mutations in the GCDH gene (c.1060A>G, c.1154C>T. These results reinforce the notion that abnormal metabolite levels in newborns may lead to the diagnosis of adult metabolic disease in the mother and potentially other family members.

  9. Newborn hearing screening: a regional example for national care.

    LENUS (Irish Health Repository)

    Adelola, O A

    2010-05-01

    Congenital Permanent Childhood Hearing Impairment (PCHI) is known to have a negative effect on language acquisition, cognitive development and social integration. Since 2000 our department has implemented a UNHS program in the West of Ireland. We describe our experience and detail our results to date. All neonates born from October 2000 to November 2007 were screened using a 2-stage protocol. Transient evoked oto-acoustic emissions (TEOAEs) were used to screen all neonates, followed by automated auditory brainstem response (AABR) in those who did not pass TEOAE, and all neonates at audiological risk. 26,281 babies were born over the eight year period. 25,742 underwent the screening process, achieving a coverage rate of 98%. The prevalence of PCHI in the population tested was 1.21\\/1000 live births (31\\/25,731). Our results show that a hospital based 2-stage UNHS protocol using TEOAEs and AABR is accurate, feasible and effective.

  10. Applications of ambient mass spectrometry in high-throughput screening.

    Science.gov (United States)

    Li, Li-Ping; Feng, Bao-Sheng; Yang, Jian-Wang; Chang, Cui-Lan; Bai, Yu; Liu, Hu-Wei

    2013-06-07

    The development of rapid screening and identification techniques is of great importance for drug discovery, doping control, forensic identification, food safety and quality control. Ambient mass spectrometry (AMS) allows rapid and direct analysis of various samples in open air with little sample preparation. Recently, its applications in high-throughput screening have been in rapid progress. During the past decade, various ambient ionization techniques have been developed and applied in high-throughput screening. This review discusses typical applications of AMS, including DESI (desorption electrospray ionization), DART (direct analysis in real time), EESI (extractive electrospray ionization), etc., in high-throughput screening (HTS).

  11. [The comparison of two newborn cytomegalovirus IgG antibody screening ELISA kits].

    Science.gov (United States)

    Zhang, Shun-Xian; He, Xiao-Zhou; Wang, Shi-Wen; Wang, Xiao-Fang

    2013-10-01

    This study compared two newborn Cytomegalovirus (CMV) IgG antibody screening ELISA kits and evaluated the detection effectiveness of Abnova kit. CMV IgG antibodies were detected by both SeraQuest and Abnova kits from dried blood spot (DBS) samples of 488 newborn heel sticks. The detection abilities of these two kits were compared in different sample dilution concentrations. Relative detection effectiveness of the Abnova kit was defined by statistical method using the SeraQuest kit as a point of comparison. Compared to the SeraQuest screening test kit, the Abnova kit revealed a sensitivity of 98.9%, specificity of 78.6%, positive predictive value of 99.3%, negative predictive value of 68.8%, and the coincidence rate for these two screening test kits at 98.3%. The consistency check of both kits based on interpretation of the kappa statistic was relatively good. For the Abnova kit, the "area under the ROC curve" was 0.887, which indicates moderate accuracy. Abnova kit can be applied to newborn screening for congenital CMV infections. However, repeating the test for ambiguous results is suggested to increase the specificity and negative predictive value.

  12. Systematic review of knowledge of, attitudes towards, and practices for newborn hearing screening among healthcare professionals.

    Science.gov (United States)

    Ravi, Rohit; Gunjawate, Dhanshree R; Yerraguntla, Krishna; Rajashekhar, Bellur

    2018-01-01

    The success of newborn hearing screening programs lies in the timely identification, diagnosis, and management of children with hearing loss accomplished via a multidisciplinary newborn hearing screening (NHS) team. The team is typically comprised of various healthcare professionals who act as decision makers as well as facilitators for different stages in the screening process. Team members' knowledge of, attitudes towards, and practices for early hearing detection and intervention programs are critical for success and prevention of loss to follow up. In this context, it becomes crucial to understand their knowledge of, attitudes towards, and practices for towards newborn hearing screening. A systematic review was conducted on the following databases; PubMed/Medline, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, Web of Science, Science Direct and Cochrane Library. This search was carried out using various keywords such as practitioners, newborn hearing screening, knowledge, attitudes, and practices in different combinations. The review was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-analyses statement guidelines. A total of 271 hits were obtained of which 20 articles were found suitable for inclusion in the final review. Overall, similar results were found regarding team members' knowledge of NHS programs, regardless of country of origin. Similarly, attitudes toward NHS programs were positive. Team members' experiences with NHS programs varied from country-to-country and across healthcare professionals. Results consistently showed gaps in team members' knowledge suggesting the need for outreach and professional education programs on NHS. NHS teams members from different countries, healthcare systems, and early hearing detection and intervention programs show gaps in critical knowledge warranting outreach and educational programs. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Clinical evaluation of the Nanoduct sweat test system in the diagnosis of cystic fibrosis after newborn screening

    NARCIS (Netherlands)

    Vernooij-van Langen, Annette; Dompeling, Edward; Yntema, Jan-Bart; Arets, HGM; Tiddens, Harm; Loeber, Gerard; Dankert-Roelse, Jeannette

    After a positive newborn screening test for cystic fibrosis (CF), a sweat test is performed to confirm the diagnosis. The success rate of the generally acknowledged methods (Macroduct/Gibson and Cooke) in newborns varies between 73 and 99 %. The Nanoduct sweat test system is easier to perform and

  14. First Colombian multicentric newborn screening for congenital toxoplasmosis.

    Directory of Open Access Journals (Sweden)

    Jorge Enrique Gómez-Marin

    Full Text Available AIMS: To determine the incidence of congenital toxoplasmosis in Colombian newborns from 19 hospital or maternal child health services from seven different cities of five natural geographic regions (Caribbean, Central, Andean, Amazonia and Eastern. MATERIALS AND METHODS: We collected 15,333 samples from umbilical cord blood between the period of March 2009 to May 2010 in 19 different hospitals and maternal-child health services from seven different cities. We applied an IgM ELISA assay (Vircell, Spain to determine the frequency of IgM anti Toxoplasma. The results in blood cord samples were confirmed either by western blot and repeated ELISA IgM assay. In a sub-sample of 1,613 children that were negative by the anti-Toxoplasma IgM assay, the frequency of specific anti-Toxoplasma IgA by the ISAGA assay was determined. All children with positive samples by IgM, IgA, clinical diagnosis or treatment during pregnancy were recalled for confirmatory tests after day 10 of life. RESULTS: 61 positive samples for specific IgM (0.39% and 9 positives for IgA (0.5% were found. 143 questionnaires were positive for a clinical diagnosis or treatment for toxoplasmosis during pregnancy. 109 out of the 218 children that had some of the criteria for postnatal confirmatory tests were followed. Congenital toxoplasmosis infection was confirmed in 15 children: 7 were symptomatic, and three of them died before the first month of life (20% of lethality. A significant correlation was found between a high incidence of markers for congenital toxoplasmosis and higher mean annual rainfall for the city. CONCLUSIONS: Incidence for congenital toxoplasmosis is significantly different between hospitals or maternal child health services from different cities in Colombia. Mean annual rainfall was correlated with incidence of congenital toxoplasmosis.

  15. Infrastructure and Educational Needs of Newborn Screening Short-Term Follow-Up Programs within the Southeast Regional Newborn Screening & Genetics Collaborative: A Pilot Survey

    Directory of Open Access Journals (Sweden)

    Cecelia A. Bellcross

    2015-10-01

    Full Text Available Newborn screening (NBS follow-up protocols vary significantly by state, and there is a need to better understand the infrastructure and communication flow of NBS programs. In addition, assessment of the educational needs of families and providers with regard to the implications of NBS results is required to inform the development of appropriate informational resources and training opportunities. To begin to address these issues, we administered a web-based survey to state NBS coordinators within the Southeast Regional Newborn Screening & Genetics Collaborative (SERC. Fourteen coordinators responded to the survey, including at least one from each of the 10 SERC states/territories. Over one-third of respondents had never received formal training regarding the metabolic conditions identified on NBS. Most communicated results via telephone or fax, though two centers indicated use of a web-based platform. Only two programs were involved in directly reporting results to the family. Four programs reported a long-term follow-up protocol. Deficits were noted for primary care provider (PCP knowledge of metabolic disorders identified on NBS, and how to inform parents of abnormal results. Close to half indicated that the adequacy of the number of genetic counselors, dietitians, and medical/biochemical geneticists was minimal to insufficient. Respondents uniformly recognized the importance of providing additional educational and informational resources in multiple categories to NBS staff, PCPs, and families.

  16. Common criteria among States for storage and use of dried blood spot specimens after newborn screening

    Directory of Open Access Journals (Sweden)

    Carlo Petrini

    2012-06-01

    Full Text Available Biological samples collected in biobanks are a resource with significant research potential. The Italian Joint Group cNB - cNBBSV (National committee of Bioethics - National committee for Biosecurity, Biotechnologies and Life Sciences published a document reporting recommendations on storage and use of dried blood spot (DBS and on the development of a National Network of Regional Newborn Screening Repositories for collection of residual DBS. Several ethical questions (about consent, possible use of genetic information, unanticipated possible usages for research purposes rise from residual newborn screening specimens collections. Moreover, legal and ethical controversies are accentuated by the conflicts between the interests of sample donors, biobank holders, researchers and the public. To overcome these difficulties the identification of a few criteria for storage and research usage of DBS is crucial.

  17. Good laboratory practices for biochemical genetic testing and newborn screening for inherited metabolic disorders.

    Science.gov (United States)

    2012-04-06

    Biochemical genetic testing and newborn screening are essential laboratory services for the screening, detection, diagnosis, and monitoring of inborn errors of metabolism or inherited metabolic disorders. Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) regulations, laboratory testing is categorized on the basis of the level of testing complexity as either waived (i.e., from routine regulatory oversight) or nonwaived testing (which includes tests of moderate and high complexity). Laboratories that perform biochemical genetic testing are required by CLIA regulations to meet the general quality systems requirements for nonwaived testing and the personnel requirements for high-complexity testing. Laboratories that perform public health newborn screening are subject to the same CLIA regulations and applicable state requirements. As the number of inherited metabolic diseases that are included in state-based newborn screening programs continues to increase, ensuring the quality of performance and delivery of testing services remains a continuous challenge not only for public health laboratories and other newborn screening facilities but also for biochemical genetic testing laboratories. To help ensure the quality of laboratory testing, CDC collaborated with the Centers for Medicare & Medicaid Services, the Food and Drug Administration, the Health Resources and Services Administration, and the National Institutes of Health to develop guidelines for laboratories to meet CLIA requirements and apply additional quality assurance measures for these areas of genetic testing. This report provides recommendations for good laboratory practices that were developed based on recommendations from the Clinical Laboratory Improvement Advisory Committee, with additional input from the Secretary's Advisory Committee on Genetics, Health, and Society; the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children; and representatives of newborn

  18. Universal newborn screening for congenital CMV infection: what is the evidence of potential benefit?†

    OpenAIRE

    Cannon, Michael J.; Griffiths, Paul D.; Aston, Van; Rawlinson, William D.

    2014-01-01

    Congenital CMV infection is a leading cause of childhood disability. Many children born with congenital CMV infection are asymptomatic or have nonspecific symptoms and therefore are typically not diagnosed. A strategy of newborn CMV screening could allow for early detection and intervention to improve clinical outcomes. Interventions might include antiviral drugs or nonpharmaceutical therapies such as speech-language therapy or cochlear implants. Using published data from developed countries,...

  19. Parental knowledge reduces long term anxiety induced by false-positive test results after newborn screening for cystic fibrosis

    NARCIS (Netherlands)

    Vernooij-van Langen, A.M.M.; Pal, S.M. van der; Reijntjens, A.J.T.; Loeber, J.G.; Dompeling, E.; Dankert-Roelse, J.E.

    2014-01-01

    Background: False-positive screening results in newborn screening for cystic fibrosis may lead to parental stress, family relationship problems and a changed perception of the child's health. Aim of the study: To evaluate whether parental anxiety induced by a false positive screening result

  20. Saliva Polymerase-Chain-Reaction Assay for Cytomegalovirus Screening in Newborns

    Science.gov (United States)

    Boppana, Suresh B.; Ross, Shannon A.; Shimamura, Masako; Palmer, April L.; Ahmed, Amina; Michaels, Marian G.; Sánchez, Pablo J.; Bernstein, David I.; Tolan, Robert W.; Novak, Zdenek; Chowdhury, Nazma; Britt, William J.; Fowler, Karen B.

    2011-01-01

    BACKGROUND Congenital cytomegalovirus (CMV) infection is an important cause of hearing loss, and most infants at risk for CMV-associated hearing loss are not identified early in life because of failure to test for the infection. The standard assay for newborn CMV screening is rapid culture performed on saliva specimens obtained at birth, but this assay cannot be automated. Two alternatives — real-time polymerase-chain-reaction (PCR)–based testing of a liquid-saliva or dried-saliva specimen obtained at birth — have been developed. METHODS In our prospective, multicenter screening study of newborns, we compared real-time PCR assays of liquid-saliva and dried-saliva specimens with rapid culture of saliva specimens obtained at birth. RESULTS A total of 177 of 34,989 infants (0.5%; 95% confidence interval [CI], 0.4 to 0.6) were positive for CMV, according to at least one of the three methods. Of 17,662 newborns screened with the use of the liquid-saliva PCR assay, 17,569 were negative for CMV, and the remaining 85 infants (0.5%; 95% CI, 0.4 to 0.6) had positive results on both culture and PCR assay. The sensitivity and specificity of the liquid-saliva PCR assay were 100% (95% CI, 95.8 to 100) and 99.9% (95% CI, 99.9 to 100), respectively, and the positive and negative predictive values were 91.4% (95% CI, 83.8 to 96.2) and 100% (95% CI, 99.9 to 100), respectively. Of 17,327 newborns screened by means of the dried-saliva PCR assay, 74 were positive for CMV, whereas 76 (0.4%; 95% CI, 0.3 to 0.5) were found to be CMV-positive on rapid culture. Sensitivity and specificity of the dried-saliva PCR assay were 97.4% (95% CI, 90.8 to 99.7) and 99.9% (95% CI, 99.9 to 100), respectively. The positive and negative predictive values were 90.2% (95% CI, 81.7 to 95.7) and 99.9% (95% CI, 99.9 to 100), respectively. CONCLUSIONS Real-time PCR assays of both liquid- and dried-saliva specimens showed high sensitivity and specificity for detecting CMV infection and should be

  1. Newborn Hearing Screening and Early Diagnostic in the NICU

    Directory of Open Access Journals (Sweden)

    Maria Francisca Colella-Santos

    2014-01-01

    Full Text Available The aim was to describe the outcome of neonatal hearing screening (NHS and audiological diagnosis in neonates in the NICU. The sample was divided into Group I: neonates who underwent NHS in one step and Group II: neonates who underwent a test and retest NHS. NHS procedure was automated auditory brainstem response. NHS was performed in 82.1% of surviving neonates. For GI, referral rate was 18.6% and false-positive was 62.2% (normal hearing in the diagnostic stage. In GII, with retest, referral rate dropped to 4.1% and false-positive to 12.5%. Sensorineural hearing loss was found in 13.2% of infants and conductive in 26.4% of cases. There was one case of auditory neuropathy spectrum (1.9%. Dropout rate in whole process was 21.7% for GI and 24.03% for GII. We concluded that it was not possible to perform universal NHS in the studied sample or, in many cases, to apply it within the first month of life. Retest reduced failure and false-positive rate and did not increase evasion, indicating that it is a recommendable step in NHS programs in the NICU. The incidence of hearing loss was 2.9%, considering sensorineural hearing loss (0.91%, conductive (1.83% and auditory neuropathy spectrum (0.19%.

  2. Psychological effects of false-positive results in expanded newborn screening in China.

    Directory of Open Access Journals (Sweden)

    Wen-Jun Tu

    Full Text Available OBJECTIVES: As more families participate expanded newborn screening for metabolic disorders in China, the overall number of false positives increases. Our goal was to assess the potential impact on parental stress, perceptions of the child's health, and family relationships. METHODS: Parents of 49 infants with false-positive screening results for metabolic disorders in the expanded newborn screening panel were compared with parents of 42 children with normal screening results. Parents first completed structured interview using likert scales, closed and open questions. Parents also completed the parenting stress index. RESULTS: A total of 88 mothers and 41 fathers were interviewed. More mothers in the false-positive group reported that their children required extra parental care (21%, compared with 5% of mothers in the normal-screened group (P<0.001. 39% of mothers in the false-positive group reported that they worry about their child's future development, compared with 10% of mothers in the normal-screened group (P<0.001. Fathers in the false-positive group did not differ from fathers in the normal-screened group in reporting worry about their child's extra care requirements, and their child's future development. Children with false-positive results compared with children with normal results were triple as likely to experience hospitalization (27%vs 9%, respectively; P<0.001. CONCLUSIONS: The results showing false-positive screening results may affect parental stress and the parent-child relationship. Parental stress and anxiety can be reduced with improved education and communication to parents about false-positive results.

  3. Congenital cytomegalovirus infection : disease burden and screening tools : towards newborn screening

    NARCIS (Netherlands)

    Vries, Jutte Jacoba Catharina de

    2012-01-01

    Cytomegalovirus (CMV) infection is the most common congenital viral infection worldwide. The symptom of congenital CMV infection encountered most frequently is sensorineural hearing loss, which will affect approximately one out of five congenitally infected newborns. Because of the late-onset nature

  4. Impact of age at onset and newborn screening on outcome in organic acidurias

    DEFF Research Database (Denmark)

    Heringer, Jana; Valayannopoulos, Vassili; Lund, Allan M

    2016-01-01

    analyses, symptomatic patients were divided into those presenting with first symptoms during (i.e. early onset, EO) or after the newborn period (i.e. late onset, LO). RESULTS: Patients identified by newborn screening (NBS) had a significantly lower median age of diagnosis (8 days) compared to the LO group...... % versus 39 %, p = 0.002; GA1: 26 % versus 73 %, p age-adjusted intake of natural protein and calories was significantly higher in LO patients than in EO patients reflecting different disease severities. Variable drug...... combinations, ranging from 12 in MMA-Cbl(-) to two in isovaleric aciduria, were used for maintenance treatment. The effects of specific metabolic treatment strategies on the health outcomes remain unclear because of the strong influences of age at onset (EO versus LO), diagnostic mode (NBS versus selective...

  5. NEWBORN SCREENING PROGRAM: WHY TO COLLECT IN HIGH THE HOSPITAL ONE?

    Directory of Open Access Journals (Sweden)

    Maria Ribeiro Lacerda

    2003-12-01

    Full Text Available The National Program of Newborn Screening for research of the Phenylketonuria, Congenital Hypothyroidism,Cystic Fibrosis, Sickle Cell Disease and other Hemoglobinopathies, it has as objective precociously todetect and to treat illnesses that, if prevented, prevent sequels as the mental deficiency and others. We intend,through this article, to awake the attention of the health professionals, mainly of the nurses, who act in the attendanceof the just-been newborn, of the gestante, the woman in labor and in puerperium, on the importance of theprecocious diagnosis of the diseases searched in the Program, with primordial purposes to assist the suckle for itsgood physical, neurological, psychological and intellectual development, besides offering to familiar the o geneticadvise. The examination gratuitous and is supported by law, and so that the prevention is effective, all the Maternitiesmust always carry through the collections of sample of blood of the heel of the high baby in the hospital one.

  6. Evaluation of TSH Levels in the Program of Congenital Hypothyroidism Newborn Screening in a Pilot Study of Preterm Newborns in Bogotá, Colombia

    Directory of Open Access Journals (Sweden)

    Gustavo Adolfo Giraldo

    2015-07-01

    Full Text Available Introduction: Preterm infants (<37 weeks of gestation have low levels of thyroid hormones due to multiple factors. Objective: To evaluate levels of thyroid-stimulation hormone (TSH in the program congenital hypothyroidism (CH newborn screening in a sample of preterm infants in the city of Bogotá, Colombia. Methods: The Secretaría de Salud Distrital screening protocol for CH (blood sample is collected from the umbilical cord in all the newborns remeasured the serum TSH and heel TSH when preterm infants completed 37 weeks of gestation. Results: A total of 59 preterm neonates were rescreened, of which 2 neonates had elevated levels of TSH and 1 neonate had transient hypothyroxinemia. The Kolmogorov-Smirnov 2-sample/bilateral statistical test was used to compare the neonatal TSH levels of preterm and full-term newborns, which do not follow the same distribution. Conclusion: In our pilot study, 2 of the rescreened infants presented high levels of TSH and 1 had transient hyperthyrotropinemia, suggesting the need for rescreening of preterm infants. Additionally, a larger study should be performed to determine the screening cutoff values for preterm newborns.

  7. Analysis of risk factors associated with unilateral hearing loss in children who initially passed newborn hearing screening.

    Science.gov (United States)

    Appelbaum, Eric N; Howell, Jessica B; Chapman, Derek; Pandya, Arti; Dodson, Kelley M

    2018-03-01

    To analyze 2007 Joint Committee on Infant Hearing (JCIH) risk factors in children with confirmed unilateral hearing loss (UHL) who initially passed newborn hearing screening. Retrospective record review of 16,108 infants who passed newborn hearing screening but had one or more JCIH risk factors prompting subsequent follow-up through the universal newborn hearing screening (UNHS) program in Virginia from 2010 to 2012. The study was reviewed and qualified as exempt by the Virginia Commonwealth University Institutional Review Board (IRB) and the Virginia Department of Health. Over the 2-year study period, 14896 (4.9% of total births) children passed UNHS but had the presence of one or more JCIH risk factor. Ultimately, we identified 121 babies from this group with confirmed hearing loss (0.7%), with 48 babies (0.2%) showing UHL. The most common risk factors associated with the development of confirmed UHL after passing the initial screen were neonatal indicators, craniofacial anomalies, family history, and stigmata of syndrome associated with hearing loss. Neonatal indicators and craniofacial anomalies were the categories most often found in children with confirmed unilateral hearing loss who initially passed their newborn hearing screen. While neonatal indicators were also the most common associated risk factor in all hearing loss, craniofacial abnormalities are relatively more common in children with UHL who initially passed newborn hearing screening. Further studies assessing the etiology underlying the hearing loss and risk factor associations are warranted. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Tandem mass spectrometry, but not T-cell receptor excision circle analysis, identifies newborns with late-onset adenosine deaminase deficiency.

    Science.gov (United States)

    la Marca, Giancarlo; Canessa, Clementina; Giocaliere, Elisa; Romano, Francesca; Duse, Marzia; Malvagia, Sabrina; Lippi, Francesca; Funghini, Silvia; Bianchi, Leila; Della Bona, Maria Luisa; Valleriani, Claudia; Ombrone, Daniela; Moriondo, Maria; Villanelli, Fabio; Speckmann, Carsten; Adams, Stuart; Gaspar, Bobby H; Hershfield, Michael; Santisteban, Ines; Fairbanks, Lynette; Ragusa, Giovanni; Resti, Massimo; de Martino, Maurizio; Guerrini, Renzo; Azzari, Chiara

    2013-06-01

    Adenosine deaminase (ADA)-severe combined immunodeficiency (SCID) is caused by genetic variants that disrupt the function of ADA. In its early-onset form, it is rapidly fatal to infants. Delayed or late-onset ADA-SCID is characterized by insidious progressive immunodeficiency that leads to permanent organ damage or death. Quantification of T-cell receptor excision circles (TRECs) or tandem mass spectrometry (tandem-MS) analysis of dried blood spots (DBSs) collected at birth can identify newborns with early-onset ADA-SCID and are used in screening programs. However, it is not clear whether these analyses can identify newborns who will have delayed or late-onset ADA-SCID before symptoms appear. We performed a retrospective study to evaluate whether tandem-MS and quantitative TREC analyses of DBSs could identify newborns who had delayed-onset ADA-SCID later in life. We tested stored DBSs collected at birth from 3 patients with delayed-onset ADA-SCID using tandem-MS (PCT EP2010/070517) to evaluate levels of adenosine and 2'-deoxyadenosine and real-time PCR to quantify TREC levels. We also analyzed DBSs from 3 newborns with early-onset ADA-SCID and 2 healthy newborn carriers of ADA deficiency. The DBSs taken at birth from the 3 patients with delayed-onset ADA-SCID had adenosine levels of 10, 25, and 19 μmol/L (normal value, <1.5 μmol/L) and 2'-deoxyadenosine levels of 0.7, 2.7, and 2.4 μmol/L (normal value, <0.07 μmol/L); the mean levels of adenosine and 2'-deoxyadenosine were respectively 12.0- and 27.6-fold higher than normal values. DBSs taken at birth from all 3 patients with delayed-onset ADA deficiency had normal TREC levels, but TRECs were undetectable in blood samples taken from the same patients at the time of diagnosis. Tandem-MS but not TREC quantification identifies newborns with delayed- or late-onset ADA deficiency. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  9. Newborn Screening for Primary Immunodeficiency Diseases: The Past, the Present and the Future

    Directory of Open Access Journals (Sweden)

    Jovanka King

    2017-08-01

    Full Text Available Primary immunodeficiency diseases (PID are a heterogeneous group of disorders caused by inborn errors of immunity, with affected children presenting with severe, recurrent or unusual infections. Over 300 distinct genetic molecular abnormalities resulting in PID have been identified, and this number continues to rise. Newborn screening for PID has been established in many countries, with the majority of centers using a PCR-based T cell receptor excision circle (TREC assay to screen for severe combined immunodeficiency (SCID and other forms of T cell lymphopenia. Multiplexed screening including quantitation of kappa-recombining exclusion circles (KREC has also been described, offering advantages over TREC screening alone. Screening technologies are also expanding to include protein-based assays to identify complement deficiencies and granulocyte disorders. Given the rapid advances in genomic medicine, a potential future direction is the application of next-generation sequencing (NGS technologies to screen infants for a panel of genetic mutations, which would enable identification of a wide range of diseases. However, several ethical and economic issues must be considered before moving towards this screening strategy.

  10. Susceptibility of pregnant women to toxoplasma infection--potential benefits for newborn screening.

    LENUS (Irish Health Repository)

    Ferguson, W

    2008-08-20

    Congenital toxoplasmosis (CT) arises as a result of new acquisition of Toxoplasma infection by a susceptible woman during pregnancy. Early detection of CT through neonatal screening programmes could optimize management and improve infant outcome. This study sought to estimate the prevalence of Toxoplasma susceptibility in pregnant women. As detection of Toxoplasma antibodies in neonatal blood reflects maternal exposure history, maternal antibody seroprevalence was determined using anonymized residual blood from newborn screening cards. A total of 20,252 cards were tested in 1 year. 4,991 (24.6%) cards tested positive for Toxoplasma antibody. Results were stratified by county. Toxoplasma antibody seroprevalence rates of 25% indicated that Toxoplasma infection is common in Ireland and that up to 75% of women remain susceptible to primary infection during pregnancy. This study aimed to a) determine the seroprevalence of Toxoplasma antibody in pregnant women, and hence b) estimate the risk for acquisition of primary toxoplasmosis in pregnancy in order to support an application to fund a pilot newborn screening programme.

  11. Universal newborn screening for congenital CMV infection: what is the evidence of potential benefit?

    Science.gov (United States)

    Cannon, Michael J; Griffiths, Paul D; Aston, Van; Rawlinson, William D

    2014-09-01

    Congenital CMV infection is a leading cause of childhood disability. Many children born with congenital CMV infection are asymptomatic or have nonspecific symptoms and therefore are typically not diagnosed. A strategy of newborn CMV screening could allow for early detection and intervention to improve clinical outcomes. Interventions might include antiviral drugs or nonpharmaceutical therapies such as speech-language therapy or cochlear implants. Using published data from developed countries, we analyzed existing evidence of potential benefit that could result from newborn CMV screening. We first estimated the numbers of children with the most important CMV-related disabilities (i.e. hearing loss, cognitive deficit, and vision impairment), including the age at which the disabilities occur. Then, for each of the disabilities, we examined the existing evidence for the effectiveness of various interventions. We concluded that there is good evidence of potential benefit from nonpharmaceutical interventions for children with delayed hearing loss that occurs by 9 months of age. Similarly, we concluded that there is fair evidence of potential benefit from antiviral therapy for children with hearing loss at birth and from nonpharmaceutical interventions for children with delayed hearing loss occurring between 9 and 24 months of age and for children with CMV-related cognitive deficits. We found poor evidence of potential benefit for children with delayed hearing loss occurring after 24 months of age and for children with vision impairment. Overall, we estimated that in the United States, several thousand children with congenital CMV could benefit each year from newborn CMV screening, early detection, and interventions. Copyright © 2014 John Wiley & Sons, Ltd.

  12. Universal newborn screening for congenital CMV infection: what is the evidence of potential benefit?†

    Science.gov (United States)

    Cannon, Michael J.; Griffiths, Paul D.; Aston, Van; Rawlinson, William D.

    2015-01-01

    SUMMARY Congenital CMV infection is a leading cause of childhood disability. Many children born with congenital CMV infection are asymptomatic or have nonspecific symptoms and therefore are typically not diagnosed. A strategy of newborn CMV screening could allow for early detection and intervention to improve clinical outcomes. Interventions might include antiviral drugs or nonpharmaceutical therapies such as speech-language therapy or cochlear implants. Using published data from developed countries, we analyzed existing evidence of potential benefit that could result from newborn CMV screening. We first estimated the numbers of children with the most important CMV-related disabilities (i.e. hearing loss, cognitive deficit, and vision impairment), including the age at which the disabilities occur. Then, for each of the disabilities, we examined the existing evidence for the effectiveness of various interventions. We concluded that there is good evidence of potential benefit from nonpharmaceutical interventions for children with delayed hearing loss that occurs by 9 months of age. Similarly, we concluded that there is fair evidence of potential benefit from antiviral therapy for children with hearing loss at birth and from nonpharmaceutical interventions for children with delayed hearing loss occurring between 9 and 24 months of age and for children with CMV-related cognitive deficits. We found poor evidence of potential benefit for children with delayed hearing loss occurring after 24 months of age and for children with vision impairment. Overall, we estimated that in the United States, several thousand children with congenital CMV could benefit each year from newborn CMV screening, early detection, and interventions. Copyright © 2014 John Wiley & Sons, Ltd. PMID:24760655

  13. Screening Tool for Early Postnatal Prediction of Retinopathy of Prematurity in Preterm Newborns (STEP-ROP).

    Science.gov (United States)

    Ricard, Caroline A; Dammann, Christiane E L; Dammann, Olaf

    2017-01-01

    Retinopathy of prematurity (ROP) is a disorder of the preterm newborn characterized by neurovascular disruption in the immature retina that may cause visual impairment and blindness. To develop a clinical screening tool for early postnatal prediction of ROP in preterm newborns based on risk information available within the first 48 h of postnatal life. Using data submitted to the Vermont Oxford Network (VON) between 1995 and 2015, we created logistic regression models based on infants born <28 completed weeks gestational age. We developed a model with 60% of the data and identified birth weight, gestational age, respiratory distress syndrome, non-Hispanic ethnicity, and multiple gestation as predictors of ROP. We tested the model in the remaining 40%, performed tenfold cross-validation, and tested the score in ELGAN study data. Of the 1,052 newborns in the VON database, 627 recorded an ROP status. Forty percent had no ROP, 40% had mild ROP (stages 1 and 2), and 20% had severe ROP (stages 3-5). We created a weighted score to predict any ROP based on the multivariable regression model. A cutoff score of 5 had the best sensitivity (95%, 95% CI 93-97), while maintaining a strong positive predictive value (63%, 95% CI 57-68). When applied to the ELGAN data, sensitivity was lower (72%, 95% CI 69-75), but PPV was higher (80%, 95% CI 77-83). STEP-ROP is a promising screening tool. It is easy to calculate, does not rely on extensive postnatal data collection, and can be calculated early after birth. Early ROP screening may help physicians limit patient exposure to additional risk factors, and may be useful for risk stratification in clinical trials aimed at reducing ROP. © 2017 S. Karger AG, Basel.

  14. Newborn Congenital Cytomegalovirus Screening Based on Clinical Manifestations and Evaluation of DNA-based Assays for In Vitro Diagnostics.

    Science.gov (United States)

    Fujii, Tomoyuki; Oka, Akira; Morioka, Ichiro; Moriuchi, Hiroyuki; Koyano, Shin; Yamada, Hideto; Saito, Shigeru; Sameshima, Hiroshi; Nagamatsu, Takeshi; Tsuchida, Shinya; Inoue, Naoki

    2017-10-01

    To establish a strategy for congenital cytomegalovirus (cCMV) screening and to establish confirmatory assays approved as in vitro diagnostics by the regulatory authorities, we evaluated the clinical risks and performance of diagnostic assays developed by commercial companies, since cCMV infection has significant clinical consequences. Newborns with clinical manifestations considered to be consequences of cCMV infection (n = 575) were screened for the presence of cytomegalovirus (CMV) DNA in urine specimens collected onto filter paper placed in their diapers using the polymerase chain reaction-based assay reported previously. Liquid urine specimens were obtained from all of 20 CMV-positive newborns and 107 of the CMV-negative newborns identified in the screening. We used these 127 specimens, as well as 12 from cCMV cases identified in a previous study and 41 from healthy newborns, to compare the performance of 2 commercial assays and 1 in-house assay. The risk-based screening allowed the identification of cCMV cases at least 10-fold more efficiently than our previous universal screening, although there appears to be a limit to the identification of asymptomatically infected newborns. Although CMV-specific IgM during pregnancy was found frequently in mothers of cCMV newborns, CMV-IgM alone is not an effective diagnostic marker. The urine-filter-based assay and the 3 diagnostic assays yielded identical results. Although risk-based and universal newborn screening strategies for cCMV infection each have their respective advantages and disadvantages, urine-filter-based assay followed by confirmatory in vitro diagnostics assays is able to identify cCMV cases efficiently.

  15. First Year of Israeli Newborn Screening for Severe Combined Immunodeficiency—Clinical Achievements and Insights

    Directory of Open Access Journals (Sweden)

    Erez Rechavi

    2017-11-01

    Full Text Available Severe combined immunodeficiency (SCID, the most severe form of T cell immunodeficiency, is detectable through quantification of T cell receptor excision circles (TRECs in dried blood spots obtained at birth. Herein, we describe the results of the first year of the Israeli SCID newborn screening (NBS program. This important, life-saving screening test is available at no cost for every newborn in Israel. Eight SCID patients were diagnosed through the NBS program in its first year, revealing an incidence of 1:22,500 births in the Israeli population. Consanguine marriages and Muslim ethnic origin were found to be a risk factor in affected newborns, and a founder effect was detected for both IL7Rα and DCLRE1C deficiency SCID. Lymphocyte subset analysis and TREC quantification in the peripheral blood appear to be sufficient for confirmation of typical and leaky SCID and ruling out false positive (FP results. Detection of secondary targets (infants with non-SCID lymphopenia did not significantly affect the management or outcomes of these infants in our cohort. In the general, non-immunodeficient population, TREC rises along with gestational age and birth weight, and is significantly higher in females and the firstborn of twin pairs. Low TREC correlates with both gestational age and birth weight in extremely premature newborns. Additionally, the rate of TREC increase per week consistently accelerates with gestational age. Together, these findings mandate a lower cutoff or a more lenient screening algorithm for extremely premature infants, in order to reduce the high rate of FPs within this group. A significant surge in TREC values was observed between 28 and 30 weeks of gestation, where median TREC copy numbers rise by 50% over 2 weeks. These findings suggest a maturational step in T cell development around week 29 gestation, and imply moderate to late preterms should be screened with the same cutoff as term infants. The SCID NBS program is still

  16. Neurological outcomes in symptomatic congenital cytomegalovirus-infected infants after introduction of newborn urine screening and antiviral treatment.

    Science.gov (United States)

    Nishida, Kosuke; Morioka, Ichiro; Nakamachi, Yuji; Kobayashi, Yoko; Imanishi, Takamitsu; Kawano, Seiji; Iwatani, Sota; Koda, Tsubasa; Deguchi, Masashi; Tanimura, Kenji; Yamashita, Daisuke; Nibu, Ken-Ichi; Funakoshi, Toru; Ohashi, Masanobu; Inoue, Naoki; Iijima, Kazumoto; Yamada, Hideto

    2016-02-01

    Newborn screening for urinary cytomegalovirus (CMV) and early introduction of antiviral treatment are expected to improve neurological outcomes in symptomatic congenital CMV-infected infants. This cohort study prospectively evaluated neurological outcomes in symptomatic congenital CMV-infected infants following the introduction of hospital-based newborn urinary CMV screening and antiviral treatment. Following institutional review board approval and written informed consent from their parents, newborns were prospectively screened from 2009 to 2014 for urinary CMV-DNA by PCR within 1 week after birth at Kobe University Hospital and affiliated hospitals. CMV-positive newborns were further examined at Kobe University Hospital, and those diagnosed as symptomatic were treated with valganciclovir for 6 weeks plus immunoglobulin. Clinical neurological outcomes were evaluated at age ⩾12 months and categorized by the presence and severity of neurologic sequelae. Urine samples of 6348 newborns were screened, with 32 (0.50%) positive for CMV. Of these, 16 were diagnosed with symptomatic infection and 12 received antiviral treatment. Four infants developed severe impairment (33%), three developed mild impairment (25%), and five developed normally (42%). This is the first Japanese report of neurological assessments in infants with symptomatic congenital CMV infection who received early diagnosis and antiviral treatment. Urinary screening, resulting in early diagnosis and treatment, may yield better neurological outcomes in symptomatic congenital CMV-infected infants. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  17. Newborn Screening for Sickle Cell Disease in Liberia: A Pilot Study.

    Science.gov (United States)

    Tubman, Venée N; Marshall, Roseda; Jallah, Wilhemina; Guo, Dongjing; Ma, Clement; Ohene-Frempong, Kwaku; London, Wendy B; Heeney, Matthew M

    2016-04-01

    In malaria-endemic countries in West Africa, sickle cell disease (SCD) contributes to childhood mortality. Historically, Liberia had regions wherein hemoglobin S and beta-thalassemia trait were mutually exclusive. Data on hemoglobinopathies in the Monrovia, the capital, are outdated and do not reflect urban migration. Updating the epidemiology of SCD is necessary to plan a public health and clinical agenda. Neither newborn screening (NBS) nor screening tools were available in country. This pilot study aimed to determine the feasibility of NBS using a South-South partnership and define the incidence of sickle cell trait (SCT) and SCD in Monrovia. This descriptive epidemiologic feasibility study collected dried blood spots from 2,785 consecutive newborns delivered at a hospital in Monrovia. Samples were analyzed by isoelectric focusing at a regional reference laboratory. Infants with SCD were referred for preventive care. SCT occurred in 10.31% of infants screened. SCD occurred in 33 infants screened [1.19% (95% confidence interval [CI]: 0.79-1.59%)] (FS: 28/33, FSB: 2/33, FSA: 2/33, FSX: 1/33). There were no infants with FSC phenotype observed. Nonsickling hemoglobin phenotypes "FC" and "F" were each present in three infants screened. Seventy-six percent of infants with SCD were brought to care, demonstrating the feasibility of our approach. The incidence of SCD and other hemoglobinopathies remains high in Liberia. Additional studies are needed to clarify sickle genotypes and identify the contribution of silent beta-thalassemia alleles. By developing regional partnerships, countries similar to Liberia can acquire current data to inform NBS as an important public health initiative toward improving child health. © 2016 Wiley Periodicals, Inc.

  18. Viral load in children with congenital cytomegalovirus infection identified on newborn hearing screening.

    Science.gov (United States)

    Kawada, Jun-ichi; Torii, Yuka; Kawano, Yoshihiko; Suzuki, Michio; Kamiya, Yasuko; Kotani, Tomomi; Kikkawa, Fumitaka; Kimura, Hiroshi; Ito, Yoshinori

    2015-04-01

    Congenital cytomegalovirus (CMV) infection is the most common non-genetic cause of sensorineural hearing loss (SNHL) in children. However, congenital SNHL without other clinical abnormalities is rarely diagnosed as CMV-related in early infancy. The aim of this study was to identify and treat patients with congenital CMV-related SNHL or CMV-related clinical abnormalities other than SNHL. The association between CMV load and SNHL was also evaluated. Newborns who had abnormal hearing screening results or other clinical abnormalities were screened for congenital CMV infection by PCR of saliva or urine specimens, and identified infected patients were treated with valganciclovir (VGCV) for 6 weeks. The CMV load of patients with or without SNHL was compared at regular intervals during as well as after VGCV treatment. Of 127 infants with abnormal hearing screening results, and 31 infants with other clinical abnormalities, CMV infection was identified in 6 and 3 infants, respectively. After VGCV treatment, 1 case had improved hearing but the other 5 SNHL cases had little or no improvement. Among these 9 patients with or without SNHL at 1 year of age, there was no significant difference in CMV blood or urine load at diagnosis, but both were significantly higher in patients with SNHL during VGCV treatment. Selective CMV screening of newborns having an abnormal hearing screening result would be a reasonable strategy for identification of symptomatic congenital CMV infection. Prolonged detection of CMV in blood could be a risk factor for SNHL. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Universal newborn hearing screening: preliminary experience at the University Hospital of Cagliari

    Directory of Open Access Journals (Sweden)

    Giulia Pinna

    2012-10-01

    Full Text Available Bilateral congenital or acquired sensorineural hearing loss is a pathological condition affecting 1-2 children per 1,000 live births; it represents a major issue in public health because its late identification can negatively affect speech and language development. The aim of hearing screening is to obtain diagnosis and management of hearing loss as soon as possible; in fact early diagnosis and treatment allow children with congenital hearing impairment to acquire adequate linguistic competence. The present study reports our preliminary experience in newborn hearing screening at Neonatology services of University of Cagliari (Italy. During the first semester of surveillance, between January 2012 and June 2012, hearing screening was performed on a total of 901 babies using two different methods, TEOAEs in healthy neonates and automated ABR in high-risk babies. All infants were screened prior to hospital discharge; in some cases, especially for preterm infants of Neonatal Intensive Care Unit and Puericulture Institute, the screening was performed after discharge, to achieve a possible better global and acoustic maturation; 5 cases of hearing impairment were found. In the present study the Authors confirmed that it is possible to start a universal hearing screening in a relatively short time reaching the percentages suggested by Joint Committee on Infant Hearing.

  20. Evaluating the feasibility of integrating salivary testing for congenital CMV into the Newborn Hearing Screening Programme in the UK.

    Science.gov (United States)

    Kadambari, Seilesh; Luck, Suzanne; Davis, Adrian; Walter, Simone; Agrup, Charlotte; Atkinson, Claire; Stimson, Laura; Williams, Eleri; Berrington, Janet; Griffiths, Paul; Sharland, Mike

    2015-08-01

    Congenital cytomegalovirus (cCMV) accounts for 20% of all childhood sensorineural hearing loss (SNHL) but is not routinely tested for at birth. Valganciclovir has been shown to prevent hearing deterioration and improve neurocognitive outcomes if started in the first month of life. This study aimed to assess the feasibility of integrating testing for cCMV using salivary swabs into the Newborn Hearing Screening Programme (NHSP). Parents of newborns newborn hearing screen for further audiological testing, were approached by hearing screeners to obtain a saliva sample for CMV DNA polymerase chain reaction (PCR). Eighty percent (203/255) of newborns who were eligible had a saliva swab taken by the hearing screener. Over 99% of results were delivered within the first month of life. Two newborns were identified with cCMV and both seen on day 10 of life by the paediatric specialist. All saliva samples tested delivered a result using real-time PCR. It is feasible for hearing screeners to obtain saliva swabs to test for CMV DNA using real-time PCR in newborns referred after their initial hearing screen. Rapid diagnostic testing for cCMV needs a more detailed clinical and cost-effectiveness analysis.

  1. Results of ultrasound screening of the hips in newborns and infants

    Directory of Open Access Journals (Sweden)

    Džoleva-Tolevska Roza

    2012-01-01

    Full Text Available The aim of this study is to analyze the results of ultrasound screening of the hips in newborns and infants and to establish the importance of ultrasonography in early diagnosis and treatment of developmental dysplasia of the hips (DDH. Material and Methods: In 2010, at the Clinic for orthopedic surgery in Skopje, 6333 newborns and infants were examined. They were classified in 2 groups: first group consisted of patients with normal ultrasound findings and second group consisted of patients with DDH on ultrasound finding. Patients underwent clinical examination and ultrasonography of the hips. Results: We examined 6333 newborns and infants up to 6 months of age. 3213 were female and 3120 were male. In the first group there were 5932 (93.67% patients with normal ultrasound of the hip-Graf Type 1. In the second group there were 401 (6.33% patients with DDH on ultrasound. The patients of the second group were divided in 3 types according to Graf method. Graf Type 2-Patients with dysplasia 378 (5.97% subdivided in 2a- 260 (4.11% patients, 2b 85 (1.34% patients and 2c 33 (0.52% patients. Graf Type 3 - Patients with subluxation of the hip 9 (0.1%, subdivided in 3a 3 (0.05% patients and 3b 3 (0.5% patients. Graf Type 4 -Patients with luxation of the hip 17 (0.27% patients. 124 patients (30.5% with DDH had an associated risk factors (65 patients with positive family history, 48 patients with breech delivery and 11 patients with clubfoot deformity. 387 patients with dysplasia and subluxation of the hips were treated with abduction brace and Pavlik harness. 17 patients with luxation of the hips were treated with exercises and overhead traction of the muscles, close reduction of the hip placed in spica cast or open reduction. Conclusion: Ultrasound screening of hips in newborns and infants is important for early diagnosis of DDH. This is necessary for adequate treatments. If this disease is not treated properly it gives long term morbidity such as gait

  2. Newborn hearing screening programme in Belgium: a consensus recommendation on risk factors.

    Science.gov (United States)

    Vos, Bénédicte; Senterre, Christelle; Lagasse, Raphaël; Levêque, Alain

    2015-10-16

    Understanding the risk factors for hearing loss is essential for designing the Belgian newborn hearing screening programme. Accordingly, they needed to be updated in accordance with current scientific knowledge. This study aimed to update the recommendations for the clinical management and follow-up of newborns with neonatal risk factors of hearing loss for the newborn screening programme in Belgium. A literature review was performed, and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system assessment method was used to determine the level of evidence quality and strength of the recommendation for each risk factor. The state of scientific knowledge, levels of evidence quality, and graded recommendations were subsequently assessed using a three-round Delphi consensus process (two online questionnaires and one face-to-face meeting). Congenital infections (i.e., cytomegalovirus, toxoplasmosis, and syphilis), a family history of hearing loss, consanguinity in (grand)parents, malformation syndromes, and foetal alcohol syndrome presented a 'high' level of evidence quality as neonatal risk factors for hearing loss. Because of the sensitivity of auditory function to bilirubin toxicity, hyperbilirubinaemia was assessed at a 'moderate' level of evidence quality. In contrast, a very low birth weight, low Apgar score, and hospitalisation in the neonatal intensive care unit ranged from 'very low' to 'low' levels, and ototoxic drugs were evidenced as 'very low'. Possible explanations for these 'very low' and 'low' levels include the improved management of these health conditions or treatments, and methodological weaknesses such as confounding effects, which make it difficult to conclude on individual risk factors. In the recommendation statements, the experts emphasised avoiding unidentified neonatal hearing loss and opted to include risk factors for hearing loss even in cases with weak evidence. The panel also highlighted the cumulative effect

  3. Biochemical and molecular characteristics of patients with organic acidaemias and urea cycle disorders identified through newborn screening.

    Science.gov (United States)

    Barends, M; Pitt, J; Morrissy, S; Tzanakos, N; Boneh, A

    2014-01-01

    In recent years it has become clear that newborn screening (NBS) programmes using tandem mass spectrometry identify "patients" with "classical" inborn errors of metabolism who are asymptomatic. This observation raises issues regarding medicalization of "non-diseases," potentially unnecessary treatment and unnecessary anxiety to parents. This study aims to identify possible markers that may assist in predicting the need for treatment of infants with "classical" organic acidaemias (OA) and urea cycle disorders (UCD) diagnosed through NBS. Medical records of all patients with classical OA and UCD detected through the Victorian NBS programme from February 2002 to January 2014, or diagnosed clinically between 1990 and January 2002 were retrospectively reviewed. Neonatal presentation did not always predict the need for on-going strict treatment. Blood concentrations of amino acids and acyl-carnitines and the changes thereof in follow-up samples correlated with severity in citrullinaemia-I, possibly isovaleric acidaemia but not in argininosuccinic aciduria or propionic acidaemia. Some specific mutations correlate with "attenuated" citrullinaemia-I. Gender may affect clinical outcome in propionic acidaemia. Changes in blood concentration of certain metabolites (amino acids, acyl-carnitines) in the first weeks of life may be predictive of the need for treatment in some disorders but not in others. Mutation analysis may be predictive in some disorders but whether or not this should be considered as second-tier testing in NBS should be discussed separately. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Parental attitudes toward newborn screening for Duchenne/Becker muscular dystrophy and spinal muscular atrophy.

    Science.gov (United States)

    Wood, Molly F; Hughes, Sarah C; Hache, Lauren P; Naylor, Edwin W; Abdel-Hamid, Hoda Z; Barmada, M Michael; Dobrowolski, Steven F; Stickler, David E; Clemens, Paula R

    2014-06-01

    Disease inclusion in the newborn screening (NBS) panel should consider the opinions of those most affected by the outcome of screening. We assessed the level and factors that affect parent attitudes regarding NBS panel inclusion of Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and spinal muscular atrophy (SMA). The attitudes toward NBS for DMD, BMD, and SMA were surveyed and compared for 2 categories of parents, those with children affected with DMD, BMD, or SMA and expectant parents unselected for known family medical history. The level of support for NBS for DMD, BMD, and SMA was 95.9% among parents of children with DMD, BMD, or SMA and 92.6% among expectant parents. There was strong support for NBS for DMD, BMD, and SMA in both groups of parents. Given advances in diagnostics and promising therapeutic approaches, discussion of inclusion in NBS should continue. Copyright © 2013 Wiley Periodicals, Inc.

  5. Delay in blood sampling for routine newborn screening is associated with increased risk of schizophrenia

    DEFF Research Database (Denmark)

    Nordentoft, Merete; Tidselbak Larsen, Janne; Pedersen, Carsten Bøcker

    2015-01-01

    for this association. Therefore, we investigated whether the increased risk can be explained by other risk factors for schizophrenia. METHODS: A case-control design was applied. A total of 846 cases with schizophrenia were selected from the Danish Psychiatric Case Register. One control was selected for each case......BACKGROUND: The Danish Neonatal Screening Biobank, containing dried blood spot samples from all newborn in Denmark, is a unique source of data that can be utilized for analyses of genetic and environmental exposures related to schizophrenia and other mental disorders. In previous analyses, we have...... found that early and late blood sampling, compared to sampling at day 5, was associated with increased risk of schizophrenia. As delay in sampling of blood for neonatal screening cannot in itself influence the risk of schizophrenia, it must be seen as a proxy for unknown underlying causes responsible...

  6. Newborn screening blood spot analysis in the UK: influence of spot size, punch location and haematocrit.

    Science.gov (United States)

    Lawson, A J; Bernstone, L; Hall, S K

    2016-03-01

    In dried blood spot analysis, punch location and variations in applied sample volume and haematocrit can produce different measured concentrations of analytes. We investigated the magnitude of these effects in newborn screening in the UK. Heparinized blood spiked with thyroid stimulating hormone (TSH), phenylalanine, tyrosine, leucine, methionine, octanoyl carnitine (C8), and immunoreactive trypsinogen (IRT) was spotted onto filter paper: (i) at a constant haematocrit of 50% at various volumes, and (ii) at a range of haematocrits using a constant volume. Subpunches (3.2 mm) of the dried blood spots were then analysed. Compared with a central punch from a 50 µL blood spot with 50% haematocrit, 10 µL spots can have significantly lower measured concentrations of all analytes, with decreases of 15% or more observed for leucine, methionine, phenylalanine, and tyrosine. Punching at the edge of a spot can increase measured concentrations up to 35%. Higher haematocrit decreased measured TSH and C8 yet increased amino acids and IRT by 15% compared with 50% haematocrit. Lower haematocrits had the opposite effect, but only with higher concentrations of some analytes. Differences in blood spot size, haematocrit and punch location substantially affect measured concentrations for analytes used in the UK newborn screening programme, and this could affect false positive and negative rates. To minimize analytical bias, these variables should be controlled or adjusted for where possible. © The Author(s) 2015.

  7. Fostering caring relationships: Suggestions to rethink liberal perspectives on the ethics of newborn screening.

    Science.gov (United States)

    van der Burg, Simone; Oerlemans, Anke

    2018-03-01

    Newborn screening (NBS) involves the collection of blood from the heel of a newborn baby and testing it for a list of rare and inheritable disorders. New biochemical screening technologies led to expansions of NBS programs in the first decade of the 21st century. It is expected that they will in time be replaced by genetic sequencing technologies. These developments have raised a lot of ethical debate. We reviewed the ethical literature on NBS, analyzed the issues and values that emerged, and paid particular interest to the type of impacts authors think NBS should have on the lives of children and their families. Our review shows that most authors keep their ethical reflection confined to policy decisions, about for instance (a) the purpose of the program, and (b) its voluntary or mandatory nature. While some authors show appreciation of how NBS information empowers parents to care for their (diseased) children, most authors consider these aspects to be 'private' and leave their evaluation up to parents themselves. While this division of moral labor fits with the liberal conviction to leave individuals free to decide how they want to live their private lives, it also silences the ethical debate about these issues. Given the present and future capacity of NBS to offer an abundance of health-related information, we argue that there is good reason to develop a more substantive perspective to whether and how NBS can contribute to parents' good care for children. © 2018 The Authors. Bioethics Published by John Wiley & Sons Ltd.

  8. Delayed cystic fibrosis presentation in children in the absence of newborn screening.

    LENUS (Irish Health Repository)

    Jackson, A

    2010-04-01

    Newborn cystic fibrosis (CF) screening facilitates early diagnosis and nutritional intervention, which prevents malnourishment and improves growth in childhood. To provide baseline information on the natural history of CF in the Republic of Ireland, where newborn screening has not yet been introduced and CF incidence is high (1:1353 live births), we examined the effect of presentation mode, symptom type and gender on age at diagnosis. Median age at diagnosis was calculated by gender and for presentation mode\\/symptom type for 601 CF registry children diagnosed 1986-2007. Modes of presentation were each significantly associated with delayed presentation. An adjusted odds ratio of 4.5 (95% CI: 1.8, 11.1) was determined for presentation with family history, 43.1 for gastrointestinal symptoms presentation (95% CI: 18.3, 101.4), 96.9 for both respiratory and gastrointestinal symptoms (95% CI: 38.6, 243,4), and 115.4 for respiratory symptoms (95% CI: 45.2, 294.7). Children with respiratory symptoms had the greatest likelihood of delayed diagnosis (median age: 20.4 months), followed by those with respiratory and gastrointestinal symptoms (9.2 months). Gender was not significantly associated with a delayed presentation when presentation mode was taken into account.

  9. Newborn screening for dihydrolipoamide dehydrogenase deficiency: Citrulline as a useful analyte

    Directory of Open Access Journals (Sweden)

    Shane C. Quinonez

    2014-01-01

    Full Text Available Dihydrolipoamide dehydrogenase deficiency, also known as maple syrup urine disease (MSUD type III, is caused by the deficiency of the E3 subunit of branched chain alpha-ketoacid dehydrogenase (BCKDH, α-ketoglutarate dehydrogenase (αKGDH, and pyruvate dehydrogenase (PDH. DLD deficiency variably presents with either a severe neonatal encephalopathic phenotype or a primarily hepatic phenotype. As a variant form of MSUD, it is considered a core condition recommended for newborn screening. The detection of variant MSUD forms has proven difficult in the past with no asymptomatic DLD deficiency patients identified by current newborn screening strategies. Citrulline has recently been identified as an elevated dried blood spot (DBS metabolite in symptomatic patients affected with DLD deficiency. Here we report the retrospective DBS analysis and second-tier allo-isoleucine testing of 2 DLD deficiency patients. We show that an elevated citrulline and an elevated allo-isoleucine on second-tier testing can be used to successfully detect DLD deficiency. We additionally recommend that DLD deficiency be included in the “citrullinemia/elevated citrulline” ACMG Act Sheet and Algorithm.

  10. Contamination of dried blood spots - an underestimated risk in newborn screening.

    Science.gov (United States)

    Winter, Theresa; Lange, Anja; Hannemann, Anke; Nauck, Matthias; Müller, Cornelia

    2018-01-26

    Newborn screening (NBS) is an established screening procedure in many countries worldwide, aiming at the early detection of inborn errors of metabolism. For decades, dried blood spots have been the standard specimen for NBS. The procedure of blood collection is well described and standardized and includes many critical pre-analytical steps. We examined the impact of contamination of some anticipated common substances on NBS results obtained from dry spot samples. This possible pre-analytical source of uncertainty has been poorly examined in the past. Capillary blood was obtained from 15 adult volunteers and applied to 10 screening filter papers per volunteer. Nine filter papers were contaminated without visible trace. The contaminants were baby diaper rash cream, baby wet wipes, disinfectant, liquid infant formula, liquid infant formula hypoallergenic (HA), ultrasonic gel, breast milk, feces, and urine. The differences between control and contaminated samples were evaluated for 45 NBS quantities. We estimated if the contaminations might lead to false-positive NBS results. Eight of nine investigated contaminants significantly altered NBS analyte concentrations and potentially caused false-positive screening outcomes. A contamination with feces was most influential, affecting 24 of 45 tested analytes followed by liquid infant formula (HA) and urine, affecting 19 and 13 of 45 analytes, respectively. A contamination of filter paper samples can have a substantial effect on the NBS results. Our results underline the importance of good pre-analytical training to make the staff aware of the threat and ensure reliable screening results.

  11. Newborn hearing screening: analysis and outcomes after 100,000 births in Upper-Normandy French region.

    Science.gov (United States)

    Caluraud, Sophie; Marcolla-Bouchetemblé, Aurore; de Barros, Angélique; Moreau-Lenoir, Florence; de Sevin, Emmanuel; Rerolle, Stéphane; Charrière, Elisabeth; Lecler-Scarcella, Véronique; Billet, François; Obstoy, Marie-Françoise; Amstutz-Montadert, Isabelle; Marie, Jean-Paul; Lerosey, Yannick

    2015-06-01

    Neonatal hearing impairment is a common disorder with a prevalence of 1 to 2‰ worldwide, with significant consequences on overall development when rehabilitated too late. New-born hearing screening has been implemented in the 1990s in most European countries and the USA. The Upper-Normandy region of France has been conducting a pilot program since 1999. The aim of this prospective study was to evaluate and critically analyse it. The Upper-Normandy universal new-born hearing screening program is performed in two steps. Between 1999 and 2004, first, we administered a Transient Evoked Oto Acoustic Emission (TEOAE) test was administered a few days after birth for healthy newborns without risk factors. For newborns admitted to a neonatal intensive care unit (NICU) or presenting risk factors, was administered an automated auditory brainstem response (AABR) test prior to discharge. Second, newborns who failed the initial hearing screening were retested as outpatients using TEOAE. Since 2004, infants who failed the initial screen were tested with AABR 3 to 4 weeks later as outpatients, providing an opportunity to compare the two protocols. Overall screening coverage in the Upper-Normandy region is 99.8%. First step coverage is 99.58% in well-infant nurseries and 97.09% in the NICU. The test-retest procedure during the first step and the use of AABR for the second resulted in higher follow-up rates and lower false positive rates. The Upper-Normandy region universal newborn hearing screening program facilitated diagnosis and rehabilitation of infants before age of 9 months, most notably when severe to profound hearing impairment was found. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Maternal knowledge and attitudes to universal newborn hearing screening: Reviewing an established program.

    Science.gov (United States)

    Lam, Maggie Yee Yan; Wong, Eddie Chi Ming; Law, Chi Wai; Lee, Helena Hui Ling; McPherson, Bradley

    2018-02-01

    To facilitate early diagnosis of infants with hearing loss, a universal newborn hearing screening program (UNHS) has been implemented in Hong Kong's public hospitals for over a decade. However, there have been no known studies investigating parent attitudes to, and satisfaction with, UNHS since its launch in Hong Kong. The present study aimed to investigate knowledge of UNHS as well as infant hearing development, and attitudes and satisfaction with UNHS, in Hong Kong mothers with newborns. The study was designed to help evaluate and improve an established UNHS public hospital program, based on the perspectives of service users. A researcher-developed questionnaire was administered to 102 mothers whose newborn had received UNHS in the postnatal wards of a large public hospital in Hong Kong. The questionnaire considered parental knowledge of UNHS and infant hearing development, attitudes and satisfaction toward public hospital UNHS. In the knowledge dimension, parents' preferred time and location for pre-test information delivery, interpretation of screening results, and knowledge of hearing developmental milestones were surveyed. In addition, maternal attitudes to and satisfaction with UNHS screening services, the potential impact of UNHS on parent emotions and parent-baby bonding, attitudes toward informed consent, and willingness to comply with diagnostic assessment referral were also be surveyed. Mean participant scores on knowledge of infant hearing development were relatively low (M = 2.59/6.0, SD = 0.90). Many mothers also underestimated the potential ongoing risks of hearing impairment in babies. Around 80% of mothers thought an infant could not have hearing impairment after passing the screening. In addition, one-third of mothers thought a baby could not later develop hearing impairment in infancy or childhood. In terms of attitudes and satisfaction, participants gave somewhat negative ratings for questions regarding receiving sufficient information

  13. Newborn screening for congenital cytomegalovirus using real-time polymerase chain reaction in umbilical cord blood.

    Science.gov (United States)

    Barkai, Galia; Barzilai, Asher; Mendelson, Ella; Tepperberg-Oikawa, Michal; Roth, Daphne Ari-Even; Kuint, Jacob

    2013-06-01

    Congenital cytomegalovirus (C-CMV) infection affects 0.4-2% of newborn infants in Israel, most of whom are asymptomatic. Of these, 10-20% will subsequently develop hearing impairment and may have benetitted from early detection by neonatal screeing. To retrospectively anaIyze the results of a screening program for C-CMV performed at the Sheba Medical Center, Tel, Hashomer, during a 1 year period, using real-time polymerase chain reaction (rt-PCR) from umbilical cord blood. CMV DNA was detected by rt-PCR performed on infants' cord blood. C-CMV was confirmed by urine culture (Shell-vial). All confirmed cases were further investigated for C-CMV manifestations by head ultrasound, complete blood count, liver enzyme measurement, ophthalmology examination and hearing investigation. During the period 1 June 2009 to 31 May 2010, 11,022 infants were born at the Sheba Medical Center, of whom 8105 (74%) were screened. Twenty-three (0.28%) were positive for CMV and 22 of them (96%) were confirmed by urine culture. Two additional infants, who had not been screened, were detected after clinical suspicion. All 24 infants were further Investigated, and 3 (12.5%) had central nervous system involvement (including hearing impairment) and were offered intravenous ganciclovir for 6 weeks. Eighteen infants (82%) would not otherwise have been diagnosed. The relatively low incidence of C-CMV detected in our screening program probably reflects the low sensitivity of cord blood screening. Nevertheless, this screening program reliably detected a non-negligible number of infants who could benefit from early detection. Other screening methods using saliva should be investigated further.

  14. Contribution of targeted saliva screening for congenital CMV-related hearing loss in newborns who fail hearing screening.

    Science.gov (United States)

    Ari-Even Roth, Daphne; Lubin, Daniel; Kuint, Jacob; Teperberg-Oikawa, Michal; Mendelson, Ella; Strauss, Tzipora; Barkai, Galia

    2017-11-01

    We previously reported a 2.2% rate of infants born with sensorineural hearing loss (SNHL) due to congenital cytomegalovirus (cCMV) infection identified by universal neonatal screen for cCMV using saliva. To evaluate the contribution of targeted saliva screening for cCMV to the detection of infants born with cCMV-related SNHL who failed universal newborn hearing screening (UNHS). We retrospectively reviewed the audiological and medical records of infants who failed UNHS and were tested for cCMV using saliva sample prior to discharge at Sheba Medical Center between 2014 and 2015. Positive cases were confirmed by urine sample. Two hundred (1%) of the 19 830 infants tested during the study period failed in-hospital hearing screening. A saliva specimen was obtained prior to discharge in 187 infants (93.5% of those who failed UNHS). In 178 infants saliva testing was performed at ≤21 days of chronological age and yielded results. cCMV infection was identified in 4/178 tested infants (2.25%, 95% CI 0.8% to 5.3%), of whom three were diagnosed with SNHL (1.7%, 95% CI 0.5% to 4.4%) and offered antiviral treatment. Two of the tested infants (1.12%, 95% CI 0.2% to 3.6%) were diagnosed with cCMV solely due to failure in UNHS. Occult central nervous system (CNS) symptoms of cCMV infection were detected in 2/4 infants following targeted investigation. Targeted cCMV screening in newborns who failed UNHS contributed to the early detection of infants born with cCMV-related isolated SNHL or with occult CNS symptoms who could potentially benefit from antiviral treatment. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. [Using an employee survey as a means of quality assurance in newborn hearing screening].

    Science.gov (United States)

    Depenbrock, A; Matulat, P; am Zehnhoff-Dinnesen, A

    2013-03-01

    Studies drawing information not only from technical data but also from surveying human resources behind the universal newborn hearing screening (UNHS) appear to be a rarity. This study aims at showing how the state of both knowledge and practical skills among the screening staff are essential aspects in future quality management. A self-developed questionnaire was sent to hospital staff addressing a total of 710 nurses who were registered as having undertaken a UNHS training course. Questions were aimed at aspects of organization, personal practical skills, current problems and improvement possibilities. High rates of occupancy, lack of trained personnel, technical issues and background noise disturbances were considered to be factors that increased time pressure and slowed down procedures. Of the participants 16 % considered communicating a "refer" result to parents a difficult step and 8 % felt insecure when explaining the aims and procedures to parents. There was a high interest in further training sessions. This survey served well to reveal aspects of improvement in screening procedures and meeting staff needs. The training sessions should outline practical aspects of conducting screening and also professional, sensitive communication to parents.

  16. Critical Newborn Screens in Double Heterozygotes of Inborn Errors of Metabolism—A Clinical Report and Recommendations

    Directory of Open Access Journals (Sweden)

    Katherine G. Langley

    2016-11-01

    Full Text Available The practice of newborn screening has been in place in the USA since the 1960s, with individual states initially screening for different numbers of disorders. In the early 2000s many efforts were made to standardize the various disorders being screened. Currently, there are at least 34 disorders that each state is mandated to include on their screening panel. Of those 34 disorders, the majority are inborn errors of metabolism (IEM which include urea cycle disorders (UCD, citrullinemia (CIT and argininosuccinic aciduria (ASA, as well as a number of fatty acid oxidation disorders. We present here four cases of infants who had critical newborn screens (NBS in the Commonwealth of Virginia and underwent genetic testing because their clinical presentation and follow-up laboratory studies were not consistent with the disorder that was flagged by NBS. These newborns were found to be carriers for two different IEMs (in three cases or compound heterozygotes (in one case. Currently no guidelines exist with respect to the appropriate way to manage these children who may or may not be symptomatic in the newborn period. We propose some general recommendations for management based on our experience with these four probands, and discuss the necessity for further conversation and collaboration between physicians encountering these not-so-infrequent presentations.

  17. Phenylketonuria screening in the Republic of Macedonia.

    Science.gov (United States)

    Kocova, Mirjana; Anastasovska, Violeta

    2016-08-05

    Phenylketonuria is an autosomal recessive inborn error of metabolism which can be prevented by early and continuous treatment. Therefore newborn screening for phenylketonuria has been introduced in many countries. We present here the results of the selective newborn screening for inborn errors of metabolism, including PKU, performed by tandem mass spectrometry which has been introduced in Macedonia since 2011.

  18. Putting newborn hearing screening on the political agenda in Belgium: local initiatives toward a community programme - a qualitative study.

    Science.gov (United States)

    Vos, Bénédicte; Lagasse, Raphaël; Levêque, Alain

    2014-07-01

    The Kingdon model, based on the convergence of three streams (problem, policy, and politics) and the opening of a policy window, analyses the process by which a health issue is placed on the political agenda. We used this model to document the political agenda-setting process of the newborn hearing screening programme in Belgium. A qualitative study based on a document review and on semi-directed interviews was carried out. The interviews were conducted with nine people who had played a role in putting the issue in question on the political agenda, and the documents reviewed included scientific literature and internal reports and publications from the newborn hearing screening programme. The thematic analysis of the data collected was carried out on the basis of the Kingdon model's three streams. The political agenda-setting of this screening programme was based on many factors. The problem stream included factors external to the context under study, such as the technological developments and the contribution of the scientific literature which led to the recommendation to provide newborn hearing screening. The two other streams (policy and politics) covered factors internal to the Belgian context. The fact that it was locally feasible with financial support, the network of doctors convinced of the need for newborn hearing screening, the drafting of various proposals, and the search for financing were all part of the policy stream. The Belgian political context and the policy opportunities concerning preventive medicine were identified as significant factors in the third stream. When these three streams converged, a policy window opened, allowing newborn hearing screening onto the political agenda and enabling the policy decision for its introduction. The advantage of applying the Kingdon model in our approach was the ability to demonstrate the political agenda-setting process, using the three streams. This made it possible to identify the many factors involved in

  19. After the Introduction into the National Newborn Screening Program : Who Is Receiving Genetic Counseling for Hemoglobinopathies in The Netherlands?

    NARCIS (Netherlands)

    Kaufmann, J. O.; Krapels, I. P. C.; Van Brussel, B. T. J.; Zekveld-Vroon, R. C.; Oosterwijk, J. C.; van Erp, F.; van Echtelt, J.; Zwijnenburg, P. J. G.; Petrij, F.; Bakker, E.; Giordano, P. C.

    2014-01-01

    OBJECTIVE: Universal newborn screening for hemoglobinopathies started in The Netherlands in 2007. Herewith severe conditions, such as sickle cell disease, β-thalassemia major and hemoglobin H disease are putatively identified. Additionally, at least 1,800 carriers of hemoglobin variants associated

  20. T-Cell Lymphopenia Detected by Newborn Screening in Two Siblings with an Xq13.1 Duplication

    Directory of Open Access Journals (Sweden)

    Xavier Rios

    2017-07-01

    Full Text Available Newborn screening for severe combined immunodeficiency has proven successful in identifying infants with T-cell deficiencies before they become severely ill. Additionally, the newborn screen can detect subtle early phenotypes that may become severe later in life. We present the case of siblings with features suggestive of T-cell lymphopenia identified as having low T-cell receptor excision circles counts by newborn screening. Expanded immune testing showed robust lymphocyte mitogen and antigen responses with normal vaccine responses and immunoglobulin levels for both boys over time. Genetic analysis revealed an Xq13.1 duplication in each child not found in the mother. The variant is downstream of the IL2RG gene with potential regulatory significance, suggesting a mechanism for the T-cell lymphopenia. The newborn screen provided these patients heightened surveillance and patient-specific management, including delayed live vaccines and Pneumocystis jiroveci pneumonia prophylaxis. Fortunately, the brothers have not suffered invasive or opportunistic infections and are well at ages 3 and 4 years. In this report, we illustrate the challenges of managing seemingly asymptomatic immunodeficient patients without a definitive genetic diagnosis and show how unbiased genetic analysis can expand understanding about primary immunodeficiency phenotypes.

  1. Variability in State-Based Recommendations for Management of Alpha Thalassemia Trait and Silent Carrier Detected on the Newborn Screen.

    Science.gov (United States)

    Fogel, Benjamin N; Nguyen, Hong Loan T; Smink, Gayle; Sekhar, Deepa L

    2018-04-01

    We conducted an inventory of state-based recommendations for follow-up of alpha thalassemia silent carrier and trait identified on newborn screen. We found wide variability in the nature and timing of these recommendations. We recommend a standardized recommendation to guide pediatricians in evidenced-based care for this population. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Parental Intentions to Enroll Children in a Voluntary Expanded Newborn Screening Program

    Science.gov (United States)

    Paquin, Ryan S.; Peay, Holly L.; Gehtland, Lisa M.; Lewis, Megan A.; Bailey, Donald B.

    2016-01-01

    Background and Objectives Nearly all babies in the United States are tested at birth for rare, serious, and treatable disorders through mandatory state newborn screening (NBS). Recently, there have been calls for an expanded, voluntary model to facilitate early diagnosis and treatment of a wider range of disorders. We applied the reasoned action framework to examine parental intentions to participate in voluntary expanded screening. Methods We recruited a national cohort of recent and expectant parents living in the U.S. who completed a self-administered online survey (N = 1,001). Using a mixed-level fractional factorial experiment, we studied parental participation intentions and preferences for timing of consent, cost, consent format, and testing options. Results We conducted a hierarchical regression analysis assessing parental intentions to participate in voluntary expanded NBS. Attitudes, perceived normative influence, and perceived behavioral control explained substantial variance in intention, with perceived normative influence emerging as the strongest predictor. We found no evidence that the manipulated program features altered mean levels of intention, but timing of parental permission, cost, and permission format moderated the relative importance of reasoned action constructs on intention. Conclusion Program design features may impact the psychological mechanisms underlying parental decision making for voluntary expanded screening. These results have important implications for parent education, outreach, and informed parental permission procedures. PMID:27526258

  3. Parental intentions to enroll children in a voluntary expanded newborn screening program.

    Science.gov (United States)

    Paquin, Ryan S; Peay, Holly L; Gehtland, Lisa M; Lewis, Megan A; Bailey, Donald B

    2016-10-01

    Nearly all babies in the United States are tested at birth for rare, serious, and treatable disorders through mandatory state newborn screening (NBS). Recently, there have been calls for an expanded, voluntary model to facilitate early diagnosis and treatment of a wider range of disorders. We applied the reasoned action framework to examine parental intentions to participate in voluntary expanded screening. We recruited a national cohort of recent and expectant parents living in the U.S. who completed a self-administered online survey (N = 1001). Using a mixed-level fractional factorial experiment, we studied parental participation intentions and preferences for timing of consent, cost, consent format, and testing options. We conducted a hierarchical regression analysis assessing parental intentions to participate in voluntary expanded NBS. Attitudes, perceived normative influence, and perceived behavioral control explained substantial variance in intention, with perceived normative influence emerging as the strongest predictor. We found no evidence that the manipulated program features altered mean levels of intention, but timing of parental permission, cost, and permission format moderated the relative importance of reasoned action constructs on intention. Program design features may impact the psychological mechanisms underlying parental decision making for voluntary expanded screening. These results have important implications for parent education, outreach, and informed parental permission procedures. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Biobank participant support of newborn screening for disorders with variable treatment and intervention options.

    Science.gov (United States)

    Bunnell, Megan E; Tarini, Beth A; Petros, Michael; Goldenberg, Aaron J; Arjunan, Aishwarya; Wicklund, Catherine

    2016-10-01

    We aimed to better understand biobank participant opinions of the benefits of newborn screening (NBS) for certain disorder types and how terminology used in NBS discourse might impact stakeholder opinion. We conducted a between-subjects randomized survey of 5840 members of the Northwestern University Biobank. The survey contained 12 scenarios, each describing a disorder and its treatment. For each scenario, we varied the terminology used to describe treatment options. One survey version used the term intervention and the other treatment. The outcome measured for each scenario was perceived benefit (for the infant) and importance of testing (for participants). Comparisons were made between participants and between scenarios. Ratings of benefit and importance were not influenced by the use of the term intervention versus treatment within scenarios. Nuances existed in ratings of benefit to the infant and importance to participants amongst scenarios. Participants were most likely to perceive benefit and importance in screening for a disorder if treatment/intervention offered a high chance of improved outcomes. While participants perceived benefit to the infant and importance to themselves in screening for most disorders, nuances in inter-scenario ratings suggest participants weighed availability and type of treatment/intervention in consideration of the benefits of NBS.

  5. Tele-health: assessment of websites on newborn hearing screening in Portuguese Language.

    Science.gov (United States)

    Chaves, Juliana Nogueira; Libardi, Ana Lívia; Agostinho-Pesse, Raquel Sampaio; Morettin, Marina; Alvarenga, Kátia de Freitas

    2015-01-01

    To verify the aspects of technical quality and the content of websites on neonatal hearing screening in Portuguese. Eighteen audiologists, invited to participate according to the inclusion criteria, selected descriptors of websites for research using the Delphi technique. Later, they were fed into Google Trends to get the possible terms to be used by parents in finding information on the Internet about the subject. They were then fed into Google to search the websites. The following assessment instruments were used: list of topics on newborn hearing screening, Flesch Reading Ease Score Formula, Health-Related Web Site Evaluation Emory Form, and PageRank. The most discussed topics in the 19 websites were on the objectives and benefits of neonatal hearing screening, as well as the process of audiological diagnosis. The least discussed were about the false-negative result, development of hearing and language, false-positive results, audiologic, interpretation of results - "Pass"/"Do not pass", retest, and protocol. Difficult reading level was prevalent, with aspects of technical quality considered the best quality-related content, audience, navigation, and structure. The results also showed there is no culture of inserting links on Brazilian national websites, so they had little relevance on Google. The sites differed in the aspects addressed because there is a need to revise the reading level of the content and quality of the technical aspects regarding the accuracy and timeliness of information, authorship, and links.

  6. Characterization of mortality in children with sickle cell disease diagnosed through the Newborn Screening Program.

    Science.gov (United States)

    Sabarense, Alessandra P; Lima, Gabriella O; Silva, Lívia M L; Viana, Marcos Borato

    2015-01-01

    To characterize the deaths of 193 children with sickle cell disease screened by a neonatal program from 1998 to 2012 and contrast the initial years with the final years. Deaths were identified by active surveillance of children absent to scheduled appointments in Blood Bank Clinical Centers (Hemominas). Clinical and epidemiological data came from death certificates, neonatal screening database, medical records, and family interviews. Between 1998 and 2012, 3,617,919 children were screened and 2,591 had sickle cell disease (1:1,400). There were 193 deaths (7.4%): 153 with SS/Sβ(0)-thalassemia, 34 SC and 6 Sβ(+)thalassemia; 76.7% were younger than five years; 78% died in the hospital and 21% at home or in transit. The main causes of death were infection (45%), indeterminate (28%), and acute splenic sequestration (14%). In 46% of death certificates, the term "sickle cell" was not recorded. Seven-year death rate for children born between 1998 and 2005 was 5.43% versus 5.12% for those born between 2005 and 2012 (p = 0.72). Medical care was provided to 75% of children; 24% were unassisted. Medical care was provided within 6 hours of symptom onset in only half of the interviewed cases. In 40.5% of cases, death occurred within the first 24 hours. Low family income was recorded in 90% of cases, and illiteracy in 5%. Although comprehensive and effective, neonatal screening for sickle cell disease was not sufficient to significantly reduce mortality in a newborn screening program. Economic and social development and increase of the knowledge on sickle cell disease among health professionals and family are needed to overcome excessive mortality. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  7. Characterization of mortality in children with sickle cell disease diagnosed through the Newborn Screening Program

    Directory of Open Access Journals (Sweden)

    Alessandra P. Sabarense

    2015-06-01

    Full Text Available OBJECTIVE: To characterize the deaths of 193 children with sickle cell disease screened by a neonatal program from 1998 to 2012 and contrast the initial years with the final years. METHODS: Deaths were identified by active surveillance of children absent to scheduled appointments in Blood Bank Clinical Centers (Hemominas. Clinical and epidemiological data came from death certificates, neonatal screening database, medical records, and family interviews. RESULTS: Between 1998 and 2012, 3,617,919 children were screened and 2,591 had sickle cell disease (1:1,400. There were 193 deaths (7.4%: 153 with SS/Sß0-talassemia, 34 SC and 6 Sß+thalassemia; 76.7% were younger than five years; 78% died in the hospital and 21% at home or in transit. The main causes of death were infection (45%, indeterminate (28%, and acute splenic sequestration (14%. In 46% of death certificates, the term "sickle cell" was not recorded. Seven-year death rate for children born between 1998 and 2005 was 5.43% versus 5.12% for those born between 2005 and 2012 (p = 0.72. Medical care was provided to 75% of children; 24% were unassisted. Medical care was provided within 6 hours of symptom onset in only half of the interviewed cases. In 40.5% of cases, death occurred within the first 24 hours. Low family income was recorded in 90% of cases, and illiteracy in 5%. CONCLUSIONS: Although comprehensive and effective, neonatal screening for sickle cell disease was not sufficient to significantly reduce mortality in a newborn screening program. Economic and social development and increase of the knowledge on sickle cell disease among health professionals and family are needed to overcome excessive mortality.

  8. Screening of Pregnant Women for Anti-Toxoplasma Antibodies and their Newborn for Vertical Transmission

    Directory of Open Access Journals (Sweden)

    Aysha Yasmeen

    2017-10-01

    the pregnant women in Kolar region, possess anti-Toxoplasma IgG antibodies and are immune to toxoplasmosis. The rest, constituting a large proportion, are susceptible and run the risk of infection during pregnancy. Routine screening of women for Toxoplasma infections during pregnancy and screening of newborns for congenital toxoplasmosis are recommended.

  9. Radiological evaluation of the lungs in children with cystic fibrosis diagnosed during newborn screening examinations

    International Nuclear Information System (INIS)

    Iwanowska, B.; Kopys-Wiszniewska, I.; Sands, D.

    2006-01-01

    Cystic fibrosis is an inherited, autosomal, recessive disease. This disorder is caused by defects in the gene for cystic fibrosis transmembrane conductance regulator (CFTR), which encodes for a protein that functions as a chloride channel. Mutations in the gene for CFTR result in ion disorders, and consequently in disturbances of exocrine glands in the respiratory, gastrointestinal, and genitourinary tracts. Pulmonary involvement occurs in 90% of patients, and is the main cause of death. The diagnosis of CF in Poland is based on clinical symptoms and positive results of the sweat test. Diacrisis is usually reached late in the 3 rd year of life. In 1999-2003, newborn screening examinations were performed at the Mother and Child Institute. The idea of these studies was to establish a diagnosis and begin treatment as early as possible, even in the asymptomatic period of the disease. The level of immunoreactive trypsinogen was determined in the blood of 4-6-day-old newborns, as well as the mutation of gene CFTR. The mean age of CF diagnosis was about 38 days. The aim of our study was to assess the influence of early commencement of treatment on the rapidity of progression of pulmonary involvement. 59 children with CF diagnosed by screening were examined by chest radiography in various periods of the disease, the earliest in the neonatal period. Pulmonary involvement (hyperinflation, periobronchial thickening, pulmonary nodules, cysts, parenchymal density, atelectasis and fibrous changes) were assessed according to Brasfield score. The control group consisted of 19 children with symptomatic CF, born in 1997-2003.They were also examined by chest radiography. Various pulmonary changes were recognized in 42 children diagnosed by screening. In the control group pulmonary involvement was found in 16 children. In both groups progression was found in 28% of the children, but significant progression was seen in 7% of those children with a screening diagnosis, and in 25% of the

  10. Novel heparan sulfate assay by using automated high-throughput mass spectrometry: Application to monitoring and screening for mucopolysaccharidoses.

    Science.gov (United States)

    Shimada, Tsutomu; Kelly, Joan; LaMarr, William A; van Vlies, Naomi; Yasuda, Eriko; Mason, Robert W; Mackenzie, William; Kubaski, Francyne; Giugliani, Roberto; Chinen, Yasutsugu; Yamaguchi, Seiji; Suzuki, Yasuyuki; Orii, Kenji E; Fukao, Toshiyuki; Orii, Tadao; Tomatsu, Shunji

    2014-01-01

    Mucopolysaccharidoses (MPS) are caused by deficiency of one of a group of specific lysosomal enzymes, resulting in excessive accumulation of glycosaminoglycans (GAGs). We previously developed GAG assay methods using liquid chromatography tandem mass spectrometry (LC-MS/MS); however, it takes 4-5 min per sample for analysis. For the large numbers of samples in a screening program, a more rapid process is desirable. The automated high-throughput mass spectrometry (HT-MS/MS) system (RapidFire) integrates a solid phase extraction robot to concentrate and desalt samples prior to direction into the MS/MS without chromatographic separation; thereby allowing each sample to be processed within 10s (enabling screening of more than one million samples per year). The aim of this study was to develop a higher throughput system to assay heparan sulfate (HS) using HT-MS/MS, and to compare its reproducibility, sensitivity and specificity with conventional LC-MS/MS. HS levels were measured in the blood (plasma and serum) from control subjects and patients with MPS II, III, or IV and in dried blood spots (DBS) from newborn controls and patients with MPS I, II, or III. Results obtained from HT-MS/MS showed 1) that there was a strong correlation of levels of disaccharides derived from HS in the blood, between those calculated using conventional LC-MS/MS and HT-MS/MS, 2) that levels of HS in the blood were significantly elevated in patients with MPS II and III, but not in MPS IVA, 3) that the level of HS in patients with a severe form of MPS II was higher than that in an attenuated form, 4) that reduction of blood HS level was observed in MPS II patients treated with enzyme replacement therapy or hematopoietic stem cell transplantation, and 5) that levels of HS in newborn DBS were elevated in patients with MPS I, II or III, compared to those of control newborns. In conclusion, HT-MS/MS provides much higher throughput than LC-MS/MS-based methods with similar sensitivity and specificity

  11. Beyond Critical Congenital Heart Disease: Newborn Screening Using Pulse Oximetry for Neonatal Sepsis and Respiratory Diseases in a Middle-Income Country.

    Science.gov (United States)

    Jawin, Vida; Ang, Hak-Lee; Omar, Asma; Thong, Meow-Keong

    2015-01-01

    Studies on pulse oximetry screening for neonatal sepsis and respiratory disease in a middle-income country are lacking. Newborn screening for critical congenital heart disease (CCHD) using pulse oximetry is an effective and life-saving strategy in developed countries. While most studies have reported false-positive results during CCHD screening, they have not elaborated on the detected disease types. We studied the effectiveness and outcomes of pulse oximetry newborn screening for non-cardiac hypoxemic diseases such as neonatal sepsis, respiratory diseases, and CCHD in a middle-income country. In a pilot study performed at the University Malaya Medical Centre (UMMC), Malaysia, all apparently healthy term newborns, delivered at UMMC were screened pre-discharge using pulse oximetry. Echocardiography was performed for newborns that had positive screening results on two separate occasions, 1-h apart. Newborns with normal echocardiograms were evaluated and treated for other non-cardiac diseases. Fifteen of 5247 term newborns had positive screening results. The median age at screening was 20 h. Thirteen newborns (0.24%) had significant non-cardiac diseases: sepsis (n = 2) and respiratory diseases (n = 11) that required hospitalization and treatment. The remaining two newborns with normal antenatal ultrasonograms had positive screening test and confirmed to have CCHD. Another 18 newborns with negative screening test were later admitted for treatment of sepsis (n = 16) and penumonia (n = 2). All newborns were treated and alive at the end of the study. The sensitivity and specificity of pulse oximetry screening for non-cardiac diseases were 42% and 99.9% respectively, and 100% and 99.7% for CCHD, respectively. Routine pulse oximetry screening test was effective in identifying newborns with CCHD and other hypoxemia illnesses, which may led to potential life-threatening condition. This study showed that the expanded use of pulse oximetry has immediate implications for low

  12. Sensorineural and conductive hearing loss in infants diagnosed in the program of universal newborn hearing screening.

    Science.gov (United States)

    Wroblewska-Seniuk, Katarzyna; Dabrowski, Piotr; Greczka, Grazyna; Szabatowska, Katarzyna; Glowacka, Agata; Szyfter, Witold; Mazela, Jan

    2018-02-01

    The aim of this study was to analyze infants diagnosed with sensorineural or conductive hearing deficit and to identify risk factors associated with these defects. A retrospective analysis of infants diagnosed with hearing deficit based on the database of the universal newborn hearing screening program and medical records of the patients. 27 935 infants were covered by the universal neonatal hearing screening program. 109 (0.39%) were diagnosed with hearing deficit and referred for treatment and rehabilitation. 56 (51.4%) children were diagnosed with conductive, 38 (34.9%) with sensorineural and 15 (13.8%) with mixed type of hearing deficit. Children with sensorineural hearing deficit more frequently suffered from hyperbilirubinemia (p conductive hearing loss were more frequently diagnosed with isolated craniofacial anomalies (p hearing deficit occurred almost 3 times more often bilaterally than unilaterally (p hearing deficit, the difference was not significant. In children with conductive and mixed type of hearing loss the impairment was mainly mild while among those with sensorineural hearing deficit in almost 45% it was severe and profound (p hearing screening test by means of otoacoustic emissions and the final diagnosis of hearing deficit we found that the highest agreement rate was observed in children with sensorineural hearing loss (p hearing deficit was similar in children with sensorineural, conductive and mixed type of hearing loss, only hyperbilirubinemia seemed to predispose to sensorineural hearing deficit and isolated craniofacial malformations seemed to be associated with conductive hearing loss. Sensorineural hearing deficit usually occurred bilaterally and was severe or profound, while conductive and mixed type of hearing deficit were most often of mild degree. Most children with the final diagnosis of sensorineural hearing deficit had positive result of hearing screening by means of otoacoustic emissions. Copyright © 2017 Elsevier B.V. All

  13. Ethical, legal, and social issues in health technology assessment for prenatal/preconceptional and newborn screening: a workshop report.

    Science.gov (United States)

    Potter, B K; Avard, D; Entwistle, V; Kennedy, C; Chakraborty, P; McGuire, M; Wilson, B J

    2009-01-01

    Prenatal/preconceptional and newborn screening programs have been a focus of recent policy debates that have included attention to ethical, legal, and social issues (ELSIs). In parallel, there has been an ongoing discussion about whether and how ELSIs may be addressed in health technology assessment (HTA). We conducted a knowledge synthesis study to explore both guidance and current practice regarding the consideration of ELSIs in HTA for prenatal/preconceptional and newborn screening. As the concluding activity for this project, we held a Canadian workshop to discuss the issues with a diverse group of stakeholders. Based on key workshop themes integrated with our study results, we suggest that population-based genetic screening programs may present particular types of ELSIs and that a public health ethics perspective is potentially highly relevant when considering them. We also suggest that approaches to addressing ELSIs in HTA for prenatal/preconceptional and newborn screening may need to be flexible enough to respond to diversity in HTA organizations, cultural values, stakeholder communities, and contextual factors. Finally, we highlight a need for transparency in the way that HTA producers move from evidence to conclusions and the ways in which screening policy decisions are made. Copyright © 2008 S. Karger AG, Basel.

  14. ABR-based newborn hearing screening with MB11 BERAphone® using an optimized chirp for acoustical stimulation.

    Science.gov (United States)

    Cebulla, Mario; Shehata-Dieler, Wafaa

    2012-04-01

    At our center, the Maico MB11 BERAphone(®) device is used for newborn hearing screening based on Auditory Brainstem Responses (ABR). In 2006, an optimized chirp stimulus was implemented in the device to increase the reliability and quality of the screening method. In 2002, an automated response detection algorithm had been implemented. This study analyzes the screening results using the MB11 BERAphone(®) device with the implemented chirp stimulus and automated response detection method. The data presented were collected in the well-baby nursery as part of the newborn hearing screening program following a two stage screening protocol. To focus the study on the typical routine screening, data from at-risk babies were not included. Overall, data from 6866 babies (3604 males and 3262 females) screened from March 2006 to April 2011 were analyzed in this study. Out of the 6866 babies screened, 6607 passed bilaterally prior to hospital discharge (defined as 1st stage in this hearing screening program). Therefore, the pre-discharge pass rate of the hearing screening with the MB11 BERAphone(®) device was 96.2%. The resulting referral rate was 3.8%. The median test time per ear (excluding time for preparation and data reporting) was 28s with a range of 15-112s (5-95th percentile). The number of infants referred for 2nd stage, post-discharge re-screening was 259. Of this group, 71 passed bilaterally and 188 failed the re-screening in one or both ears. Therefore, including both the pre-discharge and post-discharge screening results, the bilateral pass rate was 97.3% and 2.7% were referred for diagnostic evaluation. Diagnostic testing was performed on all of the 188 infants who were referred. Results showed that 47 of these babies had hearing loss. This equates to a positive predictive value for a refer result of 25%. The observed prevalence of hearing impairment in our population was 0.684%. Diagnostic results for 141 of the referred newborns proved that they had normal

  15. MASS SPECTROMETRY PROTEOMICS METHOD AS A RAPID SCREENING TOOL FOR BACTERIAL CONTAMINATION OF FOOD

    Science.gov (United States)

    2017-06-01

    MASS SPECTROMETRY PROTEOMICS METHOD AS A RAPID SCREENING TOOL FOR BACTERIAL CONTAMINATION OF FOOD ECBC-TR...TITLE AND SUBTITLE Mass Spectrometry Proteomics Method as a Rapid Screening Tool for Bacterial Contamination of Food 5a. CONTRACT NUMBER 5b...the MSPM to correctly classify whether or not food samples were contaminated with Salmonella enterica serotype Newport in this blinded pilot study

  16. Funding Decisions for Newborn Screening: A Comparative Review of 22 Decision Processes in Europe

    Directory of Open Access Journals (Sweden)

    Katharina Elisabeth Fischer

    2014-05-01

    Full Text Available Decision-makers need to make choices to improve public health. Population-based newborn screening (NBS is considered as one strategy to prevent adverse health outcomes and address rare disease patients’ needs. The aim of this study was to describe key characteristics of decisions for funding new NBS programmes in Europe. We analysed past decisions using a conceptual framework. It incorporates indicators that capture the steps of decision processes by health care payers. Based on an internet survey, we compared 22 decisions for which answers among two respondents were validated for each observation. The frequencies of indicators were calculated to elicit key characteristics. All decisions resulted in positive, mostly unrestricted funding. Stakeholder participation was diverse focusing on information provision or voting. Often, decisions were not fully transparent. Assessment of NBS technologies concentrated on expert opinion, literature review and rough cost estimates. Most important appraisal criteria were effectiveness (i.e., health gain from testing for the children being screened, disease severity and availability of treatments. Some common and diverging key characteristics were identified. Although no evidence of explicit healthcare rationing was found, processes may be improved in respect of transparency and scientific rigour of assessment.

  17. Permanent Childhood Hearing Impairment: Aetiological Evaluation of Infants identified through the Irish Newborn Hearing Screening Programme

    LENUS (Irish Health Repository)

    Smith, A

    2017-11-01

    The Newborn Hearing Screening Programme (NHSP) was established in Cork University Maternity Hospital (CUMH) in April 2011. Between April 2011 and July 2014, 42 infants were identified with a Permanent Childhood Hearing Impairment (PCHI). Following this diagnosis, infants underwent a paediatric assessment according to recognised guidelines with the intention of identifying the underlying aetiology of the PCHI. The aim of this study was to assess the findings of this aetiological workup via retrospective chart review. PCHI data was obtained from the eSP database. This is a web based information system (eSP) used to track each baby through the screening and referral process A retrospective chart review of these patients was performed. Sixteen (38%) infants were diagnosed with a bilateral sensorineural hearing loss. Two infants had congenital CMV infection. A Connexin 26 gene mutation was detected in one infant. Two infants were diagnosed with Waardenburg syndrome, One with Pendred syndrome and one with Pfeiffer syndrome. Five babies underwent cochlear implantation. Through adherence to the recommended protocol a possible cause of PCHI may be determined. This study has identified areas of future improvement for this service in Ireland.

  18. Retinal and Optic Nerve Hemorrhages in the Newborn Infant: One-year Results of the Newborn Eye Screen Test (NEST) Study

    Science.gov (United States)

    Callaway, Natalia F.; Ludwig, Cassie A.; Blumenkranz, Mark S.; Jones, Jennifer Michelle; Fredrick, Douglas R.; Moshfeghi, Darius M.

    2016-01-01

    Purpose To report the birth prevalence, risk factors, characteristics and location of fundus hemorrhages (FH) of the retina and optic nerve present in newborns at birth. Design Prospective cohort study at Stanford University School of Medicine. Participants All infants who were 37 weeks postmenstrual age or older and were deemed stable by their pediatrician were eligible for screening. Infants who were anophthalmic or had known or suspected infectious conjunctivitis were excluded. Methods Infants born at Lucile Packard Children's Hospital (LPCH) from July 25, 2013 through July 25, 2014 were offered universal newborn screening via wide-angle digital retinal photography in the Newborn Eye Screen Test (NEST) study. Maternal, obstetric, and neonatal factors were obtained by reviewing hospital records prior to discharge. The location, retinal layer, and laterality of FH were recorded by one pediatric vitreoretinal specialist. Main Outcome Measures Birth prevalence of FH. Secondary outcomes included rate of adverse events, risk factors for FH, hemorrhage characteristics and adverse events. Results The birth prevalence of FH in this study was 20.3% (41/202 infants). Ninety-five percent of FHs involved the periphery, 83% involved the macula, and 71% involved multiple layers of the retina. The fovea was involved in 15% of FH cases (birth prevalence, 3.0%). No cases of bilateral foveal hemorrhage were found. Fundus hemorrhages were more common in the left eye than the right. Fundus hemorrhages were most commonly optic nerve flame hemorrhages (48%) and white-centered retinal hemorrhages (30%). Retinal hemorrhages were found most frequently in all 4 quadrants (35%) and more often were multiple than solitary. Macular hemorrhages most often were intraretinal (40%). Among the risk factors examined in this study, vaginal delivery compared with cesarean section (odds ratio [OR], 9.34; 95% confidence interval [CI], 2.57-33.97) showed the greatest level of association with FH. Self

  19. Newborn Bilirubin Screening for Preventing Severe Hyperbilirubinemia and Bilirubin Encephalopathy: A Rapid Review.

    Science.gov (United States)

    Bhardwaj, Kalpana; Locke, Tiffany; Biringer, Anne; Booth, Allyson; Darling, Elizabeth K; Dougan, Shelley; Harrison, Jane; Hill, Stephen; Johnson, Ana; Makin, Susan; Potter, Beth; Lacaze-Masmonteil, Thierry; Little, Julian

    2017-01-01

    According to the 2004 American Academy of Pediatrics guideline on the management of hyperbilirubinemia, every newborn should be assessed for the risk of developing severe hyperbilirubinemia with the help of predischarge total serum bilirubin or transcutaneous bilirubin measurements and/or assessments of clinical risk factors. The aim of this rapid review is 1) to review the evidence for 1) predicting and preventing severe hyperbilirubinemia and bilirubin encephalopathy, 2) determining the efficacy of home/community treatments (home phototherapy) in the prevention of severe hyperbilirubinemia, and 3) non-invasive/transcutaneous methods for estimating serum bilirubin level. In this rapid review, studies were identified through the Medline database. The main outcomes of interest were severe hyperbilirubinemia and encephalopathy. A subset of articles was double screened and all articles were critically appraised using the SIGN and AMSTAR checklists. This review investigated if systems approach is likely to reduce the occurrence of severe hyperbilirubinemia. Fifty-two studies met the inclusion criteria. Included studies assessed the association between bilirubin measurement early in neonatal life and the subsequent development of severe hyperbilirubinemia and chronic bilirubin encephalopathy/kernicterus. It was observed that, highest priority should be given to (i) universal bilirubin screening programs; (ii) implementation of community and midwife practice; (iii) outreach to communities for education of prospective parents; and (iv) development of clinical pathways to monitor, evaluate and track infants with severe hyperbilirubinemia. We found substantial observational evidence that severe hyperbilirubinemia can be accurately predicted and prevented through universal bilirubin screening. So far, there is no evidence of any harm. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Have we stopped looking for a red reflex in newborn screening?

    LENUS (Irish Health Repository)

    Sotomi, O

    2012-02-03

    Best medical evidence indicates that surgical treatment of significant congenital cataracts is required within the first 3 months of life for optimal visual outcome. The aim of the present study was to review when the diagnosis of congenital cataracts was made in our region, by whom it was made, and the visual outcome at 2 years of age or more. This was a retrospective study in a region with a population of 546,000 and approximately 8500 births per annum, served by a single Regional Ophthalmology centre. All children under 15 years, diagnosed with Congenital Cataract over a 10-year period (1991-2002), were identified using the Hospital In-Patient Enquiry [HIPE] database. Children with cataract(s) from infancy from a congenital cause and those first presenting outside infancy but with salient clinical features indicating early cataract were included in the study. 27 cases of congenital and infantile cataract 15 (56%) males, 12 (44%) females were retrieved. 17 infants (63%) were diagnosed with bilateral disease, while the remainder were unilateral 10 (37%). Most of the cases 17 (63%) were diagnosed following presentation with parental\\/carer concerns about visual function (usually a squint). However only 2 of these 17 cases presented before 3 months of age. The remaining cases of congenital cataracts were diagnosed by general practitioners 8 (24%), paediatricians 4 (12%), ophthalmologists 3 (9%) or School Medical Officer (1, 3%). No case of congenital cataract was diagnosed by newborn screening examination. Six of 8 infants diagnosed with congenital cataracts before three months of age had a good visual outcome, (visual acuity < 6\\/24 at 2 years or more). In contrast only 3 of 19 cases who were diagnosed after 3 months of age had good visual outcomes. Despite their relative rarity, it is imperative that congenital cataracts are diagnosed and treated within 3 months of birth. The onus of diagnosis rests with newborn screening examiners at birth and with general

  1. Prenatal Education of Parents About Newborn Screening and Residual Dried Blood Spots: A Randomized Clinical Trial.

    Science.gov (United States)

    Botkin, Jeffrey R; Rothwell, Erin; Anderson, Rebecca A; Rose, Nancy C; Dolan, Siobhan M; Kuppermann, Miriam; Stark, Louisa A; Goldenberg, Aaron; Wong, Bob

    2016-06-01

    Research clearly indicates that current approaches to newborn blood spot screening (NBS) education are ineffective. Incorporating NBS education into prenatal care is broadly supported by lay and professional opinion. To determine the efficacy and effect of prenatal education about newborn screening and use of residual dried blood spots (DBS) in research on parental knowledge, attitudes, and behaviors. A randomized clinical trial of prenatal educational interventions, with outcomes measured by survey at 2 to 4 weeks postpartum. Participants were recruited from obstetric clinics in Salt Lake City, Utah; San Francisco, California; and the Bronx, New York. Eligible women were English- or Spanish-speaking adults and did not have a high-risk pregnancy. A total of 901 women were enrolled. Participants who completed the follow-up survey included 212 women in the usual care group (70% retention), 231 in the NBS group (77% retention), and 221 women in the NBS + DBS group (75% retention). Those who completed the survey were similar across the 3 groups with respect to age, ethnicity, race, education, marital status, income, obstetric history, and language. Participants were randomized into 1 of 3 groups: usual care (n = 305), those viewing an NBS movie and brochure (n = 300), and those viewing both the NBS and DBS movies and brochures (n = 296). Two to four weeks postpartum, women completed a 91-item survey by telephone, addressing knowledge, attitudes, and behavior with respect to opting out of NBS or DBS for their child. A total of 901 women (mean age, 31 years) were randomized and 664 completed the follow-up survey. The total correct responses on the knowledge instrument in regard to NBS were 69% in the usual care group, 79% in the NBS group, and 75% in the NBS + DBS group, a significant between-group difference (P Educational interventions can be implemented in the prenatal clinic, using multimedia tools and electronic platforms. Prenatal education is

  2. Measurement of fecal elastase improves performance of newborn screening for cystic fibrosis.

    Science.gov (United States)

    Barben, Juerg; Rueegg, Corina S; Jurca, Maja; Spalinger, Johannes; Kuehni, Claudia E

    2016-05-01

    The aim of newborn screening (NBS) for CF is to detect children with 'classic' CF where early treatment is possible and improves prognosis. Children with inconclusive CF diagnosis (CFSPID) should not be detected, as there is no evidence for improvement through early treatment. No algorithm in current NBS guidelines explains what to do when sweat test (ST) fails. This study compares the performance of three different algorithms for further diagnostic evaluations when first ST is unsuccessful, regarding the numbers of children detected with CF and CFSPID, and the time until a definite diagnosis. In Switzerland, CF-NBS was introduced in January 2011 using an IRT-DNA-IRT algorithm followed by a ST. In children, in whom ST was not possible (no or insufficient sweat), 3 different protocols were applied between 2011 and 2014: in 2011, ST was repeated until it was successful (protocol A), in 2012 we proceeded directly to diagnostic DNA testing (protocol B), and 2013-2014, fecal elastase (FE) was measured in the stool, in order to determine a pancreas insufficiency needing immediate treatment (protocol C). The ratio CF:CFSPID was 7:1 (27/4) with protocol A, 2:1 (22/10) with protocol B, and 14:1 (54/4) with protocol C. The mean time to definite diagnosis was significantly shorter with protocol C (33days) compared to protocol A or B (42 and 40days; p=0.014 compared to A, and p=0.036 compared to B). The algorithm for the diagnostic part of the newborn screening used in the CF centers is important and affects the performance of a CF-NBS program with regard to the ratio CF:CFSPID and the time until definite diagnosis. Our results suggest to include FE after initial sweat test failure in the CF-NBS guidelines to keep the proportion of CFSPID low and the time until definite diagnosis short. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  3. Newborn hearing screening program: association between hearing loss and risk factors

    OpenAIRE

    Pereira, Priscila Karla Santana; Martins, Adriana de Souza; Vieira, Márcia Ribeiro; Azevedo, Marisa Frasson de

    2007-01-01

    BACKGROUND: hearing loss in newborns. Aim: to verify the prevalence of auditory alterations in newborns of Hospital São Paulo (hospital), observing if there are any correlations with the following variables: birth weight, gestational age, relation weight/gestational age and risk factors for hearing loss. METHOD: A retrospective analysis of the hospital records of 1696 newborns; 648 records of preterm infants and 1048 records of infants born at term. All of the infants had been submitted to an...

  4. Education and parental involvement in decision-making about newborn screening: understanding goals to clarify content.

    Science.gov (United States)

    Potter, Beth K; Etchegary, Holly; Nicholls, Stuart G; Wilson, Brenda J; Craigie, Samantha M; Araia, Makda H

    2015-06-01

    A challenge in designing effective education for parents about newborn screening (NBS) has been uncertainty about appropriate content. Arguing that the goals of education may be usefully tied to parental decision-making, we sought to: (1) explore how different ways of implementing NBS differ in their approaches to parental engagement in decision-making; (2) map the potential goals of education onto these "implementation models"; and (3) consider the content that may be needed to support these goals. The resulting conceptual framework supports the availability of comprehensive information about NBS for parents, irrespective of the model of implementation. This is largely because we argue that meeting parental expectations and preferences for communication is an important goal regardless of whether or notparents are actively involved in making a decision. Our analysis supports a flexible approach, in which some educational messages are emphasized as important for all parents to understand while others are made available depending on parents' preferences. We have begun to define the content of NBS education for parents needed to support specific goals. Further research and discussion is important to determine the most appropriate strategies for delivering the tailored approach to education that emerged from our analysis.

  5. Utility of newborn screening cards for detecting CMV infection in cases of stillbirth.

    Science.gov (United States)

    Howard, Jonathan; Hall, Beverley; Brennan, Lyndall Eve; Arbuckle, Susan; Craig, Maria E; Graf, Nicole; Rawlinson, William

    2009-03-01

    CMV infection may cause intrauterine deaths including stillbirths (intrauterine deaths at > or =20 weeks gestation). In 2005, there were 1979 stillbirths in Australia, which is almost double the number of deaths reported for all children between 1 and 14 years age. We evaluated the diagnostic utility of testing for the presence of CMV in newborn blood screening cards (NBSC) collected from stillborn babies, who had no known cause of death after post-mortem. Blood taken at post-mortem by cardiac puncture of 107 stillborn babies between July 2005 and December 2006, was spotted onto NBSC. CMV infection was detected using nested PCR targeting the glycoprotein gene, gp58. Of the 107 stillborn infants, 10 (9%) were CMV positive. The rate of CMV infection did not differ between early stillbirths (8%) and late stillbirths (9%). The use of NBSC is a convenient and accurate method for CMV detection in stillbirths. It is easily collected, less laborious than viral culture, diagnostically useful and could be applied for epidemiological and retrospective investigation of the virus in the stillbirth population.

  6. Psychosocial effects in parents and children 12 years after newborn genetic screening for type 1 diabetes

    Science.gov (United States)

    Kerruish, Nicola J; Healey, Dione M; Gray, Andrew R

    2017-01-01

    Little is known about the psychosocial consequences of testing newborns for genetic susceptibility to multifactorial diseases. This study reports quantitative psychosocial evaluations of parents and children 12 years after screening for type 1 diabetes (T1D). Two parent-child cohorts participated: children at increased genetic risk of T1D and children at low genetic risk. T1D risk status was determined at birth as part of a prospective study investigating potential environmental triggers of autoimmunity. Parent measures included ratings of children's emotional, behavioural and social functioning (Child Behaviour Checklist) and parenting style (Alabama Parenting Questionnaire). Child self-concept was assessed using the self-description questionnaire (SDQ1). Statistical analyses were conducted to test for differences between the groups. Twelve years after testing there was no evidence that knowledge of a child's increased genetic risk of T1D adversely affected parental ratings of their child's emotional, behavioural or social functioning, or impacted upon parenting style. There was no adverse effect upon the child's assessment of their self-concept. This study provides important preliminary data concerning longer-term psychosocial effects of incorporating tests for genetic risk of complex disorders into NBS panels. While it is reassuring that no significant adverse effects have been detected, more data will be required to adequately inform policy. PMID:28120838

  7. Radio-immuno-assay for trypsin in newborn-screening for cystic fibrosis

    International Nuclear Information System (INIS)

    Sander, J.; Niehaus, C.

    1982-01-01

    In 4,956 infants the concentration of immunoreactive trypsin was measured in dried blood on filter paper using a double antibody radioimmuno assay. About 90% of all results were below 40 ng/ml. In 13 infants the concentration of immunoreactive trypsin exceeded 80 ng/ml. These infants were examined clinically, including sweationtophoresis. We found three children suffering from cystic fibrosis. One further child showing an elevated concentration of chloride in the sweat (60 mval/ml) could not be reexamined. The concentration of immunoreactive trypsin in the cystic fibrosis children was 230, 297, and in one case 108 ng/ml at the 76th day of life, whereas the values for the 9 other children were between 80 and 154 ng/ml. We believe these results justify to use this test for a much higher number of infants, especially because it is inexpensive and can easily be added to existing newborn screening programs for inborn errors of metabolism. (orig.) [de

  8. Newborn Screening for Severe Combined Immunodeficiency-A History of the TREC Assay

    Directory of Open Access Journals (Sweden)

    Mary T. Bausch-Jurken

    2017-06-01

    Full Text Available Infants born with T cell lymphopenias, especially severe combined immunodeficiency (SCID are at risk for serious, often fatal infections without intervention within the first year or two of life. The majority of these disorders can be detected through the use of the T cell recombination excision circle assay (TREC assay. The TREC assay detects the presence of non-replicating, episomal DNA that is formed during T cell development. This assay initially developed to measure thymic output during aging and HIV infection, has undergone modifications for the purpose of newborn screening (NBS for SCID. To meet the requirements for inclusion on NBS panels, the assay needed to utilize blood from dried blood spots on NBS cards, and be both sensitive and specific, avoiding the costs of false positives. Currently, the assay relies upon real time, quantitative PCR (RT-qPCR to detect TRECs in punches taken from dried blood spots. This review seeks to highlight some of the early work leading up to the initial implementation of the TREC assay for SCID detection, and the subsequent revisions made to optimize the assay.

  9. Abnormal TREC-Based Newborn Screening Test in a Premature Neonate with Massive Perivillous Fibrin Deposition of the Placenta

    Directory of Open Access Journals (Sweden)

    Stefan Kostadinov

    2016-01-01

    Full Text Available Severe combined immunodeficiency (SCID, a primary immunodeficiency arising from variable defects in lymphocyte development and survival, is characterized by significant deficiency of thymus derived (T- lymphocytes and variable defects in the B-lymphocyte population. Newborn screening for SCID is based on detection of low numbers of T-cell receptor excision circles (TRECs by real time quantitative PCR (RT-qPCR. This screening allows for early identification of individuals with SCID and other disorders characterized by T-lymphopenia. Higher rates of abnormal screens are commonly seen in premature and critically ill neonates, often representing false positives. It is possible that many abnormal screens seen in these populations are result of conditions that are characterized by systemic inflammation or stress, possibly in the context of stress-induced thymic involution. We present a case of a male infant delivered at 27 weeks, 6 days of gestation, with severe intrauterine growth restriction who had an abnormal TREC screen and a massive perivillous fibrin deposition (MPFD of the placenta. This association has not been reported previously. We are raising the awareness to the fact that conditions, such as MPFD, that can create adverse intrauterine environment are capable of causing severe stress-induced thymic involution of the fetus which can present with abnormal TREC results on newborn screening.

  10. What follows newborn screening? An evaluation of a residential education program for parents of infants with newly diagnosed cystic fibrosis.

    Science.gov (United States)

    Sawyer, Susan M; Glazner, Judith A

    2004-08-01

    The diagnosis of a severe life-limiting condition, such as cystic fibrosis (CF), is generally followed by assessment and treatment of the child and education and counseling for parents. The introduction of newborn screening for CF provides an opportunity for standardized assessment and education. The aim of this study was to evaluate a 5-day residential assessment and education program for parents of infants who receive a diagnosis of CF after newborn screening. Eligible parents had a 6- to 30-month-old infant with CF diagnosed by newborn screening. Parents were interviewed by telephone using a structured questionnaire that addressed 3 main themes: 1) initial communication of the diagnosis of CF, 2) the perceived value of the 5-day assessment and education program, and 3) the perceived advantages and disadvantages of the residential component (Care-By-Parent unit) of the program. Fifteen of 17 eligible families took part in the 5-day assessment and education program, 12 of whom used the residential Care-By-Parent unit. At the end of the program, parents believed that they had the knowledge and skills required to manage their child's CF at home. One hundred percent endorsed the timing of the assessment and education program immediately after the child's diagnosis and would recommend it to other families in the same situation. Perceived advantages of the residential program were not having to travel (89%), being able to concentrate on CF (50%), and the benefit of a "home base" at the hospital (39%). Twenty-two percent reported that financial costs related to participation (paternal time off work) were a disadvantage, 17% reported additional strain on family members caring for siblings, and 17% mentioned lack of comfort within the unit. This time-intensive residential program was evaluated positively by parents of children with newly diagnosed CF. It provides a model for education programs after the diagnosis of CF by newborn screening, as well as for other pediatric

  11. High throughput reaction screening using desorption electrospray ionization mass spectrometry.

    Science.gov (United States)

    Wleklinski, Michael; Loren, Bradley P; Ferreira, Christina R; Jaman, Zinia; Avramova, Larisa; Sobreira, Tiago J P; Thompson, David H; Cooks, R Graham

    2018-02-14

    We report the high throughput analysis of reaction mixture arrays using methods and data handling routines that were originally developed for biological tissue imaging. Desorption electrospray ionization (DESI) mass spectrometry (MS) is applied in a continuous on-line process at rates that approach 10 4 reactions per h at area densities of up to 1 spot per mm 2 (6144 spots per standard microtiter plate) with the sprayer moving at ca. 10 4 microns per s. Data are analyzed automatically by MS using in-house software to create ion images of selected reagents and products as intensity plots in standard array format. Amine alkylation reactions were used to optimize the system performance on PTFE membrane substrates using methanol as the DESI spray/analysis solvent. Reaction times can be screening of processes like N -alkylation and Suzuki coupling reactions as reported herein. Products and by-products were confirmed by on-line MS/MS upon rescanning of the array.

  12. Healthcare professionals' and parents' experiences of the confirmatory testing period: a qualitative study of the UK expanded newborn screening pilot.

    Science.gov (United States)

    Moody, Louise; Atkinson, Lou; Kehal, Isher; Bonham, James R

    2017-05-08

    With further expansion of the number of conditions for which newborn screening can be undertaken, it is timely to consider the impact of positive screening results and the confirmatory testing period on the families involved. This study was undertaken as part of a larger programme of work to evaluate the Expanded Newborn Screening (ENBS) programme in the United Kingdom (UK). It was aimed to determine the views and experiences of healthcare professionals (HCPs) and parents on communication and interaction during the period of confirmatory testing following a positive screening result. Semi-structured interviews were undertaken with parents of children who had received a positive ENBS result and HCPs who had been involved with the diagnosis and support of parents. Ten parents and 11 healthcare professionals took part in the in-depth interviews. Questions considered the journey from the positive screening result through confirmatory testing to a confirmed diagnosis and the communication and interaction between the parents and HCPs that they had been experienced. Key themes were identified through thematic analysis. The results point to a number of elements within the path through confirmatory testing that are difficult for parents and could be further developed to improve the experience. These include the way in which the results are communicated to parents, rapid turnaround of results, offering a consistent approach, exploring interventions to support family relationships and reviewing the workload and scheduling implications for healthcare professionals. As technology enables newborn screening of a larger number of conditions, there is an increasing need to consider and mediate the potentially negative effects on families. The findings from this study point to a number of elements within the path through confirmatory testing that are difficult for parents and could be further developed to benefit the family experience.

  13. Delay in blood sampling for routine newborn screening is associated with increased risk of schizophrenia.

    Science.gov (United States)

    Nordentoft, Merete; Larsen, Janne Tidselbak; Pedersen, Carsten Bøcker; Sørensen, Holger Jelling; Hollegaard, Mads Villiam; Hougaard, David Michael; Mortensen, Preben Bo; Petersen, Liselotte

    2015-03-01

    The Danish Neonatal Screening Biobank, containing dried blood spot samples from all newborn in Denmark, is a unique source of data that can be utilized for analyses of genetic and environmental exposures related to schizophrenia and other mental disorders. In previous analyses, we have found that early and late blood sampling, compared to sampling at day 5, was associated with increased risk of schizophrenia. As delay in sampling of blood for neonatal screening cannot in itself influence the risk of schizophrenia, it must be seen as a proxy for unknown underlying causes responsible for this association. Therefore, we investigated whether the increased risk can be explained by other risk factors for schizophrenia. A case-control design was applied. A total of 846 cases with schizophrenia were selected from the Danish Psychiatric Case Register. One control was selected for each case, matched on sex and exact date of birth. Both early and late blood sampling was associated with increased risk for schizophrenia. Compared to blood sampling at day 5, sampling at days 0 to 4 after birth was associated with an incidence rate ratio (IRR) of 1.46 (95% CI 1.15-1.87) for development of schizophrenia, and sampling at days 6 to 9 and at days 10 to 53 was associated with an IRR of 1.5 (95% CI 1.13-1.98) and 3.00 (95% CI 1.59-5.67), respectively. After adjusting the estimates for place of birth, both parents' psychiatric illness, maternal and paternal age, parents' country of origin, child admission, and parental education and income, the estimates were slightly different. Thus, blood collection at 0-4days was associated with an IRR of 1.27 (95% CI 0.94-1.71), 6-9days 1.31 (95% CI 0.94-1.84) and 10+days 3.52 (95% CI 1.50 to 8.24). After adjusting risk estimates for well-known risk factors, delay in sampling of blood for neonatal screening was associated with unexplained increased risk of schizophrenia. Thus, a key finding is that age at test is a proxy for unobserved risk factors

  14. Screening for congenital dislocation of the hip in the newborn: The role of clinical, ultrasonographic and radiographic examination

    International Nuclear Information System (INIS)

    Dunn, P.M.

    1987-01-01

    The concept of examining all young infants for congenital dislocation of the hip (CDH) dates back to Le Damany in 1914, though it was Ortolani who stimulated widespread clinical screening with the publication of his method of examination in 1948. His technique was improved by Barlow and others and is now often referred to as the Ortolani/Barlow manoeuvre. Meanwhile, following the method of Hilgenreiner, Putti advocated in 1933 radiological screening of all newborn hips. In 1958 Andren and Von Rosen described their new radiological technique in which hip subluxation was provoked prior to x-ray. Although radiological examination has been criticised as a screening method, it is still apparently widely used in Europe, especially in German-speaking countries. More recently dynamic sonographic examination of the hips has been used for neonatal screening

  15. Challenges and Opportunities in Establishing and Maintaining Newborn Screening in a Rural Area of Andhra Pradesh - Task Force Study by Indian Council of Medical Research.

    Science.gov (United States)

    Radha Rama Devi, A; Ananthalakshmi, Y; Srimannarayana Rao, K

    2018-02-19

    The primary objective was to evaluate the feasibility of setting up newborn screening in rural areas in India. Secondary objective was to enhance the knowledge and awareness towards early detection of diseases by newborn screening, management of the affected baby and to impart genetic counseling. Awareness programs were conducted at different mandals in the district for the medical practioners during the preparatory phase of the Task Force Project. Educative lectures and clinical meetings regarding the importance and relevance of newborn screening were held every 3 months initially and half yearly later. Families were counselled during antenatal check-ups. Good co-operation was obtained from medical doctors and their willingness to participate in sample collection from the hospitals. Families accepted screening after an initial period of resistance. The fact that screening of this kind will help their babies made a positive impact. Many families started promoting newborn screening to their friends and relations. Confirmation of diagnosis, treatment, and follow-up were satisfactory with almost negligible number of cases lost to follow-up. With proper planning and commitment on the part of health authorities, it is possible to implement newborn screening in rural areas in India as well.

  16. Detection of cytomegalovirus DNA in dried blood spots of Minnesota infants who do not pass newborn hearing screening.

    Science.gov (United States)

    Choi, K Yeon; Schimmenti, Lisa A; Jurek, Anne M; Sharon, Bazak; Daly, Kathy; Khan, Cindy; McCann, Mark; Schleiss, Mark R

    2009-12-01

    Up to 15% of infants with asymptomatic congenital cytomegalovirus (CMV) infection will experience some degree of sensorineural hearing loss. Many infants who fail newborn hearing screening (NHS) are likely to have congenital CMV infection, but may escape definitive virologic identification because diagnostic evaluation may not commence until several weeks or months of age, making differentiation between congenital and postnatal CMV infection difficult. Early diagnosis linking virologic identification of congenital CMV infection to infants failing NHS may improve diagnostic precision and enhance opportunities for therapeutic intervention. The goal of this study was to compare newborn dried blood spots from Minnesota infants who had failed NHS, and were designated for referral, with control infants who passed NHS, for the presence of CMV DNA by real-time PCR, using hybridization probes for the CMV gene UL54. Of 479 infants with a failed NHS (bilateral failure), 13 had CMV DNA present in the blood spot (2.7%). This compared with only 2/479 positive results from a control group of infants who passed the NHS (0.4%; P = 0.007, Fisher exact test). Comparisons of the glycoprotein B (gB) genotype as well as direct DNA sequencing of selected positives revealed that PCR positive samples represented unique clinical isolates. The mean viral load among the 15 positive samples was 1.6 x 10(3) genomes/microgram of total DNA. Newborn bloodspot CMV screening by real-time PCR may be a useful and rapid adjunct to functional NHS and may enable more rapid etiologic diagnosis of sensorineural hearing loss in newborns.

  17. Are We Ready for Fragile X Newborn Screening Testing?—Lessons Learnt from a Feasibility Study

    Directory of Open Access Journals (Sweden)

    Tiffany Wotton

    2018-02-01

    Full Text Available Fragile X syndrome (FXS is the most prevalent heritable cause of cognitive impairment but is not yet included in a newborn screening (NBS program within Australia. This paper aims to assess the feasibility and reliability of population screening for FXS using a pilot study in one hospital. A total of 1971 mothers consented for 2000 newborns to be tested using routine NBS dried blood spot samples. DNA was extracted and a modified PCR assay with a chimeric CGG primer was used to detect fragile X alleles in both males and females in the normal, premutation, and full mutation ranges. A routine PCR-based fragile X assay was run in parallel to validate the chimeric primer assay. Babies with CGG repeat number ≥59 were referred for family studies. One thousand nine hundred and ninety NBS samples had a CGG repeat number less than 55 (1986 < 50; 10 had premutation alleles >54 CGG repeats (1/123 females and 1/507 males. There was complete concordance between the two PCR-based assays. A recent review revealed no clinically identified cases in the cohort up to 5 years later. The cost per test was $AUD19. Fragile X status can be determined on routine NBS samples using the chimeric primer assay. However, whilst this assay may not be considered cost-effective for population screening, it could be considered as a second-tier assay to a developed immunoassay for fragile X mental retardation protein (FMRP.

  18. [Evaluations of newborn screening program performance and enzymatic diagnosis of glucose-6-phosphate dehydrogenase deficiency in Guangzhou].

    Science.gov (United States)

    Tang, F; Huang, Y L; Jiang, X; Jia, X F; Li, B; Feng, Y; Chen, Q Y; Tang, C F

    2018-05-02

    Objective: To reveal the molecular epidemiologic characteristics of glucose-6-phosphate dehydrogenase (G6PD) gene and to evaluate based on the genetic analysis the newborn screening program performance and enzymatic diagnosis of G6PD deficiency in Guangzhou. Methods: G6PD enzyme activities were measured by quantitative fluorescence assay in dry blood spots of 16 319 newborns(8 725 males, 7 594 females) 3-7 days after birth in Guangzhou Newborn Center. They were born in Guangzhou form Oct. 1 to 20, 2016. The cutoff value of G6PD was less than 2.6 U/g Hb in dry blood spots. G6PD deficiency was diagnosed when G6PDblood cells. Genetic analysis of G6PD gene was performed on the dry blood spot samples of 823 newborns (including positive 346, negative 477)with various levels of G6PD enzyme activities through fluorescence PCR melting curve analysis(FMCA) to detect 15 kinds of mutations reported to be common among Chinese.G6PD gene Sanger sequency was performed in seven highly suspicious patients with negative results by FMCA. Results: (1) Using the cutoff value of G6PDT, c.551C>T, c.835A>T hemizygote were found in 3 male's samples, respectively. (3) The estimated prevalence of harboring mutation was 6.0% in males and 13.5% in females according to rates of mutation in samples with various levels of G6PD enzyme activities. Six common mutations were c.1388G>A、c.1376G>T, c.95A> G, c.871G>A, c.1024C>T, c.392G>T, accounting for 95.5% of detected alleles .(4) based on results of G6PD gene analysis, the newborn scereening of G6PD deficiency with cutoff value G6PDblood cells were 95.5%, 97.2%, respectively. Conclusions: The prevalence of G6PD deficiency in males was 6.0% in Guangzhou. Six mutations c.1388G>A, c.1376G>T, c.95A>G, c.871G>A, c.1024C>T, c.392G>T accounted for 95.5%. The cutoff value of G6PD<2.6 U/g Hb innewborn screening program and the criteria of biochemical diagnosis could accurately identify G6PD deficiency . Combined with biochemical and molecular analysis will

  19. Cost-Effectiveness/Cost-Benefit Analysis of Newborn Screening for Severe Combined Immune Deficiency in Washington State.

    Science.gov (United States)

    Ding, Yao; Thompson, John D; Kobrynski, Lisa; Ojodu, Jelili; Zarbalian, Guisou; Grosse, Scott D

    2016-05-01

    To evaluate the expected cost-effectiveness and net benefit of the recent implementation of newborn screening (NBS) for severe combined immunodeficiency (SCID) in Washington State. We constructed a decision analysis model to estimate the costs and benefits of NBS in an annual birth cohort of 86 600 infants based on projections of avoided infant deaths. Point estimates and ranges for input variables, including the birth prevalence of SCID, proportion detected asymptomatically without screening through family history, screening test characteristics, survival rates, and costs of screening, diagnosis, and treatment were derived from published estimates, expert opinion, and the Washington NBS program. We estimated treatment costs stratified by age of identification and SCID type (with or without adenosine deaminase deficiency). Economic benefit was estimated using values of $4.2 and $9.0 million per death averted. We performed sensitivity analyses to evaluate the influence of key variables on the incremental cost-effectiveness ratio (ICER) of net direct cost per life-year saved. Our model predicts an additional 1.19 newborn infants with SCID detected preclinically through screening, in addition to those who would have been detected early through family history, and 0.40 deaths averted annually. Our base-case model suggests an ICER of $35 311 per life-year saved, and a benefit-cost ratio of either 5.31 or 2.71. Sensitivity analyses found ICER values <$100 000 and positive net benefit for plausible assumptions on all variables. Our model suggests that NBS for SCID in Washington is likely to be cost-effective and to show positive net economic benefit. Published by Elsevier Inc.

  20. Surface-enhanced Raman scattering (SERS) for detection of phenylketonuria for newborn screening

    Science.gov (United States)

    Javanmard, M.; Davis, R. W.

    2014-02-01

    Diagnosis of Phenylketonuria (PKU) in newborns is important because it can potentially help prevent mental retardation since it is treatable by dietary means. PKU results in phenylketonurics having phenylalanine levels as high as 2 mM whereas the normal upper limit in healthy newborns is 120 uM. To this end, we are developing a microfluidic platform integrated with a SERS substrate for detection of high levels of phenylalanine. We have successfully demonstrated SERS detection of phenylalanine using various SERS substrates fabricated using nanosphere lithography, which exhibit high levels of field enhancement. We show detection of SERS at clinically relevant levels.

  1. Severe hemolytic disease of fetus and newborn caused by red blood cell antibodies undetected at first-trimester screening (CME).

    Science.gov (United States)

    Dajak, Slavica; Stefanović, Vedran; Capkun, Vesna

    2011-07-01

    The objective was to determine clinical consequences of anti-D and non-D antibodies undetected at first-trimester screening for infant or fetus. This retrospective cohort study included all pregnant women with red blood cell (RBC) antibodies who were tested between 1993 and 2008. Data were obtained from the forms for tracking immunization at the transfusion department. Each form was analyzed for three data sets: the order of screening at which the antibodies were detected (initial or repeated screening), the order of pregnancy (first pregnancy or higher), and whether the antibodies caused severe hemolytic disease of fetus and newborn (HDFN). In D- women, anti-D was detected in 1.3% of cases. The anti-D was undetected in 72 (37%) cases on the first-trimester screening, of which eight cases were complicated by severe HDFN. In this group, three patients were primigravidae. An overall non-D incidence of 0.2% was observed. In 16 cases, non-D were undetected on the first-trimester screening (10 anti-c, two anti-E, two anti-C, one anti-S, and one case of anti-Rh17). Non-D antibodies undetected on initial screening caused 11 cases of severe HDFN (27% of all severe non-D HDFN). Ten of them were in multiparous women. Seven of 11 cases with severe HDFN that were missed were caused by anti-c. The third-trimester screening may detect RBC antibodies that were not present or detected on the first-trimester screening. Such screening may be especially relevant in D+ multiparous women due to the risk of HDFN. © 2010 American Association of Blood Banks.

  2. Screening for seemingly healthy newborns with congenital cytomegalovirus infection by quantitative real-time polymerase chain reaction using newborn urine: an observational study

    OpenAIRE

    Yamaguchi, Akira; Oh-ishi, Tsutomu; Arai, Takashi; Sakata, Hideaki; Adachi, Nodoka; Asanuma, Satoshi; Oguma, Eiji; Kimoto, Hirofumi; Matsumoto, Jiro; Fujita, Hidetoshi; Uesato, Tadashi; Fujita, Jutaro; Shirato, Ken; Ohno, Hideki; Kizaki, Takako

    2017-01-01

    Objective Approximately 8?10% of newborns with asymptomatic congenital cytomegalovirus (cCMV) infection develop sensorineural hearing loss (SNHL). However, the relationship between CMV load, SNHL and central nervous system (CNS) damage in cCMV infection remains unclear. This study aimed to examine the relationship between urinary CMV load, SNHL and CNS damage in newborns with cCMV infection. Study design The study included 23?368 newborns from two maternity hospitals in Saitama Prefecture, Ja...

  3. Etiology and one-year follow-up results of hearing loss identified by screening of newborn hearing in Japan.

    Science.gov (United States)

    Adachi, Nodoka; Ito, Ken; Sakata, Hideaki; Yamasoba, Tatsuya

    2010-07-01

    To evaluate the incidence of newborn hearing loss in a Japanese population and to elucidate etiological factors and one-year prognosis. Screening of newborn hearing. Children's tertiary referral center. Between 1999 and 2008, 101,912 newborn infants were screened, with 693 infants (0.68%) referred. Etiology investigation included CT, detection of cytomegalovirus (CMV) DNA, and connexin 26 mutation. Abnormal results (auditory brainstem response [ABR] threshold > or = 35 normal hearing level [dB nHL] in either side) were observed in 312 infants (0.31%), and 133 subjects (0.13%) with ABR thresholds > or = 50 dB nHL on both sides were classified into the habilitation group. In this group, inner ear/internal auditory meatus anomalies were detected in 20 of 121 subjects (17%) tested, middle/external ear anomalies in 14 of 121 subjects (12%), CMV DNA in 13 of 77 subjects (17%), and connexin 26 mutation in 28 of 89 subjects (31%). In 68 subjects undergoing all three investigations (CT, CMV, and connexin 26), 41 (60%) had positive results in at least one test. With inclusion of otitis media with effusion and perinatal problems, this rate amounted to 78% (53 subjects). Of the 97 infants in the habilitation group successfully followed up to one year, 36 (37%) showed a threshold change of 20 dB or more in either ear: 11 (11%) progression and 25 (26%) improvement, and 15 infants (15%) were reclassified into a less severe classification. Considering that 26 percent of infants with bilateral moderate to severe hearing loss showed improvement in one year, habilitation protocols, especially very early cochlear implantation within one year of birth, should be reconsidered. 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.

  4. A patient with an inborn error of vitamin B12 metabolism (cblF) detected by newborn screening.

    Science.gov (United States)

    Armour, Christine M; Brebner, Alison; Watkins, David; Geraghty, Michael T; Chan, Alicia; Rosenblatt, David S

    2013-07-01

    A neonate, who was found to have an elevated C3/C2 ratio and minimally elevated propionylcarnitine on newborn screening, was subsequently identified as having the rare cblF inborn error of vitamin B12 (cobalamin) metabolism. This disorder is characterized by the retention of unmetabolized cobalamin in lysosomes such that it is not readily available for cellular metabolism. Although cultured fibroblasts from the patient did not show the expected functional abnormalities of the cobalamin-dependent enzymes, methylmalonyl-CoA mutase and methionine synthase, they did show reduced synthesis of the active cobalamin cofactors adenosylcobalamin and methylcobalamin. Mutation analysis of LMBRD1 established that the patient had the cblF disorder. Treatment was initiated promptly, and the patient showed a robust response to regular injections of cyanocobalamin, and she was later switched to hydroxocobalamin. Currently, at 3 years of age, the child is clinically well, with appropriate development. Adjusted newborn screening cutoffs in Ontario allowed detection of a deficiency that might not have otherwise been identified, allowing early treatment and perhaps preventing the adverse sequelae seen in some untreated patients.

  5. The Effect of Maternal Body Composition and Triglyceride Levels on Newborn Weight in Non-Diabetic Women with Positive Diabetic Screens

    OpenAIRE

    Cüneyt Eftal Taner; Seçil Kurtulmuş; Ümit Nayki; Ayşen Kızılyar; Yasemin Baskın

    2008-01-01

    OBJECTIVE: To determine the effect of maternal body composition and triglyceride levels on newborn weight in nondiabetic women with positive diabetic screening. STUDY DESIGN : 40 pregnant women with positive diabetic screenings and negative glucose tolerance tests were enrolled as the study group. 72 pregnant women with negative diabetic screenings were enrolled as the control group. 50-gram glucose challenge tests were performed at 24-32 weeks of gestations and serum lipid levels were mea...

  6. Association of US State Implementation of Newborn Screening Policies for Critical Congenital Heart Disease With Early Infant Cardiac Deaths.

    Science.gov (United States)

    Abouk, Rahi; Grosse, Scott D; Ailes, Elizabeth C; Oster, Matthew E

    2017-12-05

    In 2011, critical congenital heart disease was added to the US Recommended Uniform Screening Panel for newborns, but whether state implementation of screening policies has been associated with infant death rates is unknown. To assess whether there was an association between implementation of state newborn screening policies for critical congenital heart disease and infant death rates. Observational study with group-level analyses. A difference-in-differences analysis was conducted using the National Center for Health Statistics' period linked birth/infant death data set files for 2007-2013 for 26 546 503 US births through June 30, 2013, aggregated by month and state of birth. State policies were classified as mandatory or nonmandatory (including voluntary policies and mandates that were not yet implemented). As of June 1, 2013, 8 states had implemented mandatory screening policies, 5 states had voluntary screening policies, and 9 states had adopted but not yet implemented mandates. Numbers of early infant deaths (between 24 hours and 6 months of age) coded for critical congenital heart disease or other/unspecified congenital cardiac causes for each state-month birth cohort. Between 2007 and 2013, there were 2734 deaths due to critical congenital heart disease and 3967 deaths due to other/unspecified causes. Critical congenital heart disease death rates in states with mandatory screening policies were 8.0 (95% CI, 5.4-10.6) per 100 000 births (n = 37) in 2007 and 6.4 (95% CI, 2.9-9.9) per 100 000 births (n = 13) in 2013 (for births by the end of July); for other/unspecified cardiac causes, death rates were 11.7 (95% CI, 8.6-14.8) per 100 000 births in 2007 (n = 54) and 10.3 (95% CI, 5.9-14.8) per 100 000 births (n = 21) in 2013. Early infant deaths from critical congenital heart disease through December 31, 2013, decreased by 33.4% (95% CI, 10.6%-50.3%), with an absolute decline of 3.9 (95% CI, 3.6-4.1) deaths per 100 000 births after

  7. Raising Awareness of False Positive Newborn Screening Results Arising from Pivalate-Containing Creams and Antibiotics in Europe When Screening for Isovaleric Acidaemia

    Directory of Open Access Journals (Sweden)

    James R. Bonham

    2018-02-01

    Full Text Available While the early and asymptomatic recognition of treatable conditions offered by newborn screening confers clear health benefits for the affected child, the clinical referral of patients with screen positive results can cause significant harm for some families. The use of pivalate-containing antibiotics and more recently the inclusion of neopentanoate as a component within moisturising creams used as nipple balms by nursing mothers can result in a significant number of false positive results when screening for isovaleric acidaemia (IVA by measuring C5 acylcarnitine. A recent survey conducted within centres from nine countries indicated that this form of contamination had been or was a significant confounding factor in the detection of IVA in seven of the nine who responded. In three of these seven the prominent cause was believed to derive from the use of moisturising creams and in another three from antibiotics containing pivalate; one country reported that the cause was mixed. As a result, four of these seven centres routinely perform second tier testing to resolve C5 isobars when an initial C5 result is elevated, and a fifth is considering making this change within their national programme. The use of creams containing neopentanoate by nursing mothers and evolving patterns in the prescription of pivalate-containing antibiotics during pregnancy require those involved in the design and operation of newborn screening programmes used to detect IVA and the doctors who receive clinical referrals from these programmes to maintain an awareness of the potential impact of this form of interference on patient results.

  8. Clinical and molecular profile of newborns with confirmed or suspicious congenital adrenal hyperplasia detected after a public screening program implementation.

    Science.gov (United States)

    Kopacek, Cristiane; Prado, Mayara J; da Silva, Claudia M D; de Castro, Simone M; Beltrão, Luciana A; Vargas, Paula R; Grandi, Tarciana; Rossetti, Maria L R; Spritzer, Poli Mara

    2018-04-30

    To describe the results obtained in a neonatal screening program after its implementation and to assess the clinical and molecular profiles of confirmed and suspicious congenital adrenal hyperplasia cases. A cross-sectional study was conducted. Newborns with suspected disease due to high 17-hydroxyprogesterone levels and adjusted for birth weight were selected. Classical congenital adrenal hyperplasia (salt-wasting and simple virilizing forms) was diagnosed by an increase in 17-hydroxyprogesterone levels as confirmed in the retest, clinical evaluation, and genotype determined by SNaPshot and multiplex ligation-dependent probe amplification. After 24 months, 15 classic congenital adrenal hyperplasia cases were diagnosed in a total of 217,965 newborns, with an estimated incidence of 1:14,531. From 132 patients, seven non-classical and 14 heterozygous patients were screened for CYP21A2 mutations, and 96 patients presented false positives with wild type CYP21A2. On retest, increased 17-hydroxyprogesterone levels were found in classical congenital adrenal hyperplasia patients and showed significant correlation with genotype-related classical genital adrenal hyperplasia. The most frequent mutations were IVS2-13A/C>G followed by gene deletion or rearrangement events in the classical form. In non-classical and heterozygous diseases, p.Val282Leu was the most common mutation. The results underscore the effectiveness of congenital adrenal hyperplasia neonatal screening in the public health system and indicate that the adopted strategy was appropriate. The second sample collection along with genotyping of suspected cases helped to properly diagnose both severe and milder cases and delineate them from false positive patients. Copyright © 2018. Published by Elsevier Editora Ltda.

  9. [Primary care follow-up of newborns with sickle cell disease detected in neonatal screening in the Community of Madrid].

    Science.gov (United States)

    Rodríguez-Moldes, B; Carbajo, A J; Sánchez, B; Fernández, M; Garí, M; Fernández, M C; Álvarez, J; García, A; Cela, E

    2015-04-01

    The main aim of the study was to assess the effects of the recommended preventive program in the population affected with Sickle Cell Disease in Primary Care. The program included, antibiotic prophylaxis, immunizations and health education, following the introduction of universal neonatal screening program for Sickle Cell Disease in the Community of Madrid. A cross-sectional observational study was performed with retrospective data collected from a cohort of newborns with Sickle Cell Disease diagnosed by neonatal screening test in the Community of Madrid. From the data obtained from a sample of 20 patients, it was found that 95% had been diagnosed by the newborn screening test performed between 5 and 13 days of life. The mean age was 39 months when the study was conducted. During follow-up, from Primary Care Paediatric clinic, it was observed that the compliance for antibiotic prophylaxis was 90%, and the coverage for the official vaccination schedule was 85%. Specific vaccine coverage as a risk population was highly variable (85% for pneumococcal 23V, 50% for influenza, and 15% for hepatitis A). Health education only reached one in every four families. Acceptable compliance with antibiotic prophylaxis was observed during the follow-up of patients with sickle cell disease in Primary Care, but a low coverage of routine immunization, as well as specific immunizations. Coverage of health education was very low. Improving these parameters would require greater coordination and involvement of Primary Care Professionals so that these patients were followed up appropriately, and could be translated into a reduction of disease complications and an improvement in the quality of life of these patients. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  10. [Systematic hearing screening for newborns in the Champagne-Ardennes region: 32,500 births in 2 years of experience].

    Science.gov (United States)

    Schmidt, P; Leveque, M; Danvin, J-B; Leroux, B; Chays, A

    2007-09-01

    To report a Universal Newborn Hearing Screening (UNHS) program developed in the Champagne-Ardennes region in 2004-2005. A team of ENT specialists and pediatricians set up a UNHS program designed to reduce the age of diagnosis and care of bilateral congenital deafness. The program was mainly based on automated acoustic otoacoustic emissions and a strict follow-up by the Regional Neonatal Screening Center. In 2004 and 2005, 29,944 neonates from 30,518 births were screened (98.11%). Of the neonates screened, 409 (1.38%) failed the test and were referred. The average retest delay was 2 weeks. Eleven were lost to follow-up, 371 (94%) had a successful second test on one or both ears, 27 (7%) failed the test a second time and had a diagnosis of ABR. Twenty-four cases of bilateral deafness were identified early, 14 of which had no risk factors. One of the children lost to follow-up was actually deaf, which was diagnosed at 18 months of age. Since the beginning of the UNHS program, the average age of diagnosis was lowered to less than 3 months. Our experience tends to demonstrate that UNHS is possible and the program allows an early diagnosis of bilateral congenital hearing loss.

  11. Conductive hearing loss and middle ear pathology in young infants referred through a newborn universal hearing screening program in Australia.

    Science.gov (United States)

    Aithal, Sreedevi; Aithal, Venkatesh; Kei, Joseph; Driscoll, Carlie

    2012-10-01

    Although newborn hearing screening programs have been introduced in most states in Australia, the prevalence of conductive hearing loss and middle ear pathology in the infants referred through these programs is not known. This study was designed to (1) evaluate the prevalence of conductive hearing loss and middle ear pathology in infants referred by a newborn hearing screening program in north Queensland, (2) compare prevalence rates of conductive hearing loss and middle ear pathology in indigenous and nonindigenous infants, and (3) review the outcomes of those infants diagnosed with conductive hearing loss and middle ear pathology. Retrospective chart review of infants referred to the Audiology Department of The Townsville Hospital was conducted. Chart review of 234 infants referred for one or both ears from a newborn hearing screening program in north Queensland was conducted. A total of 211 infants attended the diagnostic appointment. Review appointments to monitor hearing status were completed for 46 infants with middle ear pathology or conductive hearing loss. Diagnosis of hearing impairment was made using an age-appropriate battery of audiological tests. Results were analyzed for both initial and review appointments. Mean age at initial diagnostic assessment was 47.5 days (SD = 31.3). Of the 69 infants with middle ear pathology during initial diagnostic assessment, 18 had middle ear pathology with normal hearing, 47 had conductive hearing loss, and 4 had mixed hearing loss. Prevalence of conductive hearing loss in the newborns was 2.97 per 1,000 while prevalence of middle ear pathology (with or without conductive hearing loss) was 4.36 per 1,000. Indigenous Australians or Aboriginal and Torres Strait Islander (ATSI) infants had a significantly higher prevalence of conductive hearing loss and middle ear pathology than non-ATSI infants (35.19 and 44.45% vs 17.83 and 28.66%, respectively). ATSI infants also showed poor resolution of conductive hearing loss

  12. Alterações condutivas em neonatos que falharam na triagem auditiva neonatal Conductive impairment in newborn who failed the newborn hearing screening

    Directory of Open Access Journals (Sweden)

    Priscila Karla Santana Pereira

    2010-06-01

    Full Text Available Na triagem auditiva neonatal pouca importância é atribuída às alterações de orelha média. As crianças que apresentam otites secretoras no período neonatal são de risco para desenvolver otite média no primeiro ano de vida. OBJETIVO: Verificar se as crianças que falharam na triagem auditiva por alteração condutiva têm mais episódios de comprometimento condutivo durante o primeiro ano de vida. MATERIAL E MÉTODO: O grupo estudo foi constituído por 62 crianças que falharam na triagem por comprometimento condutivo. O controle foi formado por 221 que passaram. Ambos tiveram acompanhamento audiológico e otorrinolaringológico e foram comparados quanto à ocorrência de comprometimento condutivo. Foram utilizados para análise estatística o teste Exato de Fisher e modelos de Regressão Logística. O estudo foi prospectivo e retrospectivo. RESULTADOS: As crianças que falharam na triagem por comprometimento condutivo tiveram mais episódios de otite média durante o primeiro ano de vida do que as que não falharam, com diferença significante. CONCLUSÃO: Os neonatos que falharam na triagem no primeiro mês de vida por alteração condutiva têm maior chance de apresentarem otite no primeiro ano de vida. A elevada ocorrência de otite indica a necessidade da atuação conjunta com otorrinolaringologista para o diagnóstico de tais alterações.In newborn hearing screening little importance is attributed to changes in the middle ear. Children with secretory otitis in the neonatal period are at risk for developing otitis media in the first year of life. AIM: To determine if children who failed the hearing screening because of conductive hearing loss have more episodes of conductive hearing impairment during their first years of life. MATERIALS AND METHODS: The study group comprised 62 children who failed the screening for conductive impairment. The control was made up of 221 who passed. Both had audiologic and otolaryngological

  13. Universal screening for hepatitis B among pregnant women led to 96% vaccination coverage among newborns of HBsAg positive mothers in Denmark

    DEFF Research Database (Denmark)

    Harder, Katja Majlund; Cowan, Susan; Eriksen, Mette Brandt

    2011-01-01

    to examine the effectiveness of universal HBV-screening of pregnant women and HBV-immunizations of their newborn, and to provide a prevalence-estimate for HBV in Denmark. On a opt out basis all women in Denmark attending antenatal care were tested for hepatitis B serology. Vaccination data of the newborns...... follow-up two transmissions (0.5%) have been notified. Among children born of the positive mothers prior to the trial-period 7.3% had been notified. Thus the prevalence of HBV positive mothers has more than doubled in Denmark over the last 40 years, but among women of Danish origin it has decreased 10......-fold. By replacing selective screening with universal, identification of newborns in need of HBV-immunization was increased from 50% to almost complete coverage, and also identifies mothers with high viral load for evaluation of pre-term treatment to interrupt in utero transmission....

  14. High-protein goat's milk diet identified through newborn screening: clinical warning of a potentially dangerous dietetic practice.

    Science.gov (United States)

    Maines, Evelina; Gugelmo, Giorgia; Tadiotto, Elisa; Pietrobelli, Angelo; Campostrini, Natascia; Pasini, Andrea; Ion-Popa, Florina; Vincenzi, Monica; Teofoli, Francesca; Camilot, Marta; Bordugo, Andrea

    2017-10-01

    Breast-feeding is an unequalled way of providing optimal food for infants' healthy growth and development and the WHO recommends that infants should be exclusively breast-fed for the first 6 months of life. For mothers who are unable to breast-feed or who decide not to, infant formulas are the safest alternative. Despite recommendations, it is possible that parents make potentially harmful nutritional choices for their children because of cultural beliefs or misinformation on infant nutrition. We describe a possible health risk of not breast-feeding, highlighting a potentially dangerous dietetic practice. Design/Setting/Subjects We report the case of a newborn who was fed with undiluted goat's milk because her mother could not breast-feed and was not aware of infant formulas. The dietary mistake was detected because of a positive expanded newborn screening result, characterized by severe hypertyrosinaemia with high methionine and phenylalanine levels, a pattern suggestive of severe liver impairment. The pattern of plasma amino acids was related to a goat's milk diet, because of its very different composition compared with human milk and infant formula. Our experience demonstrates that, when breast-feeding is not possible or is not exclusive, infants may be at risk of dangerous nutritional practices, including diets with very high protein content, such as a goat's milk diet. Families of not breast-fed infants may need appropriate advice on safe alternatives for infant nutrition to avoid the risks of inappropriate diets.

  15. Incidence and Interrelated Factors in Patients With Congenital Hypothyroidism as Detected by Newborn Screening in Guangxi, China

    Directory of Open Access Journals (Sweden)

    Xin Fan MD

    2015-01-01

    Full Text Available Background. A newborn screening program (NSP for congenital hypothyroidism (CH was carried out in Guangxi in order to understand the incidence of CH and the factors interrelated to major types of CH in this region of China. Methods. During 2009 to 2013, data from 930 612 newborns attending NSP in Guangxi were collected. Patients were classified with either permanent CH (PCH or transient CH (TCH after 2 years of progressive study. Results. A total of 1210 patients were confirmed with CH with an incidence of 1/769, including 68 PCH and 126 TCH cases with incidences of 1/6673 and 1/3385, respectively. The frequency of thyroid stimulating hormone values greater than 5 mIU/L was 7.2%, which, based on WHO guidelines, suggests that the population was mildly iodine deficient. Conclusions. The incidence of CH was high in Guangxi. Approximately two thirds of CH patients were TCH, which may be due to a deficiency in iodine within the population.

  16. Factors associated with failure to screen newborns for retinopathy of prematurity.

    Science.gov (United States)

    Bain, Lisa Charo; Dudley, R Adams; Gould, Jeffrey B; Lee, Henry C

    2012-11-01

    To evaluate ROP screening rates in a population-based cohort; and to identify characteristics of patients that were missed. We used the California Perinatal Quality Care Collaborative data from 2005-2007 for a cross-sectional study. Using eligibility criteria, screening rates were calculated for each hospital. Multivariable regression was used to assess associations between patient clinical and sociodemographic factors and the odds of missing screening. Overall rates of missed ROP screening decreased from 18.6% in 2005 to 12.8% in 2007. Higher gestational age (OR = 1.25 for increase of 1 week, 95% CI, 1.21-1.29), higher birth weight (OR = 1.13; 95% CI, 1.10-1.15), and singleton birth (OR = 1.2; 95% CI, 1.07-1.34) were associated with higher probability of missing screening. Level II neonatal intensive care units and neonatal intensive care units with lower volume were more likely to miss screenings. Although ROP screening rates improved over time, larger and older infants are at risk for not receiving screening. Furthermore, large variations in screening rates exist among hospitals in California. Identification of gaps in quality of care creates an opportunity to improve ROP screening rates and prevent impaired vision in this vulnerable population. Copyright © 2012 Mosby, Inc. All rights reserved.

  17. Family, Community, and Health System Considerations for Reducing the Burden of Pediatric Sickle Cell Disease in Uganda Through Newborn Screening

    Directory of Open Access Journals (Sweden)

    Nancy S. Green MD

    2016-04-01

    Full Text Available Sickle cell disease (SCD is associated with high mortality for children under 5 years of age in sub-Saharan Africa. Newborn sickle screening program and enhanced capacity for SCD treatment are under development to reduce disease burden in Uganda and elsewhere in the region. Based on an international stakeholder meeting and a family-directed conference on SCD in Kampala in 2015, and interviews with parents, multinational experts, and other key informants, we describe health care, community, and family perspectives in support of these initiatives. Key stakeholder meetings, discussions, and interviews were held to understand perspectives of public health and multinational leadership, patients and families, as well as national progress, resource needs, medical and social barriers to program success, and resources leveraged from HIV/AIDS. Partnering with program leadership, professionals, patients and families, multinational stakeholders, and leveraging resources from existing programs are needed for building successful programs in Uganda and elsewhere in sub-Saharan Africa.

  18. Effect of screening for red cell antibodies, other than anti-D, to detect hemolytic disease of the fetus and newborn: a population study in the Netherlands

    NARCIS (Netherlands)

    Koelewijn, J. M.; Vrijkotte, T. G. M.; van der Schoot, C. E.; Bonsel, G. J.; de Haas, M.

    2008-01-01

    BACKGROUND: Hemolytic disease of the fetus and newborn (HDFN) is a severe disease, resulting from maternal red cell (RBC) alloantibodies directed against fetal RBCs. The effect of a first-trimester antibody screening program on the timely detection of HDFN caused by antibodies other than anti-D was

  19. How to motivate newborn hearing screening in the absence of a national programme: a collaboration between parents and professionals.

    Science.gov (United States)

    Cutler, Jodi; Lenzi, Giovanni; Berrettini, Stefano; Martini, Alessandro; Martinelli, Stefano

    2012-10-01

    The establishment of the Italian Pediatric Federation Newborn Hearing Screening Network and the Italian Society of Neonatology Infant Hearing Study Group is the result of an international collaboration between Parents and Medical Professionals in order to promote an effective model in developing Early Hearing Detection Intervention Programs that recognize the role of parents as partners in the process. Among other factors, one important component frequently underestimated in most early intervention programs, both in the USA and other countries, involves the role of parental involvement within the Early Hearing Detection Intervention (EHDI) process. When a parent receives the news of their child's hearing loss, reactions may include, but are not limited to denial, grief, guilt, shame, fear and impotency. A parent may begin to ask certain questions: How do we know if the professionals in our children's lives are capable, educated, trained, up to date in their chosen fields of expertise? Do they respect our children and us as parents? Do they understand the needs of children who are deaf or hard of hearing? A life-long health professional - parental collaboration begins at the moment of the diagnosis of that child. When analyzing the habilitation process of a deaf child, the relationship between health professionals and the crucial role of parents in raising that child is a 50-50 shared responsibility. An objective of EHDI programs must be to empower parents by providing support from the beginning of the process. Distributing informative literature regarding the newborn hearing screening process and providing parents with access to resources such as parental support groups upon diagnosis equips parents with the tools necessary to immediately begin advocating for their children. The Italian Federation Pediatric Audiology Network was created by combining the parental perspective and medical protocols in order to establish the roots for stronger EHDI programs.

  20. Neurodevelopmental profiles of children with glutaric aciduria type I diagnosed by newborn screening: a follow-up case series.

    Science.gov (United States)

    Brown, Amy; Crowe, Louise; Beauchamp, Miriam H; Anderson, Vicki; Boneh, Avihu

    2015-01-01

    Glutaric aciduria type I (GA-I) is an inherited metabolic disorder that may lead to severe motor disorder and cognitive impairment. GA-I is now included in the newborn screening programme in many countries as early detection allows for prompt treatment and effectively reduces the risk of poor developmental outcome. Information regarding the long-term neurodevelopmental outcome of children with GA-I treated early is sparse.We recruited children with a confirmed diagnosis of GA-I diagnosed via newborn screening, treated in our centre and >3 years of age (n = 6). Children were assessed at two time points using a comprehensive neuropsychological test battery. Four of these had been the subject of a previous report. All participants were male, 3-6 years at the initial assessment and 6-12 years of age at the follow-up assessment.Fine motor skills were below average in all patients. Speech, which was affected in all four patients reported previously, improved following speech therapy. IQ scores remained generally stable within the normal range. Executive functioning was average to high average in four patients. Behaviour, as assessed through parental questionnaires, was problematic in two patients. Compounding factors included child neglect, family history of autism and multiple admissions to hospital (n = 1 in each).GA-I affects fine motor skills and speech, regardless of early treatment, but not IQ scores. Patients with GA-I should be referred for assessment and appropriate early intervention. Further research is needed to correlate specific neuropsychological deficits with neuroimaging.

  1. Differential Rapid Screening of Phytochemicals by Leaf Spray Mass Spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, Thomas; Graham Cooks, R. [Univ. of Innsbruck, Innsbruck (Austria)

    2014-03-15

    Ambient ionization can be achieved by generating an electrospray directly from plant tissue ('leaf spray'). The resulting mass spectra are characteristic of ionizable phytochemicals in the plant material. By subtracting the leaf spray spectra recorded from the petals of two hibiscus species H. moscheutos and H. syriacus one gains rapid access to the metabolites that differ most in the two petals. One such compound was identified as the sambubioside of quercitin (or delphinidin) while others are known flavones. Major interest centered on a C{sub 19}H{sub 29}NO{sub 5} compound that occurs only in the large H. moscheutos bloom. Attempts were made to characterize this compound by mass spectrometry alone as a test of such an approach. This showed that the compound is an alkaloid, assigned to the polyhydroxylated pyrrolidine class, and bound via a C{sub 3} hydrocarbon unit to a monoterpene.

  2. Differential Rapid Screening of Phytochemicals by Leaf Spray Mass Spectrometry

    International Nuclear Information System (INIS)

    Mueller, Thomas; Graham Cooks, R.

    2014-01-01

    Ambient ionization can be achieved by generating an electrospray directly from plant tissue ('leaf spray'). The resulting mass spectra are characteristic of ionizable phytochemicals in the plant material. By subtracting the leaf spray spectra recorded from the petals of two hibiscus species H. moscheutos and H. syriacus one gains rapid access to the metabolites that differ most in the two petals. One such compound was identified as the sambubioside of quercitin (or delphinidin) while others are known flavones. Major interest centered on a C 19 H 29 NO 5 compound that occurs only in the large H. moscheutos bloom. Attempts were made to characterize this compound by mass spectrometry alone as a test of such an approach. This showed that the compound is an alkaloid, assigned to the polyhydroxylated pyrrolidine class, and bound via a C 3 hydrocarbon unit to a monoterpene

  3. [Universal cytomegalovirus infection screening in premature newborns less than 1500 g].

    Science.gov (United States)

    Botet, F; Figueras Aloy, J; Álvarez, E; de Alba, C; Dorronsolo, I; Echaniz Urcelay, I; Rite, S; Moreno, J; Fernández Lorenzo, J R; Herranz Carrillo, G; Salguero, E; Sánchez Luna, M

    2014-10-01

    Cytomegalovirus (CMV) infection is endemic, and children who attend day care are the most important source of infection. To establish recommendations based on the medical evidence on the vertical transmission of cytomegalovirus in preterm infants weighing less than 1500g at birth. Infection in pregnant women may be primary or secondary. Although there is fetal infection, 85% of newborn infants are asymptomatic. Symptoms of infection include low birth weight, hepatosplenomegaly, thrombocytopenia, microcephaly and neurological disorders. The prognosis of symptomatic children is very poor, with high mortality and neurological disorders. The virus can be reactivated during breast feeding, and early infection is possible through breast milk, probably with little impact in term infants, although the long-term neurological outcome worsens in preterm infants. The diagnostic method of choice is the identification of CMV in urine; the determination in the first two weeks of life suggests congenital infection; later it can be acquired at birth or through breast milk or contaminated blood transfusion. Determine viral DNA at 4-6 weeks of life by protease chain reaction. If it is positive, monitoring of samples from the first days of life and breast milk are mandatory. This should allow the newborn to be classified into three states: "Without CMV infection", "Congenital CMV infection", "Acquired CMV infection". Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  4. Neonatal screening for life-threatening conditions persistent – pulmonary hypertension in newborns and critical congenital heart disease – by the method of pulse oximetry

    Directory of Open Access Journals (Sweden)

    D. I. Sadykova

    2017-01-01

    Full Text Available Research objective: to assess the diagnostic significance of the pulse oximetry performed by the newborn for the 3rd hour of life to identify critical conditions and to justify the expediency of further introduction of this technology in the work of obstetric institutions.Results. In 5 maternity hospitals of the Republic of Tatarstan, from April 2016 to February 2017, 8358 88.4% of newborns were pulsometrically screened. Positive results were obtained in 95 (1.14% patients. Because of screening, 13 newborns were diagnosed with congenital heart defects, not diagnosed in utero, in the first hours of life, five of them were critical. All newborns with critical congenital heart defects were successfully operated. Besides, 20 patients had persistent pulmonary hypertension, 30 had intrauterine pneumonia.Conclusions. The measurement of saturation at the 3rd hour of life of a newborn allows avoiding life-threatening complications in children with critical congenital heart defects and persistent pulmonary hypertension and in a stable state to transfer them to a further treatment stage.

  5. Current role of liquid chromatography coupled to mass spectrometry in clinical toxicology screening methods.

    Science.gov (United States)

    Viette, Véronique; Fathi, Marc; Rudaz, Serge; Hochstrasser, Denis; Veuthey, Jean-Luc

    2011-07-01

    Abstract Toxicological screening is the analysis of a biological specimen to detect and identify compounds in patients admitted to the hospital with acute intoxication of unknown origin. The screening of a wide range of toxicologically relevant compounds in biological samples is a serious challenge for clinical laboratories. The high selectivity and sensitivity of liquid chromatography coupled to mass spectrometry or tandem mass spectrometry technology provides an attractive alternative to the current methods. For these reasons, an increasing number of applications for multi-target screening or general screening of unknown compounds in biological matrices are being published. This paper is an overview of sample clean-up, chromatographic separation and mass spectrometry detection procedures which can be combined to obtain screening methods adapted to the constraints and needs of various laboratories, and none specifically in clinical toxicology. Currently the techniques are in the hands of specialists, principally in academic institutes. However, the evolution in technology should allow application of the techniques as a tool in toxicology laboratories and thus more widespread exploitation of their potential.

  6. Otoacoustic Emissions in Rural Nicaragua: Cost Analysis and Implications for Newborn Hearing Screening.

    Science.gov (United States)

    Wong, Lye-Yeng; Espinoza, Francisca; Alvarez, Karen Mojica; Molter, Dave; Saunders, James E

    2017-05-01

    Objective (1) Determine the incidence and risk factors for congenital hearing loss. (2) Perform cost analysis of screening programs. Study Design Proportionally distributed cross-sectional survey. Setting Jinotega, Nicaragua. Subjects and Methods Otoacoustic emissions (OAEs) were used to screen 640 infants home birth settings. Data on 15 risk factors were analyzed. Cost of 4 implementation strategies was studied: universal screening, screening at the regional health center (RHC), targeted screening, and screening at the RHC plus targeted screening. Cost-effectiveness analysis over 10 years was based on disability-adjusted life year estimates, with the World Health Organization standard of cost-effectiveness ratio (CER) / gross domestic product (GDP) births, 325 (50.8%) were in the RHC, 69 (10.8%) in the neonatal intensive care unit, and 29 (4.5%) at home. Family history and birth defect were significant in univariate analysis; birth defect was significant in multivariate analysis. Cost-effectiveness analysis demonstrated that OAE screening is cost-effective without treatment (CER/GDP = 0.06-2.00) and with treatment (CER/GDP = 0.58-2.52). Conclusions Our rate of OAE failures was comparable to those of developed countries and lower than hearing loss rates noted among Nicaraguan schoolchildren, suggesting acquired or progressive etiology in the latter. Birth defects and familial hearing loss correlated with OAE failure. OAE screening of infants is feasible and cost-effective in rural Nicaragua, although highly influenced by estimated hearing loss severity in identified infants and the high travel costs incurred in a targeted screening strategy.

  7. Critical Evaluation of Native Electrospray Ionization Mass Spectrometry for Fragment-Based Screening.

    Science.gov (United States)

    Göth, Melanie; Badock, Volker; Weiske, Jörg; Pagel, Kevin; Kuropka, Benno

    2017-08-08

    Fragment-based screening presents a promising alternative to high-throughput screening and has gained great attention in recent years. So far, only a few studies have discussed mass spectrometry as a screening technology for fragments. Herein, we report the application of native electrospray ionization mass spectrometry (MS) for screening defined sets of fragments against four different target proteins. Fragments were selected from a primary screening conducted with a thermal shift assay (TSA) and represented different binding categories. Our data indicated that, beside specific complex formation, many fragments show extensive multiple binding and also charge-state shifts. Both of these factors complicate automated data analysis and decrease the attractiveness of native MS as a primary screening tool for fragments. A comparison of the hits identified by native MS and TSA showed good agreement for two of the proteins. Furthermore, we discuss general challenges, including the determination of an optimal fragment concentration and the question of how to rank fragment hits according to their affinity. In conclusion, we consider native MS to be a highly valuable tool for the validation and deeper investigation of promising fragment hits rather than a method for primary screening. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Tc99m-pertechnetate thyroid scintigraphy in newborns with neonatal TSH levels > 20uUI/ml, detected in the national program of newborn screening of congenital hypothyroidism (CH)

    International Nuclear Information System (INIS)

    Lobo, G.; Ladron de Guevara, D.; Perez, A.; Donoso, G.; Jimenez, C.; Arnello, F.; Vivanco, X.

    2002-01-01

    The aim of this study was to analyse the thyroid scintigraphy (TS) findings in 279 newborn with neonatal TSH (TSHnn) levels above 20 uUI/ml, detected in the national program of newborn screening of CH and phenylketonuria, and to compare them with: 1) final diagnosis, estimating its positive (PPV) and negative predictive value (NPV) and 2) TSHnn levels. Materials and Method: Thyroid scintigraphy of 279 newborn (57.3% girls) who presented TSHnn levels > 20 uUI/ml were revised, classifying them in eutopic gland (EuG), ectopic gland (EcG) and absence of contrast (AC). EuG was classified by visual and quantitative criteria in: normal contrast and size, goiter, and decreased contrast (DC). Tc99m-pertechnetate TS was performed average at 19th life's day (SD:11 days) with a gammacamera- computer system. The patients were separated according to hormonal confirmatory levels in: CH, hyperthyrotropinaemia (HT) and euthyroid. We compared TS results with final diagnosis and also with TSHnn levels (>= or 50 uUI/ml group (p<0.001). Moreover, the former group presented bigger proportion of CH newborns and of EcG scans than < 50uUI/ml patients (p<0.001). EcG and goiter condition had a PPV for CH of 100% and 79.6%, respectively. The NPV of normal TS was 86.7%. Conclusion: 1) Newborns with TSHnn levels larger than 20 uUI/ml show a high frequency of abnormal TS. 2) The EcG is highly predictive of CH. 3) Goiter and AC associated to TSHnn levels above 50 uUI/ml support strongly CH diagnosis. 4) Normal TS correspond very likely to euthyroid newborn, specially when TSHnn is lower than 50 uUI/ml

  9. Evaluation of high-resolution mass spectrometry for urine toxicology screening in a pain management setting.

    Science.gov (United States)

    Crews, Bridgit O; Pesce, Amadeo J; West, Robert; Nguyen, Hugh; Fitzgerald, Robert L

    2012-01-01

    To evaluate liquid chromatography-high-resolution mass spectrometry (LC-HR-MS) for urine toxicology screening, 29 analytes were quantitated in 152 urine specimens from patients with chronic pain using two unique mass spectrometry platforms. De-identified specimens were quantitated in April of 2011 by liquid chromatography-triple quadrupole mass spectrometry (LC-MS-MS) and by full-scan LC-HR-MS at Millennium Laboratories. Considering LC-MS-MS as the reference method, false positive results were identified in 19 specimens measured by LC-HR-MS. Application of relative retention times using deuterium labeled internal standards improved the rate of false positive detection to only five specimens, with four occurring for the same analyte. Ultra-high-resolution mass spectrometry (R = 100,000 at m/z 200) showed no improvement over high-resolution mass spectrometry (R = 10,000 at m/z 200) in the number of false positives detected. Quantitative results measured by LC-MS-MS and LC-HR-MS showed good agreement over four orders of dynamic range. This study demonstrates that LC-HR-MS is a suitable platform for toxicology screening for a pain management population and that quantitative accuracy and sensitivity are comparable to that achieved with LC-MS-MS. The specificity of LC-HR-MS is improved by the addition of deuterium labeled internal standards and the implementation of relative retention time matching.

  10. A Call to Include Severe Combined Immunodeficiency in Newborn Screening Program

    OpenAIRE

    Raz Somech; Amos Etzioni

    2014-01-01

    Quantification of the T cell receptor excision circles (TRECs) has recently emerged as a useful non-invasive clinical and research tool to investigate thymic activity. It allows the identification of T cell production by the thymus. Quantification of TREC copies has recently been implemented as the preferred test to screen neonates with severe combined immunodeficiency (SCID) or significant lymphopenia. Neonatal genetic screening for SCID is highly important in countries with high rates of co...

  11. Knowledge of parents regarding newborn screening test, after accessing the website “Babies’ Portal” - Heel prick test

    Directory of Open Access Journals (Sweden)

    Caroline Antonelli Mendes

    Full Text Available ABSTRACT Purpose: to assess the knowledge of mothers about the heel prick test, develop contents on this test to make it available on the "Babies’ Portal" website, evaluate and validate the informative material developed. Methods: this study was conducted in three stages, that is, the first stage which is about a descriptive study involving 105 mothers of newborn children before performing the neonatal screening "Heel Prick Test", the second one consisting in the development of the website "Babies’ Portal", and the third stage, the evaluation and validation of this material carried out by 20 parents of children between zero and 36 months old, who underwent the neonatal screening Heel Prick Test by accessing the website “Babies’ Portal”. Results: although the interviewed mothers knew that their children had the right to be tested, they showed no knowledge of the diseases that can be prevented, time of diagnosis, nor the consequences arising from the lack of early diagnosis and treatment. The website creation and validation gathered basic information about the Heel Prick Test, and the participants regarded the content from satisfactory to excellent. Conclusion: it is necessary that families know not only about the procedures their children will undergo, but also the reason they are performed and the consequences of failing in doing so.

  12. [A temporal bone CT study of the infants with hearing loss referred from universal newborn hearing screening].

    Science.gov (United States)

    Tao, Zheng; Li, Yun; Hou, Zheng; Cheng, Lan

    2007-02-01

    To explore the high resolution CT image of temporal bone in infants with hearing loss, and its value in evaluating the cause of hearing loss. In 2005, 0.12 million newborns have been included in the hearing screening system in Shanghai, and 1077 infants have failed to pass the hearing screening. One hundred and eight four infants were diagnosed as congenital hearing loss from mild to profound. A temporal bone HRCT scanning was performed to these infants. Among the 184 patients with congenital hearing loss, HRCT showed that 26 cases (14.1%) were associated with external ear malformation, and 21 cases (11.4%) were associated with middle ear malformation, 31 cases (16.8%) associated with inner ear malformation. The patients with inner ear malformation included 12 cases with Mondini malformation, 1 case with common cavity malformation, 6 cases with large vestibule malformation, 5 cases with internal auditory canal abnormalities, and 10 cases with vestibule, semicircular canals abnormalities. In addition, there were 20 cases (10.8%) with fluid in middle ear. HRCT image play an important role in the differential diagnosis and treatment of infants with congenital hearing loss.

  13. High-Throughput Screening Using Mass Spectrometry within Drug Discovery.

    Science.gov (United States)

    Rohman, Mattias; Wingfield, Jonathan

    2016-01-01

    In order to detect a biochemical analyte with a mass spectrometer (MS) it is necessary to ionize the analyte of interest. The analyte can be ionized by a number of different mechanisms, however, one common method is electrospray ionization (ESI). Droplets of analyte are sprayed through a highly charged field, the droplets pick up charge, and this is transferred to the analyte. High levels of salt in the assay buffer will potentially steal charge from the analyte and suppress the MS signal. In order to avoid this suppression of signal, salt is often removed from the sample prior to injection into the MS. Traditional ESI MS relies on liquid chromatography (LC) to remove the salt and reduce matrix effects, however, this is a lengthy process. Here we describe the use of RapidFire™ coupled to a triple-quadrupole MS for high-throughput screening. This system uses solid-phase extraction to de-salt samples prior to injection, reducing processing time such that a sample is injected into the MS ~every 10 s.

  14. Timing of specimen collection is crucial in urine screening of drug dependent mothers and newborns.

    Science.gov (United States)

    Halstead, A C; Godolphin, W; Lockitch, G; Segal, S

    1988-01-01

    We compared results of urine drug analysis with clinical data and history to test the usefulness of peripartum drug screening and to establish guidelines for optimal testing. Urine from 28 mothers and 52 babies was analysed. Drugs not suspected by history were found in 10 mothers and six babies. Results assisted in the management of neonatal withdrawal in three babies. Drugs suspected by history were not found in 11/22 mothers and 23/35 babies. About half of these results were associated with delayed urine collection. In 12/28 mothers, drugs administered in hospital could have confused interpretation of screen results. We conclude that urine drug screening without strict protocols for specimen collection is of limited usefulness for management of drug abuse in pregnancy and neonatal drug withdrawal. We favour testing of maternal urine obtained before drugs are administered in hospital. Neonatal urine, if used, should be collected in the first day of life.

  15. Tandem mass spectrometry screening for very long-chain acyl-CoA dehydrogenase deficiency: the value of second-tier enzyme testing.

    Science.gov (United States)

    Spiekerkoetter, Ute; Haussmann, Ulrike; Mueller, Martina; ter Veld, Frank; Stehn, Maren; Santer, Rene; Lukacs, Zoltan

    2010-10-01

    To evaluate newborn screening (NBS) for very long-chain acyl-CoA dehydrogenase deficiency (VLCADD), we further characterized newborns with elevation of one or all C14-carnitine derivatives on NBS from a total of 90 338 newborns. Palmitoyl-CoA oxidation was performed in lymphocytes to define very long-chain acyl-CoA dehydrogenase function. Molecular analysis followed in children with residual activitiesvalues and acylcarnitine ratios did not allow correct identification of the newborn as a patient with VLCADD. Reliable diagnosis is not feasible with acylcarnitine analysis alone. Enzyme analysis in lymphocytes is a reliable and rapid method for correctly assessing all newborns with VLCADD and should be carried out in all newborns identified during the first screening, regardless of the results of a later acylcarnitine profile. Copyright (c) 2010 Mosby, Inc. All rights reserved.

  16. Affinity selection-mass spectrometry and its emerging application to the high throughput screening of G protein-coupled receptors.

    Science.gov (United States)

    Whitehurst, Charles E; Annis, D Allen

    2008-07-01

    Advances in combinatorial chemistry and genomics have inspired the development of novel affinity selection-based screening techniques that rely on mass spectrometry to identify compounds that preferentially bind to a protein target. Of the many affinity selection-mass spectrometry techniques so far documented, only a few solution-based implementations that separate target-ligand complexes away from unbound ligands persist today as routine high throughput screening platforms. Because affinity selection-mass spectrometry techniques do not rely on radioactive or fluorescent reporters or enzyme activities, they can complement traditional biochemical and cell-based screening assays and enable scientists to screen targets that may not be easily amenable to other methods. In addition, by employing mass spectrometry for ligand detection, these techniques enable high throughput screening of massive library collections of pooled compound mixtures, vastly increasing the chemical space that a target can encounter during screening. Of all drug targets, G protein coupled receptors yield the highest percentage of therapeutically effective drugs. In this manuscript, we present the emerging application of affinity selection-mass spectrometry to the high throughput screening of G protein coupled receptors. We also review how affinity selection-mass spectrometry can be used as an analytical tool to guide receptor purification, and further used after screening to characterize target-ligand binding interactions, enabling the classification of orthosteric and allosteric binders.

  17. Rapid screening of pharmaceutical drugs using thermal desorption – SALDI mass spectrometry

    International Nuclear Information System (INIS)

    Grechnikov, A A; Kubasov, A E; Borodkov, A S; Georgieva, V B; Nikiforov, S M; Simanovsky, Ya O; Alimpiev, S S

    2012-01-01

    A novel approach to the rapid screening of pharmaceutical drugs by surface assisted laser desorption-ionization (SALDI) mass spectrometry with the rotating ball interface coupled with temperature programmed thermal desorption has been developed. Analytes were thermally desorbed and deposited onto the surface of amorphous silicon substrate attached to the rotating ball. The ball was rotated and the deposited analytes were analyzed using SALDI. The effectiveness of coupling SALDI mass spectrometry with thermal desorption was evaluated by the direct and rapid analysis of tablets containing lidocaine, diphenhydramine and propranolol without any sample pretreatment. The overall duration of the screening procedure was 30÷40 sec. Real urine samples were studied for drug analysis. It is shown that with simple preparation steps, urine samples can be quantitatively analyzed using the proposed technique with the detection limits in the range of 0.2÷0.5 ng/ml.

  18. Comparison of Newborn Hearing Screening in Well-Baby Nursery and NICU: A Study Applied to Reduce Referral Rate in NICU.

    Science.gov (United States)

    Li, Pei-Chun; Chen, Wei-I; Huang, Chih-Ming; Liu, Ching-Ju; Chang, Hsiu-wen; Lin, Hung-Ching

    2016-01-01

    To determine whether newborn hearing screening in a well-baby nursery (WBN) and neonatal intensive care unit (NICU) nursery: 1) meet three targeted, screening, referral, and diagnostic follow-up rates; 2) compare the average age of diagnosis for infants admitted to the WIN and NICU; and 3) determine prevalence of hearing loss in neonatal population; and 4) try to find a practical newborn hearing screening time algorithm to reduce refer rate in NICU. It examined 15,624 newborns in the WBN (13,676) and NICU (1948) screened for congenital HL using AABR. The variables analyzed in it were the screening rate, referral rate, follow-up rate, diagnostic rate and diagnostic age, prevalence rate, degrees of congenital bilateral HL. The study was approved by the hospital's institutional review board (13MMHISO23). The screening rates were 99.8% and 99.6% in the WBN and NICU groups, respectively, without significant difference. The referral rates were 0.7% and 2.8% in the WBN and NICU groups, with significant difference. Furthermore, the diagnostic follow-up rates were 76.7% and 89.1% in the WBN and NICU groups, without significant difference. The average initial diagnostic ages were 1.9 months and 3.8 months in the WBN and NICU groups, with significant difference. The prevalence of congenital bilateral hearing loss were 0.27% and 1.6% in the WBN and NICU groups, with significant difference. The screening, referral and follow-up rate in the WBN and NICU groups were equivalent to the quality indicators. For NICU group, screening and diagnostic follow up were performed later than those in WBN group; however the lower referral rate in our NICU group was successfully achieved in this study and can be applied clinically. The prevalence of congenital bilateral hearing loss was higher in the NICU group than in the WBN group.

  19. Decision-making in healthcare: a practical application of partial least square path modelling to coverage of newborn screening programmes.

    Science.gov (United States)

    Fischer, Katharina E

    2012-08-02

    Decision-making in healthcare is complex. Research on coverage decision-making has focused on comparative studies for several countries, statistical analyses for single decision-makers, the decision outcome and appraisal criteria. Accounting for decision processes extends the complexity, as they are multidimensional and process elements need to be regarded as latent constructs (composites) that are not observed directly. The objective of this study was to present a practical application of partial least square path modelling (PLS-PM) to evaluate how it offers a method for empirical analysis of decision-making in healthcare. Empirical approaches that applied PLS-PM to decision-making in healthcare were identified through a systematic literature search. PLS-PM was used as an estimation technique for a structural equation model that specified hypotheses between the components of decision processes and the reasonableness of decision-making in terms of medical, economic and other ethical criteria. The model was estimated for a sample of 55 coverage decisions on the extension of newborn screening programmes in Europe. Results were evaluated by standard reliability and validity measures for PLS-PM. After modification by dropping two indicators that showed poor measures in the measurement models' quality assessment and were not meaningful for newborn screening, the structural equation model estimation produced plausible results. The presence of three influences was supported: the links between both stakeholder participation or transparency and the reasonableness of decision-making; and the effect of transparency on the degree of scientific rigour of assessment. Reliable and valid measurement models were obtained to describe the composites of 'transparency', 'participation', 'scientific rigour' and 'reasonableness'. The structural equation model was among the first applications of PLS-PM to coverage decision-making. It allowed testing of hypotheses in situations where there

  20. Decision-making in healthcare: a practical application of partial least square path modelling to coverage of newborn screening programmes

    Directory of Open Access Journals (Sweden)

    Fischer Katharina E

    2012-08-01

    Full Text Available Abstract Background Decision-making in healthcare is complex. Research on coverage decision-making has focused on comparative studies for several countries, statistical analyses for single decision-makers, the decision outcome and appraisal criteria. Accounting for decision processes extends the complexity, as they are multidimensional and process elements need to be regarded as latent constructs (composites that are not observed directly. The objective of this study was to present a practical application of partial least square path modelling (PLS-PM to evaluate how it offers a method for empirical analysis of decision-making in healthcare. Methods Empirical approaches that applied PLS-PM to decision-making in healthcare were identified through a systematic literature search. PLS-PM was used as an estimation technique for a structural equation model that specified hypotheses between the components of decision processes and the reasonableness of decision-making in terms of medical, economic and other ethical criteria. The model was estimated for a sample of 55 coverage decisions on the extension of newborn screening programmes in Europe. Results were evaluated by standard reliability and validity measures for PLS-PM. Results After modification by dropping two indicators that showed poor measures in the measurement models’ quality assessment and were not meaningful for newborn screening, the structural equation model estimation produced plausible results. The presence of three influences was supported: the links between both stakeholder participation or transparency and the reasonableness of decision-making; and the effect of transparency on the degree of scientific rigour of assessment. Reliable and valid measurement models were obtained to describe the composites of ‘transparency’, ‘participation’, ‘scientific rigour’ and ‘reasonableness’. Conclusions The structural equation model was among the first applications of PLS-PM to

  1. A Call to Include Severe Combined Immunodeficiency in Newborn Screening Program

    Directory of Open Access Journals (Sweden)

    Raz Somech

    2014-01-01

    Full Text Available Quantification of the T cell receptor excision circles (TRECs has recently emerged as a useful non-invasive clinical and research tool to investigate thymic activity. It allows the identification of T cell production by the thymus. Quantification of TREC copies has recently been implemented as the preferred test to screen neonates with severe combined immunodeficiency (SCID or significant lymphopenia. Neonatal genetic screening for SCID is highly important in countries with high rates of consanguinous marriages, such as Israel, and can be used for early diagnosis, enabling prompt therapeutic intervention that will save lives and improve the outcome of these patients. TREC measurement is also applicable in clinical settings where T cell immunity is involved, including any T cell immunodeficiencies, HIV infection, the aging process, autoimmune diseases, and immune reconstitution after bone marrow transplantation.

  2. Cord blood IgE. I. IgE screening in 2814 newborn children

    DEFF Research Database (Denmark)

    Hansen, L G; Høst, A; Halken, S

    1992-01-01

    Screening of total IgE in 2814 cord blood samples was analysed by Phadebas IgE PRIST in 2 1-year birth cohorts (1983-1984 and 1985-1986) in Denmark (n = 1189 + 1625). 48.6% of the sera contained less IgE than the detection limit 0.1 kU/l. Cord blood IgE values greater than or equal to 0.5 kU/l we...

  3. Study of the knowledge of Pediatricians and Senior Residents Relating to the Importance of Hearing Impairment and Deafness Screening Among Newborns in Isfahan city in 2012

    Directory of Open Access Journals (Sweden)

    Mehrdad Rogha

    2014-04-01

    Full Text Available Introduction: Newborn hearing screening leads to the early detection of hearing impairment. The aim of screening is to decrease or remove the effect of hearing impairment on development of speech and language by timely diagnosis and effective treatment. A number of risk factors lead to delayed start of decreased hearing ability including: 1. Congenital infection with cytomegalovirus  (CMV virus, 2. Meningitis, 3. Mumps, 4. Positive family history, 5. Head trauma, 6. Chemotherapy, 7. Syndrome pertaining to delayed start of decreased hearing. Unfortunately, lack of attention to early diagnosis of hearing impairment is becoming a general health problem. No research has yet been carried out relating to the knowledge of pediatricians on this issue, particularly the importance of hearing impairment and hearing screening. The aim of this study was to determine the attitude to newborn hearing screening among pediatricians.   Materials and Methods: This cross-sectional, descriptive-analytic study was conducted in Isfahan in 2012 among 300 pediatricians and final-year pediatric residents. An adjusted 22-question version of the Early Hearing Detection and Intervention (EHDI questionnaire was used to collect data. The validity and reliability of the EHDI questionnaire was previously demonstrated by Boys Town National Research Hospital and its Farsi translated version was validated by the EDC Center at the Isfahan University of Medical Sciences.   Results: In our study, 83% of pediatricians agreed on the importance of hearing impairment screening for all infants. However 65% were not aware of special needs for hearing-impaired patients.   Conclusion:  Newborn hearing impairment and deafness screening is important, irrespective of the costs, and lack of timely diagnosis results in both individual and social consequences. The majority of physicians use textbooks to gain information about hearing screening, but recognize that this is insufficient. Although

  4. Use of newborn screening program blood spots for exposure assessment: declining levels of perluorinated compounds in New York State infants.

    Science.gov (United States)

    Spliethoff, Henry M; Tao, Lin; Shaver, Shannon M; Aldous, Kenneth M; Pass, Kenneth A; Kannan, Kurunthachalam; Eadon, George A

    2008-07-15

    Temporal biomonitoring studies can assess changes in population exposures to contaminants, but collection of biological specimens with adequate representation and sufficient temporal resolution can be resource-intensive. Newborn Screening Programs (NSPs) collect blood as dried spots on filter paper from nearly all infants born in the United States (U.S.). In this study, we investigated the use of NSP blood spots for temporal biomonitoring by analyzing perfluorooctane sulfonate (PFOS), perfluorooctane sulfonamide (PFOSA), perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) in 110 New York State (NYS) NSP blood spot composite specimens collected between 1997 and 2007, representing a total of 2640 infants. All analytes were detected in > or =90% of the specimens. Concentrations of PFOS, PFOSA, PFHxS, and PFOA exhibited significant exponential declines after the year 2000, coinciding with the phase-out in PFOS production in the U.S. Calculated disappearance half-lives for PFOS, PFHxS, and PFOA (4.4, 8.2, and 4.1 years, respectively) were similar to biological half-lives reported for retired fluorochemical workers. Our results suggest sharp decreases in perinatal exposure of NYS infants to PFOS, PFOSA, PFHxS, and PFOA and demonstrate, for the first time, the utility of NSP blood spots for assessment of temporal trends in exposure.

  5. Biochemical and molecular diagnosis of tyrosinemia type I with two novel FAH mutations in a Hong Kong chinese patient: recommendation for expanded newborn screening in Hong Kong.

    Science.gov (United States)

    Mak, Chloe Miu; Lam, Ching-Wan; Chim, Stella; Siu, Tak-Shing; Ng, King-Fai; Tam, Sidney

    2013-01-01

    Tyrosinemia type I is an autosomal recessive disorder in tyrosine metabolism. In areas without expanded newborn screening, patients present with acute hepatorenal failure in early infancy. Diagnosis can be elusive when clinical presentation is non-specific and biochemical abnormalities are masked by secondary changes. This is the first Hong Kong Chinese report. A two-month-old Chinese male infant with unremarkable antenatal and postnatal history presented with progressive abdominal distension for three days. He suffered from end-stage liver failure, hypoglycemia and hepatic encephalopathy. Diagnostic work-up was complicated starting from rule-out sepsis, intestinal obstruction, volvulus, peritonitis, septic ileus, poisoning to metabolic diseases. Clinical, biochemical and genetic data was described. The patient showed increases in multiple plasma amino acids including tyrosine, phenylalanine and methionine, and hyper-excretions of 4-hydroxyphenyl-acetate, -pyruvate, and -lactate, as well as N-acetyltyrosine which could be seen in liver failure due to both tyrosinemia type I and non-metabolic conditions. Because of the volatile nature, succinylacetone was almost undetectable. The diagnosis was confirmed by genetic analysis of FAH with two novel mutations, viz. NM_000137.2:c.1063-1G>A and NM_000137.2:c.1035_1037del. Living-related liver transplantation was done. However, the patient still suffered many complications after the severe metabolic insult with hypoxic ischemic encephalopathy, cerebral atrophy, global developmental delay and cortical visual impairment. Because of the lack of expanded newborn screening in Hong Kong, this child unfortunately presented in the most severe form of tyrosinemia type I. Expanded newborn screening can save life and reduce the burden of diagnostic complexity. This illustrates the need for expanded newborn screening in Hong Kong. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights

  6. Alpha chain hemoglobins with electrophoretic mobility similar to that of hemoglobin S in a newborn screening program

    Directory of Open Access Journals (Sweden)

    Marcilene Rezende Silva

    2013-01-01

    Full Text Available OBJECTIVE: To characterize alpha-chain variant hemoglobins with electric mobility similar to that of hemoglobin S in a newborn screening program. METHODS: βS allele and alpha-thalassemia deletions were investigated in 14 children who had undefined hemoglobin at birth and an electrophoretic profile similar to that of hemoglobin S when they were six months old. Gene sequencing and restriction enzymes (DdeI, BsaJI, NlaIV, Bsu36I and TaqI were used to identify hemoglobins. Clinical and hematological data were obtained from children who attended scheduled medical visits. RESULTS: The following alpha chain variants were found: seven children with hemoglobin Hasharon [alpha2 47(CE5 Asp>His, HbA2:c.142G>C], all associated with alpha-thalassemia, five with hemoglobin Ottawa [alpha1 15(A13 Gly>Arg, HBA1:c.46G>C], one with hemoglobin St Luke's [alpha1 95(G2 Pro>Arg, HBA1:c.287C>G] and another one with hemoglobin Etobicoke [alpha212 84(F5 Ser>Arg, HBA212:c.255C>G]. Two associations with hemoglobin S were found: one with hemoglobin Ottawa and one with hemoglobin St Luke's. The mutation underlying hemoglobin Etobicoke was located in a hybrid α212 allele in one child. There was no evidence of clinically relevant hemoglobins detected in this study. CONCLUSION: Apparently these are the first cases of hemoglobin Ottawa, St Luke's, Etobicoke and the α212 gene described in Brazil. The hemoglobins detected in this study may lead to false diagnosis of sickle cell trait or sickle cell disease when only isoelectric focusing is used in neonatal screening. Additional tests are necessary for the correct identification of hemoglobin variants.

  7. Alpha chain hemoglobins with electrophoretic mobility similar to that of hemoglobin S in a newborn screening program.

    Science.gov (United States)

    Silva, Marcilene Rezende; Sendin, Shimene Mascarenhas; Araujo, Isabela Couto de Oliveira; Pimentel, Fernanda Silva; Viana, Marcos Borato

    2013-01-01

    To characterize alpha-chain variant hemoglobins with electric mobility similar to that of hemoglobin S in a newborn screening program. β(S) allele and alpha-thalassemia deletions were investigated in 14 children who had undefined hemoglobin at birth and an electrophoretic profile similar to that of hemoglobin S when they were six months old. Gene sequencing and restriction enzymes (DdeI, BsaJI, NlaIV, Bsu36I and TaqI) were used to identify hemoglobins. Clinical and hematological data were obtained from children who attended scheduled medical visits. THE FOLLOWING ALPHA CHAIN VARIANTS WERE FOUND: seven children with hemoglobin Hasharon [alpha2 47(CE5) Asp>His, HbA2:c.142G>C], all associated with alpha-thalassemia, five with hemoglobin Ottawa [alpha1 15(A13) Gly>Arg, HBA1:c.46G>C], one with hemoglobin St Luke's [alpha1 95(G2) Pro>Arg, HBA1:c.287C>G] and another one with hemoglobin Etobicoke [alpha212 84(F5) Ser>Arg, HBA212:c.255C>G]. Two associations with hemoglobin S were found: one with hemoglobin Ottawa and one with hemoglobin St Luke's. The mutation underlying hemoglobin Etobicoke was located in a hybrid α212 allele in one child. There was no evidence of clinically relevant hemoglobins detected in this study. Apparently these are the first cases of hemoglobin Ottawa, St Luke's, Etobicoke and the α212 gene described in Brazil. The hemoglobins detected in this study may lead to false diagnosis of sickle cell trait or sickle cell disease when only isoelectric focusing is used in neonatal screening. Additional tests are necessary for the correct identification of hemoglobin variants.

  8. Tay-Sachs and Sandhoff diseases: enzymatic diagnosis in dried blood spots on filter paper: retrospective diagnoses in newborn-screening cards.

    Science.gov (United States)

    Chamoles, Néstor A; Blanco, Mariana; Gaggioli, Daniela; Casentini, Carina

    2002-04-01

    Tay-Sachs disease (TSD), Sandhoff disease (SD) and variants are caused by deficient activity of the lysosomal enzymes hexosaminidase A (HA) and total hexosaminidase (TH) (hexosaminidase A plus B), respectively. For diagnosis, these enzymes are usually measured in plasma or extracts of leukocytes. We describe methods for the assay of hexosaminidase A and total hexosaminidase activities in dried blood spots (DBSs) on filter paper. We studied 163 healthy controls, 9 Tay-Sachs patients, 4 Sandhoff patients, 18 obligate carriers and the newborn-screening cards from two patients with Tay-Sachs and one patient with Sandhoff disease. To tubes containing a 3-mm-diameter blood spot, we added elution liquid and substrate solution. After incubation at 37 degrees C, the amount of hydrolyzed product was compared with a calibrator to allow the quantification of enzyme activity. The described methodology is useful to distinguish patients with Tay-Sachs disease or Sandhoff disease from carriers and controls using samples that are sufficiently stable to be transported to the testing laboratory by mail. The diagnosis of both diseases from a newborn-screening card (NSC) was clearly demonstrated, even after storage for up to 38 months at room temperature. The newborn-screening card has been added to the biological materials that allow the identification of patients with Tay-Sachs disease and Sandhoff disease.

  9. Efficient linking of birth certificate and newborn screening databases for laboratory investigation of congenital cytomegalovirus infection and preterm birth: Florida, 2008.

    Science.gov (United States)

    DePasquale, John M; Freeman, Karen; Amin, Minal M; Park, Sohyun; Rivers, Samantha; Hopkins, Richard; Cannon, Michael J; Dy, Bonifacio; Dollard, Sheila C

    2012-02-01

    The objectives of this study are (1) to design an accurate method for linking newborn screening (NBS) and state birth certificate databases to create a de-identified study database; (2) To assess maternal cytomegalovirus (CMV) seroprevalence by measuring CMV IgG in newborn dried blood spots; (3) To assess congenital CMV infection among newborns and possible association with preterm birth. NBS and birth databases were linked and patient records were de-identified. A stratified random sample of records based on gestational age was selected and used to retrieve blood spots from the state NBS laboratory. Serum containing maternal antibodies was eluted from blood spots and tested for the presence of CMV IgG. DNA was extracted from blood spots and tested for the presence of CMV DNA. Analyses were performed with bivariable and multivariable logistic regression models. Linkage rates and specimen collection exceeded 98% of the total possible yielding a final database with 3,101 newborn blood spots. CMV seroprevalence was 91% among Black mothers, 83% among Hispanic mothers, 59% among White mothers, and decreased with increasing amounts of education. The prevalence of CMV infection in newborns was 0.45% and did not vary significantly by gestational age. Successful methods for database linkage, newborn blood spots collection, and de-identification of records can serve as a model for future congenital exposure surveillance projects. Maternal CMV seroprevalence was strongly associated with race/ethnicity and educational level. Congenital CMV infection rates were lower than those reported by other studies and lacked statistical power to examine associations with preterm birth.

  10. [Application of liquid chromatography-high resolution mass spectrometry in toxicological screening].

    Science.gov (United States)

    Li, Xiao-Wen; Shen, Bao-Hua; Zhuo, Xian-Yi

    2011-10-01

    Due to the diversity of toxicologically relevant substances, the uncertainty of target compounds and the specificity of samples, toxicological screening techniques have always been valued by the forensic toxicologists. Depending on its powerful separation ability, superhigh resolution and accurate mass measurement, combined with the two levels spectrum database matching and abundance ratio of isotope ion, the liquid chromatography-high resolution mass spectrometry (LC-HRMS) analyzers have increasingly advantage in screening and identification of chemical compound. This review focuses on the applications of LC-HRMS in screening and identification of drug-of-abuse, prescription drugs, pesticide and stimulant. The prospect of LC-HRMS in forensic toxicology analysis is also included.

  11. Maternal and neonatal factors associated with mode of delivery under a universal newborn hearing screening programme in Lagos, Nigeria

    Directory of Open Access Journals (Sweden)

    Solanke Olumuyiwa A

    2009-09-01

    Full Text Available Abstract Background Emerging evidence from a recent pilot universal newborn hearing screening (UNHS programme suggests that the burden of obstetric complications associated with mode of delivery is not limited to maternal and perinatal mortality but may also include outcomes that undermine optimal early childhood development of the surviving newborns. However, the potential pathways for this association have not been reported particularly in the context of a resource-poor setting. This study therefore set out to establish the pattern of delivery and the associated neonatal outcomes under a UNHS programme. Methods A cross-sectional study in which all consenting mothers who delivered in an inner-city tertiary maternity hospital in Lagos, Nigeria from May 2005 to December 2007 were enrolled during the UNHS programme. Socio-demographic, obstetric and neonatal factors independently associated with vaginal, elective and emergency caesarean deliveries were determined using multinomial logistic regression analyses. Results Of the 4615 mothers enrolled, 2584 (56.0% deliveries were vaginal, 1590 (34.4% emergency caesarean and 441 (9.6% elective caesarean section. Maternal age, parity, social class and all obstetric factors including lack of antenatal care, maternal HIV and multiple gestations were associated with increased risk of emergency caesarean delivery compared with vaginal delivery. Only parity, lack of antenatal care and prolonged/obstructed labour were associated with increased risk of emergency compared with elective caesarean delivery. Infants delivered by vaginal method or by emergency caesarean section were more likely to be associated with the risk of sensorineural hearing loss but less likely to be associated with hyperbilirubinaemia compared with infants delivered by elective caesarean section. Emergency caesarean delivery was also associated with male gender, low five-minute Apgar scores and admission into special care baby unit compared

  12. Determinants of caregivers' awareness of Universal Newborn Hearing Screening in Malaysia.

    Science.gov (United States)

    Abdul Majid, Abdul Halim; Zakaria, Mohd Normani; Abdullah, Nor Azimah Chew; Hamzah, Sulaiman; Mukari, Siti Zamratol-Mai Sarah

    2017-10-01

    This paper aims to investigate the effects of perceived attitude and anxiety on awareness of UNHS among caregivers in Malaysia. Using cross sectional research approach, data were collected and some 46 out of 87 questionnaires distributed to caregivers attending UNHS programs at selected public hospitals were usable for analysis (response rate of 52.8%). Partial Least Squares Method (PLS) algorithm and bootstrapping technique were employed to test the hypotheses of the study. R square value is 0.205, and it implies that exogenous latent variables explained 21% of the variance of the endogenous latent variable. This value indicates moderate and acceptable level of R-squared values. Findings from PLS structural model evaluation revealed that anxiety has no significant influence (β = -0.091, t = 0.753, p > 0.10) on caregivers' awareness; but perceived attitude has significant effect (β = -0.444, t = 3.434, p economic situation of the caregivers may have contributed to their failure to honor UNHS screening appointments as some of them may need to work to earn a living while some may perceive it a waste of time honoring such appointments. Non-significant relationship between anxiety and caregivers' awareness may be due to religious beliefs of caregivers. Limitations and suggestions were discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Assessment of the feasibility and coverage of a modified universal hearing screening protocol for use with newborn babies of migrant workers in Beijing.

    Science.gov (United States)

    Qi, Beier; Cheng, Xiaohua; En, Hui; Liu, Bo; Peng, Shichun; Zhen, Yong; Cai, Zhenghua; Huang, Lihui; Zhang, Luo; Han, Demin

    2013-08-08

    Although migrant workers account for the majority of newborns in Beijing, their children are less likely to undergo appropriate universal newborn hearing screening/rescreening (UNHS) than newborns of local non-migrant residents. We hypothesised that this was at least in part due to the inadequacy of the UNHS protocol currently employed for newborn babies, and therefore aimed to modify the protocol to specifically reflect the needs of the migrant population. A total of 10,983 healthy babies born to migrant mothers between January 2007 and December 2009 at a Beijing public hospital were investigated for hearing abnormalities according to a modified UNHS protocol. This incorporated two additional/optional otoacoustic emissions (OAE) tests at 24-48 hours and 2 months after birth. Infants not passing a screening test were referred to the next test, until any hearing loss was confirmed by the auditory brainstem response (ABR) test. A total of 98.91% (10983/11104) of all newborn children underwent the initial OAE test, of which 27.22% (2990/10983) failed the test. 1712 of the failed babies underwent the second inpatient OAE test, with739 failing again; thus significantly decreasing the overall positive rate for abnormal hearing from 27.22% to 18.36% ([2990-973 /10983)]; p = 0). Overall, 1147(56.87%) babies underwent the outpatient OAE test again after1-month, of whom 228 failed and were referred for the second outpatient OAE test (i.e. 2.08% (228/10983) referral rate at 1month of age). 141 of these infants underwent the referral test, of whom 103 (73.05%) tested positive again and were referred for a final ABR test for hearing loss (i.e. final referral rate of 1.73% ([228-38/10983] at 2 months of age). Only 54 infants attended the ABR test and 35 (0.32% of the original cohort tested) were diagnosed with abnormal hearing. Our study shows that it is feasible and practical to achieve high coverage rates for screening hearing loss and decrease the referral rates in

  14. Current advances in screening for bioactive components from medicinal plants by affinity ultrafiltration mass spectrometry.

    Science.gov (United States)

    Chen, Guilin; Huang, Bill X; Guo, Mingquan

    2018-05-21

    Medicinal plants have played an important role in maintaining human health for thousands of years. However, the interactions between the active components in medicinal plants and some certain biological targets during a disease are still unclear in most cases. To conduct the high-throughput screening for small active molecules that can interact with biological targets, which is of great theoretical significance and practical value. The ultrafiltration mass spectrometry (UF-LC/MS) is a powerful bio-analytical method by combining affinity ultrafiltration and liquid chromatography-mass spectrometry (LC/MS), which could rapidly screen and identify small active molecules that bind to biological targets of interest at the same time. Compared with other analytical methods, affinity UF-LC/MS has the characteristics of fast, sensitive and high throughput, and is especially suitable for the complicated extracts of medicinal plants. In this review, the basic principle, characteristics and some most recent challenges in UF-LC/MS have been demonstrated. Meanwhile, the progress and applications of affinity UF-LC/MS in the discovery of the active components from natural medicinal plants and the interactions between small molecules and biological target proteins are also briefly summarised. In addition, the future directions for UF-LC/MS are also prospected. Affinity UF-LC/MS is a powerful tool in studies on the interactions between small active molecules and biological protein targets, especially in the high-throughput screening of active components from the natural medicinal plants. Copyright © 2018 John Wiley & Sons, Ltd.

  15. Communication of carrier status information following universal newborn screening for sickle cell disorders and cystic fibrosis: qualitative study of experience and practice.

    Science.gov (United States)

    Kai, J; Ulph, F; Cullinan, T; Qureshi, N

    2009-11-01

    To describe and explore current practice, methods and experience of communicating carrier status information following newborn screening for cystic fibrosis (CF) and sickle cell (SC) disorders, to inform practice and further research. Three linked qualitative studies. All nine health regions in England. Child health screening coordinators in all English health regions, health professionals communicating results to parents and parents of newborn carriers. A preliminary phase of semi-structured telephone interviews with child health screening coordinators in all nine English health regions, and thematic analysis of data; semi-structured face-to-face interviews with purposeful samples of 67 family members of 51 infants identified by universal newborn screening as carriers of CF or SC with data analysis by constant comparison; and semi-structured telephone interviews, and focus groups, with a key informant sample of 16 differing health professionals currently tasked with communicating results to parents in a range of ways, with thematic analysis of data. Methods for and respondents' experiences of communication of carrier results varied considerably within and between regions, and within and between SC and CF contexts. Approaches ranged from letter or telephone call alone, to in-person communication in the clinic or at home, with health professionals from haemoglobinopathy, CF, screening and genetics backgrounds, or from community and primary care, such as health visitors with SC carrier results. Health professionals identified pros and cons of different methods, preferring opportunity for face-to-face communication with parents where possible, particularly for CF carrier results. They were concerned by regional variations in protocols, the lack of availability of translated information on SC carrier results, and the feasibility of sustaining more 'specialist' involvement at current levels, particularly for SC carriers. Parents were often poorly prepared for the

  16. Newborn jaundice

    Science.gov (United States)

    Jaundice of the newborn; Neonatal hyperbilirubinemia; Bili lights - jaundice; Infant - yellow skin; Newborn - yellow skin ... newborns have some yellowing of the skin, or jaundice. This is called physiological jaundice. It is often ...

  17. Air trapping on chest CT is associated with worse ventilation distribution in infants with cystic fibrosis diagnosed following newborn screening.

    Directory of Open Access Journals (Sweden)

    Graham L Hall

    Full Text Available BACKGROUND: In school-aged children with cystic fibrosis (CF structural lung damage assessed using chest CT is associated with abnormal ventilation distribution. The primary objective of this analysis was to determine the relationships between ventilation distribution outcomes and the presence and extent of structural damage as assessed by chest CT in infants and young children with CF. METHODS: Data of infants and young children with CF diagnosed following newborn screening consecutively reviewed between August 2005 and December 2009 were analysed. Ventilation distribution (lung clearance index and the first and second moment ratios [LCI, M(1/M(0 and M(2/M(0, respectively], chest CT and airway pathology from bronchoalveolar lavage were determined at diagnosis and then annually. The chest CT scans were evaluated for the presence or absence of bronchiectasis and air trapping. RESULTS: Matched lung function, chest CT and pathology outcomes were available in 49 infants (31 male with bronchiectasis and air trapping present in 13 (27% and 24 (49% infants, respectively. The presence of bronchiectasis or air trapping was associated with increased M(2/M(0 but not LCI or M(1/M(0. There was a weak, but statistically significant association between the extent of air trapping and all ventilation distribution outcomes. CONCLUSION: These findings suggest that in early CF lung disease there are weak associations between ventilation distribution and lung damage from chest CT. These finding are in contrast to those reported in older children. These findings suggest that assessments of LCI could not be used to replace a chest CT scan for the assessment of structural lung disease in the first two years of life. Further research in which both MBW and chest CT outcomes are obtained is required to assess the role of ventilation distribution in tracking the progression of lung damage in infants with CF.

  18. Native State Mass Spectrometry, Surface Plasmon Resonance, and X-ray Crystallography Correlate Strongly as a Fragment Screening Combination.

    Science.gov (United States)

    Woods, Lucy A; Dolezal, Olan; Ren, Bin; Ryan, John H; Peat, Thomas S; Poulsen, Sally-Ann

    2016-03-10

    Fragment-based drug discovery (FBDD) is contingent on the development of analytical methods to identify weak protein-fragment noncovalent interactions. Herein we have combined an underutilized fragment screening method, native state mass spectrometry, together with two proven and popular fragment screening methods, surface plasmon resonance and X-ray crystallography, in a fragment screening campaign against human carbonic anhydrase II (CA II). In an initial fragment screen against a 720-member fragment library (the "CSIRO Fragment Library") seven CA II binding fragments, including a selection of nonclassical CA II binding chemotypes, were identified. A further 70 compounds that comprised the initial hit chemotypes were subsequently sourced from the full CSIRO compound collection and screened. The fragment results were extremely well correlated across the three methods. Our findings demonstrate that there is a tremendous opportunity to apply native state mass spectrometry as a complementary fragment screening method to accelerate drug discovery.

  19. High-throughput screening of small molecule libraries using SAMDI mass spectrometry.

    Science.gov (United States)

    Gurard-Levin, Zachary A; Scholle, Michael D; Eisenberg, Adam H; Mrksich, Milan

    2011-07-11

    High-throughput screening is a common strategy used to identify compounds that modulate biochemical activities, but many approaches depend on cumbersome fluorescent reporters or antibodies and often produce false-positive hits. The development of "label-free" assays addresses many of these limitations, but current approaches still lack the throughput needed for applications in drug discovery. This paper describes a high-throughput, label-free assay that combines self-assembled monolayers with mass spectrometry, in a technique called SAMDI, as a tool for screening libraries of 100,000 compounds in one day. This method is fast, has high discrimination, and is amenable to a broad range of chemical and biological applications.

  20. Benign and Deleterious Cystic Fibrosis Transmembrane Conductance Regulator Mutations Identified by Sequencing in Positive Cystic Fibrosis Newborn Screen Children from California.

    Science.gov (United States)

    Salinas, Danieli B; Sosnay, Patrick R; Azen, Colleen; Young, Suzanne; Raraigh, Karen S; Keens, Thomas G; Kharrazi, Martin

    2016-01-01

    Of the 2007 Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mutations, 202 have been assigned disease liability. California's racially diverse population, along with CFTR sequencing as part of newborn screening model, provides the opportunity to examine the phenotypes of children with uncategorized mutations to help inform disease liability and penetrance. We conducted a retrospective cohort study based on children screened from 2007 to 2011 and followed for two to six years. Newborns that screened positive were divided into three genotype groups: those with two CF-causing mutations (CF-C); those with one mutation of varying clinic consequence (VCC); and those with one mutation of unknown disease liability (Unknown). Sweat chloride tests, pancreatic sufficiency status, and Pseudomonas aeruginosa colonization were compared. Children with two CF-causing mutations had a classical CF phenotype, while 5% of VCC (4/78) and 11% of Unknown (27/244) met diagnostic criteria of CF. Children carrying Unknown mutations 2215insG with D836Y, and T1036N had early and classical CF phenotype, while others carrying 1525-42G>A, L320V, L967S, R170H, and 296+28A>G had a benign clinical presentation, suggesting that these are non-CF causing. While most infants with VCC and Unknown CFTR mutations do not meet diagnostic criteria for CF, a small proportion do. These findings highlight the range of genotypes and phenotypes in the first few years of life following CF newborn screening when CFTR sequencing is performed.

  1. Benign and Deleterious Cystic Fibrosis Transmembrane Conductance Regulator Mutations Identified by Sequencing in Positive Cystic Fibrosis Newborn Screen Children from California.

    Directory of Open Access Journals (Sweden)

    Danieli B Salinas

    Full Text Available Of the 2007 Cystic Fibrosis Transmembrane Conductance Regulator (CFTR mutations, 202 have been assigned disease liability. California's racially diverse population, along with CFTR sequencing as part of newborn screening model, provides the opportunity to examine the phenotypes of children with uncategorized mutations to help inform disease liability and penetrance.We conducted a retrospective cohort study based on children screened from 2007 to 2011 and followed for two to six years. Newborns that screened positive were divided into three genotype groups: those with two CF-causing mutations (CF-C; those with one mutation of varying clinic consequence (VCC; and those with one mutation of unknown disease liability (Unknown. Sweat chloride tests, pancreatic sufficiency status, and Pseudomonas aeruginosa colonization were compared.Children with two CF-causing mutations had a classical CF phenotype, while 5% of VCC (4/78 and 11% of Unknown (27/244 met diagnostic criteria of CF. Children carrying Unknown mutations 2215insG with D836Y, and T1036N had early and classical CF phenotype, while others carrying 1525-42G>A, L320V, L967S, R170H, and 296+28A>G had a benign clinical presentation, suggesting that these are non-CF causing.While most infants with VCC and Unknown CFTR mutations do not meet diagnostic criteria for CF, a small proportion do. These findings highlight the range of genotypes and phenotypes in the first few years of life following CF newborn screening when CFTR sequencing is performed.

  2. Effects of Diagnosis by Newborn Screening for Cystic Fibrosis on Weight and Length in the First Year of Life.

    Science.gov (United States)

    Leung, Daniel H; Heltshe, Sonya L; Borowitz, Drucy; Gelfond, Daniel; Kloster, Margaret; Heubi, James E; Stalvey, Michael; Ramsey, Bonnie W

    2017-06-01

    Since the implementation of universal newborn screening (NBS) for cystic fibrosis (CF), the timing and magnitude of growth deficiency or its association with correlates of disease among infants with CF who underwent NBS has not been well described. To examine incremental weight gain, linear growth, and clinical features in the first year of life among infants with CF who underwent NBS. The Baby Observational and Nutrition Study (BONUS), a multicenter, longitudinal, observational cohort study, was conducted during regular CF clinic visits in the first 12 months of life at 28 US Cystic Fibrosis Foundation-accredited Care Centers from January 7, 2012, through May 31, 2015. Participants included 231 infants younger than 3.5 months who underwent NBS and had confirmed CF, with a gestational age of at least 35 weeks, birth weight of at least 2.5 kg, and toleration of full oral feeds. Of these, 222 infants (96.1%) had follow-up beyond 6 months of age and 215 (93.1%) completed 12 months of follow-up. Cystic fibrosis. Attained weight and length for age and World Health Organization normative z scores at ages 1 to 6 and 8, 10, and 12 months (defined a priori). Of the 231 infants enrolled, 110 infants (47.6%) were female and 121 (52.4%) were male, with a mean (SD) age of 2.58 (0.69) months. BONUS infants had lower than mean birth weights (mean z score, -0.15; 95% CI, -0.27 to -0.04) and higher birth lengths (mean z score, 0.44; 95% CI, 0.26 to 0.62). They achieved normal weight by 12 months, a significant improvement over a prescreening cohort of newborns with CF from 20 years before the contemporary cohort (mean z score increase, 0.57; 95% CI, 0.37-0.77). However, length was lower than the mean at 12 months (mean z score, -0.56; 95% CI, -0.70 to -0.42). Only 30 infants (13.6%) were at less than the 10th percentile of weight for age, whereas 53 (23.9%) were at less than the 10th percentile of length for age at more than half their visits. Male sex, pancreatic insufficiency

  3. Trends in Scottish newborn screening programme for congenital hypothyroidism 1980-2014: strategies for reducing age at notification after initial and repeat sampling.

    Science.gov (United States)

    Mansour, Chourouk; Ouarezki, Yasmine; Jones, Jeremy; Fitch, Moira; Smith, Sarah; Mason, Avril; Donaldson, Malcolm

    2017-10-01

    To determine ages at first capillary sampling and notification and age at notification after second sampling in Scottish newborns referred with elevated thyroid-stimulating hormone (TSH). Referrals between 1980 and 2014 inclusive were grouped into seven 5-year blocks and analysed according to agreed standards. Of 2 116 132 newborn infants screened, 919 were referred with capillary TSH elevation ≥8 mU/L of whom 624 had definite (606) or probable (18) congenital hypothyroidism. Median age at first sampling fell from 7 to 5 days between 1980 and 2014 (standard 4-7 days), with 22, 8 and 3 infants sampled >7 days during 2000-2004, 2005-2009 and 2010-2014. Median age at notification was consistently ≤14 days, range falling during 2000-2004, 2005-2009 and 2010-2014 from 6 to 78, 7-52 and 7-32 days with 12 (14.6%), 6 (5.6%) and 5 (4.3%) infants notified >14 days. However 18/123 (14.6%) of infants undergoing second sampling from 2000 onwards breached the ≤26-day standard for notification. By 2010-2014, the 91 infants with confirmed congenital hypothyroidism had shown favourable median age at first sample (5 days) with start of treatment (10.5 days) approaching age at notification. Most standards for newborn thyroid screening are being met by the Scottish programme, but there is a need to reduce age range at notification, particularly following second sampling. Strategies to improve screening performance include carrying out initial capillary sampling as close to 96 hours as possible; introducing 6-day laboratory reporting and use of electronic transmission for communicating repeat requests. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. Living with an inborn error of metabolism detected by newborn screening-parents' perspectives on child development and impact on family life.

    Science.gov (United States)

    Gramer, Gwendolyn; Haege, Gisela; Glahn, Esther M; Hoffmann, Georg F; Lindner, Martin; Burgard, Peter

    2014-03-01

    Newborn screening for inborn errors of metabolism is regarded as highly successful by health professionals. Little is known about parents' perspectives on child development and social impact on families. Parents of 187 patients with metabolic disorders detected by newborn screening rated child development, perceived burdens on child and family, and future expectations on a questionnaire with standardized answers. Parental ratings were compared with standardized psychometric test results. Regression analysis was performed to identify factors associated with extent of perceived burden. In 26.2% of patients, parents perceived delays in global development and/or specific developmental domains (physical, social, intellectual, language). Parents expected normal future development in 95.7%, and an independent adult life for their child in 94.6%. Comparison with psychometric test results showed that parents of children with cognitive impairments tended to overrate their child's abilities. Mild/medium burden posed on the family (child) by the metabolic disorder was stated by 56.1% (48.9%) of parents, severe/very severe burden by 19.3% (8.6%). One third of families reported financial burden due to the metabolic disorder. Dietary treatment and diagnoses with risk for metabolic decompensation despite treatment were associated with higher perceived burden for the family. Disorders rated as potentially very burdensome by experts were not rated accordingly by parents, demonstrating different perspectives of professionals and parents. Although newborn screening leads to favourable physical and cognitive outcome, living with a metabolic disorder may cause considerable stress on patients and families, emphasizing the need for comprehensive multidisciplinary care including psychological and social support.

  5. Newborn Screening Tests

    Science.gov (United States)

    ... don't have enough biotinidase, an enzyme that recycles biotin (a B vitamin) in the body. Biotinidase ... about additional tests: Do you have a family history of an inherited disorder? Have you previously given ...

  6. Newborn Screening for CF

    Science.gov (United States)

    ... Active Cycle of Breathing Technique Airway Clearance Techniques Autogenic Drainage Basics of Lung Care Chest Physical Therapy ... care. Clinician Awards Clinician Career Development Awards Clinician Training Awards Mutation Analysis Program Network News Network News: ...

  7. Application of a diagnostic methodology by quantification of 26:0 lysophosphatidylcholine in dried blood spots for Japanese newborn screening of X-linked adrenoleukodystrophy

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    Chen Wu

    2017-09-01

    Full Text Available X-linked adrenoleukodystrophy (X-ALD is a rare inherited metabolic disease that results in the accumulation of very long chain fatty acids (VLCFA in plasma and all tissues. Recent studies regarding cerebral X-ALD (CALD treatment emphasize the importance of its early diagnosis. 26:0 lysophosphatidylcholine (LysoPC is a sensitive biomarker for newborn screening of X-ALD, while its application for Japanese DBS is unclear. Therefore, we evaluated the feasibility of 20:0 LysoPC and 24:0 LysoPC along with 26:0 LysoPC for diagnosing X-ALD in a cohort of newborns (n = 604, healthy adults (n = 50 and patients (n = 4. Results indicated that 26:0 LysoPC had strong significance for discrimination of patients by the amounts of 2.0 to 4.0 and 0.1 to 1.9 pmol/punch for patients and newborns/healthy adults, respectively. Based on these values, we recommend that further diagnostic confirmation is essential if the amount of 26:0 LysoPC in DBS is above 1.7 pmol/punch.

  8. Integrating HIV, hepatitis B and syphilis screening and treatment through the Maternal, Newborn and Child Health platform to reach global elimination targets

    Directory of Open Access Journals (Sweden)

    Joseph Woodring

    2017-12-01

    Full Text Available Every year, an estimated 180 000 babies in the Western Pacific Region are infected by hepatitis B, 13 000 by syphilis and 1400 by HIV through mother-to-child transmission.1 These infections can be largely prevented by antenatal screening, treatment and timely vaccination for newborns. Despite challenges in controlling each disease, major achievements have been made. National immunization programmes have reduced the regional hepatitis B prevalence from over 8% in 1990 to 0.93% among children born in 2012. In addition, HIV testing and treatment have helped keep the regional prevalence of HIV infections at 0.1%. In contrast, the number of maternal syphilis cases is still high in the Western Pacific Region, with an estimated 45 million cases in 2012. Elimination of mother-to-child transmission of these infections cannot be achieved through vertically applied programming and require using and augmenting to the shared Maternal, Newborn and Child Health platform to coordinate, integrate and enable cost efficiencies for these elimination efforts. The Regional Framework for Triple Elimination of Mother-to-Child Transmission of HIV, Hepatitis B and Syphilis in Asia and the Pacific 2018–2030 offers such a coordinated approach towards achieving the triple elimination of mother-to-child transmission of HIV, hepatitis B and syphilis and provides guidance for decision-makers, managers and health professionals working in programmes addressing maternal, newborn and child health, HIV, hepatitis, sexually transmitted infections and immunization.

  9. Fast screening of analytes for chemical reactions by reactive low-temperature plasma ionization mass spectrometry.

    Science.gov (United States)

    Zhang, Wei; Huang, Guangming

    2015-11-15

    Approaches for analyte screening have been used to aid in the fine-tuning of chemical reactions. Herein, we present a simple and straightforward analyte screening method for chemical reactions via reactive low-temperature plasma ionization mass spectrometry (reactive LTP-MS). Solution-phase reagents deposited on sample substrates were desorbed into the vapor phase by action of the LTP and by thermal desorption. Treated with LTP, both reagents reacted through a vapor phase ion/molecule reaction to generate the product. Finally, protonated reagents and products were identified by LTP-MS. Reaction products from imine formation reaction, Eschweiler-Clarke methylation and the Eberlin reaction were detected via reactive LTP-MS. Products from the imine formation reaction with reagents substituted with different functional groups (26 out of 28 trials) were successfully screened in a time of 30 s each. Besides, two short-lived reactive intermediates of Eschweiler-Clarke methylation were also detected. LTP in this study serves both as an ambient ionization source for analyte identification (including reagents, intermediates and products) and as a means to produce reagent ions to assist gas-phase ion/molecule reactions. The present reactive LTP-MS method enables fast screening for several analytes from several chemical reactions, which possesses good reagent compatibility and the potential to perform high-throughput analyte screening. In addition, with the detection of various reactive intermediates (intermediates I and II of Eschweiler-Clarke methylation), the present method would also contribute to revealing and elucidating reaction mechanisms. Copyright © 2015 John Wiley & Sons, Ltd.

  10. Droplet electrospray ionization mass spectrometry for high throughput screening for enzyme inhibitors.

    Science.gov (United States)

    Sun, Shuwen; Kennedy, Robert T

    2014-09-16

    High throughput screening (HTS) is important for identifying molecules with desired properties. Mass spectrometry (MS) is potentially powerful for label-free HTS due to its high sensitivity, speed, and resolution. Segmented flow, where samples are manipulated as droplets separated by an immiscible fluid, is an intriguing format for high throughput MS because it can be used to reliably and precisely manipulate nanoliter volumes and can be directly coupled to electrospray ionization (ESI) MS for rapid analysis. In this study, we describe a "MS Plate Reader" that couples standard multiwell plate HTS workflow to droplet ESI-MS. The MS plate reader can reformat 3072 samples from eight 384-well plates into nanoliter droplets segmented by an immiscible oil at 4.5 samples/s and sequentially analyze them by MS at 2 samples/s. Using the system, a label-free screen for cathepsin B modulators against 1280 chemicals was completed in 45 min with a high Z-factor (>0.72) and no false positives (24 of 24 hits confirmed). The assay revealed 11 structures not previously linked to cathepsin inhibition. For even larger scale screening, reformatting and analysis could be conducted simultaneously, which would enable more than 145,000 samples to be analyzed in 1 day.

  11. Spectrum analysis of common inherited metabolic diseases in Chinese patients screened and diagnosed by tandem mass spectrometry.

    Science.gov (United States)

    Han, Lianshu; Han, Feng; Ye, Jun; Qiu, Wenjuan; Zhang, Huiwen; Gao, Xiaolan; Wang, Yu; Ji, Wenjun; Gu, Xuefan

    2015-03-01

    Information concerning inherited metabolic diseases in China is scarce. We investigated the prevalence and age distributions of amino acid, organic acid, and fatty acid oxidation disorders in Chinese patients. Blood levels of amino acids and acylcarnitines (tandem mass spectrometry) were measured in 18,303 patients with suspected inherited metabolic diseases. Diagnosis was based on clinical features, blood levels of amino acids or acylcarnitines, urinary organic acid levels (gas chromatography-mass spectrometry), and (in some) gene mutation tests. Inherited metabolic diseases were confirmed in 1,135 patients (739 males, 396 females). Median age was 12 months (1 day to 59 years). There were 28 diseases: 12 amino acid disorders (580 patients, 51.1%), with hyperphenylalaninemia (HPA) being the most common; nine organic acidemias (408 patients, 35.9%), with methylmalonic acidemia (MMA) as the most common; and seven fatty acid oxidation defects (147 patients, 13.0%), with multiple acyl-coenzyme A dehydrogenase deficiency (MADD) being the most common. Onset was mainly at 1-6 months for citrin deficiency, 0-6 months for MMA, and in newborns for ornithine transcarbamylase deficiency (OTCD). HPA was common in patients aged 1-3 years, and MADD was common in patients >18 years. In China, HPA, citrin deficiency, MMA, and MADD are the most common inherited disorders, particularly in newborns/infants. © 2014 Wiley Periodicals, Inc.

  12. A Qualitative Secondary Evaluation of Statewide Follow-Up Interviews for Abnormal Newborn Screening Results for Cystic Fibrosis and Sickle Cell Hemoglobinopathy

    Science.gov (United States)

    La Pean, Alison; Collins, Jenelle L.; Christopher, Stephanie A.; Eskra, Kerry L.; Roedl, Sara; Tluczek, Audrey; Farrell, Michael H.

    2011-01-01

    Purpose The purpose of this qualitative analysis was to assess parental acceptability of large-scale, telephone follow-up regarding their infants' newborn screening (NBS) results indicating carrier status for sickle cell hemoglobinopathy (SCH) and cystic fibrosis (CF). Methods Analysis of 195 interview transcripts focused on parents' responses to two open-ended questions “What was your reaction to being called by me?” and “What do you think of the state newborn screening program having follow-up people calling parents like you?” Responses were coded using conventional content analysis procedures and non-parametric tests were performed to analyze quantitative data. Results Most parents reported favorable opinions about the follow-up. Favorable opinions were associated with several emotional reactions to receiving follow-up (pinterview beneficial (pinterview. Conclusion Parents of CF and SCH carrier infants had favorable opinions and identified specific benefits to receiving follow-up contact. This analysis demonstrates an information deficit among carrier parents and illustrates the importance of NBS follow-up and need for comprehensive communication and counseling. PMID:22261754

  13. Cascade carrier testing after a child is diagnosed with cystic fibrosis through newborn screening: investigating why most relatives do not have testing.

    Science.gov (United States)

    McClaren, Belinda J; Aitken, Maryanne; Massie, John; Amor, David; Ukoumunne, Obioha C; Metcalfe, Sylvia A

    2013-07-01

    Newborn screening for cystic fibrosis is increasingly available, but cascade testing following the diagnosis in a child has received little attention. We previously reported low levels of cascade testing over time, and this study investigated motivators as well as barriers to testing. Parents were interviewed about communicating the genetic information and also asked to recruit their relatives to receive a specifically developed questionnaire. Thirty parents were interviewed and addresses of 284 relatives were provided; completed questionnaires were received from 225 (79%). A relative's relationship to the child, as well as knowledge, is associated with having had carrier testing. Relatives' reasons for testing included curiosity and wanting information for other relatives and for reproductive planning. Reasons for not testing were perceived irrelevance, lacking awareness, and viewing it as something to do in the future. Parents communicated the genetic information to relatives in various ways, which contributed to whether relatives accessed carrier testing. Newborn screening programs should provide support to parents to aid communication of genetic information to relatives. (Ir)relevance of testing is often linked to life stage; ongoing support and communication may allow relatives to learn of their risk and then seek testing, if they wish, at a time perceived to be most relevant to them.

  14. Current use of high-resolution mass spectrometry in drug screening relevant to clinical and forensic toxicology and doping control.

    Science.gov (United States)

    Ojanperä, Ilkka; Kolmonen, Marjo; Pelander, Anna

    2012-05-01

    Clinical and forensic toxicology and doping control deal with hundreds or thousands of drugs that may cause poisoning or are abused, are illicit, or are prohibited in sports. Rapid and reliable screening for all these compounds of different chemical and pharmaceutical nature, preferably in a single analytical method, is a substantial effort for analytical toxicologists. Combined chromatography-mass spectrometry techniques with standardised reference libraries have been most commonly used for the purpose. In the last ten years, the focus has shifted from gas chromatography-mass spectrometry to liquid chromatography-mass spectrometry, because of progress in instrument technology and partly because of the polarity and low volatility of many new relevant substances. High-resolution mass spectrometry (HRMS), which enables accurate mass measurement at high resolving power, has recently evolved to the stage that is rapidly causing a shift from unit-resolution, quadrupole-dominated instrumentation. The main HRMS techniques today are time-of-flight mass spectrometry and Orbitrap Fourier-transform mass spectrometry. Both techniques enable a range of different drug-screening strategies that essentially rely on measuring a compound's or a fragment's mass with sufficiently high accuracy that its elemental composition can be determined directly. Accurate mass and isotopic pattern acts as a filter for confirming the identity of a compound or even identification of an unknown. High mass resolution is essential for improving confidence in accurate mass results in the analysis of complex biological samples. This review discusses recent applications of HRMS in analytical toxicology.

  15. High-performance liquid chromatography-mass spectrometry-based acetylcholinesterase assay for the screening of inhibitors in natural extracts

    NARCIS (Netherlands)

    de Jong, C.F.; Derks, R.J.E.; Bruyneel, B.; Niessen, W.M.A.; Irth, H.

    2006-01-01

    The present paper describes a High-performance liquid chromatography-mass spectrometry (LC-MS) methodology for the screening of acetylcholinesterase (AChE) inhibitors in natural extracts. AChE activity of sample components is monitored by a post-column biochemical assay that is based on the

  16. Desorption electrospray ionisation mass spectrometry: A rapid screening tool for veterinary drug preparations and forensic samples from hormone crime investigations

    NARCIS (Netherlands)

    Nielen, M.W.F.; Hooijerink, H.; Claassen, F.C.; Engelen, M.C.; Beek, van T.A.

    2009-01-01

    Hormone and veterinary drug screening and forensics can benefit from the recent developments in desorption electrospray ionisation (DESI) mass spectrometry (MS). In this work the feasibility of DESI application has been studied. Using a linear ion trap or quadrupole time-of-flight (TOF) MS

  17. A high throughput mass spectrometry screening analysis based on two-dimensional carbon microfiber fractionation system.

    Science.gov (United States)

    Ma, Biao; Zou, Yilin; Xie, Xuan; Zhao, Jinhua; Piao, Xiangfan; Piao, Jingyi; Yao, Zhongping; Quinto, Maurizio; Wang, Gang; Li, Donghao

    2017-06-09

    A novel high-throughput, solvent saving and versatile integrated two-dimensional microscale carbon fiber/active carbon fiber system (2DμCFs) that allows a simply and rapid separation of compounds in low-polar, medium-polar and high-polar fractions, has been coupled with ambient ionization-mass spectrometry (ESI-Q-TOF-MS and ESI-QqQ-MS) for screening and quantitative analyses of real samples. 2DμCFs led to a substantial interference reduction and minimization of ionization suppression effects, thus increasing the sensitivity and the screening capabilities of the subsequent MS analysis. The method has been applied to the analysis of Schisandra Chinensis extracts, obtaining with a single injection a simultaneous determination of 33 compounds presenting different polarities, such as organic acids, lignans, and flavonoids in less than 7min, at low pressures and using small solvent amounts. The method was also validated using 10 model compounds, giving limit of detections (LODs) ranging from 0.3 to 30ngmL -1 , satisfactory recoveries (from 75.8 to 93.2%) and reproducibilities (relative standard deviations, RSDs, from 1.40 to 8.06%). Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Time of flight secondary ion mass spectrometry: A powerful high throughput screening tool

    International Nuclear Information System (INIS)

    Smentkowski, Vincent S.; Ostrowski, Sara G.

    2007-01-01

    Combinatorial materials libraries are becoming more complicated; successful screening of these libraries requires the development of new high throughput screening methodologies. Time of flight secondary ion mass spectrometry (ToF-SIMS) is a surface analytical technique that is able to detect and image all elements (including hydrogen which is problematic for many other analysis instruments) and molecular fragments, with high mass resolution, during a single measurement. Commercial ToF-SIMS instruments can image 500 μm areas by rastering the primary ion beam over the region of interest. In this work, we will show that large area analysis can be performed, in one single measurement, by rastering the sample under the ion beam. We show that an entire 70 mm diameter wafer can be imaged in less than 90 min using ToF-SIMS stage (macro)rastering techniques. ToF-SIMS data sets contain a wealth of information since an entire high mass resolution mass spectrum is saved at each pixel in an ion image. Multivariate statistical analysis (MVSA) tools are being used in the ToF-SIMS community to assist with data interpretation; we will demonstrate that MVSA tools provide details that were not obtained using manual (univariate) analysis

  19. Triagem neonatal: o panorama atual no estado do Amapá | Newborn screening: current situation in the state of Amapá

    Directory of Open Access Journals (Sweden)

    Grace Suzan Lopes Lacerda

    2017-05-01

    Full Text Available A triagem neonatal conhecida como teste do pezinho é um conjunto de exames que tem como finalidade detectar patologias em recém-nascidos e que deve ser realizado preferencialmente entre o 3º e o 7º mês de vida do neonato. O teste detecta seis anomalias congênitas: fenilcetonúria, hipotireoidismo congênito, anemia falciforme, fibrose cística, deficiência de biotinidase e hiperplasia adrenal congênita. Para o Ministério da Saúde, em 2007, a menor cobertura populacional de teste do pezinho no Brasil ocorreu no Amapá. Através de uma metodologia qualitativa, foram coletados dados institucionais no laboratório de referência do estado, Instituto de Hematologia e Hemoterapia do Amapá (Hemoap, usando também como instrumento de pesquisa um questionário dirigido às mães e/ou responsáveis dos neonatos no momento de realização do exame. Dos resultados obtidos somente cinco municípios dos 16 realizam a coleta do teste do pezinho, dando uma cobertura de 31,2%. Quanto aos questionários, mostrou-se majoritário o número de indivíduos que não têm conhecimentos sobre a importância do exame. Em contrapartida, 100,0% dos entrevistados responderam que tinham interesse em retornar para buscar o resultado do exame, contudo o estudo levantou dados negligenciados dos anos de 2013 a 2015, demonstrando ser grande o desinteresse das mães e/ou responsáveis que levam o neonato para realizar o teste. Tais dados mostram que o Programa Nacional de Triagem Neonatal no Amapá está longe de obter uma cobertura completa e que os bancos de dados são escassos quanto a informações sobre o estado. ============================================= Newborn screening comprises a set of tests that aim to detect pathologies in newborns and should be performed preferably between the 3rd and 7th month of life. The scree-ning detects six congenital anomalies: phenylketonuria, congenital hypothyroidism, sickle cell anemia, cystic fibrosis, biotinidase deficiency

  20. Affinity imaging mass spectrometry (AIMS): high-throughput screening for specific small molecule interactions with frozen tissue sections.

    Science.gov (United States)

    Yoshimi, T; Kawabata, S; Taira, S; Okuno, A; Mikawa, R; Murayama, S; Tanaka, K; Takikawa, O

    2015-11-07

    A novel screening system, using affinity imaging mass spectrometry (AIMS), has been developed to identify protein aggregates or organ structures in unfixed human tissue. Frozen tissue sections are positioned on small (millimetre-scale) stainless steel chips and incubated with an extensive library of small molecules. Candidate molecules showing specific affinity for the tissue section are identified by imaging mass spectrometry (IMS). As an example application, we screened over a thousand compounds against Alzheimer's disease (AD) brain tissue and identified several compounds with high affinity for AD brain sections containing tau deposits compared to age-matched controls. It should also be possible to use AIMS to isolate chemical compounds with affinity for tissue structures or components that have been extensively modified by events such as oxidation, phosphorylation, acetylation, aggregation, racemization or truncation, for example, due to aging. It may also be applicable to biomarker screening programs.

  1. Reconciling newborn screening and a novel splice variant in BTD associated with partial biotinidase deficiency: A BabySeq Project case report.

    Science.gov (United States)

    Murry, Jaclyn B; Machini, Kalotina; Ceyhan-Birsoy, Ozge; Kritzer, Amy; Krier, Joel B; Lebo, Matthew S; Fayer, Shawn; Genetti, Casie A; Vannoy, Grace E; Yu, Timothy W; Agrawal, Pankaj B; Parad, Richard B; Holm, Ingrid A; McGuire, Amy L; Green, Robert C; Beggs, Alan H; Rehm, Heidi L; Project, The BabySeq

    2018-05-04

    Here, we report a newborn female infant from the well-baby cohort of the BabySeq Project who was identified with compound heterozygous BTD gene variants. The two identified variants included a well-established pathogenic variant (c.1612C>T, p.Arg538Cys) that causes profound biotinidase deficiency (BTD) in homozygosity. In addition, a novel splice variant (c.44+1G>A, p.?) was identified in the invariant splice donor region of intron 1, potentially predictive of loss of function. The novel variant was predicted to impact splicing of exon 1; however, given the absence of any reported pathogenic variants in exon 1 and the presence of alternative splicing with exon 1 absent in most tissues in the GTEx database, we assigned an initial classification of uncertain significance. Follow-up medical record review of state mandated newborn screen (NBS) results revealed an initial out-of-range biotinidase activity level. Levels from a repeat NBS sample barely passed cut-off into the normal range. To determine whether the infant was biotinidase deficient, subsequent diagnostic enzyme activity testing was performed, confirming partial BTD, and resulted in a change of management for this patient. This led to reclassification of the novel splice variant based on these results. In conclusion, combining the genetic and NBS results together prompted clinical follow-up that confirmed partial biotinidase deficiency, and informed this novel splice site's reclassification emphasizing the importance of combining iterative genetic and phenotypic evaluations. Cold Spring Harbor Laboratory Press.

  2. Qualitative screening of undesirable compounds from feeds to fish by liquid chromatography coupled to mass spectrometry.

    Science.gov (United States)

    Nácher-Mestre, Jaime; Ibáñez, María; Serrano, Roque; Pérez-Sánchez, Jaume; Hernández, Félix

    2013-03-06

    This paper describes the development, validation, and application of a rapid screening method for the detection and identification of undesirable organic compounds in aquaculture products. A generic sample treatment was applied without any purification or preconcentration step. After extraction of the samples with acetonitrile/water 80:20 (0.1% formic acid), the extracts were centrifuged and directly injected in the LC-HRMS system, consisting of ultra-high performance liquid chromatography coupled to hybrid quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS). A qualitative validation was carried out for over 70 representative compounds, including antibiotics, pesticides, and mycotoxins, in fish feed and fish fillets spiked at 20 and 100 μg/kg. At the highest level, the great majority of compounds were detected (using the most abundant ion, typically the protonated molecule) and unequivocally identified (on the basis of the presence of two accurate-mass measured ions). At the 20 μg/kg level, many contaminants could already be detected, although identification using two ions was not fully reached for some of them, mainly in fish feed due to the complexity of this matrix. Subsequent application of this screening methodology to aquaculture samples made it possible to find several compounds from the target list, such as the antibiotic ciprofloxacin, the insecticide pirimiphos-methyl, and the mycotoxins fumonisin B2 and zearalenone. A retrospective analysis of accurate-mass full-spectrum acquisition data provided by QTOF MS was also made, without either reprocessing or injecting the samples. This allowed the detection and tentative identification of other organic undesirables different from those included in the validated list.

  3. T-cell receptor and K-deleting recombination excision circles in newborn screening of T- and B-cell defects: review of the literature and future challenges

    Directory of Open Access Journals (Sweden)

    Marco Chiarini

    2013-05-01

    Full Text Available Since its introduction as a public health programme in the United States in the early 1960s, newborn blood screening (NBS has evolved from the detection of phenylalanine levels on filter paper to the application of DNA-based technologies to identify T-cell lymphopenia in infants with severe combined immunodeficiency. This latter use of NBS has required the development of an assay for T-cell lymphopenia based on the quantification of T-cell receptor excision circles (TRECs that could be performed on dried blood spots routinely collected from newborn infants. The TREC-based NBS was developed six years ago, and there have already been 7 successful pilot studies since then. Similarly, efforts are now being made to establish a screen for B-cell defects, in particular agammaglobulinaemia, taking advantage of the introduction of the method for the quantification of K-deleting recombination excision circles (KRECs. A further achievement of NBS could be the simultaneous recognition of T- and B-cell defects using the combined quantification of TRECs and KRECs from Guthrie card blood spots. This approach may help the early identification of infants with T- and B-cell deficiencies so that they can then be referred to specialised paediatric centres, where a precise diagnosis of severe combined immunodeficiency and agammaglobulinaemia can be performed, and where then they can immediately receive specific therapy. Simultaneous TREC and KREC quantification should also allow classification of patients into subgroups and help identify children with less serious primary immunodeficiencies. This would help avoid the opportunistic infections and frequent hospitalisations that result from a late or lack of diagnosis.

  4. Effect of screening for red cell antibodies, other than anti-D, to detect hemolytic disease of the fetus and newborn: a population study in the Netherlands.

    Science.gov (United States)

    Koelewijn, J M; Vrijkotte, T G M; van der Schoot, C E; Bonsel, G J; de Haas, M

    2008-05-01

    Hemolytic disease of the fetus and newborn (HDFN) is a severe disease, resulting from maternal red cell (RBC) alloantibodies directed against fetal RBCs. The effect of a first-trimester antibody screening program on the timely detection of HDFN caused by antibodies other than anti-D was evaluated. Nationwide, all women (1,002 in 305,000 consecutive pregnancies during 18 months) with alloantibodies other than anti-D, detected by a first-trimester antibody screen, were included in a prospective index-cohort study. In a parallel-coverage validation study, patients with HDFN caused by antibodies other than anti-D, that were missed by the screening program, were retrospectively identified. The prevalence of positive antibody screens at first-trimester screening was 1,232 in 100,000; the prevalence of alloantibodies other than anti-D was 328 in 100,000, of which 191 of 100,000 implied a risk for occurrence of HDFN because the father carried the antigen. Overall, severe HDFN, requiring intrauterine or postnatal (exchange) transfusions, occurred in 3.7 percent of fetuses at risk: for anti-K in 11.6 percent; anti-c in 8.5 percent; anti-E in 1.1 percent; Rh antibodies other than anti-c, anti-D, or anti-E in 3.8 percent; and for antibodies other than Rh antibodies or anti-K, in none of the fetuses at risk. All affected children, where antibodies were detected, were promptly treated and healthy at the age of 1 year. The coverage validation study showed a sensitivity of the screening program of 75 percent. Five of 8 missed cases were caused by anti-c, with delay-induced permanent damage in at least 1. First-trimester screening enables timely treatment of HDFN caused by antibodies other than anti-D, however, with a sensitivity of only 75 percent. A second screening at Week 30 of c- women will enhance the screening program. Severe HDFN, caused by antibodies other than anti-D, is associated with anti-K, anti-c, and to a lesser extent with other Rh-alloantibodies.

  5. Investigación de cocaína y marihuana en meconio de neonatos atendidos en un hospital público: Primera experiencia realizada en la ciudad Córdoba, Argentina Screening of cocaine and marijuana in meconium of newborns from a public hospital of city of Córdoba, Argentina

    Directory of Open Access Journals (Sweden)

    Andrés Suárez

    2009-12-01

    Full Text Available Se investigaron cocaína y marihuana en meconio de neonatos nacidos en la Maternidad Provincial de la Ciudad de Córdoba y se relacionaron los resultados con las semanas de gestación y los pesos al nacer. Las determinaciones se realizaron utilizando inmunoensayo y cromatografía gaseosa-espectrometría de masas. Se analizaron 48 muestras de meconio recolectadas durante un año (2007-2008. De los 48 meconios analizados, 17 correspondieron a neonatos masculinos y 31 a neonatos femeninos. Se procesaron en paralelo 15 muestras de meconio como controles normales (niños no expuestos a drogas seleccionados por historia clínica y controles prenatales. De las 48 muestras de meconio 13 fueron positivas para cocaína y/o marihuana. El peso y las semanas de gestación de los neonatos cuyas muestras fueron positivas se compararon frente a un grupo control normal, hallándose mayores diferencias estadísticamente significativas (α=0,05 - pWe investigated cocaine and marijuana in meconium of newborns attended at the Hospital Materno Provincial of Córdoba City and the results were correlated with birthweight and weeks of pregnancy. The samples were analyzed using immunoassay (FPIA and gas chromatography-mass spectrometry (GC-MS for confirmation. Forty eight samples of meconium were collected during one year period (2007-2008. Of the 48 samples screened, 17 correspond to masculine sex and 31 to feminine. Fifteen samples of meconium from normal newborns (newborns not exposed to drugs selected by maternal self report, pregnancy controls were processed as control group. The results obtained in 48 samples of meconium showed 13 cases tested positive for cocaine and/or marijuana. Birth weight and weeks of gestation of newborn with positive sample results were compared with a control group. A statistically significant difference (α= 0.05 - p<0.0001 was found in relation to birth weight. Although these results arise from a small number of samples, these data have

  6. Avaliação econômica em saúde: triagem neonatal da galactosemia Newborn screening for galactosemia: a health economics evaluation

    Directory of Open Access Journals (Sweden)

    José Simon Camelo Junior

    2011-04-01

    Full Text Available Este trabalho avalia a eficiência da adição do exame da galactosemia junto ao Teste do Pezinho. Baseado na incidência média estimada de galactosemia, de 1:19.984 recém-nascidos, no Estado de São Paulo, Brasil, este estudo desenvolve um modelo de análise de custo-benefício, utilizando a relação benefício/custo (B/C, a taxa de juros de 9,25% ao ano para descapitalização dos resultados obtidos. Também se realiza uma análise de sensibilidade, em função da variação da taxa de juros entre 0 e 20% e do intervalo de 95% de confiança da incidência da galactosemia (1:7.494 a 1:59.953 recém-nascidos. A economia obtida com a melhora da saúde das crianças doentes identificadas precocemente é superior aos custos (B/C = 1,33, caracterizando como eficiente a política de adição do exame neonatal para galactosemia no Teste do Pezinho. Quanto menor a taxa de juros vigente na economia, mais eficiente é a política de triagem neonatal, não considerados os custos sociais intangíveis evitados.This study assesses the efficiency of the galactosemia add-on test in neonatal screening performed on regular Guthrie card blood spots. Based on estimated average incidence of galactosemia (1:19,984 newborns in São Paulo State, Brazil, the study develops a cost-benefit analysis model, using a B/C ratio and a 9.25% annual interest rate in order to decapitalize the results. Sensitivity analysis is also performed, varying (as a function of the interest or discount rate from 0 and 20% and according to the 95% confidence interval (1:7,494-1:59,953 newborns. The results show that the savings obtained by improved health of galactosemic patients detected early by add-on neonatal screening is superior to the costs (B/C=1.33, characterizing galactosemia add-on testing in neonatal screening as an efficient policy. The lower the prevailing interest rate in the economy, the more efficient the neonatal screening policy.

  7. [Screening differentially expressed plasma proteins in cold stress rats based on iTRAQ combined with mass spectrometry technology].

    Science.gov (United States)

    Liu, Yan-zhi; Guo, Jing-ru; Peng, Meng-ling; Ma, Li; Zhen, Li; Ji, Hong; Yang, Huan-min

    2015-09-01

    Isobaric tags for relative and absolute quantitation (iTRAQ) combined with mass spectrometry were used to screen differentially expressed plasma proteins in cold stress rats. Thirty health SPF Wistar rats were randomly divided into cold stress group A and control group B, then A and B were randomly divided into 3 groups (n = 5): A1, A2, A3 and B1, B2, B3. The temperature of room raising was (24.0 +/- 0.1) degrees C, and the cold stress temperature was (4.0 +/- 0.1) degrees C. The rats were treated with different temperatures until 12 h. The abdominal aortic blood was collected with heparin anticoagulation suction tube. Then, the plasma was separated for protein extraction, quantitative, enzymolysis, iTHAQ labeling, scx fractionation and mass spectrometry analysis. Totally, 1085 proteins were identified in the test, 39 differentially expressed proteins were screened, including 29 up-regulated proteins and 10 down-regulated proteins. Three important differentially expressed proteins related to cold stress were screened by bioinfonnatics analysis (Minor histocompatihility protein HA-1, Has-related protein Rap-1b, Integrin beta-1). In the experiment, the differentially expressed plasma proteins were successfully screened in cold stress rats. iTRAQ technology provided a good platform to screen protein diaguostic markers on cold stress rats, and laid a good foundation for further. study on animal cold stress mechanism.

  8. Gamma-ray spectrometry of ultra low levels of radioactivity within the material screening program for the GERDA experiment.

    Science.gov (United States)

    Budjás, D; Gangapshev, A M; Gasparro, J; Hampel, W; Heisel, M; Heusser, G; Hult, M; Klimenko, A A; Kuzminov, V V; Laubenstein, M; Maneschg, W; Simgen, H; Smolnikov, A A; Tomei, C; Vasiliev, S I

    2009-05-01

    In present and future experiments in the field of rare events physics a background index of 10(-3) counts/(keV kg a) or better in the region of interest is envisaged. A thorough material screening is mandatory in order to achieve this goal. The results of a systematic study of radioactive trace impurities in selected materials using ultra low-level gamma-ray spectrometry in the framework of the GERDA experiment are reported.

  9. Does the introduction of newborn hearing screening improve vocabulary development in hearing-impaired children? A population-based study in Japan.

    Science.gov (United States)

    Ohmori, Shuhei; Sugaya, Akiko; Toida, Naomi; Suzuki, Etsuji; Izutsu, Masato; Tsutsui, Tomoko; Kataoka, Yuko; Maeda, Yukihide; Fukushima, Kunihiro; Nishizaki, Kazunori

    2015-02-01

    Permanent hearing impairment has a life-long impact on children and its early identification is important for language development. A newborn hearing screening (NHS) program has started in Okayama Prefecture, Japan, in 1999 to detect hearing impairment immediately after birth. We aim to examine the effect of this screening program on vocabulary development in pre-school children in a before and after comparative study design. A total of 107 5-year-old children who graduated from Okayama Kanariya Gakuen (an auditory center for hearing-impaired children) between 1998 and 2011 were enrolled in this study. The pre-NHS group (n=40) was defined as those who graduated between 1998 and 2003, while the post-NHS group (n=67) was defined as those who graduated between 2004 and 2011. The primary outcome was receptive vocabulary, which was assessed by the Picture Vocabulary Test [score vocabulary, or the number of productive words, which was assessed by an original checklist [vocabulary development and compared both groups. The adjusted Picture Vocabulary Test score and number of productive words were significantly higher (pvocabulary and 4.17 (95% confidence interval: 1.69-10.29) for productive vocabulary. The introduction of NHS in Okayama Prefecture significantly improved both receptive and productive vocabulary development in hearing-impaired children. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Deficiência auditiva na toxoplasmose congênita detectada pela triagem neonatal Hearing loss in congenital toxoplasmosis detected by newborn screening

    Directory of Open Access Journals (Sweden)

    Gláucia Manzan Queiroz de Andrade

    2008-02-01

    Full Text Available A toxoplasmose congênita pode causar déficit neurossensorial em até 20% dos casos e o tratamento no primeiro ano de vida melhora o prognóstico. No Brasil, desconhece-se o impacto da infecção na hipoacusia. OBJETIVO: Avaliar a audição de crianças com toxoplasmose congênita identificadas pela triagem neonatal. MATERIAL E MÉTODO: Estudo prospectivo de crianças com toxoplasmose congênita identificadas pela triagem neonatal (IgM anti-T. gondii em Belo Horizonte, durante 2003/2004. Realizada sorologia confirmatória (mãe/filho e consideradas positivas as crianças apresentando IgM e/ou IgA nos primeiros seis meses ou IgG aos 12 meses de vida. Avaliações auditivas ao diagnóstico e após 12 meses incluíram Audiometria Comportamental, Emissões Otoacústicas, Imitanciometria, Audiometria de Tronco Encefálico. RESULTADOS: Dentre 30.808 crianças triadas (97% dos nascidos vivos, 20 apresentavam toxoplasmose congênita, 15 (75% com infecção subclínica. Dezenove crianças realizaram avaliação auditiva. Quatro apresentaram déficit neurossensorial (21,1%. Uma criança apresentou outros fatores de risco para hipoacusia; nas outras três, a toxoplasmose foi o único fator observado. Duas crianças, tratadas adequadamente com antiparasitários, apresentaram déficit auditivo, em desacordo com a literatura. CONCLUSÃO: Os achados sugerem que a toxoplasmose congênita, prevalente no Brasil, é um fator de risco para hipoacusia e o impacto dessa infecção nas perdas auditivas deve ser estudado.Congenital toxoplasmosis may cause sensorineural deficit in up to 20% of the patients and proper treatment in the first year improves prognosis. In Brazil, this infection’s impact on hearing impairment is unknown. AIM: To evaluate hearing of newborns with congenital toxoplasmosis identified by the newborn screening service. METHOD: This prospective study analyzed children with congenital toxoplasmosis identified by newborn screening (IgM anti

  11. Triagem auditiva neonatal: das alterações auditivas à análise molecular Newborn hearing screening: from audiological alterations to molecular analyses

    Directory of Open Access Journals (Sweden)

    Jaqueline Medeiros de Mello

    2011-10-01

    Full Text Available OBJETIVO: verificar a prevalência da deficiência auditiva em um programa de triagem auditiva neonatal e investigar mutações do gene GJB2 naqueles com suspeita de deficiência auditiva. MÉTODO: foi realizado estudo longitudinal com 908 RN a termo, pós-termo e pré-termo que foram submetidos à realização da triagem auditiva por meio do teste de Emissão Otoacústica Evocada por Estímulo Transiente (EOA-T e reflexo cócleo-palpebral (RCP. Para os recém-nascidos, em que houve falha na triagem auditiva em uma ou ambas as orelhas, eram encaminhados para uma segunda avaliação. No reteste, quando o teste de EOA-T resultasse em não passa em uma ou ambas as orelhas, a criança era encaminhada para avaliação e conduta otorrinolaringológica. Após realização do Potencial Evocado Auditivo de Tronco Encefálico (PEATE a equipe de avaliadores decidia se deveria encaminhar a criança para investigação da mutação. Quando havia suspeita de deficiência auditiva era colhido 3 mL de sangue venoso periférico para a pesquisa de mutação do gene da conexina 26. RESULTADOS: foi constatado a presença de deficiência auditiva condutiva em 2 recém-nascidos (0,22% e neurossensorial em 1 (0,11%. Na criança com deficiência auditiva neurossensorial foi detectada a presença da mutação 35delG. CONCLUSÃO: a avaliação audiológica em conjunto com exames moleculares das principais mutações do gene GJB2 em recém-nascidos com suspeita da deficiência auditiva contribuiu para a rapidez do diagnóstico audiológico, visando uma intervenção precoce, aconselhamento genético e prognóstico educacional da criança.PURPOSE: to assess the prevalence of hearing loss in a newborn hearing screening program and investigate mutations in the GJB2 gene in those with suspected hearing loss. METHOD: we performed longitudinal study of 908 term infants, post-term and preterm infants who underwent hearing screening by the test Emission Transient Evoked

  12. Fluorographene as a Mass Spectrometry Probe for High-Throughput Identification and Screening of Emerging Chemical Contaminants in Complex Samples.

    Science.gov (United States)

    Huang, Xiu; Liu, Qian; Huang, Xiaoyu; Nie, Zhou; Ruan, Ting; Du, Yuguo; Jiang, Guibin

    2017-01-17

    Mass spectrometry techniques for high-throughput analysis of complex samples are of profound importance in many areas such as food safety, omics studies, and environmental health science. Here we report the use of fluorographene (FG) as a new mass spectrometry probe for high-throughput identification and screening of emerging chemical contaminants in complex samples. FG was facilely synthesized by one-step exfoliation of fluorographite. With FG as a matrix or probe in matrix-assisted or surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (MALDI- or SELDI-TOF MS), higher sensitivity (detection limits at ppt or subppt levels), and better reproducibility were achieved than with other graphene-based materials due to the unique chemical structure and self-assembly properties of FG. The method was validated with different types of real complex samples. By using FG as a SELDI probe, we could easily detect trace amount of bisphenol S in paper products and high-fat canned food samples. Furthermore, we have successfully identified and screened as many as 28 quaternary ammonium halides in sewage sludge samples collected from municipal wastewater treatment plants. These results demonstrate that FG probe is a powerful tool for high-throughput analysis of complex samples by MS.

  13. RBC Antibody Screen

    Science.gov (United States)

    ... C Cystic Fibrosis (CF) Gene Mutations Testing Cytomegalovirus (CMV) Tests D-dimer Dengue Fever Testing Des-gamma- ... Index of Screening Recommendations Not Listed? Not Listed? Newborn Screening Screening Tests for Infants Screening Tests for ...

  14. Development of newborn screening connect (NBS connect): a self-reported patient registry and its role in improvement of care for patients with inherited metabolic disorders.

    Science.gov (United States)

    Osara, Yetsa; Coakley, Kathryn; Devarajan, Aishwarya; Singh, Rani H

    2017-07-19

    Newborn Screening Connect (NBS Connect) is a web-based self-reported patient registry and resource for individuals and families affected by disorders included in the newborn screening panel. NBS Connect was launched in 2012 by Emory University after years of planning and grassroots work by professionals, consumers, and industry. Individuals with phenylketonuria (PKU), maple syrup urine disease (MSUD) or tyrosinemia (TYR) have been recruited through distribution of outreach materials, presentations at parent organization meetings and direct recruitment at clinic appointments. Participants complete online profiles generating data on diagnosis, treatment, symptoms, outcomes, barriers to care, and quality of life. Resources such as education materials, information on the latest research and clinical trials, recipes, interactive health tracking systems, and professional support tools are described. In addition, to examine the ability of NBS Connect to generate data that guides hypothesis-driven research, data pertaining to age at diagnosis, bone health, and skin conditions in individuals with PKU were assessed. The objective of this paper is to describe the development of NBS Connect and highlight its data, resources and research contributions. In September 2016, NBS Connect had 442 registered participants: 314 (71%) individuals with PKU, 68 (15%) with MSUD, 20 (5%) with TYR, and 40 (9%) with other disorders on the NBS panel. Age at diagnosis was less than 4 weeks in 285 (89%) of 319 respondents to this question and between 1 month and 14 years in 29 (9%) individuals. Of 216 respondents with PKU, 33 (15%) had a DXA scan in the past year. Of 217 respondents with PKU, 99 (46%) reported at least one skin condition. NBS Connect was built and refined with feedback from all stakeholders, including individuals with inherited metabolic disorders. Based on patient-reported data, future studies can be initiated to test hypotheses such as the relationship between PKU and skin

  15. The Evolution of MALDI-TOF Mass Spectrometry toward Ultra-High-Throughput Screening: 1536-Well Format and Beyond.

    Science.gov (United States)

    Haslam, Carl; Hellicar, John; Dunn, Adrian; Fuetterer, Arne; Hardy, Neil; Marshall, Peter; Paape, Rainer; Pemberton, Michelle; Resemannand, Anja; Leveridge, Melanie

    2016-02-01

    Mass spectrometry (MS) offers a label-free, direct-detection method, in contrast to fluorescent or colorimetric methodologies. Over recent years, solid-phase extraction-based techniques, such as the Agilent RapidFire system, have emerged that are capable of analyzing samples in high-throughput screening (HTS). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) offers an alternative for high-throughput MS detection. However, sample preparation and deposition onto the MALDI target, as well as interference from matrix ions, have been considered limitations for the use of MALDI for screening assays. Here we describe the development and validation of assays for both small-molecule and peptide analytes using MALDI-TOF coupled with nanoliter liquid handling. Using the JMJD2c histone demethylase and acetylcholinesterase as model systems, we have generated robust data in a 1536 format and also increased sample deposition to 6144 samples per target. Using these methods, we demonstrate that this technology can deliver fast sample analysis time with low sample volume, and data comparable to that of current RapidFire assays. © 2015 Society for Laboratory Automation and Screening.

  16. Screening Samples for Arsenic by Inductively Coupled Plasma-Mass Spectrometry for Treaty Samples

    Science.gov (United States)

    2014-02-01

    quality system in accordance with International Organization for Standardization/International Electrotechnical Commission ( ISO / IEC ) 17025 :2005...plasma-mass spectrometry ISO / IEC International Organization for Standardization/International Electrotechnical Commission L lewisite MDL method

  17. Normal Levels of Plasma Free Carnitine and Acylcarnitines in Follow-Up Samples From a Presymptomatic Case of Carnitine Palmitoyl Transferase 1 (CPT1) Deficiency Detected Through Newborn Screening in Denmark

    DEFF Research Database (Denmark)

    Borch, Luise; Lund, Allan; Wibrand, Flemming

    2011-01-01

    of presymptomatic CPT1A deficiency detected through newborn screening in Denmark with diagnostic levels of carnitine and acylcarnitines in the initial dried blood spot. Levels of plasma-free carnitine and acylcarnitines in follow-up samples were normal, but reverted to diagnostic levels when the patient developed...... clinical symptoms at the age of 8 months. At that time, a diagnosis of CPT1A deficiency was confirmed by sequence analysis of the CPT1A gene revealing homozygosity for a novel c.167C>T variation in exon 3. Enzyme activity measurements showed a relatively mild enzyme defect with a decreased residual enzyme...... activity of 17–25%. We conclude that CPT1A gene testing and/or enzyme assay is mandatory to confirm an abnormal newborn screen suggesting CPT1A deficiency to avoid delayed diagnoses....

  18. Newborn Jaundice

    Science.gov (United States)

    ... Legacy Society Make Gifts of Stock Donate Your Car Personal Fundraising Partnership & Support Share Your Story Spread the Word Give While You Shop Contact Us Donate Now Jaundice In Newborns Back ...

  19. Rapid screening for drugs of abuse in biological fluids by ultra high performance liquid chromatography/Orbitrap mass spectrometry.

    Science.gov (United States)

    Jagerdeo, Eshwar; Schaff, Jason E

    2016-08-01

    We present a UPLC(®)-High Resolution Mass Spectrometric method to simultaneously screen for nineteen benzodiazepines, twelve opiates, cocaine and three metabolites, and three "Z-drug" hypnotic sedatives in both blood and urine specimens. Sample processing consists of a high-speed, high-temperature enzymatic hydrolysis for urine samples followed by a rapid supported liquid extraction (SLE). The combination of ultra-high resolution chromatography with high resolution mass spectrometry allows all 38 analytes to be uniquely detected with a ten minute analytical run. Limits of detection for all target analytes are 3ng/mL or better, with only 0.3mL of specimen used for analysis. The combination of low sample volume with fast processing and analysis makes this method a suitable replacement for immunoassay screening of the targeted drug classes, while providing far superior specificity and better limits of detection than can routinely be obtained by immunoassay. Published by Elsevier B.V.

  20. A novel tandem mass spectrometry method for first-line screening of mainly beta-thalassemia from dried blood spots.

    Science.gov (United States)

    Yu, Chaowen; Huang, Shuodan; Wang, Ming; Zhang, Juan; Liu, Hao; Yuan, Zhaojian; Wang, Xingbin; He, Xiaoyan; Wang, Jie; Zou, Lin

    2017-02-10

    Traditional methods for thalassemia screening are time-consuming and easily affected by cell hemolysis or hemoglobin degradation in stored blood samples. Tandem mass spectrometry (MS/MS) proved to be an effective technology for sickle cell disorders (SCD) screening. Here, we developed a novel MS/MS method for β-thalassemia screening from dried blood spots (DBS). Stable isotopic-labeled peptides were used as internal standards for quantification and calculation of the α:β-globin ratios. We used the α:β-globin ratio cutoffs to differentiate between normal individuals and patients with thalassemia. About 781 patients and 300 normal individuals were analyzed. The α:β-globin ratios showed significant difference between normal and β-thalassemia patients (Pthalassemia mutation. In the parallel study, all cases screened for suspected thalassemia from six hundred DBS samples by using this MS/MS method were successfully confirmed by genotyping. The intra-assay and inter-assay CVs of the ratios ranged from 2.4% to 3.9% and 4.7% to 7.1%, and there was no significant sample carryover or matrix effect for this MS/MS method. Combined with SCD screening, this MS/MS method could be used as a first-line screening assay for both structural and expression abnormalities of human hemoglobin. Traditional methods for thalassemia screening were depending on the structural integrity of tetramers and could be affected by hemolysis and degradation of whole blood samples, especially when stored. We used proteospecific peptides produced by the tryptic digestion of each globin to evaluate the production ratio between α- and β-globin chains, which turned out to be quite stable even when stored for more than two months. Though most of the peptides were specific to α-globin or β-globin, we only chose four most informative peptides and its stable isotopic-labeled peptides as internal standards for analysis, which could obtain a high accuracy. Currently, we are the first to address the

  1. High Throughput Screening Method for Systematic Surveillance of Drugs of Abuse by Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry.

    Science.gov (United States)

    DiBattista, Alicia; Rampersaud, Dianne; Lee, Howard; Kim, Marcus; Britz-McKibbin, Philip

    2017-11-07

    New technologies are urgently required for reliable drug screening given a worldwide epidemic of prescription drug abuse and its devastating socioeconomic impacts on public health. Primary screening of drugs of abuse (DoA) currently relies on immunoassays that are prone to bias and are not applicable to detect an alarming array of psychoactive stimulants, tranquilizers, and synthetic opioids. These limitations impact patient safety when monitoring for medication compliance, drug substitution, or misuse/abuse and require follow-up confirmatory testing by more specific yet lower throughput instrumental methods. Herein, we introduce a high throughput platform for nontargeted screening of a broad spectrum of DoA and their metabolites based on multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS). We demonstrate that MSI-CE-MS enables serial injections of 10 samples within a single run (high resolution MS with full-scan data acquisition. Unambiguous drug identification was achieved by four or more independent parameters, including comigration with a deuterated internal standard or in silico prediction of electromigration behavior together with accurate mass, most likely molecular formula, as well as MS/MS as required for confirmation testing. Acceptable precision was demonstrated for over 50 DoA at 3 concentration levels over 4 days (median coefficient of variance = 13%, n = 117) with minimal ion suppression, isobaric interferences, and sample carry-over (screening cutoff levels in human urine while allowing for systematic surveillance, specimen verification, and retrospective testing of designer drugs that elude conventional drug tests.

  2. Metabolic Toxicity Screening Using Electrochemiluminescence Arrays Coupled with Enzyme-DNA Biocolloid Reactors and Liquid Chromatography–Mass Spectrometry

    Science.gov (United States)

    Hvastkovs, Eli G.; Schenkman, John B.; Rusling, James F.

    2012-01-01

    New chemicals or drugs must be guaranteed safe before they can be marketed. Despite widespread use of bioassay panels for toxicity prediction, products that are toxic to a subset of the population often are not identified until clinical trials. This article reviews new array methodologies based on enzyme/DNA films that form and identify DNA-reactive metabolites that are indicators of potentially genotoxic species. This molecularly based methodology is designed in a rapid screening array that utilizes electrochemiluminescence (ECL) to detect metabolite-DNA reactions, as well as biocolloid reactors that provide the DNA adducts and metabolites for liquid chromatography–mass spectrometry (LC-MS) analysis. ECL arrays provide rapid toxicity screening, and the biocolloid reactor LC-MS approach provides a valuable follow-up on structure, identification, and formation rates of DNA adducts for toxicity hits from the ECL array screening. Specific examples using this strategy are discussed. Integration of high-throughput versions of these toxicity-screening methods with existing drug toxicity bioassays should allow for better human toxicity prediction as well as more informed decision making regarding new chemical and drug candidates. PMID:22482786

  3. Screening and identification of steroidal saponins from Anemarrhena asphodeloides employing UPLC tandem triple quadrupole linear ion trap mass spectrometry.

    Science.gov (United States)

    Xia, Yong-Gang; Guo, Xin-Dong; Liang, Jun; Yang, Bing-You; Kuang, Hai-Xue

    2017-09-01

    This study presents a practical and valid strategy for the screening and structural characterization of Anemarrhena asphodeloides Bge steroidal saponins (SSs) using ultra-high performance liquid chromatography coupled with triple quadrupole linear ion trap mass spectrometry. The whole analytical protocols integrate four-step procedures in the positive mode: (1) rational deduction of mass fragmentation pathways of A. asphodeloides SSs; (2) untargeted screening of potential A. asphodeloides SSs by multiple-ion monitoring-information-dependent-acquiring-enhanced product ion (MIM-IDA-EPI) scan through reverse phase liquid chromatography; (3) comprehensive construction of an ammoniated precursor ion database by combining untargeted MIM-IDA-EPI scans and data literature; and (4) structural interpretation of targeted A. asphodeloides SSs using MIM-IDA-EPI and multiple reaction monitoring (MRM)-IDA-EPI with an energy-resolved technique. The protocols were used to analyze SSs in A. asphodeloides; of the 87 detected SSs that were unambiguously characterized or tentatively identified, 19 compounds were the first to be reported from A. asphodeloides and 13 ones were characterized as potential new compounds. Accuracy of the analytical procedure was demonstrated by structural identification of three SSs by NMR spectroscopy. The proposed schemes hold an excellent promise in the structural prediction and interpretation of complex SSs from plant medicines by mass spectrometry. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Multi-capillary column-ion mobility spectrometry: a potential screening system to differentiate virgin olive oils.

    Science.gov (United States)

    Garrido-Delgado, Rocío; Arce, Lourdes; Valcárcel, Miguel

    2012-01-01

    The potential of a headspace device coupled to multi-capillary column-ion mobility spectrometry has been studied as a screening system to differentiate virgin olive oils ("lampante," "virgin," and "extra virgin" olive oil). The last two types are virgin olive oil samples of very similar characteristics, which were very difficult to distinguish with the existing analytical method. The procedure involves the direct introduction of the virgin olive oil sample into a vial, headspace generation, and automatic injection of the volatiles into a gas chromatograph-ion mobility spectrometer. The data obtained after the analysis by duplicate of 98 samples of three different categories of virgin olive oils, were preprocessed and submitted to a detailed chemometric treatment to classify the virgin olive oil samples according to their sensory quality. The same virgin olive oil samples were also analyzed by an expert's panel to establish their category and use these data as reference values to check the potential of this new screening system. This comparison confirms the potential of the results presented here. The model was able to classify 97% of virgin olive oil samples in their corresponding group. Finally, the chemometric method was validated obtaining a percentage of prediction of 87%. These results provide promising perspectives for the use of ion mobility spectrometry to differentiate virgin olive oil samples according to their quality instead of using the classical analytical procedure.

  5. Practical application of in silico fragmentation based residue screening with ion mobility high-resolution mass spectrometry.

    Science.gov (United States)

    Kaufmann, Anton; Butcher, Patrick; Maden, Kathry; Walker, Stephan; Widmer, Mirjam

    2017-07-15

    A screening concept for residues in complex matrices based on liquid chromatography coupled to ion mobility high-resolution mass spectrometry LC/IMS-HRMS is presented. The comprehensive four-dimensional data (chromatographic retention time, drift time, mass-to-charge and ion abundance) obtained in data-independent acquisition (DIA) mode was used for data mining. An in silico fragmenter utilizing a molecular structure database was used for suspect screening, instead of targeted screening with reference substances. The utilized data-independent acquisition mode relies on the MS E concept; where two constantly alternating HRMS scans (low and high fragmentation energy) are acquired. Peak deconvolution and drift time alignment of ions from the low (precursor ion) and high (product ion) energy scan result in relatively clean product ion spectra. A bond dissociation in silico fragmenter (MassFragment) supplied with mol files of compounds of interest was used to explain the observed product ions of each extracted candidate component (chromatographic peak). Two complex matrices (fish and bovine liver extract) were fortified with 98 veterinary drugs. Out of 98 screened compounds 94 could be detected with the in silico based screening approach. The high correlation among drift time and m/z value of equally charged ions was utilized for an orthogonal filtration (ranking). Such an orthogonal ion mobility based filter removes multiply charged ions (e.g. peptides and proteins from the matrix) as well as noise and artefacts. Most significantly, this filtration dramatically reduces false positive findings but hardly increases false negative findings. The proposed screening approach may offer new possibilities for applications where reference compounds are hardly or not at all commercially available. Such areas may be the analysis of metabolites of drugs, pyrrolizidine alkaloids, marine toxins, derivatives of sildenafil or novel designer drugs (new psychoactive substances

  6. Online screening of homogeneous catalyst performance using reaction detection mass spectrometry

    NARCIS (Netherlands)

    Martha, C.T.; Elders, N.; Krabbe, J.G.; Kool, J.; Niessen, W.M.A.; Orru, R.V.A.; Irth, H.

    2008-01-01

    An integrated online screening system was developed to rapidly screen homogeneous catalysts for activity toward a selected synthesis. The continuous-flow system comprises standard HPLC pumps for the delivery of substrates, an HPLC autosampler for the injection of homogeneous catalysts, a

  7. Sleep and Newborns

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Sleep and Newborns KidsHealth / For Parents / Sleep and Newborns ... night it is. How Long Will My Newborn Sleep? Newborns should get 14 to 17 hours of ...

  8. Thrush in newborns

    Science.gov (United States)

    Candidiasis - oral - newborn; Oral thrush - newborn; Fungal infection - mouth - newborn; Candida - oral - newborn ... thrush. You paint this medicine on your baby's mouth and tongue. If you have a yeast infection on your nipples, your provider may recommend an ...

  9. Communication and Your Newborn

    Science.gov (United States)

    ... your doctor, especially if the baby has a temperature of 100.4°F (38°C) or more. ... and Your Newborn Medical Care and Your Newborn Learning, Play, and Your Newborn Your Newborn's Hearing, Vision, ...

  10. Anemia in the Newborn

    Science.gov (United States)

    ... Overview of Horseshoe Kidney Additional Content Medical News Anemia in the Newborn By Andrew W. Walter, MS ... for the Professional Version Blood Problems in Newborns Anemia in the Newborn Hemolytic Disease of the Newborn ...

  11. Screening of acetylcholinesterase inhibitors in snake venom by electrospray mass spectrometry

    NARCIS (Netherlands)

    Liesener, A.; Perchuc, Anna-Maria; Schöni, Reto; Schebb, Nils Helge; Wilmer, Marianne; Karst, U.

    2007-01-01

    An electrospray ionization/mass spectrometry (ESI/MS)-based assay for the determination of acetylcholinesterase (AChE)-inhibiting activity in snake venom was developed. It allows the direct monitoring of the natural AChE substrate acetylcholine (AC) and the respective product choline. The assay

  12. High-throughput screening and quantitation of guanidino and ureido compounds using liquid chromatography-drift tube ion mobility spectrometry-mass spectrometry.

    Science.gov (United States)

    Fan, Ruo-Jing; Zhang, Fang; Chen, Xiu-Ping; Qi, Wan-Shu; Guan, Qing; Sun, Tuan-Qi; Guo, Yin-Long

    2017-04-08

    The present work focused on the high-throughput screening and quantitation of guanidino compounds (GCs) and ureido compounds (UCs) in human thyroid tissues. The strategy employed benzylic rearrangement stable isotope labeling (BRSIL) for the sample preparation and then detection using liquid chromatography-drift tube ion mobility spectrometry-quadrupole time of flight mass spectrometry (LC-DTIMS-QTOF MS). A short reversed-phase LC realized an on-line desalting and a measurement cycle of 5.0 min. DTIMS separation enhanced the better specificity and selectivity for the benzil labeled GCs and UCs. The elevated mass resolution of QTOF MS enabled measure of the characteristic ions at accurate mass in MS and tandem MS spectra. Collision cross section (CCS) from DTIMS and accurate mass from QTOF MS were used as two qualifiers for the profiling and identification of GCs and UCs. In addition, an integral abundance arising from 3-D ion features (retention time, drift time, m/z) was applied to quantify the GCs and UCs in human thyroid tissues. The quantitative validation indicated good linearity (coefficient values ≥ 0.9981), good precision (1.0%-12.3% for intra-day and 0.9%-7.8% for inter-day) and good accuracy (91%-109%). The results demonstrated that the developed BRSIL coupled with LC-DTIMS-QTOF MS can be a powerful analysis platform to investigate GCs and UCs in human thyroid tissues. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Imparting carrier status results detected by universal newborn screening for sickle cell and cystic fibrosis in England: a qualitative study of current practice and policy challenges

    Directory of Open Access Journals (Sweden)

    Ulph Fiona

    2007-12-01

    Full Text Available Abstract Background Universal newborn screening for early detection of children affected by sickle cell disorders and cystic fibrosis is currently being implemented across England. Parents of infants identified as carriers of these disorders must also be informed of their baby's result. However there is a lack of evidence for most effective practice internationally when doing so. This study describes current or proposed models for imparting this information in practice and explores associated challenges for policy. Methods Thematic analysis of semi-structured interviews with Child Health Coordinators from all English Health Regions. Results Diverse methods for imparting carrier results, both within and between regions, and within and between conditions, were being implemented or planned. Models ranged from result by letter to in-person communication during a home visit. Non-specialists were considered the best placed professionals to give results and a similar approach for both conditions was emphasised. While national guidance has influenced choice of models, other factors contributed such as existing service structures and lack of funding. Challenges included uncertainty about guidance specifying face to face notification; how best to balance allaying parental anxiety by using familiar non-specialist health professionals with concerns about practitioner competence; and extent of information parents should be given. Inadequate consideration of resource and service workload was seen as the main policy obstacle. Clarification of existing guidance; more specific protocols to ensure consistent countrywide practice; integration of the two programmes; and 'normalising' carrier status were suggested as improvements. Conclusion Differing models for communicating carrier results raise concerns about equity and clinical governance. However, this variation provides opportunity for evaluation. Timely and more detailed guidance on protocols with

  14. Maternal IgG Anti-A and Anti-B Titer Levels Screening in Predicting ABO Hemolytic Disease of the Newborn: A Meta-Analysis.

    Science.gov (United States)

    Li, Ping; Pang, Li-Hong; Liang, Hai-Feng; Chen, Hong-Yan; Fan, Xiao-Jing

    2015-01-01

    Maternal IgG anti-A/B titers have been considered as a susceptible factor to the risk of ABO hemolytic disease in newborn (ABO-HDN). However, the results remain controversial. This meta-analysis aimed to estimate the association between maternal IgG anti-A/B titers and the risk of ABO-HDN. Trials on the relationship between maternal IgG anti-A/B titers and the risk of ABO-HDN were collected by searching Embase, PubMed, and Cochrane Central Register of Controlled Trials (CENTRAL) electronic databases. The inclusion criteria were maternal IgG anti-A/B titers screening and the evaluation of clinical outcomes in relation to ABO-HDN. Stata 12.0 was used to analyze the data. A total of 23 trials were eligible for inclusion, of which four trials with 5,246 participants were suitable for this meta-analysis. Meta-analysis results suggested that maternal IgG anti-A/B titers were significantly associated with the risk of ABO-HDN [OR = 2.86, 95% CI = 2.50-3.28; OR = 4.67, 95% CI = 3.92-5.55; OR = 1.61, 95% CI = 1.36-1.91 in titers (128 to 256) vs. titers (64 or lower), titers (512 or higher) vs. titers (64 or lower), and titers (512 or higher) vs. titers (128-256), respectively]. Our meta-analysis suggests that maternal IgG anti-A/B titers are significantly associated with the risk of ABO-HDN. They contribute to the prediction of risk of ABO-HDN, in addition to the need for invasive treatment for antibody titers ≥512.

  15. [Breastfeeding and the anthropometric profile of children with sickle cell anemia receiving follow-up in a newborn screening reference service].

    Science.gov (United States)

    Nogueira, Zeni Drubi; Boa-Sorte, Ney; Leite, Maria Efigênia de Queiroz; Kiya, Márcia Miyuki; Amorim, Tatiana; Fonseca, Silvana Fahel da

    2015-01-01

    To study breastfeeding history (BF) and the anthropometric status of children with Sickle Cell Disease (SCD). A cross-sectional study of 357 children with SS and SC hemoglobinopathies aged between 2 and 6 years old receiving regular follow-up at a Newborn Screening Reference Service (NSRS) between November 2007 and January 2009. The outcome was anthropometric status and the exposures were: BF pattern, type of hemoglobinopathy and child's age and sex. The average (SD) age was 3.7 (1.1) years, 52.9% were boys and 53.5% had SS hemoglobinopathy. The prevalence of exclusive breastfeeding (EBR) up to six months of age was 31.5%, the median EBR times (p25-p75) was 90.0 (24.0-180.0) days and the median weaning ages (p25-p75) was 360.0 (90.0-20.0) days respectively. Normal W/H children experienced EBR for an average duration almost four times longer than malnourished children (p=0.01), and were weaned later (p<0.05). Height deficit was found in 5.0% of children, while all the children with severe short stature had SS hemoglobinopathy and were over 4 years of age. EBR time and weaning age were greater than found in the literature, which is a possible effect of the multidisciplinary follow-up. Duration of EBR and later weaning were associated with improved anthropometric indicators. Copyright © 2014 Associação de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  16. Diagnostic applications of newborn screening for α-thalassaemias, haemoglobins E and H disorders using isoelectric focusing on dry blood spots.

    Science.gov (United States)

    Jindatanmanusan, Punyanuch; Riolueang, Suchada; Glomglao, Waraporn; Sukontharangsri, Yaowapa; Chamnanvanakij, Sangkae; Torcharus, Kitti; Viprakasit, Vip

    2014-03-01

    Neonatal screening for haemoglobin (Hb) disorders is a standard of care in several developed countries with the main objective to detect Hb S. Such practice has not been established in Thailand where α-thalassaemia and haemoglobin E (Hb E) are highly prevalent. Early identification of thalassaemias could be helpful and strengthen the programme for prevention and control for severe thalassaemias. Data from isoelectric focusing (IEF) and Isoscan® for detecting types and amount (%) of each haemoglobin in 350 newborn's dried blood spots were analysed and compared with the comprehensive genotype analysis by DNA studies as a gold standard. Based on genetic profiles, there were 10 different categories: (1) normal (n = 227), (2) α(+)-thalassaemia trait (n = 14), (3) α(0)-thalassaemia trait (n = 13), (4) β(0)-thalassaemia trait (n = 7), (5) Hb E trait (n = 72), (6) Hb E trait with α(0)-thalassaemia or homozygous α(+)-thalassaemia (n = 5), (7) Hb E trait with α(+)-thalassaemia trait (n = 5), (8) homozygous Hb E (n = 3), (9) homozygous Hb E with α(0)-thalassaemia trait (n = 1) and (10) Hb H disease (n = 3). The presence of Hb Bart's and Hb E were used to identify cases with α-thalassaemia and Hb E, respectively. We set 0.25% of Hb Bart's and 1.5% of Hb E as a cut-off level to detect α(+)-thalassaemia trait (sensitivity 92.86% and specificity 74.0%) and Hb E trait with 100% of both sensitivity and specificity for IEF diagnosis. Although molecular diagnosis seems to be better for definitive diagnosis of thalassaemia syndromes at birth, however, using our reference range described herein, IEF can be applied in a resource-limiting setting with acceptable reliability.

  17. High-throughput screening and quantitation of guanidino and ureido compounds using liquid chromatography-drift tube ion mobility spectrometry-mass spectrometry

    International Nuclear Information System (INIS)

    Fan, Ruo-Jing; Zhang, Fang; Chen, Xiu-Ping; Qi, Wan-Shu; Guan, Qing; Sun, Tuan-Qi; Guo, Yin-Long

    2017-01-01

    The present work focused on the high-throughput screening and quantitation of guanidino compounds (GCs) and ureido compounds (UCs) in human thyroid tissues. The strategy employed benzylic rearrangement stable isotope labeling (BRSIL) for the sample preparation and then detection using liquid chromatography-drift tube ion mobility spectrometry-quadrupole time of flight mass spectrometry (LC-DTIMS-QTOF MS). A short reversed-phase LC realized an on-line desalting and a measurement cycle of 5.0 min. DTIMS separation enhanced the better specificity and selectivity for the benzil labeled GCs and UCs. The elevated mass resolution of QTOF MS enabled measure of the characteristic ions at accurate mass in MS and tandem MS spectra. Collision cross section (CCS) from DTIMS and accurate mass from QTOF MS were used as two qualifiers for the profiling and identification of GCs and UCs. In addition, an integral abundance arising from 3-D ion features (retention time, drift time, m/z) was applied to quantify the GCs and UCs in human thyroid tissues. The quantitative validation indicated good linearity (coefficient values ≥ 0.9981), good precision (1.0%–12.3% for intra-day and 0.9%–7.8% for inter-day) and good accuracy (91%–109%). The results demonstrated that the developed BRSIL coupled with LC-DTIMS-QTOF MS can be a powerful analysis platform to investigate GCs and UCs in human thyroid tissues. - Highlights: • The separation power of DTIMS-MS enhanced peak capacity, spectral clarity, and specificity of benzil labeled GCs and UCs. • Short-column LC for on-line desalting increased the throughput with a measurement cycle of 5.0 min. • CCS and accurate mass as a pair of qualifiers were used for the profiling and identification of GCs and UCs. • An integral abundance arising from 3-D ion features (RT, DT, m/z) was used as a novel quantifier for quantitation. • The developed method was applied to screen and quantify the GCs and UCs in human thyroid tissues.

  18. High-throughput screening and quantitation of guanidino and ureido compounds using liquid chromatography-drift tube ion mobility spectrometry-mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Fan, Ruo-Jing [National Center for Organic Mass Spectrometry in Shanghai, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032 (China); Zhang, Fang, E-mail: fzhang@sioc.ac.cn [National Center for Organic Mass Spectrometry in Shanghai, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032 (China); Chen, Xiu-Ping; Qi, Wan-Shu [National Center for Organic Mass Spectrometry in Shanghai, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032 (China); Guan, Qing [Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032 (China); Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Sun, Tuan-Qi, E-mail: tuanqisun@163.com [Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032 (China); Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Guo, Yin-Long, E-mail: ylguo@sioc.ac.cn [National Center for Organic Mass Spectrometry in Shanghai, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032 (China)

    2017-04-08

    The present work focused on the high-throughput screening and quantitation of guanidino compounds (GCs) and ureido compounds (UCs) in human thyroid tissues. The strategy employed benzylic rearrangement stable isotope labeling (BRSIL) for the sample preparation and then detection using liquid chromatography-drift tube ion mobility spectrometry-quadrupole time of flight mass spectrometry (LC-DTIMS-QTOF MS). A short reversed-phase LC realized an on-line desalting and a measurement cycle of 5.0 min. DTIMS separation enhanced the better specificity and selectivity for the benzil labeled GCs and UCs. The elevated mass resolution of QTOF MS enabled measure of the characteristic ions at accurate mass in MS and tandem MS spectra. Collision cross section (CCS) from DTIMS and accurate mass from QTOF MS were used as two qualifiers for the profiling and identification of GCs and UCs. In addition, an integral abundance arising from 3-D ion features (retention time, drift time, m/z) was applied to quantify the GCs and UCs in human thyroid tissues. The quantitative validation indicated good linearity (coefficient values ≥ 0.9981), good precision (1.0%–12.3% for intra-day and 0.9%–7.8% for inter-day) and good accuracy (91%–109%). The results demonstrated that the developed BRSIL coupled with LC-DTIMS-QTOF MS can be a powerful analysis platform to investigate GCs and UCs in human thyroid tissues. - Highlights: • The separation power of DTIMS-MS enhanced peak capacity, spectral clarity, and specificity of benzil labeled GCs and UCs. • Short-column LC for on-line desalting increased the throughput with a measurement cycle of 5.0 min. • CCS and accurate mass as a pair of qualifiers were used for the profiling and identification of GCs and UCs. • An integral abundance arising from 3-D ion features (RT, DT, m/z) was used as a novel quantifier for quantitation. • The developed method was applied to screen and quantify the GCs and UCs in human thyroid tissues.

  19. High-throughput bioaffinity mass spectrometry for screening and identification of designer anabolic steroids in dietary supplements.

    Science.gov (United States)

    Aqai, Payam; Cevik, Ebru; Gerssen, Arjen; Haasnoot, Willem; Nielen, Michel W F

    2013-03-19

    A generic high-throughput bioaffinity liquid chromatography-mass spectrometry (BioMS) approach was developed and applied for the screening and identification of known and unknown recombinant human sex hormone-binding globulin (rhSHBG)-binding designer steroids in dietary supplements. For screening, a semi-automated competitive inhibition binding assay was combined with fast ultrahigh-performance-LC-electrospray ionization-triple-quadrupole-MS (UPLC-QqQ-MS). 17β-Testosterone-D3 was used as the stable isotope label of which the binding to rhSHBG-coated paramagnetic microbeads was inhibited by any other binding (designer) steroid. The assay was performed in a 96-well plate and combined with the fast LC-MS, 96 measurements could be performed within 4 h. The concentration-dependent inhibition of the label by steroids in buffer and dietary supplements was demonstrated. Following an adjusted bioaffinity isolation procedure, suspect extracts were injected into a chip-UPLC(NanoTile)-Q-time-of-flight-MS system for full-scan accurate mass identification. Next to known steroids, 1-testosterone was identified in three of the supplements studied and the designer steroid tetrahydrogestrinone was identified in a spiked supplement. The generic steroid-binding assay can be used for high-throughput screening of androgens, estrogens, and gestagens in dietary supplements to fight doping. When combined with chip-UPLC-MS, it is a powerful tool for early warning of unknown emerging rhSHBG bioactive designer steroids in dietary supplements.

  20. Nontargeted Screening Method for Illegal Additives Based on Ultrahigh-Performance Liquid Chromatography-High-Resolution Mass Spectrometry.

    Science.gov (United States)

    Fu, Yanqing; Zhou, Zhihui; Kong, Hongwei; Lu, Xin; Zhao, Xinjie; Chen, Yihui; Chen, Jia; Wu, Zeming; Xu, Zhiliang; Zhao, Chunxia; Xu, Guowang

    2016-09-06

    Identification of illegal additives in complex matrixes is important in the food safety field. In this study a nontargeted screening strategy was developed to find illegal additives based on ultrahigh-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). First, an analytical method for possible illegal additives in complex matrixes was established including fast sample pretreatment, accurate UHPLC separation, and HRMS detection. Second, efficient data processing and differential analysis workflow were suggested and applied to find potential risk compounds. Third, structure elucidation of risk compounds was performed by (1) searching online databases [Metlin and the Human Metabolome Database (HMDB)] and an in-house database which was established at the above-defined conditions of UHPLC-HRMS analysis and contains information on retention time, mass spectra (MS), and tandem mass spectra (MS/MS) of 475 illegal additives, (2) analyzing fragment ions, and (3) referring to fragmentation rules. Fish was taken as an example to show the usefulness of the nontargeted screening strategy, and six additives were found in suspected fish samples. Quantitative analysis was further carried out to determine the contents of these compounds. The satisfactory application of this strategy in fish samples means that it can also be used in the screening of illegal additives in other kinds of food samples.

  1. Prostate cell membrane chromatography-liquid chromatography-mass spectrometry for screening of active constituents from Uncaria rhynchophylla.

    Science.gov (United States)

    He, Jianyu; Han, Shengli; Yang, Fangfang; Zhou, Nan; Wang, Sicen

    2013-01-01

    Uncaria rhynchophylla is a traditional Chinese medicinal herb used to treat hypertension and convulsive disorders such as epilepsy. Rat prostate cell membrane chromatography combined with liquid chromatography-mass spectrometry (LC-MS) was used to identify active constituents from U. rhynchophylla extracts. Four compounds (corynoxeine, isorhynchophylline, isocorynoxeine and rhynchophylline) were discovered. Competitive binding assay results indicated that the four compounds were in direct competition at a single common binding site and interacted with α1A adrenergic receptors (α1A-AR) in a manner similar to tamsulosin. Affinity constant values of the four compounds binding with α1A-AR were also measured using rat prostate cell membrane chromatography (CMC). Finally, their pharmacodynamic effects were tested on rat caudal arteries. This CMC combined LC-MS system offers a means of drug discovery by screening natural medicinal herbs for new pharmacologically active molecules targeting specific receptors.

  2. Screening for exogenous androgen anabolic steroids in human hair by liquid chromatography/orbitrap-high resolution mass spectrometry

    International Nuclear Information System (INIS)

    Strano-Rossi, Sabina; Castrignanò, Erika; Anzillotti, Luca; Odoardi, Sara; De-Giorgio, Fabio; Bermejo, Ana; Pascali, Vincenzo L.

    2013-01-01

    Graphical abstract: -- Highlights: •LC–HRMS screening method for the detection of a variety of anabolics in hair. •Detection of unmetabolized anabolic steroids and their esters in hair matrix by simple keratin pretreatment. •Identification of target compounds by retention time, accurate mass and isotopic cluster. •Quantitative determination of detected compounds. •Possibility to a retrospective re-analysis of the acquired datafile in case a further analyte is to be screened. -- Abstract: A method for the screening of various anabolic steroids and their esters in human hair, based on liquid-chromatography–high resolution mass spectrometry using an Exactive benchtop Orbitrap mass spectrometer, has been set up and validated. This method involved methanolic incubation of 30 mg of hair and analysis of the relevant extract in HPLC using a C18 column. The mass detector, with nominal resolving power of 100,000, operated in full scan mode in APCI under positive ionization mode. Analytes were identified by exact mass, correspondence of isotopic cluster and retention times. The limits of detection obtained varied from 10 to 50 pg mg −1 , and limits of quantitation were 0.5 ng mg −1 for all compounds. The method was linear for all analytes in the ranges from the LOQ to 6 ng mg −1 , giving correlation coefficients >0.99 for all analytes. Also accuracy (intended as %E) and repeatability (%CV) were always lower than 15%. Specificity was assessed by analysing ten blank samples and fifteen samples from polidrug abusers. This method was applied to a real-life case, resulting in the identification of testosterone undecanoate in the hair of a suspect. The analyte identity was confirmed by the analysis of its in-source fragmentation and comparison to a certified standard. Thanks to the scan acquisition, this method also enables retrospective re-analysis of the acquired datafile in case a further analyte needs to be screened

  3. Screening for exogenous androgen anabolic steroids in human hair by liquid chromatography/orbitrap-high resolution mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Strano-Rossi, Sabina, E-mail: sabina.stranorossi@rm.unicatt.it [Institute of Legal Medicine, Catholic University of Sacred Heart, L.go F. Vito, 1, 00168 Rome (Italy); Castrignanò, Erika; Anzillotti, Luca; Odoardi, Sara; De-Giorgio, Fabio [Institute of Legal Medicine, Catholic University of Sacred Heart, L.go F. Vito, 1, 00168 Rome (Italy); Bermejo, Ana [Institute of Legal Medicine, University of Santiago de Compostela, Av S. Francisco s/n, Santiago de Compostela (Spain); Pascali, Vincenzo L. [Institute of Legal Medicine, Catholic University of Sacred Heart, L.go F. Vito, 1, 00168 Rome (Italy)

    2013-09-02

    Graphical abstract: -- Highlights: •LC–HRMS screening method for the detection of a variety of anabolics in hair. •Detection of unmetabolized anabolic steroids and their esters in hair matrix by simple keratin pretreatment. •Identification of target compounds by retention time, accurate mass and isotopic cluster. •Quantitative determination of detected compounds. •Possibility to a retrospective re-analysis of the acquired datafile in case a further analyte is to be screened. -- Abstract: A method for the screening of various anabolic steroids and their esters in human hair, based on liquid-chromatography–high resolution mass spectrometry using an Exactive benchtop Orbitrap mass spectrometer, has been set up and validated. This method involved methanolic incubation of 30 mg of hair and analysis of the relevant extract in HPLC using a C18 column. The mass detector, with nominal resolving power of 100,000, operated in full scan mode in APCI under positive ionization mode. Analytes were identified by exact mass, correspondence of isotopic cluster and retention times. The limits of detection obtained varied from 10 to 50 pg mg{sup −1}, and limits of quantitation were 0.5 ng mg{sup −1} for all compounds. The method was linear for all analytes in the ranges from the LOQ to 6 ng mg{sup −1}, giving correlation coefficients >0.99 for all analytes. Also accuracy (intended as %E) and repeatability (%CV) were always lower than 15%. Specificity was assessed by analysing ten blank samples and fifteen samples from polidrug abusers. This method was applied to a real-life case, resulting in the identification of testosterone undecanoate in the hair of a suspect. The analyte identity was confirmed by the analysis of its in-source fragmentation and comparison to a certified standard. Thanks to the scan acquisition, this method also enables retrospective re-analysis of the acquired datafile in case a further analyte needs to be screened.

  4. A SIMPLE AND RAPID MATRIX-ASSISTED LASER DESORPTION/IONIZATION TIME OF FLIGHT MASS SPECTROMETRY METHOD TO SCREEN FISH PLASMA SAMPLES FOR ESTROGEN-RESPONSIVE BIOMARKERS

    Science.gov (United States)

    In this study, we describe and evaluate the performance of a simple and rapid mass spectral method for screening fish plasma for estrogen-responsive biomarkers using matrix assisted laster desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) couopled with a short...

  5. Screening and confirmation criteria for hormone residue analysis using liquid chromatography accurate mass time-of-flight, Fourier transform ion cyclotron resonance and orbitrap mass spectrometry techniques

    NARCIS (Netherlands)

    Nielen, M.W.F.; Engelen, M.C. van; Zuiderent, R.; Ramaker, R.

    2007-01-01

    An emerging trend is recognised in hormone and veterinary drug residue analysis from liquid chromatography tandem mass spectrometry (LC/MS/MS) based screening and confirmation towards accurate mass alternatives such as LC coupled with time-of-flight (TOF), Fourier transform ion cyclotron resonance

  6. Influence of natural organic matter on the screening of pharmaceuticals in water by using liquid chromatography with full scan mass spectrometry

    NARCIS (Netherlands)

    Herrera Rivera, Z.E.; Oosterink, J.E.; Rietveld, L.; Schoutsen, F.; Stolker, A.A.M.

    2011-01-01

    The influence of natural organic matter on the screening of pharmaceuticals in water was determined by using high resolution liquid chromatography (HRLC) combined with full scan mass spectrometry (MS) techniques like time of flight (ToF) or Orbitrap MS. Water samples containing different amount of

  7. Gas chromatography/mass spectrometry analysis of very long chain fatty acids, docosahexaenoic acid, phytanic acid and plasmalogen for the screening of peroxisomal disorders

    NARCIS (Netherlands)

    Takemoto, Yasuhiko; Suzuki, Yasuyuki; Horibe, Ryoko; Shimozawa, Nobuyuki; Wanders, Ronald J. A.; Kondo, Naomi

    2003-01-01

    Very long chain fatty acids (VLCFAs) and docosahexaenoic acid (DHA), phytanic acid, and plasmalogens are usually measured individually. A novel method for the screening of peroxisomal disorders, using gas chromatography/mass spectrometry (GC/MS), was developed. Saturated and unsaturated fatty acids,

  8. Purpose of Newborn Hearing Screening

    Science.gov (United States)

    ... Our Sponsors Ages & Stages Ages & Stages Ages and Stages Prenatal Baby (0-12 mos.) Toddler 1-3yrs. Preschool 3-5yrs Grade School 5-12yrs. Teen 12- ... the Word Shop AAP Find a Pediatrician Ages & Stages Prenatal Baby Bathing ... Teen Young Adult Healthy Children > Ages & Stages > ...

  9. Screening for exogenous androgen anabolic steroids in human hair by liquid chromatography/orbitrap-high resolution mass spectrometry.

    Science.gov (United States)

    Strano-Rossi, Sabina; Castrignanò, Erika; Anzillotti, Luca; Odoardi, Sara; De-Giorgio, Fabio; Bermejo, Ana; Pascali, Vincenzo L

    2013-09-02

    A method for the screening of various anabolic steroids and their esters in human hair, based on liquid-chromatography-high resolution mass spectrometry using an Exactive benchtop Orbitrap mass spectrometer, has been set up and validated. This method involved methanolic incubation of 30 mg of hair and analysis of the relevant extract in HPLC using a C18 column. The mass detector, with nominal resolving power of 100,000, operated in full scan mode in APCI under positive ionization mode. Analytes were identified by exact mass, correspondence of isotopic cluster and retention times. The limits of detection obtained varied from 10 to 50 pg mg(-1), and limits of quantitation were 0.5 ng mg(-1) for all compounds. The method was linear for all analytes in the ranges from the LOQ to 6 ng mg(-1), giving correlation coefficients >0.99 for all analytes. Also accuracy (intended as %E) and repeatability (%CV) were always lower than 15%. Specificity was assessed by analysing ten blank samples and fifteen samples from polidrug abusers. This method was applied to a real-life case, resulting in the identification of testosterone undecanoate in the hair of a suspect. The analyte identity was confirmed by the analysis of its in-source fragmentation and comparison to a certified standard. Thanks to the scan acquisition, this method also enables retrospective re-analysis of the acquired datafile in case a further analyte needs to be screened. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. High-throughput untargeted screening of veterinary drug residues and metabolites in tilapia using high resolution orbitrap mass spectrometry.

    Science.gov (United States)

    Jia, Wei; Chu, Xiaogang; Chang, James; Wang, Perry G; Chen, Ying; Zhang, Feng

    2017-03-08

    An analytical method was developed and validated for simultaneous analysis of one hundred and thirty-seven veterinary drug residues and metabolites from sixteen different classes in tilapia utilizing an improved fully non-targeted way of data acquisition with fragmentation. The automated on-line extraction procedure was achieved in a simple disposable pipet extraction. Ultrahigh-performance liquid chromatography and electrospray ionization quadrupole Orbitrap high-resolution mass spectrometry (UHPLC Q-Orbitrap) was used for the separation and detection of all the analytes. The methodology was validated by taking into consideration the guidelines specified in European SANCO/12571/2013 Guideline 2013 and Commission Decision 2002/657/EC. The extraction recoveries ranged from 81% to 111%. The limits of decision ranged from 0.01 to 2.73 μg kg -1 and the detection capabilities ranged from 0.01 to 4.73 μg kg -1 . The one hundred and thirty-seven compounds behave dynamic 0.1-500 μg kg -1 , with correlation coefficient >0.99. The fully non-targeted data acquisition way improves both sensitivity and selectivity for the fragments, which is beneficial for screening performance and identification capability. This validated method has been successfully applied on screening of veterinary drug residues and metabolites in muscle of tilapia, an important and intensively produced fish in aquaculture. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Rapid evaporative ionisation mass spectrometry and chemometrics for high-throughput screening of growth promoters in meat producing animals.

    Science.gov (United States)

    Guitton, Yann; Dervilly-Pinel, Gaud; Jandova, Renata; Stead, Sara; Takats, Zoltan; Le Bizec, Bruno

    2018-01-17

    In a proof of concept perspective, Rapid Evaporative Ionisation Mass Spectrometry (REIMS) was explored for the direct analysis of meat samples from β-agonist treated livestock. In this context, the combination of REIMS with untargeted metabolomics was investigated to identify carcasses from treated animals on the basis of a modification of indirect metabolites profile. The REIMS analysis generated specific lipid profiles which enabled the differentiation of meat samples collected from pigs treated with ractopamine via their feeding regime. Furthermore, the strategy was found successful when tested on different muscle types (loin, shoulder and thigh), which further expands its applicability. Classification performances were greater than 95% accurate which fully answers requirements of a screening strategy. This research indicates that REIMS implemented in an untargeted-metabolomics workflow can be considered as a high-throughput and accurate strategy for real-time meat classification in relation to ractopamine (and wider β-agonists) treatment in pig production. This approach may subsequently be implemented as a rapid screening test, at the slaughterhouse or at border inspection points, to detect such practice.

  12. Desorption electrospray ionisation mass spectrometry: A rapid screening tool for veterinary drug preparations and forensic samples from hormone crime investigations

    International Nuclear Information System (INIS)

    Nielen, M.W.F.; Hooijerink, H.; Claassen, F.C.; Engelen, M.C. van; Beek, T.A. van

    2009-01-01

    Hormone and veterinary drug screening and forensics can benefit from the recent developments in desorption electrospray ionisation (DESI) mass spectrometry (MS). In this work the feasibility of DESI application has been studied. Using a linear ion trap or quadrupole time-of-flight (TOF) MS instrument both full-scan and data-dependent collision-induced dissociation MS n spectra were acquired in seconds without sample preparation. Preliminary data are presented for the rapid screening of (pro)hormone supplement samples, an illegal steroid cocktail and forensic samples from veterinary drug investigations. The potential of this DESI approach is clearly demonstrated since compounds observed could be independently confirmed by liquid chromatography/TOFMS with accurate mass measurement, and/or proton nuclear magnetic resonance spectroscopy. Specific concerns related to false-positive and false-negative findings due to limitations in quantification and memory-effects are briefly discussed. It is envisaged that DESI will achieve a prominent role in hormone and veterinary drug analysis in the near future

  13. Toxic Cyanobacteria in Svalbard: Chemical Diversity of Microcystins Detected Using a Liquid Chromatography Mass Spectrometry Precursor Ion Screening Method

    Directory of Open Access Journals (Sweden)

    Julia Kleinteich

    2018-04-01

    Full Text Available Cyanobacteria synthesize a large variety of secondary metabolites including toxins. Microcystins (MCs with hepato- and neurotoxic potential are well studied in bloom-forming planktonic species of temperate and tropical regions. Cyanobacterial biofilms thriving in the polar regions have recently emerged as a rich source for cyanobacterial secondary metabolites including previously undescribed congeners of microcystin. However, detection and detailed identification of these compounds is difficult due to unusual sample matrices and structural congeners produced. We here report a time-efficient liquid chromatography-mass spectrometry (LC-MS precursor ion screening method that facilitates microcystin detection and identification. We applied this method to detect six different MC congeners in 8 out of 26 microbial mat samples of the Svalbard Archipelago in the Arctic. The congeners, of which [Asp3, ADMAdda5, Dhb7] MC-LR was most abundant, were similar to those reported in other polar habitats. Microcystins were also determined using an Adda-specific enzyme-linked immunosorbent assay (Adda-ELISA. Nostoc sp. was identified as a putative toxin producer using molecular methods that targeted 16S rRNA genes and genes involved in microcystin production. The mcy genes detected showed highest similarities to other Arctic or Antarctic sequences. The LC-MS precursor ion screening method could be useful for microcystin detection in unusual matrices such as benthic biofilms or lichen.

  14. Desorption electrospray ionisation mass spectrometry: A rapid screening tool for veterinary drug preparations and forensic samples from hormone crime investigations

    Energy Technology Data Exchange (ETDEWEB)

    Nielen, M.W.F. [RIKILT Institute of Food Safety, P.O. Box 230, 6700 AE Wageningen (Netherlands); Wageningen University, Laboratory of Organic Chemistry, Dreijenplein 8, 6703 HB Wageningen (Netherlands)], E-mail: michel.nielen@wur.nl; Hooijerink, H. [RIKILT Institute of Food Safety, P.O. Box 230, 6700 AE Wageningen (Netherlands); Claassen, F.C. [Wageningen University, Laboratory of Organic Chemistry, Dreijenplein 8, 6703 HB Wageningen (Netherlands); Engelen, M.C. van [RIKILT Institute of Food Safety, P.O. Box 230, 6700 AE Wageningen (Netherlands); Beek, T.A. van [Wageningen University, Laboratory of Organic Chemistry, Dreijenplein 8, 6703 HB Wageningen (Netherlands)

    2009-04-01

    Hormone and veterinary drug screening and forensics can benefit from the recent developments in desorption electrospray ionisation (DESI) mass spectrometry (MS). In this work the feasibility of DESI application has been studied. Using a linear ion trap or quadrupole time-of-flight (TOF) MS instrument both full-scan and data-dependent collision-induced dissociation MS{sup n} spectra were acquired in seconds without sample preparation. Preliminary data are presented for the rapid screening of (pro)hormone supplement samples, an illegal steroid cocktail and forensic samples from veterinary drug investigations. The potential of this DESI approach is clearly demonstrated since compounds observed could be independently confirmed by liquid chromatography/TOFMS with accurate mass measurement, and/or proton nuclear magnetic resonance spectroscopy. Specific concerns related to false-positive and false-negative findings due to limitations in quantification and memory-effects are briefly discussed. It is envisaged that DESI will achieve a prominent role in hormone and veterinary drug analysis in the near future.

  15. Rapid screening of basic colorants in processed vegetables through mass spectrometry using an interchangeable thermal desorption electrospray ionization source.

    Science.gov (United States)

    Chao, Yu-Ying; Chen, Yen-Ling; Lin, Hong-Yi; Huang, Yeou-Lih

    2018-06-20

    Thermal desorption electrospray ionization/mass spectrometry (TD-ESI-MS) employing a quickly interchangeable ionization source is a relatively new ambient ionization mass spectrometric technique that has had, to date, only a limited number of applications related to food safety control. With reallocation of resources, this direct-analysis technique has had wider use in food analysis when operated in dual-working mode (pretreatment-free qualitative screening and conventional quantitative confirmation) after switching to an ambient ionization source from a traditional atmospheric pressure ionization source. Herein, we describe the benefits and challenges associated with the use of a TD-ESI source to detect adulterants in processed vegetables (PVs), as a proof-of-concept for the detection of basic colorants. While TD-ESI can offer direct qualitative screening analyses for PVs with detection capabilities lower than those provided with liquid chromatography/UV detection within 30 s, the use of TD-ESI for semi-quantification is applicable only for homogeneous food matrices. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. [Multi-residue method for screening of pesticides in crops by liquid chromatography with tandem mass spectrometry].

    Science.gov (United States)

    Tanizawa, Haruna; Shima, Mikie; Ikehara, Chieko; Kobata, Masakazu; Sato, Motoaki

    2005-10-01

    A simple and rapid method was developed for the screening of 82 pesticides/metabolites in a wide variety of crops, using solid-phase extraction and liquid chromatography with tandem mass spectrometry (LC/MS/MS). After extraction with methanol, the filtered extracts were made up to 100 mL and a 2 mL aliquot was subjected to solid-phase extraction. Co-extractives were removed with a C18 mini-column, while pesticides were retained on 3 kinds of mini-columns (HLB, SAX, activated carbon), and then eluted with acetonitrile. Analysis was performed by LC/MS/MS, and MS acquisition parameters were established in positive and negative ESI modes. The utility of the method was demonstrated by the analysis of 6 crops (carrot, cabbage, onion, spinach, lemon, brown rice) and one mixed vegetable juice. Of 82 compounds tested, 75 in carrot and 62 in lemon were obtained with recoveries ranging from 70-120%. For all samples tested, 75 compounds could be obtained with recoveries of over 50%, and the detection limits of most compounds were lower than 0.01 microg/g. This method provides acceptable performance for analysis of these 75 compounds. Further, by using aliquots of the extracts with small-scale mini-columns, purified samples could be obtained. This proposed method with small matrix effects, is effective and suitable for screening of multiple residual pesticides by using LC/MS/MS.

  17. A sediment extraction and cleanup method for wide-scope multitarget screening by liquid chromatography-high-resolution mass spectrometry.

    Science.gov (United States)

    Massei, Riccardo; Byers, Harry; Beckers, Liza-Marie; Prothmann, Jens; Brack, Werner; Schulze, Tobias; Krauss, Martin

    2018-01-01

    Previous studies on organic sediment contaminants focused mainly on a limited number of highly hydrophobic micropollutants accessible to gas chromatography using nonpolar, aprotic extraction solvents. The development of liquid chromatography-high-resolution mass spectrometry (LC-HRMS) permits the spectrum of analysis to be expanded to a wider range of more polar and ionic compounds present in sediments and allows target, suspect, and nontarget screening to be conducted with high sensitivity and selectivity. In this study, we propose a comprehensive multitarget extraction and sample preparation method for characterization of sediment pollution covering a broad range of physicochemical properties that is suitable for LC-HRMS screening analysis. We optimized pressurized liquid extraction, cleanup, and sample dilution for a target list of 310 compounds. Finally, the method was tested on sediment samples from a small river and its tributaries. The results show that the combination of 100 °C for ethyl acetate-acetone (50:50, neutral extract) followed by 80 °C for acetone-formic acid (100:1, acidic extract) and methanol-10 mM sodium tetraborate in water (90:10, basic extract) offered the best extraction recoveries for 287 of 310 compounds. At a spiking level of 1 μg mL -1 , we obtained satisfactory cleanup recoveries for the neutral extract-(93 ± 23)%-and for the combined acidic/basic extracts-(42 ± 16)%-after solvent exchange. Among the 69 compounds detected in environmental samples, we successfully quantified several pharmaceuticals and polar pesticides.

  18. Screening halogenated environmental contaminants in biota based on isotopic pattern and mass defect provided by high resolution mass spectrometry profiling

    Energy Technology Data Exchange (ETDEWEB)

    Cariou, Ronan, E-mail: laberca@oniris-nantes.fr; Omer, Elsa; Léon, Alexis; Dervilly-Pinel, Gaud; Le Bizec, Bruno

    2016-09-14

    In the present work, we addressed the question of global seeking/screening organohalogenated compounds in a large panel of complex biological matrices, with a particular focus on unknown chemicals that may be considered as potential emerging hazards. A fishing strategy was developed based on untargeted profiling among full scan acquisition datasets provided by high resolution mass spectrometry. Since large datasets arise from such profiling, filtering useful information stands as a central question. In this way, we took advantage of the exact mass differences between Cl and Br isotopes. Indeed, our workflow involved an innovative Visual Basic for Applications script aiming at pairing features according to this mass difference, in order to point out potential organohalogenated clusters, preceded by an automated peak picking step based on the centWave function (xcms package of open access R programming environment). Then, H/Cl-scale mass defect plots were used to visualize the datasets before and after filtering. The filtering script was successfully applied to a dataset generated upon liquid chromatography coupled to ESI(−)-HRMS measurement from one eel muscle extract, allowing for realistic manual investigations of filtered clusters. Starting from 9789 initial obtained features, 1994 features were paired in 589 clusters. Hexabromocyclododecane, chlorinated paraffin series and various other compounds have been identified or tentatively identified, allowing thus broad screening of organohalogenated compounds in this extract. Although realistic, manual review of paired clusters remains time consuming and much effort should be devoted to automation. - Highlights: • We address the screening of halogenated compounds in large Full Scan HRMS datasets. • The workflow involves peak picking, pairing script and review of paired features. • The pairing script is based on exact mass differences between Cl and Br isotopes. • H/Cl scale mass defect plots are used to

  19. Screening halogenated environmental contaminants in biota based on isotopic pattern and mass defect provided by high resolution mass spectrometry profiling

    International Nuclear Information System (INIS)

    Cariou, Ronan; Omer, Elsa; Léon, Alexis; Dervilly-Pinel, Gaud; Le Bizec, Bruno

    2016-01-01

    In the present work, we addressed the question of global seeking/screening organohalogenated compounds in a large panel of complex biological matrices, with a particular focus on unknown chemicals that may be considered as potential emerging hazards. A fishing strategy was developed based on untargeted profiling among full scan acquisition datasets provided by high resolution mass spectrometry. Since large datasets arise from such profiling, filtering useful information stands as a central question. In this way, we took advantage of the exact mass differences between Cl and Br isotopes. Indeed, our workflow involved an innovative Visual Basic for Applications script aiming at pairing features according to this mass difference, in order to point out potential organohalogenated clusters, preceded by an automated peak picking step based on the centWave function (xcms package of open access R programming environment). Then, H/Cl-scale mass defect plots were used to visualize the datasets before and after filtering. The filtering script was successfully applied to a dataset generated upon liquid chromatography coupled to ESI(−)-HRMS measurement from one eel muscle extract, allowing for realistic manual investigations of filtered clusters. Starting from 9789 initial obtained features, 1994 features were paired in 589 clusters. Hexabromocyclododecane, chlorinated paraffin series and various other compounds have been identified or tentatively identified, allowing thus broad screening of organohalogenated compounds in this extract. Although realistic, manual review of paired clusters remains time consuming and much effort should be devoted to automation. - Highlights: • We address the screening of halogenated compounds in large Full Scan HRMS datasets. • The workflow involves peak picking, pairing script and review of paired features. • The pairing script is based on exact mass differences between Cl and Br isotopes. • H/Cl scale mass defect plots are used to

  20. Highly sensitive capillary electrophoresis-mass spectrometry for rapid screening and accurate quantitation of drugs of abuse in urine.

    Science.gov (United States)

    Kohler, Isabelle; Schappler, Julie; Rudaz, Serge

    2013-05-30

    The combination of capillary electrophoresis (CE) and mass spectrometry (MS) is particularly well adapted to bioanalysis due to its high separation efficiency, selectivity, and sensitivity; its short analytical time; and its low solvent and sample consumption. For clinical and forensic toxicology, a two-step analysis is usually performed: first, a screening step for compound identification, and second, confirmation and/or accurate quantitation in cases of presumed positive results. In this study, a fast and sensitive CE-MS workflow was developed for the screening and quantitation of drugs of abuse in urine samples. A CE with a time-of-flight MS (CE-TOF/MS) screening method was developed using a simple urine dilution and on-line sample preconcentration with pH-mediated stacking. The sample stacking allowed for a high loading capacity (20.5% of the capillary length), leading to limits of detection as low as 2 ng mL(-1) for drugs of abuse. Compound quantitation of positive samples was performed by CE-MS/MS with a triple quadrupole MS equipped with an adapted triple-tube sprayer and an electrospray ionization (ESI) source. The CE-ESI-MS/MS method was validated for two model compounds, cocaine (COC) and methadone (MTD), according to the Guidance of the Food and Drug Administration. The quantitative performance was evaluated for selectivity, response function, the lower limit of quantitation, trueness, precision, and accuracy. COC and MTD detection in urine samples was determined to be accurate over the range of 10-1000 ng mL(-1) and 21-1000 ng mL(-1), respectively. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Screens

    OpenAIRE

    2016-01-01

    This Sixth volume in the series The Key Debates. Mutations and Appropriations in European Film Studies investigates the question of screens in the context both of the dematerialization due to digitalization and the multiplication of media screens. Scholars offer various infomations and theories of topics such as the archeology of screen, film and media theories, contemporary art, pragmatics of new ways of screening (from home video to street screening).

  2. Newborn jaundice - discharge

    Science.gov (United States)

    ... Biliary atresia Bili lights Bilirubin blood test Bilirubin encephalopathy Exchange transfusion Jaundice and breastfeeding Newborn jaundice Premature infant Rh incompatibility Patient Instructions Newborn ...

  3. Screening of agrochemicals in foodstuffs using low-temperature plasma (LTP) ambient ionization mass spectrometry.

    Science.gov (United States)

    Wiley, Joshua S; García-Reyes, Juan F; Harper, Jason D; Charipar, Nicholas A; Ouyang, Zheng; Cooks, R Graham

    2010-05-01

    Low-temperature plasma (LTP) permits direct ambient ionization and mass analysis of samples in their native environment with minimal or no prior preparation. LTP utilizes dielectric barrier discharges (DBDs) to create a low power plasma which is guided by gas flow onto the sample from which analytes are desorbed and ionized. In this study, the potential of LTP-MS for the detection of pesticide residues in food is demonstrated. Thirteen multi-class agricultural chemicals were studied (ametryn, amitraz, atrazine, buprofezin, DEET, diphenylamine, ethoxyquin, imazalil, isofenphos-methyl, isoproturon, malathion, parathion-ethyl and terbuthylazine). To evaluate the potential of the proposed approach, LTP-MS experiments were performed directly on fruit peels as well as on fruit/vegetable extracts. Most of the agrochemicals examined displayed remarkable sensitivity in the positive ion mode, giving limits of detection (LOD) for the direct measurement in the low picogram range. Tandem mass spectrometry (MS/MS) was used to confirm identification of selected pesticides by using for these experiments spiked fruit/vegetable extracts (QuEChERS, a standard sample treatment protocol) at levels as low as 1 pg, absolute, for some of the analytes. Comparisons of the data obtained by direct LTP-MS were made with the slower but more accurate conventional LC-MS/MS procedure. Herbicides spiked in aqueous solutions were detectable at LODs as low as 0.5 microg L(-1) without the need for any sample preparation. The results demonstrate that ambient LTP-MS can be applied for the detection and confirmation of traces of agrochemicals in actual market-purchased produce and in natural water samples. Quantitative analysis was also performed in a few selected cases and displayed a relatively high degree of linearity over four orders of magnitude.

  4. High-Throughput Screening and Quantitation of Target Compounds in Biofluids by Coated Blade Spray-Mass Spectrometry.

    Science.gov (United States)

    Tascon, Marcos; Gómez-Ríos, Germán Augusto; Reyes-Garcés, Nathaly; Poole, Justen; Boyacı, Ezel; Pawliszyn, Janusz

    2017-08-15

    Most contemporary methods of screening and quantitating controlled substances and therapeutic drugs in biofluids typically require laborious, time-consuming, and expensive analytical workflows. In recent years, our group has worked toward developing microextraction (μe)-mass spectrometry (MS) technologies that merge all of the tedious steps of the classical methods into a simple, efficient, and low-cost methodology. Unquestionably, the automation of these technologies allows for faster sample throughput, greater reproducibility, and radically reduced analysis times. Coated blade spray (CBS) is a μe technology engineered for extracting/enriching analytes of interest in complex matrices, and it can be directly coupled with MS instruments to achieve efficient screening and quantitative analysis. In this study, we introduced CBS as a technology that can be arranged to perform either rapid diagnostics (single vial) or the high-throughput (96-well plate) analysis of biofluids. Furthermore, we demonstrate that performing 96-CBS extractions at the same time allows the total analysis time to be reduced to less than 55 s per sample. Aiming to validate the versatility of CBS, substances comprising a broad range of molecular weights, moieties, protein binding, and polarities were selected. Thus, the high-throughput (HT)-CBS technology was used for the concomitant quantitation of 18 compounds (mixture of anabolics, β-2 agonists, diuretics, stimulants, narcotics, and β-blockers) spiked in human urine and plasma samples. Excellent precision (∼2.5%), accuracy (≥90%), and linearity (R 2 ≥ 0.99) were attained for all the studied compounds, and the limits of quantitation (LOQs) were within the range of 0.1 to 10 ng·mL -1 for plasma and 0.25 to 10 ng·mL -1 for urine. The results reported in this paper confirm CBS's great potential for achieving subsixty-second analyses of target compounds in a broad range of fields such as those related to clinical diagnosis, food, the

  5. Rapid screening of mixed edible oils and gutter oils by matrix-assisted laser desorption/ionization mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Ng, Tsz-Tsun; So, Pui-Kin; Zheng, Bo [Food Safety and Technology Research Centre, State Key Laboratory of Chirosciences and Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom Kowloon, Hong Kong Special Administrative Region (China); Shenzhen Key Laboratory of Food Biological Safety Control and State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Shenzhen Research Institute of The Hong Kong Polytechnic University, Shenzhen (China); Yao, Zhong-Ping, E-mail: zhongping.yao@polyu.edu.hk [Food Safety and Technology Research Centre, State Key Laboratory of Chirosciences and Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom Kowloon, Hong Kong Special Administrative Region (China); Shenzhen Key Laboratory of Food Biological Safety Control and State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Shenzhen Research Institute of The Hong Kong Polytechnic University, Shenzhen (China)

    2015-07-16

    Highlights: • Simplified sample preparation method for direct analysis of edible oils by MALDI-MS. • Establishment of a preliminary MALDI-MS spectral database of edible oils. • Rapid screening of mixed edible oils and gutter oils. - Abstract: Authentication of edible oils is a long-term issue in food safety, and becomes particularly important with the emergence and wide spread of gutter oils in recent years. Due to the very high analytical demand and diversity of gutter oils, a high throughput analytical method and a versatile strategy for authentication of mixed edible oils and gutter oils are highly desirable. In this study, an improved matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) method has been developed for direct analysis of edible oils. This method involved on-target sample loading, automatic data acquisition and simple data processing. MALDI-MS spectra with high quality and high reproducibility have been obtained using this method, and a preliminary spectral database of edible oils has been set up. The authenticity of an edible oil sample can be determined by comparing its MALDI-MS spectrum and principal component analysis (PCA) results with those of its labeled oil in the database. This method is simple and the whole process only takes several minutes for analysis of one oil sample. We demonstrated that the method was sensitive to change in oil compositions and can be used for measuring compositions of mixed oils. The capability of the method for determining mislabeling enables it for rapid screening of gutter oils since fraudulent mislabeling is a common feature of gutter oils.

  6. Rapid screening of mixed edible oils and gutter oils by matrix-assisted laser desorption/ionization mass spectrometry

    International Nuclear Information System (INIS)

    Ng, Tsz-Tsun; So, Pui-Kin; Zheng, Bo; Yao, Zhong-Ping

    2015-01-01

    Highlights: • Simplified sample preparation method for direct analysis of edible oils by MALDI-MS. • Establishment of a preliminary MALDI-MS spectral database of edible oils. • Rapid screening of mixed edible oils and gutter oils. - Abstract: Authentication of edible oils is a long-term issue in food safety, and becomes particularly important with the emergence and wide spread of gutter oils in recent years. Due to the very high analytical demand and diversity of gutter oils, a high throughput analytical method and a versatile strategy for authentication of mixed edible oils and gutter oils are highly desirable. In this study, an improved matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) method has been developed for direct analysis of edible oils. This method involved on-target sample loading, automatic data acquisition and simple data processing. MALDI-MS spectra with high quality and high reproducibility have been obtained using this method, and a preliminary spectral database of edible oils has been set up. The authenticity of an edible oil sample can be determined by comparing its MALDI-MS spectrum and principal component analysis (PCA) results with those of its labeled oil in the database. This method is simple and the whole process only takes several minutes for analysis of one oil sample. We demonstrated that the method was sensitive to change in oil compositions and can be used for measuring compositions of mixed oils. The capability of the method for determining mislabeling enables it for rapid screening of gutter oils since fraudulent mislabeling is a common feature of gutter oils

  7. Language Outcomes in Deaf or Hard of Hearing Teenagers Who Are Spoken Language Users: Effects of Universal Newborn Hearing Screening and Early Confirmation.

    Science.gov (United States)

    Pimperton, Hannah; Kreppner, Jana; Mahon, Merle; Stevenson, Jim; Terlektsi, Emmanouela; Worsfold, Sarah; Yuen, Ho Ming; Kennedy, Colin R

    This study aimed to examine whether (a) exposure to universal newborn hearing screening (UNHS) and b) early confirmation of hearing loss were associated with benefits to expressive and receptive language outcomes in the teenage years for a cohort of spoken language users. It also aimed to determine whether either of these two variables was associated with benefits to relative language gain from middle childhood to adolescence within this cohort. The participants were drawn from a prospective cohort study of a population sample of children with bilateral permanent childhood hearing loss, who varied in their exposure to UNHS and who had previously had their language skills assessed at 6-10 years. Sixty deaf or hard of hearing teenagers who were spoken language users and a comparison group of 38 teenagers with normal hearing completed standardized measures of their receptive and expressive language ability at 13-19 years. Teenagers exposed to UNHS did not show significantly better expressive (adjusted mean difference, 0.40; 95% confidence interval [CI], -0.26 to 1.05; d = 0.32) or receptive (adjusted mean difference, 0.68; 95% CI, -0.56 to 1.93; d = 0.28) language skills than those who were not. Those who had their hearing loss confirmed by 9 months of age did not show significantly better expressive (adjusted mean difference, 0.43; 95% CI, -0.20 to 1.05; d = 0.35) or receptive (adjusted mean difference, 0.95; 95% CI, -0.22 to 2.11; d = 0.42) language skills than those who had it confirmed later. In all cases, effect sizes were of small size and in favor of those exposed to UNHS or confirmed by 9 months. Subgroup analysis indicated larger beneficial effects of early confirmation for those deaf or hard of hearing teenagers without cochlear implants (N = 48; 80% of the sample), and these benefits were significant in the case of receptive language outcomes (adjusted mean difference, 1.55; 95% CI, 0.38 to 2.71; d = 0.78). Exposure to UNHS did not account for significant

  8. Screening new psychoactive substances in urban wastewater using high resolution mass spectrometry.

    Science.gov (United States)

    González-Mariño, Iria; Gracia-Lor, Emma; Bagnati, Renzo; Martins, Claudia P B; Zuccato, Ettore; Castiglioni, Sara

    2016-06-01

    Analysis of drug residues in urban wastewater could complement epidemiological studies in detecting the use of new psychoactive substances (NPS), a continuously changing group of drugs hard to monitor by classical methods. We initially selected 52 NPS potentially used in Italy based on seizure data and consumption alerts provided by the Antidrug Police Department and the National Early Warning System. Using a linear ion trap-Orbitrap high resolution mass spectrometer, we designed a suspect screening and a target method approach and compared them for the analysis of 24 h wastewater samples collected at the treatment plant influents of four Italian cities. This highlighted the main limitations of these two approaches, so we could propose requirements for future research. A library of MS/MS spectra of 16 synthetic cathinones and 19 synthetic cannabinoids, for which analytical standards were acquired, was built at different collision energies and is available on request. The stability of synthetic cannabinoids was studied in analytical standards and wastewater, identifying the best analytical conditions for future studies. To the best of our knowledge, these are the first stability data on NPS. Few suspects were identified in Italian wastewater samples, in accordance with recent epidemiological data reporting a very low prevalence of use of NPS in Italy. This study outlines an analytical approach for NPS identification and measurement in urban wastewater and for estimating their use in the population.

  9. Mass spectrometry-based phytochemical screening for hypoglycemic activity of Fagioli di Sarconi beans (Phaseolus vulgaris L.).

    Science.gov (United States)

    Pascale, Raffaella; Bianco, Giuliana; Cataldi, Tommaso R I; Kopplin, Philippe-Schmitt; Bosco, Federica; Vignola, Lisiana; Uhl, Jenny; Lucio, Marianna; Milella, Luigi

    2018-03-01

    The present study deals with the evaluation of antidiabetic activities of Fagioli di Sarconi beans (Phaseolus vulgaris), including 21 ecotypes protected by the European Union with the mark PGI (i.e., Protected Geographical Indication), and cultivated in Basilicata (southern Italy). For this purpose, α-glucosidase and α-amylase assays were assessed; among all bean ecotypes, the tight green seed colour of Verdolino extracts exhibited the highest α-glucosidase and α-amylase inhibitory activity with IC 50 =1.1±0.1μg/ml and IC 50 =19.3±1.1μg/ml, respectively. Phytochemical compound screening of all Fagioli di Sarconi beans performed by flow injection-electrospray ionization-ultrahigh resolution mass spectrometry (uHRMS) and based on the calculation of elemental formulas from accurate m/z values, was helpful to annotate specific compounds, such as alkaloids, saponins, flavonoids, and terpenoids, which are most likely responsible for their biological activity. Copyright © 2017. Published by Elsevier Ltd.

  10. High throughput nanostructure-initiator mass spectrometry screening of microbial growth conditions for maximal β-glucosidase production.

    Science.gov (United States)

    Cheng, Xiaoliang; Hiras, Jennifer; Deng, Kai; Bowen, Benjamin; Simmons, Blake A; Adams, Paul D; Singer, Steven W; Northen, Trent R

    2013-01-01

    Production of biofuels via enzymatic hydrolysis of complex plant polysaccharides is a subject of intense global interest. Microbial communities are known to express a wide range of enzymes necessary for the saccharification of lignocellulosic feedstocks and serve as a powerful reservoir for enzyme discovery. However, the growth temperature and conditions that yield high cellulase activity vary widely, and the throughput to identify optimal conditions has been limited by the slow handling and conventional analysis. A rapid method that uses small volumes of isolate culture to resolve specific enzyme activity is needed. In this work, a high throughput nanostructure-initiator mass spectrometry (NIMS)-based approach was developed for screening a thermophilic cellulolytic actinomycete, Thermobispora bispora, for β-glucosidase production under various growth conditions. Media that produced high β-glucosidase activity were found to be I/S + glucose or microcrystalline cellulose (MCC), Medium 84 + rolled oats, and M9TE + MCC at 45°C. Supernatants of cell cultures grown in M9TE + 1% MCC cleaved 2.5 times more substrate at 45°C than at all other temperatures. While T. bispora is reported to grow optimally at 60°C in Medium 84 + rolled oats and M9TE + 1% MCC, approximately 40% more conversion was observed at 45°C. This high throughput NIMS approach may provide an important tool in discovery and characterization of enzymes from environmental microbes for industrial and biofuel applications.

  11. Rapid evaporative ionization mass spectrometry for high-throughput screening in food analysis: The case of boar taint.

    Science.gov (United States)

    Verplanken, Kaat; Stead, Sara; Jandova, Renata; Poucke, Christof Van; Claereboudt, Jan; Bussche, Julie Vanden; Saeger, Sarah De; Takats, Zoltan; Wauters, Jella; Vanhaecke, Lynn

    2017-07-01

    Boar taint is a contemporary off-odor present in meat of uncastrated male pigs. As European Member States intend to abandon surgical castration of pigs by 2018, this off-odor has gained a lot of research interest. In this study, rapid evaporative ionization mass spectrometry (REIMS) was explored for the rapid detection of boar taint in neck fat. Untargeted screening of samples (n=150) enabled discrimination between sow, tainted and untainted boars. The obtained OPLS-DA models showed excellent classification accuracy, i.e. 99% and 100% for sow and boar samples or solely boar samples, respectively. Furthermore, the obtained models demonstrated excellent validation characteristics (R 2 (Y)=0.872-0.969; Q 2 (Y)=0.756-0.917), which were confirmed by CV-ANOVA (phighly accurate and high-throughput (<10s) classification of tainted and untainted boar samples was achieved, rendering REIMS a promising technique for predictive modelling in food safety and quality applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Direct Growth of Bacteria in Headspace Vials Allows for Screening of Volatiles by Gas Chromatography Mass Spectrometry.

    Science.gov (United States)

    Timm, Collin M; Lloyd, Evan P; Egan, Amanda; Mariner, Ray; Karig, David

    2018-01-01

    Bacterially produced volatile organic compounds (VOCs) can modify growth patterns of eukaryotic hosts and competing/cohabiting microbes. These compounds have been implicated in skin disorders and attraction of biting pests. Current methods to detect and characterize VOCs from microbial cultures can be laborious and low-throughput, making it difficult to understand the behavior of microbial populations. In this work we present an efficient method employing gas chromatography/mass spectrometry with autosampling to characterize VOC profiles from solid-phase bacterial cultures. We compare this method to complementary plate-based assays and measure the effects of growth media and incubation temperature on the VOC profiles from a well-studied Pseudomonas aeruginosa PAO1 system. We observe that P. aeruginosa produces longer chain VOCs, such as 2-undecanone and 2-undecanol in higher amounts at 37°C than 30°C. We demonstrate the throughput of this method by studying VOC profiles from a representative collection of skin bacterial isolates under three parallel growth conditions. We observe differential production of various aldehydes and ketones depending on bacterial strain. This generalizable method will support screening of bacterial populations in a variety of research areas.

  13. Direct Growth of Bacteria in Headspace Vials Allows for Screening of Volatiles by Gas Chromatography Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Collin M. Timm

    2018-03-01

    Full Text Available Bacterially produced volatile organic compounds (VOCs can modify growth patterns of eukaryotic hosts and competing/cohabiting microbes. These compounds have been implicated in skin disorders and attraction of biting pests. Current methods to detect and characterize VOCs from microbial cultures can be laborious and low-throughput, making it difficult to understand the behavior of microbial populations. In this work we present an efficient method employing gas chromatography/mass spectrometry with autosampling to characterize VOC profiles from solid-phase bacterial cultures. We compare this method to complementary plate-based assays and measure the effects of growth media and incubation temperature on the VOC profiles from a well-studied Pseudomonas aeruginosa PAO1 system. We observe that P. aeruginosa produces longer chain VOCs, such as 2-undecanone and 2-undecanol in higher amounts at 37°C than 30°C. We demonstrate the throughput of this method by studying VOC profiles from a representative collection of skin bacterial isolates under three parallel growth conditions. We observe differential production of various aldehydes and ketones depending on bacterial strain. This generalizable method will support screening of bacterial populations in a variety of research areas.

  14. Simultaneous screening and confirmation of multiple classes of drug residues in fish by liquid chromatography-ion trap mass spectrometry.

    Science.gov (United States)

    Smith, Shani; Gieseker, Charles; Reimschuessel, Renate; Decker, Christie-Sue; Carson, Mary C

    2009-11-13

    LC-ion trap mass spectrometry was used to screen and confirm 38 compounds from a variety of drug classes in four species of fish: trout, salmon, catfish, and tilapia. Samples were extracted with acetonitrile and hexane. The acetonitrile phase was evaporated, redissolved in water and acetonitrile, and analyzed by gradient chromatography on a phenyl column. MS(2) or MS(3) spectra were monitored for each compound. Qualitative method performance was evaluated by the analysis over several days of replicate samples of control fish, fish fortified with a drug mixture at 1 ppm, 0.1 ppm and 0.01 ppm, and fish dosed with a representative from each drug class. Half of the 38 drugs were confirmed at 0.01 ppm, the lowest fortification level. This included all of the quinolones and fluoroquinolones, the macrolides, malachite green, and most of the imidazoles. Florfenicol amine, metronidazole, sulfonamides, tetracyclines, and most of the betalactams were confirmed at 0.1 ppm. Ivermectin and penicillin G were only detectable in the 1 ppm fortified samples. With the exception of amoxicillin, emamectin, metronidazole, and tylosin, residue presence was confirmed in all the dosed fish.

  15. High throughput nanostructure-initiator mass spectrometry screening of microbial growth conditions for maximal β-glucosidase production

    Directory of Open Access Journals (Sweden)

    Xiaoliang eCheng

    2013-12-01

    Full Text Available Production of biofuels via enzymatic hydrolysis of complex plant polysaccharides is a subject of intense global interest. Microbial communities are known to express a wide range of enzymes necessary for the saccharification of lignocellulosic feedstocks and serve as a powerful reservoir for enzyme discovery. However, the growth temperature and conditions that yield high cellulase activity vary widely, and the throughput to identify optimal conditions has been limited by the slow handling and conventional analysis. A rapid method that uses small volumes of isolate culture to resolve specific enzyme activity is needed. In this work, a high throughput nanostructure-initiator mass spectrometry (NIMS based approach was developed for screening a thermophilic cellulolytic actinomycete, Thermobispora bispora, for β-glucosidase production under various growth conditions. Media that produced high β-glucosidase activity were found to be I/S + glucose or microcrystalline cellulose (MCC, Medium 84 + rolled oats, and M9TE + MCC at 45 °C. Supernatants of cell cultures grown in M9TE + 1% MCC cleaved 2.5 times more substrate at 45 °C than at all other temperatures. While T. bispora is reported to grow optimally at 60 °C in Medium 84 + rolled oats and M9TE + 1% MCC, approximately 40% more conversion was observed at 45 °C. This high throughput NIMS approach may provide an important tool in discovery and characterization of enzymes from environmental microbes for industrial and biofuel applications.

  16. Study of Grape Polyphenols by Liquid Chromatography-High-Resolution Mass Spectrometry (UHPLC/QTOF and Suspect Screening Analysis

    Directory of Open Access Journals (Sweden)

    Riccardo Flamini

    2015-01-01

    Full Text Available Suspect screening analysis is a targeted metabolomics method in which the identification of compounds relies on specific available information, such as their molecular formula and isotopic pattern. This method, coupled to liquid chromatography-high-resolution mass spectrometry, is effective in the study of grape metabolomics, in particular for characterization of flavonols, stilbene derivatives, and anthocyanins. For identification of compounds expected in the samples, a new database of putative compounds was expressly constructed by using the molecular information on potential metabolites of grape and wine from the literature and other electronic databases. Currently, this database contains around 1,100 compounds. The method allows identification of several hundred grape metabolites with two analyses (positive and negative ionization modes, and performing of data reprocessing using “untargeted” algorithms also provided the identification of some flavonols and resveratrol trimers and tetramers in grape for the first time. This approach can be potentially used in the study of metabolomics of varieties of other plant species.

  17. Feasibility of Pulse Oximetry Pre-discharge Screening Implementation for detecting Critical Congenital heart Lesions in newborns in a secondary level maternity hospital in the Western Cape, South Africa: The 'POPSICLe' study.

    Science.gov (United States)

    Van Niekerk, A M; Cullis, R M; Linley, L L; Zühlke, L

    2016-07-07

    Early detection of critical congenital heart disease (CCHD) through newborn pulse oximetry (POx) screening is an effective strategy for reducing paediatric morbidity and mortality rates and has been adopted by much of the developed world. To document the feasibility of implementing pre-discharge POx screening in well babies born at Mowbray Maternity Hospital, a busy government hospital in Cape Town, South Africa. Parent and staff acceptance was assessed. We conducted a prospective study of predischarge POx screening in one postnatal ward, following informed parental consent. During the 4-month study period, 1 017 of 2 256 babies discharged (45.1%) were offered POx screening and 1 001 were screened; 94.0% of tests took <3 minutes to perform, 4.3% 3 - 5 minutes and 1.7% >5 minutes. Eighteen patients needed second screens and three required third screens. Only 3.1% protocol errors were made, all without consequence. The vast majority (91.6%) of nursing staff reported insufficient time to perform the study screening in addition to their daily tasks, but ~75% felt that with a full nursing staff complement and if done routinely (not part of a study), pre-discharge POx screening could be successfully instituted at our facility. Over 98% of the mothers had positive comments. Two babies failed screening and required echocardiograms; one was diagnosed with CCHD and the other with neonatal sepsis. The sensitivity and specificity were 50% (95% confidence interval (CI) 1.3 - 98.7%) and 99.9% (95% CI 99.4 - 100%), respectively, with a percentage correct of 99.8%. POx screening was supported and accepted by staff and parents. If there are no nursing staff shortages and if it is done routinely before discharge, not as part of a study, we conclude that POx screening could be implemented successfully without excessive false positives or errors, or any additional burden to cardiology services.

  18. Rapid screening of N-oxides of chemical warfare agents degradation products by ESI-tandem mass spectrometry.

    Science.gov (United States)

    Sridhar, L; Karthikraj, R; Lakshmi, V V S; Raju, N Prasada; Prabhakar, S

    2014-08-01

    Rapid detection and identification of chemical warfare agents and related precursors/degradation products in various environmental matrices is of paramount importance for verification of standards set by the chemical weapons convention (CWC). Nitrogen mustards, N,N-dialkylaminoethyl-2-chlorides, N,N-dialkylaminoethanols, N-alkyldiethanolamines, and triethanolamine, which are listed CWC scheduled chemicals, are prone to undergo N-oxidation in environmental matrices or during decontamination process. Thus, screening of the oxidized products of these compounds is also an important task in the verification process because the presence of these products reveals alleged use of nitrogen mustards or precursors of VX compounds. The N-oxides of aminoethanols and aminoethylchlorides easily produce [M + H](+) ions under electrospray ionization conditions, and their collision-induced dissociation spectra include a specific neutral loss of 48 u (OH + CH2OH) and 66 u (OH + CH2Cl), respectively. Based on this specific fragmentation, a rapid screening method was developed for screening of the N-oxides by applying neutral loss scan technique. The method was validated and the applicability of the method was demonstrated by analyzing positive and negative samples. The method was useful in the detection of N-oxides of aminoethanols and aminoethylchlorides in environmental matrices at trace levels (LOD, up to 500 ppb), even in the presence of complex masking agents, without the use of time-consuming sample preparation methods and chromatographic steps. This method is advantageous for the off-site verification program and also for participation in official proficiency tests conducted by the Organization for the Prohibition of Chemical Weapons (OPCW), the Netherlands. The structure of N-oxides can be confirmed by the MS/MS experiments on the detected peaks. A liquid chromatography-mass spectrometry (LC-MS) method was developed for the separation of isomeric N-oxides of aminoethanols and

  19. Triagem auditiva neonatal: motivos da evasão das famílias no processo de detecção precoce Newborn hearing screening: reasons for the evasion of families in the process of early detection

    Directory of Open Access Journals (Sweden)

    Kátia de Feitas Alvarenga

    2012-01-01

    Full Text Available OBJETIVO: Analisar os motivos da evasão familiar no programa de triagem auditiva neonatal realizado em um hospital público e correlacioná-los com a distribuição demográfica das famílias e as características do programa. MÉTODOS: Participaram 132 famílias, de um total de 739 contatadas, cujos filhos nasceram em uma maternidade no interior do estado de São Paulo de outubro/2003 a dezembro/2005 e que não haviam comparecido para a realização do teste ou reteste da triagem auditiva neonatal. Foi aplicado um questionário de levantamento das causas de evasão, contendo perguntas relacionadas à triagem auditiva, nível de escolaridade e profissão dos pais e também sobre a audição e o desenvolvimento de linguagem da criança. RESULTADOS: Realizou-se a aplicação do questionário com 132 famílias (17,86%; com as demais não foi obtido contato. Deste total, 82 haviam faltado na primeira etapa da triagem auditiva (teste e 50 não haviam retornado para realização do reteste. Os motivos mais frequentes para justificar a evasão foram o desinteresse e a dificuldade em conciliar o agendamento com a rotina familiar. Não houve associação entre os motivos da evasão e o nível de escolaridade e ocupação dos pais, nem com o profissional que realizou a orientação acerca da triagem auditiva. Não foi referido nenhum caso de alteração auditiva, nem de atraso significativo no desenvolvimento da linguagem. CONCLUSÃO: Os motivos da evasão familiar independem de variáveis voltadas à família e à dinâmica do programa de triagem auditiva.PURPOSE: To analyze the reasons for evasion of the families from the newborn hearing screening program conducted at a public hospital, and to correlate them with the demographic distribution of the families and the characteristics of the program. METHODS: Participants were 132 families, from a total of 739 contacted, whose children had been born in a maternity hospital in the interior of the state of

  20. Review: LC coupled to low- and high-resolution mass spectrometry for new psychoactive substance screening in biological matrices - Where do we stand today?

    Science.gov (United States)

    Meyer, Markus R; Maurer, Hans H

    2016-07-13

    The field of new psychoactive substances (NPS) is highly dynamic and the situation changes from year to year. Therefore, the current review provides a timely update about the latest developments to help analysts keep the pace with NPS distribution. It covers PubMed-listed studies published between January 2014 and January 2016 dealing with the application of liquid chromatography (LC) coupled low- and high-resolution mass spectrometry (MS) for broad screenings for NPS in clinical (CT) and forensic (FT) toxicology. Latest developments and applications are highlighted and selected papers critically discussed. Comprehensive tables summarizing all discussed articles complete the overview. Finally, an outlook on the future of LC coupled MS in CT and FT is provided and readers will learn why low-resolution mass spectrometry might remain the standard for the next couple of years at least for easy-to-use quantitative screening procedures. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. [Rapid screening the alkaloids of poppy shell in hot pot condiment, beef noodle soup and seasoning by direct analysis in real time-tandem mass spectrometry].

    Science.gov (United States)

    Zhang, Baile; Gao, Lihong; Xie, Yingshuang; Zhou, Wei; Chen, Xiaofeng; Lei, Chunni; Zhang, Huan

    2017-07-08

    A direct analysis in real time tandem mass spectrometry (DART-MS/MS) method was established for quickly screening five illegally added alkaloids of poppy shell from the hot pot condiment, beef noodle soup and seasoning. The samples were extracted and purified by acetonitrile, and then injected under the conditions of ionization temperature of 300℃, grid electrode voltage of 150 V and sampling rate of 0.8 mm/s using DART in the positive ion mode. The determination was conducted by tandem mass spectrometry in positive ESI mode under multiple reaction monitoring (MRM) mode. The method is simple and rapid, and can meet the requirement of rapid screening and analysis of large quantities of samples.

  2. Rapid Screening and Characterization of Acetylcholinesterase Inhibitors from Yinhuang Oral Liquid Using Ultrafiltration-liquid Chromatography-electrospray Ionization Tandem Mass Spectrometry.

    Science.gov (United States)

    Zhang, Haomin; Guo, Yinan; Meng, Lingwen; Sun, Hui; Yang, Yinping; Gao, Ying; Sun, Jiaming

    2018-01-01

    At present, approximately 17-25 million people in the world suffer from Alzheimer's disease (AD). The most efficacious and acceptable therapeutic drug clinically are the acetylcholinesterase inhibitors (AChEIs). Yinhuang oral liquid is a Chinese medicine preparation which contains AChEIs according to the literatures. However, no strategy has been presented for rapid screening and identification of AChEIs from Yinhuang oral liquid. To develop a method for rapid screening and identification of AChEIs from Yinhuang oral liquid using ultrafiltration-liquid chromatography-electrospray ionization tandem mass spectrometry (UF-LC-ESI-MS/MS). In this study, UF incubation conditions such as enzyme concentration, incubation time, and incubation temperature were optimized so as to get better screening results. The AChEIs from Yinhuang oral liquid were identified by high-performance liquid chromatography-ESI-MS and the improved Ellman method was used for the AChE inhibitory activity test in vitro . The results showed that Yinhuang oral liquid can inhibit the activity of AChE. We screened and identified seven compounds with potential AChE inhibitory activity from Yinhuang oral liquid, which provided experimental basis for the treatment and prevention of AD. The current technique was used to directly screen the active ingredients with acetylcholinesterase inhibition from complex traditional Chinese medicine, which was simple, rapid, accurate, and suitable for high-throughput screening of AChEI from complex systems. A UF-LC-ESI-MS/MS method for rapid screening and identification of AChEIs from Yinhuang oral liquid was developedSeven compounds were screened and identified with potential AChE inhibitory activity from Yinhuang oral liquidIt provided experimental basis of Yinhuang oral liquid for the treating and preventing AD. Abbreviations used: (AD): Alzheimer's disease; (UF-LC-ESI-MS/MS): ultrafiltration-liquid chromatography-electrospray ionization tandem mass spectrometry; (ACh

  3. Rapid Screening and Characterization of Acetylcholinesterase Inhibitors from Yinhuang Oral Liquid Using Ultrafiltration-liquid Chromatography-electrospray Ionization Tandem Mass Spectrometry

    Science.gov (United States)

    Zhang, Haomin; Guo, Yinan; Meng, Lingwen; Sun, Hui; Yang, Yinping; Gao, Ying; Sun, Jiaming

    2018-01-01

    Background: At present, approximately 17–25 million people in the world suffer from Alzheimer's disease (AD). The most efficacious and acceptable therapeutic drug clinically are the acetylcholinesterase inhibitors (AChEIs). Yinhuang oral liquid is a Chinese medicine preparation which contains AChEIs according to the literatures. However, no strategy has been presented for rapid screening and identification of AChEIs from Yinhuang oral liquid. Objective: To develop a method for rapid screening and identification of AChEIs from Yinhuang oral liquid using ultrafiltration–liquid chromatography–electrospray ionization tandem mass spectrometry (UF-LC-ESI-MS/MS). Materials and Methods: In this study, UF incubation conditions such as enzyme concentration, incubation time, and incubation temperature were optimized so as to get better screening results. The AChEIs from Yinhuang oral liquid were identified by high-performance liquid chromatography-ESI-MS and the improved Ellman method was used for the AChE inhibitory activity test in vitro. Results: The results showed that Yinhuang oral liquid can inhibit the activity of AChE. We screened and identified seven compounds with potential AChE inhibitory activity from Yinhuang oral liquid, which provided experimental basis for the treatment and prevention of AD. Conclusion: The current technique was used to directly screen the active ingredients with acetylcholinesterase inhibition from complex traditional Chinese medicine, which was simple, rapid, accurate, and suitable for high-throughput screening of AChEI from complex systems. SUMMARY A UF-LC-ESI-MS/MS method for rapid screening and identification of AChEIs from Yinhuang oral liquid was developedSeven compounds were screened and identified with potential AChE inhibitory activity from Yinhuang oral liquidIt provided experimental basis of Yinhuang oral liquid for the treating and preventing AD. Abbreviations used: (AD): Alzheimer's disease; (UF

  4. Screening of Carotenoids in Tomato Fruits by Using Liquid Chromatography with Diode Array-Linear Ion Trap Mass Spectrometry Detection.

    Science.gov (United States)

    Gentili, Alessandra; Caretti, Fulvia; Ventura, Salvatore; Pérez-Fernández, Virginia; Venditti, Alessandro; Curini, Roberta

    2015-08-26

    This paper presents an analytical strategy for a large-scale screening of carotenoids in tomato fruits by exploiting the potentialities of the triple quadrupole-linear ion trap hybrid mass spectrometer (QqQLIT). The method involves separation on C30 reversed-phase column and identification by means of diode array detection (DAD) and atmospheric pressure chemical ionization-mass spectrometry (APCI-MS). The authentic standards of six model compounds were used to optimize the separative conditions and to predict the chromatographic behavior of untargeted carotenoids. An information dependent acquisition (IDA) was performed with (i) enhanced-mass scan (EMS) as the survey scan, (ii) enhanced-resolution (ER) scan to obtain the exact mass of the precursor ions (16-35 ppm), and (iii) enhanced product ion (EPI) scan as dependent scan to obtain structural information. LC-DAD-multiple reaction monitoring (MRM) chromatograms were also acquired for the identification of targeted carotenoids occurring at low concentrations; for the first time, the relative abundance between the MRM transitions (ion ratio) was used as an extra tool for the MS distinction of structural isomers and the related families of geometrical isomers. The whole analytical strategy was high-throughput, because a great number of experimental data could be acquired with few analytical steps, and cost-effective, because only few standards were used; when applied to characterize some tomato varieties ('Tangerine', 'Pachino', 'Datterino', and 'Camone') and passata of 'San Marzano' tomatoes, our method succeeded in identifying up to 44 carotenoids in the 'Tangerine'" variety.

  5. High-throughput screening and confirmation of 22 banned veterinary drugs in feedstuffs using LC-MS/MS and high-resolution Orbitrap mass spectrometry.

    Science.gov (United States)

    Wang, Xufeng; Liu, Yanghong; Su, Yijuan; Yang, Jianwen; Bian, Kui; Wang, Zongnan; He, Li-Min

    2014-01-15

    A new analytical strategy based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with accurate mass high-resolution Orbitrap mass spectrometry (HR-Orbitrap MS) was performed for high-throughput screening, confirmation, and quantification of 22 banned or unauthorized veterinary drugs in feedstuffs according to Bulletin 235 of the Ministry of Agriculture, China. Feed samples were extracted with acidified acetonitrile, followed by cleanup using solid-phase extraction cartridge. The extracts were first screened by LC-MS/MS in a single selected reaction monitoring mode. The suspected positive samples were subjected to a specific pretreatment for confirmation and quantification of analyte of interest with LC-MS/MS and HR-Orbitrap MS. Mean recoveries for all target analytes (except for carbofuran and chlordimeform, which were about 35 and 45%, respectively) ranged from 52.2 to 90.4%, and the relative standard deviations were screening of real samples obtained from local feed markets and confirmation of the suspected target analytes. It provides a high-throughput, sensitive, and reliable screening, identification, and quantification of banned veterinary drugs in routine monitoring programs of feedstuffs.

  6. Análise da implantação de programa de triagem auditiva neonatal em um hospital universitário Newborn hearing screening program implantation analysis at a university hospital

    Directory of Open Access Journals (Sweden)

    Wilian Maduell de Mattos

    2009-04-01

    Full Text Available Aperda auditiva é mais prevalente que outros distúrbios já rastreados ao nascimento. Esforços têm sido feitos para identificação e tratamento precoces de perdas auditivas por meio de programas de triagem auditiva neonatal. OBJETIVO: Estudo prospectivo com objetivo caracterizar o processo de implantação do Programa de Triagem Auditiva Neonatal (PTAN num Hospital Universitário. Analisar a investigação diagnóstica de perda auditiva em recém-nascidos. Apresentar propostas para aprimoramento do PTAN. MATERIAIS E MÉTODOS: Foram estudados recém-nascidos (RNs submetidos à TAN por emissões otoacústicas transientes (EOAT, reflexo cócleo-palpebral (RCP e Potencial Evocado Auditivo de Tronco Encefálico (PEATE. RESULTADOS: Foram testadas 625 crianças. Na primeira etapa passaram 458 RNs e falharam 155. Retornaram na segunda etapa 122 RNs, sendo que 8 o fizeram por apresentar fator de alto risco para PA. Encaminhados para investigação diagnóstica 12 RNs (1,9%. Dos 5 que retornaram para PEATE, observou-se PA em dois RNs. CONCLUSÃO: O programa testou 81,7% dos candidatos. O índice de adesão ao programa foi 68,2%. Na primeira etapa falharam 26,7% dos RNs. A implantação do programa está em andamento e necessita constantemente de análise das dificuldades, visando solucioná-las a fim de tornar a Triagem Auditiva Neonatal Universal uma realidade.Hearing loss is more prevalent than other disorders found at birth. Efforts have been put up towards the early identification and treatment of hearing loss by means of neonatal hearing screening programs. AIM: prospective study with the goal of characterizing the process of implementing a Neonatal Auditory Screening Program (NASP at a University Hospital. To analyze hearing loss diagnostic investigations in newborns, and to present proposals for NASP improvement. MATERIALS AND METHODS: we studied newborns (NB submitted to Newborn Auditory Screening (NAS by transient evoked otoacoustic

  7. HighResNPS.com – an Internet Database for Liquid Chromatography - High Resolution Mass Spectrometry Screening for New Psychoactive Substances

    DEFF Research Database (Denmark)

    Dalsgaard, Petur Weihe; Mollerup, Christian Brinch; Mardal, Marie

    /Discussions: . The overlapping entries of the database verify that similar fragment ions can be observed from identical compounds across different LC-HRMS systems. The inclusion of fragment ions from other labs can reduce false positive identifications, when no reference standard is available in-house. HighResNPS can serve......Background/Introduction: The number of new psychoactive substances (NPS) is constantly increasing which makes it challenging to keep the screening libraries updated with the relevant analytical targets. Liquid chromatography coupled High Resolution Mass Spectrometry (LC-HRMS) screening methods...... with most screening platforms after minor formatting. Results: Currently, 11 users from 9 laboratories in 7 counties have contributed with 318 entries to the database with experimental data containing at least one fragment ion. 66% of the uploaded data were based on reference standards. Synthetic...

  8. Screening and identification of RhD antigen mimic epitopes from a phage display random peptide library for the serodiagnosis of haemolytic disease of the foetus and newborn.

    Science.gov (United States)

    Wang, Jiao; Song, Jingjing; Zhou, Shuimei; Fu, Yourong; Bailey, Jeffrey A; Shen, Changxin

    2018-01-16

    Identification of RhD antigen epitopes is a key component in understanding the pathogenesis of haemolytic disease of the foetus and newborn. Research has indicated that phage display libraries are useful tools for identifying novel mimic epitopes (mimotopes) which may help to determine antigen specificity. We selected the mimotopes of blood group RhD antigen by affinity panning a phage display library using monoclonal anti-D. After three rounds of biopanning, positive phage clones were identified by enzyme-linked immunosorbent assay (ELISA) and then sent for sequencing and peptides synthesis. Next, competitive ELISA and erythrocyte haemagglutination inhibition tests were carried out to confirm the inhibitory activity of the synthetic peptide. To evaluate the diagnostic performance of the synthetic peptide, a diagnostic ELISA was examined. Fourteen of 35 phage clones that were chosen randomly from the titering plate were considered to be positive. Following DNA sequencing and translation, 11 phage clones were found to represent the same peptide - RMKMLMMLMRRK (P4) - whereas each of the other three clones represented a unique peptide. Through the competitive ELISA and erythrocyte haemagglutination inhibition tests, the peptide (P4) was verified to have the ability to mimic the RhD antigen. The diagnostic ELISA for P4 proved to be sensitive (82.61%) and specific (88.57%). This study reveals that the P4 peptide can mimic RhD antigen and paves the way for the development of promising targeted diagnostic and therapeutic platforms for haemolytic disease of the foetus and newborn.

  9. Low blood sugar - newborns

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007306.htm Low blood sugar - newborns To use the sharing features on this page, please enable JavaScript. A low blood sugar level in newborn babies is also ...

  10. Senses and Your Newborn

    Science.gov (United States)

    ... will fully satisfy your baby. Why Is Touch Important? Touch is very important to a newborn. With ... your baby react to soft lullabies or other music? Even if your child passed the newborn hearing ...

  11. Hormonal effects in newborns

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/001911.htm Hormonal effects in newborns To use the sharing features on this page, please enable JavaScript. Hormonal effects in newborns occur because in the womb, babies ...

  12. Non-targeted acquisition strategy for screening doping compounds based on GC-EI-hybrid quadrupole-Orbitrap mass spectrometry: A focus on exogenous anabolic steroids.

    Science.gov (United States)

    de Albuquerque Cavalcanti, Gustavo; Rodrigues, Lucas Martins; Dos Santos, Leonardo; Zheng, Xin; Gujar, Amit; Cole, Jason; Padilha, Monica Costa; de Aquino Neto, Francisco Radler

    2018-03-01

    This is a first look at a non-targeted screening method based on Orbitrap gas chromatography-mass spectrometry (GC-MS) technology for a large number of banned compounds in sports found in urine, including exogenous anabolic steroids, β-agonists, narcotics, stimulants, hormone modulators, and diuretics. A simple sample preparation was processed in four steps: an enzymatic hydrolysis, liquid-liquid extraction, evaporation, and trimethylsilylation. All compounds were able to meet the World Anti-Doping Agency's sensitivity criteria with mass accuracies less than 1 ppm and with sufficient points across the peak by running the Orbitrap GC-MS in full-scan mode. In addition, we discuss our initial findings of using a full-scan selected ion monitoring-tandem mass spectrometry (SIM-MS/MS) approach as a way to obtain lower detection limits and reach desirable selectivity for some exogenous anabolic steroids. Copyright © 2017 John Wiley & Sons, Ltd.

  13. Rapid screening of non-steroidal anti-inflammatory drugs illegally added in anti-rheumatic herbal supplements and herbal remedies by portable ion mobility spectrometry.

    Science.gov (United States)

    Li, Mengjiao; Ma, Haiyan; Gao, Jinglin; Zhang, Lina; Wang, Xinyu; Liu, Di; Bian, Jing; Jiang, Ye

    2017-10-25

    In this work, for the first time, a high-performance ion mobility spectrometry with electrospray ionization (ESI-HPIMS) method has been employed as a rapid screening tool for the detection of acetaminophen, ibuprofen, naproxen, diclofenac sodium and indomethacin illegally added in anti-rheumatic herbal supplements and herbal remedies. Samples were dissolved and filtered through a 0.45μm microporous membrane, then the filtrate was directly injected into the high-performance ion mobility spectrometry for analysis. Using this approach, the screening of illegal additions can be accomplished in as rapid as two to three minutes with no pretreatment required. The proposed method provided a LOD of 0.06-0.33μgmL -1 , as well as a good seperation of the five NSAIDs. The precision of the method was 0.1-0.4% (repeatability, n=6) and 0.9-3.3% (reproducibility, n=3). The proposed method appeared to be simple, rapid and highly specific, thus could be effective for the in-situ screening of NSAIDs in anti-rheumatic herbal supplements and herbal remedies. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. A High-Throughput Mass Spectrometry Assay Coupled with Redox Activity Testing Reduces Artifacts and False Positives in Lysine Demethylase Screening.

    Science.gov (United States)

    Wigle, Tim J; Swinger, Kerren K; Campbell, John E; Scholle, Michael D; Sherrill, John; Admirand, Elizabeth A; Boriack-Sjodin, P Ann; Kuntz, Kevin W; Chesworth, Richard; Moyer, Mikel P; Scott, Margaret Porter; Copeland, Robert A

    2015-07-01

    Demethylation of histones by lysine demethylases (KDMs) plays a critical role in controlling gene transcription. Aberrant demethylation may play a causal role in diseases such as cancer. Despite the biological significance of these enzymes, there are limited assay technologies for study of KDMs and few quality chemical probes available to interrogate their biology. In this report, we demonstrate the utility of self-assembled monolayer desorption/ionization (SAMDI) mass spectrometry for the investigation of quantitative KDM enzyme kinetics and for high-throughput screening for KDM inhibitors. SAMDI can be performed in 384-well format and rapidly allows reaction components to be purified prior to injection into a mass spectrometer, without a throughput-limiting liquid chromatography step. We developed sensitive and robust assays for KDM1A (LSD1, AOF2) and KDM4C (JMJD2C, GASC1) and screened 13,824 compounds against each enzyme. Hits were rapidly triaged using a redox assay to identify compounds that interfered with the catalytic oxidation chemistry used by the KDMs for the demethylation reaction. We find that overall this high-throughput mass spectrometry platform coupled with the elimination of redox active compounds leads to a hit rate that is manageable for follow-up work. © 2015 Society for Laboratory Automation and Screening.

  15. Screening antiallergic components from Carthamus tinctorius using rat basophilic leukemia 2H3 cell membrane chromatography combined with high-performance liquid chromatography and tandem mass spectrometry.

    Science.gov (United States)

    Han, Shengli; Huang, Jing; Cui, Ronghua; Zhang, Tao

    2015-02-01

    Carthamus tinctorius, used in traditional Chinese medicine, has many pharmacological effects, such as anticoagulant effects, antioxidant effects, antiaging effects, regulation of gene expression, and antitumor effects. However, there is no report on the antiallergic effects of the components in C. tinctorius. In the present study, we investigated the antiallergic components of C. tinctorius and its mechanism of action. A rat basophilic leukemia 2H3/cell membrane chromatography coupled online with high-performance liquid chromatography and tandem mass spectrometry method was developed to screen antiallergic components from C. tinctorius. The screening results showed that Hydroxysafflor yellow A, from C. tinctorius, was the targeted component that retained on the rat basophilic leukemia 2H3/cell membrane chromatography column. We measured the amount of β-hexosaminidase and histamine released in mast cells and the key markers of degranulation. The release assays showed that Hydroxysafflor yellow A could attenuate the immunoglobulin E induced release of allergic cytokines without affecting cell viability from 1.0 to 50.0 μM. In conclusion, the established rat basophilic leukemia 2H3 cell membrane chromatography coupled with online high-performance liquid chromatography and tandem mass spectrometry method successfully screened and identified Hydroxysafflor yellow A from C. tinctorius as a potential antiallergic component. Pharmacological analysis elucidated that Hydroxysafflor yellow A is an effective natural component for inhibiting immunoglobulin E-antigen-mediated degranulation. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Hip sonography in the newborn

    International Nuclear Information System (INIS)

    Riboni, G.; Serantoni, S.; De Simoni, M.; Bascape', P.; Facchini, R.; Pirovano, G.

    1991-01-01

    The authors report the data relative to 1507 cases studied with clinical and US examinations, in the neonatal period, in order to exclude hip dysplasia dislocation. US examination was carried out according to Graf's technique and the newborns were classified according to US hip type, to clinical examination and to possible risk factors. The patients were included in a protocol including orthopedic and US controls. Seventeen treated infants were considered as pathologic. Ten of them had IIc or D hips ar birth; the other 7, with IIa hips at birth, presented a X-ray pathologic hip after the 4th months of life. At about one year of age all infants could normally walk, excpet for one who was being treated with herness. No statistically significant differences were observed between the number of pathologic infants in the risk group (1.7%) and that in the no-risk group (0.8%). Clinical examination of the newborn has low sensitivity in detecting pathologic hips. On the basis of their results, thw authors belive US examination of the newborn to be a valuable screening method to diagnose hip dysplasia/dislocation. Moreover, Graf's morphologic method is the best one for US screening of the hip in the neonatal period

  17. Screening anti-tumor compounds from Ligusticum wallichii using cell membrane chromatography combined with high-performance liquid chromatography and mass spectrometry.

    Science.gov (United States)

    Zhang, Tao; Ding, Yuanyuan; An, Hongli; Feng, Liuxin; Wang, Sicen

    2015-07-14

    Tyrosine 367 Cysteine-fibroblast growth factor receptor 4 cell membrane chromatography combined with high-performance liquid chromatography and mass spectrometry was developed. Tyrosine 367 Cysteine-HEK293 cells were used as cell membrane stationary phase. Specificity and reproducibility of the cell membrane chromatography was evaluated using 1-tert-butyl-3-{2-[4-(diethylamino)butylamino]-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl}urea, Nimodipine and dexamethasone acetate. Then, anti-tumor components acting on Tyrosine 367 Cysteine-fibroblast growth factor receptor 4 were screened and identified from extracts of Ligusticum wallichii. Components from the extract were retained on the cell membrane chromatographic column. The retained fraction was directly eluted into high-performance liquid chromatography with mass spectrometry system for separation and identification. Finally, Levistolide A was identified as an active component from Ligusticum wallichii extracts. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide-formazan colorimetric assay revealed that Levistolide A inhibits proliferation of overexpressing the mutated receptor cells with dose-dependent manner. Phosphorylation of fibroblast growth factor receptor 4 was also decrease under Levistolide A treatment. Flex dock simulation verified that Levistolide A could bind with the tyrosine kinase domain of fibroblast growth factor receptor 4. Therefore, Levistolide A screened by the cell membrane chromatography combined with high-performance liquid chromatography and mass spectrometry can arrest cell growth. In conclusion, the two-dimensional high-performance liquid chromatography method can screen and identify potential anti-tumor ingredients which specifically act on the tyrosine kinase domain of the mutated fibroblast growth factor receptor 4. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  18. Use of radioimmunoassay as a screen for antibiotics in confined animal feeding operations and confirmation by liquid chromatography/mass spectrometry

    Science.gov (United States)

    Meyer, M.T.; Bumgarner, J.E.; Varns, J.L.; Daughtridge, J.V.; Thurman, E.M.; Hostetler, K.A.

    2000-01-01

    Approximately one-half of the 50 000000 lb of antibiotics produced in the USA are used in agriculture. Because of the intensive use of antibiotics in the management of confined livestock operations, the potential exists for the transport of these compounds and their metabolites into our nation's water resources. A commercially available radioimmunoassay method, developed as a screen for tetracycline antibiotics in serum, urine, milk, and tissue, was adapted to analyze water samples at a detection level of approximately 1.0 ppb and a semiquantitative analytical range of 1-20 ppb. Liquid waste samples were obtained from 13 hog lagoons in three states and 52 surface- and ground-water samples were obtained primarily from areas associated with intensive swine and poultry production in seven states. These samples were screened for the tetracycline antibiotics by using the modified radioimmunoassay screening method. The radioimmunoassay tests yielded positive results for tetracycline antibiotics in samples from all 13 of the hog lagoons. Dilutions of 10-100-fold of the hog lagoon samples indicated that tetracycline antibiotic concentrations ranged from approximately 5 to several hundred parts per billion in liquid hog lagoon waste. Of the 52 surface- and ground-water samples collected all but two tested negative and these two samples contained tetracycline antibiotic concentrations less than 1 ppb. A new liquid chromatography/mass spectrometry method was used to confirm the radioimmunoassay results in 9 samples and also to identify the tetracycline antibiotics to which the radioimmunoassay test was responding. The new liquid chromatography/mass spectrometry method with online solid-phase extraction and a detection level of 0.5 ??g/l confirmed the presence of chlorotetracycline in the hog lagoon samples and in one of the surface-water samples. The concentrations calculated from the radioimmunoassay were a factor of 1-5 times less than those calculated by the liquid

  19. Prediction of collision cross section and retention time for broad scope screening in gradient reversed-phase liquid chromatography-ion mobility-high resolution accurate mass spectrometry

    DEFF Research Database (Denmark)

    Mollerup, Christian Brinch; Mardal, Marie; Dalsgaard, Petur Weihe

    2018-01-01

    artificial neural networks (ANNs). Prediction was based on molecular descriptors, 827 RTs, and 357 CCS values from pharmaceuticals, drugs of abuse, and their metabolites. ANN models for the prediction of RT or CCS separately were examined, and the potential to predict both from a single model......Exact mass, retention time (RT), and collision cross section (CCS) are used as identification parameters in liquid chromatography coupled to ion mobility high resolution accurate mass spectrometry (LC-IM-HRMS). Targeted screening analyses are now more flexible and can be expanded for suspect...

  20. Screening for potential child maltreatment in parents of a newborn baby: The predictive validity of an Instrument for early identification of Parents At Risk for child Abuse and Neglect (IPARAN).

    Science.gov (United States)

    van der Put, Claudia E; Bouwmeester-Landweer, Merian B R; Landsmeer-Beker, Eleonore A; Wit, Jan M; Dekker, Friedo W; Kousemaker, N Pieter J; Baartman, Herman E M

    2017-08-01

    For preventive purposes it is important to be able to identify families with a high risk of child maltreatment at an early stage. Therefore we developed an actuarial instrument for screening families with a newborn baby, the Instrument for identification of Parents At Risk for child Abuse and Neglect (IPARAN). The aim of this study was to assess the predictive validity of the IPARAN and to examine whether combining actuarial and clinical methods leads to an improvement of the predictive validity. We examined the predictive validity by calculating several performance indicators (i.e., sensitivity, specificity and the Area Under the receiver operating characteristic Curve [AUC]) in a sample of 4692 Dutch families with newborns. The outcome measure was a report of child maltreatment at Child Protection Services during a follow-up of 3 years. For 17 children (.4%) a report of maltreatment was registered. The predictive validity of the IPARAN was significantly better than chance (AUC=.700, 95% CI [.567-.832]), in contrast to a low value for clinical judgement of nurses of the Youth Health Care Centers (AUC=.591, 95% CI [.422-.759]). The combination of the IPARAN and clinical judgement resulted in the highest predictive validity (AUC=.720, 95% CI [.593-.847]), however, the difference between the methods did not reach statistical significance. The good predictive validity of the IPARAN in combination with clinical judgment of the nurse enables professionals to assess risks at an early stage and to make referrals to early intervention programs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Receptor-based high-throughput screening and identification of estrogens in dietary supplements using bioaffinity liquid-chromatography ion mobility mass spectrometry.

    Science.gov (United States)

    Aqai, Payam; Blesa, Natalia Gómez; Major, Hilary; Pedotti, Mattia; Varani, Luca; Ferrero, Valentina E V; Haasnoot, Willem; Nielen, Michel W F

    2013-11-01

    A high-throughput bioaffinity liquid chromatography-mass spectrometry (BioMS) approach was developed and applied for the screening and identification of recombinant human estrogen receptor α (ERα) ligands in dietary supplements. For screening, a semi-automated mass spectrometric ligand binding assay was developed applying (13)C2, (15) N-tamoxifen as non-radioactive label and fast ultra-high-performance-liquid chromatography-electrospray ionisation-triple-quadrupole-MS (UPLC-QqQ-MS), operated in the single reaction monitoring mode, as a readout system. Binding of the label to ERα-coated paramagnetic microbeads was inhibited by competing estrogens in the sample extract yielding decreased levels of the label in UPLC-QqQ-MS. The label showed high ionisation efficiency in positive electrospray ionisation (ESI) mode, so the developed BioMS approach is able to screen for estrogens in dietary supplements despite their poor ionisation efficiency in both positive and negative ESI modes. The assay was performed in a 96-well plate, and all these wells could be measured within 3 h. Estrogens in suspect extracts were identified by full-scan accurate mass and collision-cross section (CCS) values from a UPLC-ion mobility-Q-time-of-flight-MS (UPLC-IM-Q-ToF-MS) equipped with a novel atmospheric pressure ionisation source. Thanks to the novel ion source, this instrument provided picogram sensitivity for estrogens in the negative ion mode and an additional identification point (experimental CCS values) next to retention time, accurate mass and tandem mass spectrometry data. The developed combination of bioaffinity screening with UPLC-QqQ-MS and identification with UPLC-IM-Q-ToF-MS provides an extremely powerful analytical tool for early warning of ERα bioactive compounds in dietary supplements as demonstrated by analysis of selected dietary supplements in which different estrogens were identified.

  2. A simpler sampling interface of venturi easy ambient sonic-spray ionization mass spectrometry for high-throughput screening enzyme inhibitors.

    Science.gov (United States)

    Liu, Ning; Liu, Yang; Yang, YuHan; He, Lan; Ouyang, Jin

    2016-03-24

    High-throughput screening (HTS) is often required in enzyme inhibitor drugs screening. Mass spectrometry (MS) provides a powerful method for high-throughput screening enzyme inhibitors because its high speed, sensitivity and property of lable free. However, most of the MS methods need complicated sampling interface system. Overall throughput was limited by sample loading in these cases. In this study, we develop a simple interface which coupled droplet segmented system to a venturi easy ambient sonic-spray ionization mass spectrometer. It is fabricated by using a single capillary to act as both sampling probe and the emitter, which simplifies the construction, reduces the cost and shorten the sampling time. Samples sucked by venturi effect are segmented to nanoliter plugs by air, then the plugs can be detected by MS directly. This system eliminated the need for flow injection which was popular used in classic scheme. The new system is applied to screen angiotensin converting enzyme inhibitors. High-throughput was achieved in analyzing 96 samples at 1.6 s per sample. The plugs formation was at 0.5s per sample. Carry-over between samples was less than 5%, the peak height RSD was 2.92% (n = 15). Dose-response curves of 3 known inhibitors were also measured to validate its potential in drug discovery. The calculated IC50 agreed well with reported values. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Screening of HIV-1 Protease Using a Combination of an Ultra-High-Throughput Fluorescent-Based Assay and RapidFire Mass Spectrometry.

    Science.gov (United States)

    Meng, Juncai; Lai, Ming-Tain; Munshi, Vandna; Grobler, Jay; McCauley, John; Zuck, Paul; Johnson, Eric N; Uebele, Victor N; Hermes, Jeffrey D; Adam, Gregory C

    2015-06-01

    HIV-1 protease (PR) represents one of the primary targets for developing antiviral agents for the treatment of HIV-infected patients. To identify novel PR inhibitors, a label-free, high-throughput mass spectrometry (HTMS) assay was developed using the RapidFire platform and applied as an orthogonal assay to confirm hits identified in a fluorescence resonance energy transfer (FRET)-based primary screen of > 1 million compounds. For substrate selection, a panel of peptide substrates derived from natural processing sites for PR was evaluated on the RapidFire platform. As a result, KVSLNFPIL, a new substrate measured to have a ~ 20- and 60-fold improvement in k cat/K m over the frequently used sequences SQNYPIVQ and SQNYPIV, respectively, was identified for the HTMS screen. About 17% of hits from the FRET-based primary screen were confirmed in the HTMS confirmatory assay including all 304 known PR inhibitors in the set, demonstrating that the HTMS assay is effective at triaging false-positives while capturing true hits. Hence, with a sampling rate of ~7 s per well, the RapidFire HTMS assay enables the high-throughput evaluation of peptide substrates and functions as an efficient tool for hits triage in the discovery of novel PR inhibitors. © 2015 Society for Laboratory Automation and Screening.

  4. Use of ultra-high pressure liquid chromatography coupled to high resolution mass spectrometry for fast screening in high throughput doping control.

    Science.gov (United States)

    Musenga, Alessandro; Cowan, David A

    2013-05-03

    We describe a sensitive, comprehensive and fast screening method based on liquid chromatography-high resolution mass spectrometry for the detection of a large number of analytes in sports samples. UHPLC coupled to high resolution mass spectrometry with polarity switching capability is applied for the rapid screening of a large number of analytes in human urine samples. Full scan data are acquired alternating both positive and negative ionisation. Collision-induced dissociation with positive ionisation is also performed to produce fragment ions to improve selectivity for some analytes. Data are reviewed as extracted ion chromatograms based on narrow mass/charge windows (±5ppm). A simple sample preparation method was developed, using direct enzymatic hydrolysis of glucuronide conjugates, followed by solid phase extraction with mixed mode ion-exchange cartridges. Within a 10min run time (including re-equilibration) the method presented allows for the analysis of a large number of analytes from most of the classes in the World Anti-Doping Agency (WADA) Prohibited List, including anabolic agents, β2-agonists, hormone antagonists and modulators, diuretics, stimulants, narcotics, glucocorticoids and β-blockers, and does so while meeting the WADA sensitivity requirements. The high throughput of the method and the fast sample pre-treatment reduces analysis cost and increases productivity. The method presented has been used for the analysis of over 5000 samples in about one month and proved to be reliable. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Functionalized graphene quantum dots loaded with free radicals combined with liquid chromatography and tandem mass spectrometry to screen radical scavenging natural antioxidants from Licorice and Scutellariae.

    Science.gov (United States)

    Wang, Guoying; Niu, XiuLi; Shi, Gaofeng; Chen, Xuefu; Yao, Ruixing; Chen, Fuwen

    2014-12-01

    A novel screening method was developed for the detection and identification of radical scavenging natural antioxidants based on a free radical reaction combined with liquid chromatography with tandem mass spectrometry. Functionalized graphene quantum dots were prepared for loading free radicals in the complex screening system. The detection was performed with and without a preliminary exposure of the samples to specific free radicals on the functionalized graphene quantum dots, which can facilitate charge transfer between free radicals and antioxidants. The difference in chromatographic peak areas was used to identify potential antioxidants. This is a novel approach to simultaneously evaluate the antioxidant power of a component versus a free radical, and to identify it in a vegetal matrix. The structures of the antioxidants in the samples were identified using tandem mass spectrometry and comparison with standards. Fourteen compounds were found to possess potential antioxidant activity, and their free radical scavenging capacities were investigated. The order of scavenging capacity of 14 compounds was compared according to their free radical scavenging rate. 4',5,6,7-Tetrahydroxyflavone (radical scavenging rate: 0.05253 mL mg(-1) s(-1) ) showed the strongest capability for scavenging free radicals. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Fast screening of short-chain chlorinated paraffins in indoor dust samples by graphene-assisted laser desorption/ionization mass spectrometry.

    Science.gov (United States)

    Huang, Xiu; Liu, Qian; Gao, Wei; Wang, Yawei; Nie, Zhou; Yao, Shouzhuo; Jiang, Guibin

    2018-03-01

    As an important class of emerging chemical contaminants, short-chain chlorinated paraffins (SCCPs) are considered as one of the most challenging groups of compounds to analyze. In this paper, we report a new method for fast screening of SCCPs based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with graphene as a matrix and 2,5,6,9-tetrachlorodecane as an internal standard. We found that the use of graphene as MALDI matrix generated high peak intensities for SCCPs while producing few background noises. The ion fragmentation mechanisms of SCCPs in MALDI are discussed in detail. Under the optimized conditions, much lower detection limits of SCCP congeners (0.1-5ng/mL) than those reported previously were obtained. Other distinct advantages such as short analysis time and simplified sample preparation procedures are also demonstrated. The method was successfully applied in fast screening of SCCPs in indoor dust samples and monitoring of human exposure levels to SCCPs, and the results were verified by gas chromatography coupled to negative chemical ionization quadrupole time-of-flight high-resolution mass spectrometry. This work not only offers a new promising tool for SCCP studies, but also further demonstrates the promise of graphene as a new generation of MALDI matrix. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. A Machine Learning Application Based in Random Forest for Integrating Mass Spectrometry-Based Metabolomic Data: A Simple Screening Method for Patients With Zika Virus.

    Science.gov (United States)

    Melo, Carlos Fernando Odir Rodrigues; Navarro, Luiz Claudio; de Oliveira, Diogo Noin; Guerreiro, Tatiane Melina; Lima, Estela de Oliveira; Delafiori, Jeany; Dabaja, Mohamed Ziad; Ribeiro, Marta da Silva; de Menezes, Maico; Rodrigues, Rafael Gustavo Martins; Morishita, Karen Noda; Esteves, Cibele Zanardi; de Amorim, Aline Lopes Lucas; Aoyagui, Caroline Tiemi; Parise, Pierina Lorencini; Milanez, Guilherme Paier; do Nascimento, Gabriela Mansano; Ribas Freitas, André Ricardo; Angerami, Rodrigo; Costa, Fábio Trindade Maranhão; Arns, Clarice Weis; Resende, Mariangela Ribeiro; Amaral, Eliana; Junior, Renato Passini; Ribeiro-do-Valle, Carolina C; Milanez, Helaine; Moretti, Maria Luiza; Proenca-Modena, Jose Luiz; Avila, Sandra; Rocha, Anderson; Catharino, Rodrigo Ramos

    2018-01-01

    Recent Zika outbreaks in South America, accompanied by unexpectedly severe clinical complications have brought much interest in fast and reliable screening methods for ZIKV (Zika virus) identification. Reverse-transcriptase polymerase chain reaction (RT-PCR) is currently the method of choice to detect ZIKV in biological samples. This approach, nonetheless, demands a considerable amount of time and resources such as kits and reagents that, in endemic areas, may result in a substantial financial burden over affected individuals and health services veering away from RT-PCR analysis. This study presents a powerful combination of high-resolution mass spectrometry and a machine-learning prediction model for data analysis to assess the existence of ZIKV infection across a series of patients that bear similar symptomatic conditions, but not necessarily are infected with the disease. By using mass spectrometric data that are inputted with the developed decision-making algorithm, we were able to provide a set of features that work as a "fingerprint" for this specific pathophysiological condition, even after the acute phase of infection. Since both mass spectrometry and machine learning approaches are well-established and have largely utilized tools within their respective fields, this combination of methods emerges as a distinct alternative for clinical applications, providing a diagnostic screening-faster and more accurate-with improved cost-effectiveness when compared to existing technologies.

  8. Osteoblast cell membrane chromatography coupled with liquid chromatography and time-of-flight mass spectrometry for screening specific active components from traditional Chinese medicines.

    Science.gov (United States)

    Wang, Nani; Zhang, Qiaoyan; Xin, Hailiang; Shou, Dan; Qin, Luping

    2017-11-01

    A method using osteoblast membrane chromatography coupled with liquid chromatography and time-of-flight mass spectrometry was developed to recognize and identify the specific active components from traditional Chinese medicines. Primary rat osteoblasts were used for the preparation of the stationary phase in the cell chromatography method. Retention components from the cell chromatography were collected and analyzed by liquid chromatography with time-of-flight mass spectrometry. This method was applied in screening active components from extracts of four traditional Chinese medicines. In total, 24 potentially active components with different structures were retained by osteoblast cell chromatography. There were five phenolic glucosides and one triterpenoid saponin from Curculigo orchioides Gaertn, two organic acids and ten flavonoids from Epimedium sagittatum Maxim, one phthalide compound and one organic acid from Angelica sinensis Diels, and two flavonoids and two saponins from Anemarrhena asphodeloides Bunge. Among those, four components (icariin, curculigoside, ferulaic acid, and timosaponin BII) were used for in vitro pharmacodynamics validation. They significantly increased the osteoblast proliferation, alkaline phosphatase activity, levels of bone gla protein and collagen type 1, and promoted mineralized nodule formation. The developed method was an effective screening method for finding active components from complex medicines that act on bone diseases. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Phenylketonuria, congenital hypothyroidism and haemoglobinopathies: public health issues for a Brazilian newborn screening program Fenilcetonúria, hipotireoidismo congênito e hemoglobinopatias: questões de saúde pública para um programa de triagem neonatal brasileiro

    Directory of Open Access Journals (Sweden)

    Judy Botler

    2012-09-01

    Full Text Available In this study, the frequency of detected congenital hypothyroidism, phenylketonuria and haemoglobinopathies in the State of Rio de Janeiro's (Brazil Newborn Screening Program (NBSP was analyzed between the years of 2005 and 2007. There were two Newborn Screening Reference Centers (named NSRC A and B with programmatic differences. In 2007, overall detection coverage reached 80.7%. The increase in the incidence of congenital hypothyroidism (1:1,030 in 2007 was attributed to the reduction of neonatal TSH value limits over time. The incidence discrepancy of phenylketonuria between NSRC A (1:28,427 and B (1:16,522 might be partially explained by the small number of cases. The incidence of sickle cell disease and its traits were uniformly high (1:1,288 and 1:21, respectively. This was coherent with the ethnic composition of the population. The differences in laboratory methods and critical values, in addition to other programmatic issues, may explain the variances in the results and limited analysis of the role of biological and environmental determinants in the occurrence of these diseases.Neste estudo, foi analisada a frequência de detecção do hipotireoidismo congênito, fenilcetonúria e hemoglobinopatias no Programa de Triagem Neonatal do Estado do Rio de Janeiro, Brasil, entre 2005 e 2007. Havia dois Serviços de Referência em Triagem Neonatal (designados SRTN A e B com diferenças programáticas. Em 2007, a cobertura alcançou 80,7%. O aumento na incidência do hipotireoidismo congênito (1:1.030 em 2007 foi atribuído à redução no valor de corte do TSH ao longo do tempo. As incidências discrepantes da fenilcetonúria entre os modelos (SRTN A - 1:28.427; SR-TN B - 1:16.522 podem ser parcialmente explicadas pelo pequeno número de casos. A incidência da doença falciforme e do traço falcêmico foi uniformemente elevada (1:1.288 e 1:21, respectivamente, sendo coerente com a composição étnica da população. As diferenças nos m

  10. Multicomponent mixed dopant optimization for rapid screening of polycyclic aromatic hydrocarbons using ultra high performance liquid chromatography coupled to atmospheric pressure photoionization high-resolution mass spectrometry

    KAUST Repository

    Sioud, Salim

    2012-05-04

    RATIONALE To enhance the ionization efficiencies in atmospheric pressure photoionization mass spectrometry a dopant with favorable ionization energy such as chlorobenzene is typically used. These dopants are typically toxic and difficult to mix with water-soluble organic solvents. In order to achieve a more efficient and less toxic dopant, a multicomponent mixed dopant was explored. METHODS A multicomponent mixed dopant for non-targeted rapid screening of polycyclic aromatic hydrocarbons (PAHs) was developed and optimized using ultra high performance liquid chromatography (UPLC) coupled to atmospheric pressure photoionization high-resolution mass spectrometry. Various single and multicomponent mixed dopants consisting of ethanol, chlorobenzene, bromobenzene, anisole and toluene were evaluated. RESULTS Fourteen out of eighteen PAHs were successfully separated and detected at low pg/μL levels within 5 min with high mass accuracy ≤4 ppm. The optimal mixed multicomponent dopant consisted of ethanol/chlorobenzene/bromobenzene/anisole (98.975:0.1:0.9:0.025, v/v %) and it improved the limit of detection (LOD) by 2- to 10-fold for the tested PAHs compared to those obtained with pure chlorobenzene. CONCLUSIONS A novel multicomponent dopant that contains 99% ethanol and 1% mixture of chlorobenzene, bromobenzene and anisole was found to be an effective dopant mixture to ionize PAHs. The developed UPLC multicomponent dopant assisted atmospheric pressure photoionization high-resolution mass spectrometry offered a rapid non targeted screening method for detecting the PAHs at low pg/;μL levels within a 5 min run time with high mass accuracy a;circ4 ppm. Copyright © 2012 John Wiley & Sons, Ltd.

  11. Screening in veterinary drug analysis and sports doping control based on full-scan, accurate-mass spectrometry

    NARCIS (Netherlands)

    Peters, R.J.B.; Stolker, A.A.M.; Mol, J.G.J.; Lommen, A.; Lyris, E.; Angelis, Y.S.; Vonaparti, A.; Stamou, M.; Georgakopoulos, C.G.; Nielen, M.W.F.

    2010-01-01

    A common trend in food contaminants and sports doping control is towards a limited number of targeted, full-scan, accurate-mass spectrometry (MS) methods based on time-of-flight (TOF) or Fourier-transform orbital trap (Orbitrap) mass analyzers. Retrospective analysis of the full-scan datasets of

  12. Screening of plant toxins in food,feed and botanicals using full-scan high-resolution (Orbitrap) mass spectrometry

    NARCIS (Netherlands)

    Mol, J.G.J.; Dam, van R.C.J.; Zomer, P.; Mulder, P.P.J.

    2011-01-01

    A generic method based on LC with full-scan high-resolution (Orbitrap) mass spectrometry (MS) was systematically investigated for the simultaneous detection of a wide range of plant toxins in a variety of food and feed matrices. For a selection of 150 substances, representing various chemical

  13. Development of a high-throughput screening assay for stearoyl-CoA desaturase using rat liver microsomes, deuterium labeled stearoyl-CoA and mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Soulard, Patricia; McLaughlin, Meg; Stevens, Jessica; Connolly, Brendan; Coli, Rocco; Wang Leyu [Research Technology Center, Pfizer Global Research and Development, Cambridge, MA (United States); Moore, Jennifer; Kuo, Ming-Shang T. [Pfizer Global Research and Development, San Diego, CA (United States); LaMarr, William A.; Ozbal, Can C. [Biotrove, Inc., Woburn, MA (United States); Bhat, B. Ganesh [Pfizer Global Research and Development, San Diego, CA (United States)], E-mail: gbhat@gnf.org

    2008-10-03

    Several recent reports suggest that stearoyl-CoA desaturase 1 (SCD1), the rate-limiting enzyme in monounsaturated fatty acid synthesis, plays an important role in regulating lipid homeostasis and lipid oxidation in metabolically active tissues. As several manifestations of type 2 diabetes and related metabolic disorders are associated with alterations in intracellular lipid partitioning, pharmacological manipulation of SCD1 activity might be of benefit in the treatment of these disease states. In an effort to identify small molecule inhibitors of SCD1, we have developed a mass spectrometry based high-throughput screening (HTS) assay using deuterium labeled stearoyl-CoA substrate and induced rat liver microsomes. The methodology developed allows the use of a nonradioactive substrate which avoids interference by the endogenous SCD1 substrate and/or product that exist in the non-purified enzyme source. Throughput of the assay was up to twenty 384-well assay plates per day. The assay was linear with protein concentration and time, and was saturable for stearoyl-CoA substrate (K{sub m} = 10.5 {mu}M). The assay was highly reproducible with an average Z' value = 0.6. Conjugated linoleic acid and sterculic acid, known inhibitors of SCD1, exhibited IC{sub 50} values of 0.88 and 0.12 {mu}M, respectively. High-throughput mass spectrometry screening of over 1.7 million compounds in compressed format demonstrated that the enzyme target is druggable. A total of 2515 hits were identified (0.1% hit rate), and 346 were confirmed active (>40% inhibition of total SCD activity at 20 {mu}M - 14% conformation rate). Of the confirmed hits 172 had IC{sub 50} values of <10 {mu}M, including 111 <1 {mu}M and 48 <100 nM. A large number of potent drug-like (MW < 450) hits representing six different chemical series were identified. The application of mass spectrometry to high-throughput screening permitted the development of a high-quality screening protocol for an otherwise intractable

  14. Development of a high-throughput screening assay for stearoyl-CoA desaturase using rat liver microsomes, deuterium labeled stearoyl-CoA and mass spectrometry

    International Nuclear Information System (INIS)

    Soulard, Patricia; McLaughlin, Meg; Stevens, Jessica; Connolly, Brendan; Coli, Rocco; Wang Leyu; Moore, Jennifer; Kuo, Ming-Shang T.; LaMarr, William A.; Ozbal, Can C.; Bhat, B. Ganesh

    2008-01-01

    Several recent reports suggest that stearoyl-CoA desaturase 1 (SCD1), the rate-limiting enzyme in monounsaturated fatty acid synthesis, plays an important role in regulating lipid homeostasis and lipid oxidation in metabolically active tissues. As several manifestations of type 2 diabetes and related metabolic disorders are associated with alterations in intracellular lipid partitioning, pharmacological manipulation of SCD1 activity might be of benefit in the treatment of these disease states. In an effort to identify small molecule inhibitors of SCD1, we have developed a mass spectrometry based high-throughput screening (HTS) assay using deuterium labeled stearoyl-CoA substrate and induced rat liver microsomes. The methodology developed allows the use of a nonradioactive substrate which avoids interference by the endogenous SCD1 substrate and/or product that exist in the non-purified enzyme source. Throughput of the assay was up to twenty 384-well assay plates per day. The assay was linear with protein concentration and time, and was saturable for stearoyl-CoA substrate (K m = 10.5 μM). The assay was highly reproducible with an average Z' value = 0.6. Conjugated linoleic acid and sterculic acid, known inhibitors of SCD1, exhibited IC 50 values of 0.88 and 0.12 μM, respectively. High-throughput mass spectrometry screening of over 1.7 million compounds in compressed format demonstrated that the enzyme target is druggable. A total of 2515 hits were identified (0.1% hit rate), and 346 were confirmed active (>40% inhibition of total SCD activity at 20 μM - 14% conformation rate). Of the confirmed hits 172 had IC 50 values of <10 μM, including 111 <1 μM and 48 <100 nM. A large number of potent drug-like (MW < 450) hits representing six different chemical series were identified. The application of mass spectrometry to high-throughput screening permitted the development of a high-quality screening protocol for an otherwise intractable target, SCD1. Further medicinal

  15. HAMS: High-Affinity Mass Spectrometry Screening. A High-Throughput Screening Method for Identifying the Tightest-Binding Lead Compounds for Target Proteins with No False Positive Identifications.

    Science.gov (United States)

    Imaduwage, Kasun P; Go, Eden P; Zhu, Zhikai; Desaire, Heather

    2016-11-01

    A major challenge in drug discovery is the identification of high affinity lead compounds that bind a particular target protein; these leads are typically identified by high throughput screens. Mass spectrometry has become a detection method of choice in drug screening assays because the target and the ligand need not be modified. Label-free assays are advantageous because they can be developed more rapidly than assays requiring labels, and they eliminate the risk of the label interfering with the binding event. However, in commonly used MS-based screening methods, detection of false positives is a major challenge. Here, we describe a detection strategy designed to eliminate false positives. In this approach, the protein and the ligands are incubated together, and the non-binders are separated for detection. Hits (protein binders) are not detectable by MS after incubation with the protein, but readily identifiable by MS when the target protein is not present in the incubation media. The assay was demonstrated using three different proteins and hundreds of non-inhibitors; no false positive hits were identified in any experiment. The assay can be tuned to select for ligands of a particular binding affinity by varying the quantity of protein used and the immobilization method. As examples, the method selectively detected inhibitors that have K i values of 0.2 μM, 50 pM, and 700 pM. These findings demonstrate that the approach described here compares favorably with traditional MS-based screening methods. Graphical Abstract ᅟ.

  16. Resuscitation of the Newborn

    Science.gov (United States)

    Kilduff, C. J.

    1975-01-01

    All infants have some degree of hypoxia and respiratory acidosis at birth, but these conditions are more profound in the asphyxiated newborn. The newborn infant is very susceptible to cooling and may require warming. Skin temperature should be maintained between 36-36.5°.2 Resuscitation of the asphyxiated newborn must include both ventilatory and metabolic correction. Newborn infants may have cardiorespiratory problems due to asphyxia, drugs given to the mother, intrathoracic disease, anemia, hypovolemia (due to antepartum hemorrhage), hypotension, etc. There is no substitute for oxygen which is the drug of choice in respiratory depression of the newborn. The use of stimulating drugs like Coramine, picrotoxin, alphalobectine, and Megamide has no place in the resuscitation of the asphyxiated newborn. Imagesp74-ap74-bp74-cp74-d PMID:20469196

  17. A brief review on newborn screening methods for hemoglobinopathies and preliminary results selecting beta thalassemia carriers at birth by quantitative estimation of the HbA fraction.

    Science.gov (United States)

    Mantikou, Eleni; Arkesteijn, Sandra G; Beckhoven van, Jaqueline M; Kerkhoffs, Jean-Louis; Harteveld, Cornelis L; Giordano, Piero Carlo

    2009-12-01

    We present in a brief summary the basic aspects of the most rational technologies used for new born screening (NBS) of the hemoglobinopathies and we report the preliminary results for the identification of beta-thalassemia carriers at birth by measuring the expression of the HbA fraction. Separation and measurement of the Hb fractions in 1.500 cord blood samples collected among the multi-ethnic Dutch population using different methods. By using a cut of thalassemia can be preselected at birth with a reasonable degree of sensitivity and be confirmed by parent analysis.

  18. Nanoparticle-assisted laser desorption/ionization mass spectrometry: Novel sample preparation methods and nanoparticle screening for plant metabolite imaging

    Energy Technology Data Exchange (ETDEWEB)

    Yagnik, Gargey B. [Iowa State Univ., Ames, IA (United States)

    2016-02-19

    The main goal of the presented research is development of nanoparticle based matrix-assisted laser desorption ionization-mass spectrometry (MALDI-MS). This dissertation includes the application of previously developed data acquisition methods, development of novel sample preparation methods, application and comparison of novel nanoparticle matrices, and comparison of two nanoparticle matrix application methods for MALDI-MS and MALDI-MS imaging.

  19. Direct Growth of Bacteria in Headspace Vials Allows for Screening of Volatiles by Gas Chromatography Mass Spectrometry

    OpenAIRE

    Collin M. Timm; Evan P. Lloyd; Amanda Egan; Ray Mariner; David Karig

    2018-01-01

    Bacterially produced volatile organic compounds (VOCs) can modify growth patterns of eukaryotic hosts and competing/cohabiting microbes. These compounds have been implicated in skin disorders and attraction of biting pests. Current methods to detect and characterize VOCs from microbial cultures can be laborious and low-throughput, making it difficult to understand the behavior of microbial populations. In this work we present an efficient method employing gas chromatography/mass spectrometry ...

  20. High-Risk Screening for Fabry Disease: Analysis by Tandem Mass Spectrometry of Globotriaosylceramide (Gb3 ) in Urine Collected on Filter Paper.

    Science.gov (United States)

    Auray-Blais, Christiane; Lavoie, Pamela; Boutin, Michel; Abaoui, Mona

    2017-04-06

    Fabry disease is a complex, panethnic lysosomal storage disorder. It is characterized by the accumulation of glycosphingolipids in tissues, organs, the vascular endothelium, and biological fluids. The reported incidence in different populations is quite variable, ranging from 1:1400 to 1:117,000. Its complexity lies in the marked genotypic and phenotypic heterogeneity. Despite the fact that it is an X-linked disease, more than 600 mutations affect both males and females. In fact, some females may be affected as severely as males. The purpose of this protocol is to focus on the high-risk screening of patients who might have Fabry disease using a simple, rapid, non-invasive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for urinary globotriaosylceramide (Gb 3 ) analysis. Urine filter paper samples are easily collected at home by patients and sent by regular mail. This method has been successfully used for high-risk screening of patients with ophthalmologic manifestations and in an on-going study for high-risk screening of Fabry disease in patients with chronic kidney diseases. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  1. [Screening and confirmation of 24 hormones in cosmetics by ultra high performance liquid chromatography-linear ion trap/orbitrap high resolution mass spectrometry].

    Science.gov (United States)

    Li, Zhaoyong; Wang, Fengmei; Niu, Zengyuan; Luo, Xin; Zhang, Gang; Chen, Junhui

    2014-05-01

    A method of ultra high performance liquid chromatography-linear ion trap/orbitrap high resolution mass spectrometry (UPLC-LTQ/Orbitrap MS) was established to screen and confirm 24 hormones in cosmetics. Various cosmetic samples were extracted with methanol. The extract was loaded onto a Waters ACQUITY UPLC BEH C18 column (50 mm x 2.1 mm, 1.7 microm) using a gradient elution of acetonitrile/water containing 0.1% (v/v) formic acid for the separation. The accurate mass of quasi-molecular ion was acquired by full scanning of electrostatic field orbitrap. The rapid screening was carried out by the accurate mass of quasi-molecular ion. The confirmation analysis for targeted compounds was performed with the retention time and qualitative fragments obtained by data dependent scan mode. Under the optimal conditions, the 24 hormones were routinely detected with mass accuracy error below 3 x 10(-6) (3 ppm), and good linearities were obtained in their respective linear ranges with correlation coefficients higher than 0.99. The LODs (S/N = 3) of the 24 compounds were hormones in 50 cosmetic samples. The results demonstrate that the method is a useful tool for the rapid screening and identification of the hormones in cosmetics.

  2. Exploring the Potential of a Global Emerging Contaminant Early Warning Network through the Use of Retrospective Suspect Screening with High-Resolution Mass Spectrometry.

    Science.gov (United States)

    Alygizakis, Nikiforos A; Samanipour, Saer; Hollender, Juliane; Ibáñez, María; Kaserzon, Sarit; Kokkali, Varvara; van Leerdam, Jan A; Mueller, Jochen F; Pijnappels, Martijn; Reid, Malcolm J; Schymanski, Emma L; Slobodnik, Jaroslav; Thomaidis, Nikolaos S; Thomas, Kevin V

    2018-04-13

    A key challenge in the environmental and exposure sciences is to establish experimental evidence of the role of chemical exposure in human and environmental systems. High resolution and accurate tandem mass spectrometry (HRMS) is increasingly being used for the analysis of environmental samples. One lauded benefit of HRMS is the possibility to retrospectively process data for (previously omitted) compounds that has led to the archiving of HRMS data. Archived HRMS data affords the possibility of exploiting historical data to rapidly and effectively establish the temporal and spatial occurrence of newly identified contaminants through retrospective suspect screening. We propose to establish a global emerging contaminant early warning network to rapidly assess the spatial and temporal distribution of contaminants of emerging concern in environmental samples through performing retrospective analysis on HRMS data. The effectiveness of such a network is demonstrated through a pilot study, where eight reference laboratories with available archived HRMS data retrospectively screened data acquired from aqueous environmental samples collected in 14 countries on 3 different continents. The widespread spatial occurrence of several surfactants (e.g., polyethylene glycols ( PEGs ) and C12AEO-PEGs ), transformation products of selected drugs (e.g., gabapentin-lactam, metoprolol-acid, carbamazepine-10-hydroxy, omeprazole-4-hydroxy-sulfide, and 2-benzothiazole-sulfonic-acid), and industrial chemicals (3-nitrobenzenesulfonate and bisphenol-S) was revealed. Obtaining identifications of increased reliability through retrospective suspect screening is challenging, and recommendations for dealing with issues such as broad chromatographic peaks, data acquisition, and sensitivity are provided.

  3. Dual-target screening of bioactive components from traditional Chinese medicines by hollow fiber-based ligand fishing combined with liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Chen, Liang; Wang, Xin; Liu, Youping; Di, Xin

    2017-09-05

    A novel strategy was developed for dual-target screening of bioactive components from traditional Chinese medicines (TCMs). This strategy was based on the use of low-cost microporous hollow fibers filled with target enzymes as baits to "fish out" the ligands in TCM extracts, followed by identification of the ligands dissociated from the target-ligand complexes by liquid chromatography-mass spectrometry. Ganjiang Huangqin Huanglian Renshen Decoction (GHHRD), a classical TCM prescription for diabetes treatment, was chosen as a model sample to evaluate the feasibility of the proposed strategy. Three bioactive components were successfully screened out from GHHRD. Coptisine was identified as the ligand of α-glucosidase and baicalin as the ligand of angiotensin-converting enzyme (ACE). Berberine was found to be a dual inhibitor of α-glucosidase and ACE. The results were further verified by enzyme inhibitory assay and molecular docking simulation. The study suggested that our developed strategy would be a powerful tool for screening bioactive components from multi-component and multi-target TCMs. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Simultaneous Screening of Major Flame Retardants and Plasticizers in Polymer Materials Using Pyrolyzer/Thermal Desorption Gas Chromatography Mass Spectrometry (Py/TD–GC–MS

    Directory of Open Access Journals (Sweden)

    Hiroyuki Yanagisawa

    2018-03-01

    Full Text Available This study was conducted with the aim of achieving the simultaneous screening of various additives in polymer materials by utilizing a solvent-free pyrolyzer/thermal desorption gas chromatography mass spectrometry (Py/TD-GC–MS method. As a first step to achieve this goal, simultaneous screening has been examined by selecting major substances representing plasticizers and flame retardants, such as short chain chlorinated paraffins (SCCPs, decabromodiphenyl ether (DecaBDE, hexabromocyclododecane (HBCDD, and di(2-ethylhexyl phthalate (DEHP. A quantitative MS analysis was performed to check for the peak areas and sensitivities. Since Py/TD-GC–MS is fraught with the risk of thermal degradation of the sample, temperatures during the analytical process were finely tuned for securing reliable results. The instrumental sensitivity was confirmed by the S/N ratio on each component. The detection limits of all components were less than 50 mg/kg, which are sufficiently lower than the regulatory criteria. With regard to reproducibility, a relative standard deviation (RSD of about 5% was confirmed by employing a spike recovery test on a polystyrene polymer solution containing mixed standard solution (ca. 1000 mg/kg. In conclusion, the results obtained in this study indicate that Py/TD-GC–MS is applicable for the screening of major flame retardants and plasticizers in real samples with sufficient reproducibility at regulatory levels.

  5. Instant screening and verification of carbapenemase activity in Bacteroides fragilis in positive blood culture, using matrix-assisted laser desorption ionization--time of flight mass spectrometry.

    Science.gov (United States)

    Johansson, Åsa; Nagy, Elisabeth; Sóki, József

    2014-08-01

    Rapid identification of isolates in positive blood cultures are of great importance to secure correct treatment of septicaemic patients. As antimicrobial resistance is increasing, rapid detection of resistance is crucial. Carbapenem resistance in Bacteroides fragilis associated with cfiA-encoded class B metallo-beta-lactamase is emerging. In our study we spiked blood culture bottles with 26 B. fragilis strains with various cfiA-status and ertapenem MICs. By using main spectra specific for cfiA-positive and cfiA-negative B. fragilis strains, isolates could be screened for resistance. To verify strains that were positive in the screening, a carbapenemase assay was performed where the specific peaks of intact and hydrolysed ertapenem were analysed with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). We show here that it is possible to correctly identify B. fragilis and to screen for enzymic carbapenem resistance directly from the pellet of positive blood cultures. The carbapenemase assay to verify the presence of the enzyme was successfully performed on the pellet from the direct identification despite the presence of blood components. The result of the procedure was achieved in 3 h. Also the Bruker mass spectrometric β-lactamase assay (MSBL assay) prototype software was proven not only to be based on an algorithm that correlated with the manual inspection of the spectra, but also to improve the interpretation by showing the variation in the dataset. © 2014 The Authors.

  6. ABO hemolytic disease of the fetus and newborn: thirteen years of data after implementing a universal bilirubin screening and management program.

    Science.gov (United States)

    Christensen, R D; Baer, V L; MacQueen, B C; O'Brien, E A; Ilstrup, S J

    2018-02-06

    ABO hemolytic disease occurs among neonates with blood groups A or B delivered to group O women. Extreme neonatal hyperbilirubinemia due to ABO disease has been reported, but its frequency is not well known. We sought to determine the odds of developing severe ABO hemolytic disease in the 13 years since adopting universal bilirubin screening/management in the Intermountain Healthcare system. We conducted a retrospective analysis of neonates born between 2004 and 2016, defining "severe hemolytic disease" as; (1) total serum bilirubin (TSB) >25 mg/dL, or (2) hospital readmission for jaundice, or (3) bilirubin encephalopathy. Neonates born to group O (+) mothers were included and considered either; (1) Controls (not at risk for ABO disease because they were group O), (2) Study subjects (at risk for ABO disease because they were group A or B). Of 400,531 live births, 47% were to group O women; 86% of whom were group O (+). Overall, 42,529 (27%) neonates born to group O (+) women had their blood group determined; 29,729 (68%) were O, 10,682 (25%) A, and 3109 (7%) B. Peak TSBs during the first 10 days were higher in group A (11.0 ± 4.2 mg/dL) and B (11.5 ± 4.3) than group O neonates (10.3 ± 4.1). However the relative risks of a TSB ≥25 mg/dL, readmission for jaundice, or kernicterus, were the same in the control vs. study groups. In our health system, severe hemolytic disease in neonates born to group O (+) woman is not more likely in group A or B neonates than in controls (group O). We recognize that in other practices, particularly those who do not have a universal bilirubin screening/management program, ABO hemolytic disease severity might be different than in our system.

  7. High-throughput screening of vitamins and natural antioxidants in nutraceuticals from green tea extracts by liquid chromatography coupled to quadrupole orbitrap mass spectrometry.

    Science.gov (United States)

    Jia, Wei; Chu, Xiaogang; Chang, James; Zhang, Feng

    2015-08-07

    A new analytical method was developed and validated for simultaneous analysis of 52 vitamins and natural antioxidants in nutraceutical products obtained from green tea (Camellia sinensis) extracts. The automated extraction procedure was achieved in a simple disposable pipet extraction. Ultra-high performance liquid chromatography and electrospray ionization quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC Q-Orbitrap) was used for the separation and detection of all the analytes. The method was validated by taking into consideration the guidelines specified in European SANCO/12571/2013 Guideline 2013 and Commission Decision 2002/657/EC. The extraction recoveries were in a range of 84.9-112.7%, with coefficient of variation 0.99. This validated method has been successfully applied on screening of vitamins and natural antioxidants in 136 different commercial nutraceutical products from green tea extracts. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Mass spectrometry data from proteomics-based screening of immunoreactive proteins of fully virulent Brucella strains using sera from naturally infected animals

    Directory of Open Access Journals (Sweden)

    Gamal Wareth

    2015-09-01

    Full Text Available Here, we provide the dataset associated with our research article on comprehensive screening of Brucella immunoreactive proteins using sera of naturally infected hosts published in Biochemical and Biophysical Research Communications Wareth et al., 2015 [1]. Whole-cell protein extracts were prepared from Brucella abortus and Brucella melitensis, separated using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE and subsequently western blotting was carried out using sera from bovines (cows and buffaloes and small ruminants (goats and sheep. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org via the PRIDE partner repository [2] with the dataset identifiers PXD001270 and DOI:10.6019/PXD001270.

  9. High-throughput screening for various classes of doping agents using a new 'dilute-and-shoot' liquid chromatography-tandem mass spectrometry multi-target approach.

    Science.gov (United States)

    Guddat, S; Solymos, E; Orlovius, A; Thomas, A; Sigmund, G; Geyer, H; Thevis, M; Schänzer, W

    2011-01-01

    A new multi-target approach based on liquid chromatography--electrospray ionization tandem mass spectrometry (LC-(ESI)-MS/MS) is presented to screen for various classes of prohibited substances using direct injection of urine specimens. With a highly sensitive new generation hybrid mass spectrometer classic groups of drugs--for example, diuretics, beta2-agonists--stimulants and narcotics are detectable at concentration levels far below the required limits. Additionally, more challenging and various new target compounds could be implemented. Model compounds of stimulant conjugates were studied to investigate a possible screening without complex sample preparation. As a main achievement, the integration of the plasma volume expanders dextran and hydroxyethyl starch (HES), commonly analyzed in time-consuming, stand-alone procedures, is accomplished. To screen for relatively new prohibited compounds, a common metabolite of the selective androgen receptor modulator (SARMs) andarine, a metabolite of growth hormone releasing peptide (GHRP-2), and 5-amino-4-imidazolecarboxyamide ribonucleoside (AICAR) are analyzed. Following a completely new approach, conjugates of di(2-ethylhexyl) phthalate (DEHP) metabolites are monitored to detect abnormally high levels of plasticizers indicating for illicit blood transfusion. The assay was fully validated for qualitative purposes considering the parameters specificity, intra- (3.2-16.6%) and inter-day precision (0.4-19.9%) at low, medium and high concentration, robustness, limit of detection (1-70 ng/ml, dextran: 30 µg/ml, HES: 10 µg/ml) and ion suppression/enhancement effects. The analyses of post-administration and routine doping control samples demonstrates the applicability of the method for sports drug testing. This straightforward and reliable approach accomplishes the combination of different screening procedures resulting in a high-throughput method that increases the efficiency of the labs daily work. Copyright © 2011 John

  10. A Machine Learning Application Based in Random Forest for Integrating Mass Spectrometry-Based Metabolomic Data: A Simple Screening Method for Patients With Zika Virus

    Directory of Open Access Journals (Sweden)

    Carlos Fernando Odir Rodrigues Melo

    2018-04-01

    Full Text Available Recent Zika outbreaks in South America, accompanied by unexpectedly severe clinical complications have brought much interest in fast and reliable screening methods for ZIKV (Zika virus identification. Reverse-transcriptase polymerase chain reaction (RT-PCR is currently the method of choice to detect ZIKV in biological samples. This approach, nonetheless, demands a considerable amount of time and resources such as kits and reagents that, in endemic areas, may result in a substantial financial burden over affected individuals and health services veering away from RT-PCR analysis. This study presents a powerful combination of high-resolution mass spectrometry and a machine-learning prediction model for data analysis to assess the existence of ZIKV infection across a series of patients that bear similar symptomatic conditions, but not necessarily are infected with the disease. By using mass spectrometric data that are inputted with the developed decision-making algorithm, we were able to provide a set of features that work as a “fingerprint” for this specific pathophysiological condition, even after the acute phase of infection. Since both mass spectrometry and machine learning approaches are well-established and have largely utilized tools within their respective fields, this combination of methods emerges as a distinct alternative for clinical applications, providing a diagnostic screening—faster and more accurate—with improved cost-effectiveness when compared to existing technologies.

  11. Liquid chromatography with high resolution mass spectrometry for identification of organic contaminants in fish fillet: screening and quantification assessment using two scan modes for data acquisition.

    Science.gov (United States)

    Munaretto, Juliana S; May, Marília M; Saibt, Nathália; Zanella, Renato

    2016-07-22

    This study proposed a strategy to identify and quantify 182 organic contaminants from different chemical classes, as for instance pesticides, veterinary drug and personal care products, in fish fillet using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (LC-QToF/MS). For this purpose, two different scan methods (full scan and all ions MS/MS) were evaluated to assess the best option for screening analysis in spiked fish fillet samples. In general, full scan acquisition was found to be more reliable (84%) in the automatic identification and quantification when compared to all ions MS/MS with 72% of the compounds detected. Additionally, a qualitative automatic search showed a mass accuracy error below 5ppm for 77% of the compounds in full scan mode compared to only 52% in all ions MS/MS scan. However, all ions MS/MS provides fragmentation information of the target compounds. Undoubtedly, structural information of a wide number of compounds can be obtained using high resolution mass spectrometry (HRMS), but it is necessary thoroughly assess it, in order to choose the best scan mode. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Proteomic screen for multiprotein complexes in synaptic plasma membrane from rat hippocampus by blue native gel electrophoresis and tandem mass spectrometry.

    Science.gov (United States)

    Li, Xuanwen; Xie, Chunliang; Jin, Qihui; Liu, Mingjun; He, Quanyuan; Cao, Rui; Lin, Yong; Li, Jianglin; Li, Yan; Chen, Ping; Liang, Songping

    2009-07-01

    Neuronal synapses are specialized sites for information exchange between neurons. Many diseases, such as addiction and mood disorders, likely result from altered expression of synaptic proteins, or altered formation of synaptic complexes involved in neurotransmission or neuroplasticity. A detailed description of native multiprotein complexes in synaptic plasma membranes (PM) is therefore essential for understanding biological mechanisms and disease processes. For the first time in this study, two-dimensional Blue Native/SDS-PAGE electrophoresis, combined with tandem mass spectrometry, was used to screen multiprotein complexes in synaptic plasma membranes from rat hippocampus. As a result, 514 unique proteins were identified, of which 36% were integral membrane proteins. In addition, 19 potentially novel and known heterooligomeric multiprotein complexes were found, such as the SNARE and ATPase complexes. A potentially novel protein complex, involving syntaxin, synapsin I and Na+/K+ ATPase alpha-1, was further confirmed by co-immunoprecipitation and immunofluorescence staining. As demonstrated here, Blue Native-PAGE is a powerful tool for the separation of hydrophobic membrane proteins. The combination of Blue Native-PAGE and mass spectrometry could systematically identify multiprotein complexes.

  13. Facilitating high resolution mass spectrometry data processing for screening of environmental water samples: An evaluation of two deconvolution tools

    NARCIS (Netherlands)

    Bade, R.; Causanilles, A.; Emke, E.; Bijlsma, L.; Sancho, J.V.; Hernandez, F.; de Voogt, P.

    2016-01-01

    A screening approach was applied to influent and effluent wastewater samples. After injection in a LC-LTQ-Orbitrap, data analysis was performed using two deconvolution tools, MsXelerator (modules MPeaks and MS Compare) and Sieve 2.1. The outputs were searched incorporating an in-house database of >

  14. Hipotireoidismo congênito: perfil clínico dos recém-nascidos identificados pelo Programa de Triagem Neonatal de Minas Gerais Congenital hypothyroidism: the clinical profile of affected newborns identified by the Newborn Screening Program of the State of Minas Gerais, Brazil

    Directory of Open Access Journals (Sweden)

    Isabela L. Pezzuti

    2009-02-01

    Full Text Available OBJETIVO: Avaliar o perfil clínico de recém-nascidos com hipotireoidismo congênito identificados pelo Programa Estadual de Triagem Neonatal de Minas Gerais entre 2000 e 2006. MÉTODOS: A frequência das manifestações clínicas de hipotireoidismo congênito foi analisada em relação aos níveis de hormônio estimulante da tireoide T4L (determinados por quimioluminescência, valores de referência de 0,3 a 5,0 µUI/mL e 0,8 a 1,8 ng/dL, respectivamente e idades ao diagnóstico e tratamento. Estudou-se 443 crianças, sendo 55,8% do sexo feminino e 95% delas com menos 60 dias de vida. RESULTADOS: Os sinais clínicos mais prevalentes foram: hérnia umbilical (51%, fontanela anterior ampla (50,3% e fontanela posterior aberta (47,2%. Hipotonia, macroglossia e sucção débil foram os sinais mais associados com a gravidade bioquímica da doença. Em 32,1% das crianças houve atraso na idade óssea ao diagnóstico. As medianas de TSH e T4L séricos foram 120 µUI/mL e 0,62 ng/dL, respectivamente. A mediana da idade de início de tratamento foi de 28 dias. CONCLUSÃO: Existem sinais clínicos precoces que sugerem o diagnóstico de hipotireoidismo congênito. Portanto, diante de uma criança com esses sinais, devem ser avaliados TSH e T4L séricos para confirmar ou excluir a doença, independentemente do resultado do teste de triagem. A idade de início de tratamento ainda foi elevada, mas o programa vem adotando estratégias para redução da mesma.OBJECTIVE: To evaluate the clinical profile of newborns with congenital hypothyroidism identified by the Newborn Screening Program of the State of Minas Gerais, Brazil, between 2000 and 2006. METHODS: Analysis of factors involved in this profile, including: TSH and FT4 levels (determined by chemiluminescence, with limits of normality set at 0.3-5.0 µUI/mL and 0.8-1.8 ng/dL, respectively, age at diagnosis and age at treatment. The study sample consisted of 443 children, 55.8% were female and 95% were seen

  15. Reduced glutathione and glutathione disulfide in the blood of glucose-6-phosphate dehydrogenase-deficient newborns.

    Science.gov (United States)

    Gong, Zhen-Hua; Tian, Guo-Li; Huang, Qi-Wei; Wang, Yan-Min; Xu, Hong-Ping

    2017-07-20

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is commonly detected during mass screening for neonatal disease. We developed a method to measure reduced glutathione (GSH) and glutathione disulfide (GSSG) using tandem mass spectrometry (MS/MS) for detecting G6PD deficiency. The concentration of GSH and the GSH/GSSG ratio in newborn dry-blood-spot (DBS) screening and in blood plus sodium citrate for test confirmation were examined by MS/MS using labeled glycine as an internal standard. G6PD-deficient newborns had a lower GSH content (242.9 ± 15.9 μmol/L)and GSH/GSSG ratio (14.9 ± 7.2) than neonatal controls (370.0 ± 53.2 μmol/L and 46.7 ± 19.6, respectively). Although the results showed a significance of P blood measured using MS/MS on the first day of sample preparation are consistent with G6PD activity and are helpful for diagnosing G6PD deficiency.

  16. Rapid screening and identification of chemical hazards in surface and drinking water using high resolution mass spectrometry and a case-control filter.

    Science.gov (United States)

    Kaserzon, Sarit L; Heffernan, Amy L; Thompson, Kristie; Mueller, Jochen F; Gomez Ramos, Maria Jose

    2017-09-01

    Access to clean, safe drinking water poses a serious challenge to regulators, and requires analytical strategies capable of rapid screening and identification of potentially hazardous chemicals, specifically in situations when threats to water quality or security require rapid investigations and potential response. This study describes a fast and efficient chemical hazard screening strategy for characterising trace levels of polar organic contaminants in water matrices, based on liquid chromatography high resolution mass spectrometry with post-acquisition 'case-control' data processing. This method allowed for a rapid response time of less than 24 h for the screening of target, suspect and non-target unknown chemicals via direct injection analysis, and a second, more sensitive analysis option requiring sample pre-concentration. The method was validated by fortifying samples with a range of pesticides, pharmaceuticals and personal care products (n = 46); with >90% of target compounds positively screened in samples at 1 ng mL -1 , and 46% at 0.1 ng mL -1 when analysed via direct injection. To simulate a contamination event samples were fortified with compounds not present in the commercial library (designated 'non-target compounds'; fipronil and fenitrothion), tentatively identified at 0.2 and 1 ng mL -1 , respectively; and a compound not included in any known commercial library or public database (designated 'unknown' compounds; 8Cl - perfluorooctanesulfonic acid), at 0.8 ng mL -1 . The method was applied to two 'real-case' scenarios: (1) the assessment of drinking water safety during a high-profile event in Brisbane, Australia; and (2) to screen treated, re-circulated drinking water and pre-treated (raw) water. The validated workflow was effective for rapid prioritisation and screening of suspect and non-target potential hazards at trace levels, and could be applied to a wide range of matrices and investigations where comparison of organic contaminants

  17. Parents are interested in newborn genomic testing during the early postpartum period.

    Science.gov (United States)

    Waisbren, Susan E; Bäck, Danielle K; Liu, Christina; Kalia, Sarah S; Ringer, Steven A; Holm, Ingrid A; Green, Robert C

    2015-06-01

    We surveyed parents to ascertain interest in newborn genomic testing and determine whether these queries would provoke refusal of conventional state-mandated newborn screening. After a brief genetics orientation, parents rated their interest in receiving genomic testing for their healthy newborn on a 5-point Likert scale and answered questions about demographics and health history. We used logistic regression to explore factors associated with interest in genomic testing and tracked any subsequent rejection of newborn screening. We queried 514 parents within 48 hours after birth while still in hospital (mean age (SD) 32.7 (6.4) years, 65.2% female, 61.2% white, 79.3% married). Parents reported being not at all (6.4%), a little (10.9%), somewhat (36.6%), very (28.0%), or extremely (18.1%) interested in genomic testing for their newborns. None refused state-mandated newborn screening. Married participants and those with health concerns about their infant were less interested in newborn genomic testing (P = 0.012 and P = 0.030, respectively). Degree of interest for mothers and fathers was discordant (at least two categories different) for 24.4% of couples. Interest in newborn genomic testing was high among parents of healthy newborns, and the majority of couples had similar levels of interest. Surveying parents about genomic sequencing did not prompt rejection of newborn screening.Genet Med 17 6, 501-504.

  18. High-throughput screening of pesticide and veterinary drug residues in baby food by liquid chromatography coupled to quadrupole Orbitrap mass spectrometry.

    Science.gov (United States)

    Jia, Wei; Chu, Xiaogang; Ling, Yun; Huang, Junrong; Chang, James

    2014-06-20

    A new analytical method was developed and validated for simultaneous analysis of 333 pesticide and veterinary drug residues in baby food. Response surface methodology was employed to optimize a generic extraction method. Ultrahigh-performance liquid chromatography and electrospray ionization quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-ESI Q-Orbitrap) was used for the separation and detection of all the analytes. The method was validated by taking into consideration the guidelines specified in Commission Decision 2002/657/EC and SANCO/12571/2013. The extraction recoveries were in a range of 79.8-110.7%, with coefficient of variation 0.99. The limits of detection for the analytes are in the range 0.01-5.35μgkg(-1). The limits of quantification for the analytes are in the range 0.01-9.27μgkg(-1). This method has been successfully applied on screening of pesticide and veterinary drugs in ninety-three commercial baby food samples, and tilmicosin, fenbendazole, tylosin tartrate and thiabendazole were detected in some samples tested in this study. The present study is very useful for fast screening of different food contaminants. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. A high-throughput inhibition screening of major human cytochrome P450 enzymes using an in vitro cocktail and liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Qin, Chong-Zhen; Ren, Xian; Tan, Zhi-Rong; Chen, Yao; Yin, Ji-Ye; Yu, Jing; Qu, Jian; Zhou, Hong-Hao; Liu, Zhao-Qian

    2014-02-01

    A sensitive and high-throughput inhibition screening liquid chromatography-mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous quantification of five probe metabolites (7-hydroxycoumarin, CYP2A6; 4-hydroxytolbutamide, CYP2C9; 4'-hydroxymephenytoin, CYP2C19; α-hydroxymetoprolol, CYP2D6; and 1-hydroxymidazolam, CYP3A4) for in vitro cytochrome P450 activity determination in human liver microsome and recombinant. All the metabolites and the internal standard, tramadol, were separated on a Waters 2695 series liquid chromatograph with a Phenomenex Luna C18 column (150 × 2.0 mm, 5 µm). Quality control samples and a positive control CYP inhibitor were included in the method. The IC50 values determined for typical CYP inhibitors were reproducible and in agreement with the literature. The method was selective and showed good accuracy (99.13-103.37%), and inter-day (RSD high-quality and -throughput cocktail provides suitable information in drug discovery and screening for new drug entities. Copyright © 2013 John Wiley & Sons, Ltd.

  20. A simple, fast and cheap non-SPE screening method for antibacterial residue analysis in milk and liver using liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Martins, Magda Targa; Melo, Jéssica; Barreto, Fabiano; Hoff, Rodrigo Barcellos; Jank, Louise; Bittencourt, Michele Soares; Arsand, Juliana Bazzan; Schapoval, Elfrides Eva Scherman

    2014-11-01

    In routine laboratory work, screening methods for multiclass analysis can process a large number of samples in a short time. The main challenge is to develop a methodology to detect as many different classes of residues as possible, combined with speed and low cost. An efficient technique for the analysis of multiclass antibacterial residues (fluoroquinolones, tetracyclines, sulfonamides and trimethoprim) was developed based on simple, environment-friendly extraction for bovine milk, cattle and poultry liver. Acidified ethanol was used as an extracting solvent for milk samples. Liver samples were treated using EDTA-washed sand for cell disruption, methanol:water and acidified acetonitrile as extracting solvent. A total of 24 antibacterial residues were detected and confirmed using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), at levels between 10, 25 and 50% of the maximum residue limit (MRL). For liver samples a metabolite (sulfaquinoxaline-OH) was also monitored. A validation procedure was conducted for screening purposes in accordance with European Union requirements (2002/657/EC). The detection capability (CCβ) false compliant rate was less than 5% at the lowest level for each residue. Specificity and ruggedness were also discussed. Incurred and routine samples were analyzed and the method was successfully applied. The results proved that this method can be an important tool in routine analysis, since it is very fast and reliable. Copyright © 2014. Published by Elsevier B.V.

  1. Screening of oil sources by using comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry and multivariate statistical analysis.

    Science.gov (United States)

    Zhang, Wanfeng; Zhu, Shukui; He, Sheng; Wang, Yanxin

    2015-02-06

    Using comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC/TOFMS), volatile and semi-volatile organic compounds in crude oil samples from different reservoirs or regions were analyzed for the development of a molecular fingerprint database. Based on the GC×GC/TOFMS fingerprints of crude oils, principal component analysis (PCA) and cluster analysis were used to distinguish the oil sources and find biomarkers. As a supervised technique, the geological characteristics of crude oils, including thermal maturity, sedimentary environment etc., are assigned to the principal components. The results show that tri-aromatic steroid (TAS) series are the suitable marker compounds in crude oils for the oil screening, and the relative abundances of individual TAS compounds have excellent correlation with oil sources. In order to correct the effects of some other external factors except oil sources, the variables were defined as the content ratio of some target compounds and 13 parameters were proposed for the screening of oil sources. With the developed model, the crude oils were easily discriminated, and the result is in good agreement with the practical geological setting. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Beyond Naphthenic Acids: Environmental Screening of Water from Natural Sources and the Athabasca Oil Sands Industry Using Atmospheric Pressure Photoionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry.

    Science.gov (United States)

    Barrow, Mark P; Peru, Kerry M; Fahlman, Brian; Hewitt, L Mark; Frank, Richard A; Headley, John V

    2015-09-01

    There is a growing need for environmental screening of natural waters in the Athabasca region of Alberta, Canada, particularly in the differentiation between anthropogenic and naturally-derived organic compounds associated with weathered bitumen deposits. Previous research has focused primarily upon characterization of naphthenic acids in water samples by negative-ion electrospray ionization methods. Atmospheric pressure photoionization is a much less widely used ionization method, but one that affords the possibility of observing low polarity compounds that cannot be readily observed by electrospray ionization. This study describes the first usage of atmospheric pressure photoionization Fourier transform ion cyclotron resonance mass spectrometry (in both positive-ion and negative-ion modes) to characterize and compare extracts of oil sands process water, river water, and groundwater samples from areas associated with oil sands mining activities. When comparing mass spectra previously obtained by electrospray ionization and data acquired by atmospheric pressure photoionization, there can be a doubling of the number of components detected. In addition to polar compounds that have previously been observed, low-polarity, sulfur-containing compounds and hydrocarbons that do not incorporate a heteroatom were detected. These latter components, which are not amenable to electrospray ionization, have potential for screening efforts within monitoring programs of the oil sands.

  3. A simultaneous screening and quantitative method for the multiresidue analysis of pesticides in spices using ultra-high performance liquid chromatography-high resolution (Orbitrap) mass spectrometry.

    Science.gov (United States)

    Goon, Arnab; Khan, Zareen; Oulkar, Dasharath; Shinde, Raviraj; Gaikwad, Suresh; Banerjee, Kaushik

    2018-01-12

    A novel screening and quantitation method is reported for non-target multiresidue analysis of pesticides using ultra-HPLC-quadrupole-Orbitrap mass spectrometry in spice matrices, including black pepper, cardamom, chili, coriander, cumin, and turmeric. The method involved sequential full-scan (resolution = 70,000), and variable data independent acquisition (vDIA) with nine consecutive fragmentation events (resolution = 17,500). Samples were extracted by the QuEChERS method. The introduction of an SPE-based clean-up step through hydrophilic-lipophilic-balance (HLB) cartridges proved advantageous in minimizing the false negatives. For coriander, cumin, chili, and cardamom, the screening detection limit was largely at 2 ng/g, while it was 5 ng/g for black pepper, and turmeric. When the method was quantitatively validated for 199 pesticides, the limit of quantification (LOQ) was mostly at 10 ng/g (excluding black pepper, and turmeric with LOQ = 20 ng/g) with recoveries within 70-120%, and precision-RSDs <20%. Furthermore, the method allowed the identification of suspected non-target analytes through retrospective search of the accurate mass of the compound-specific precursor and product ions. Compared to LC-MS/MS, the quantitative performance of this Orbitrap-MS method had agreements in residue values between 78-100%. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. [Rapid screening and confirmation of 205 pesticide residues in rice by QuEChERS and liquid chromatography-mass spectrometry].

    Science.gov (United States)

    Chen, Xi; Cheng, Lei; Qu, Shichao; Huang, Daliang; Liu, Jiacheng; Cui, Han; Jia, Yanbo; Ji, Mingshan

    2015-10-01

    A method for rapid screening and confirmation of 205 pesticide residues in rice was developed by combining QuEChERS and high performance liquid chromatography-triple quadrupole-linear ion trap mass spectrometry (LC-Q-TRAP/MS). The rice samples were extracted with acetonitrile, and then cleaned up with primary secondary amine (PSA), anhydrous magnesium sulfate (MgSO4) and C18 adsorbent. Finally, the samples were detected by LC-Q-TRAP/MS in multiple reaction monitoring with information-dependent acquisition of enhanced product ion (MRM-IDA-EPI) mode followed with database searching. A total of 205 pesticide residues were confirmed by retention times, ion pairs and the database searching using EPI library, and quantified by external standard method. All the pesticides showed good linearities with linear correlation coefficients all above 0.995. The limits of quantification (LOQs) for the 205 pesticides were 0.5-10.0 μg/kg. The average recoveries of the 205 pesticides ranged from 62.4% to 127.1% with the relative standard deviations (RSDs) of 1.0% - 20.0% at spiked levels of 10 μg/kg and 50 μg/kg, and only 20 min were needed for the analysis of an actual rice sample. In brief, the method is fast, accurate and highly sensitive, and is suitable for the screening and confirmation of pesticide residues in rice.

  5. Facilitating high resolution mass spectrometry data processing for screening of environmental water samples: An evaluation of two deconvolution tools

    Energy Technology Data Exchange (ETDEWEB)

    Bade, Richard [Research Institute for Pesticides and Water, University Jaume I, Avda. Sos Baynat s/n, E-12071 Castellón (Spain); Causanilles, Ana; Emke, Erik [KWR Watercycle Research Institute, Chemical Water Quality and Health, P.O. Box 1072, 3430 BB Nieuwegein (Netherlands); Bijlsma, Lubertus; Sancho, Juan V.; Hernandez, Felix [Research Institute for Pesticides and Water, University Jaume I, Avda. Sos Baynat s/n, E-12071 Castellón (Spain); Voogt, Pim de, E-mail: w.p.devoogt@uva.nl [KWR Watercycle Research Institute, Chemical Water Quality and Health, P.O. Box 1072, 3430 BB Nieuwegein (Netherlands); Institute for Biodiversity and Ecosystem Dynamics, University of Amsterdam, P.O. Box 94248, 1090 GE Amsterdam (Netherlands)

    2016-11-01

    A screening approach was applied to influent and effluent wastewater samples. After injection in a LC-LTQ-Orbitrap, data analysis was performed using two deconvolution tools, MsXelerator (modules MPeaks and MS Compare) and Sieve 2.1. The outputs were searched incorporating an in-house database of > 200 pharmaceuticals and illicit drugs or ChemSpider. This hidden target screening approach led to the detection of numerous compounds including the illicit drug cocaine and its metabolite benzoylecgonine and the pharmaceuticals carbamazepine, gemfibrozil and losartan. The compounds found using both approaches were combined, and isotopic pattern and retention time prediction were used to filter out false positives. The remaining potential positives were reanalysed in MS/MS mode and their product ions were compared with literature and/or mass spectral libraries. The inclusion of the chemical database ChemSpider led to the tentative identification of several metabolites, including paraxanthine, theobromine, theophylline and carboxylosartan, as well as the pharmaceutical phenazone. The first three of these compounds are isomers and they were subsequently distinguished based on their product ions and predicted retention times. This work has shown that the use deconvolution tools facilitates non-target screening and enables the identification of a higher number of compounds. - Highlights: • A hidden target non-target screening method is utilised using two databases • Two software (MsXelerator and Sieve 2.1) used for both methods • 22 compounds tentatively identified following MS/MS reinjection • More information gleaned from this combined approach than individually.

  6. Facilitating high resolution mass spectrometry data processing for screening of environmental water samples: An evaluation of two deconvolution tools

    International Nuclear Information System (INIS)

    Bade, Richard; Causanilles, Ana; Emke, Erik; Bijlsma, Lubertus; Sancho, Juan V.; Hernandez, Felix; Voogt, Pim de

    2016-01-01

    A screening approach was applied to influent and effluent wastewater samples. After injection in a LC-LTQ-Orbitrap, data analysis was performed using two deconvolution tools, MsXelerator (modules MPeaks and MS Compare) and Sieve 2.1. The outputs were searched incorporating an in-house database of > 200 pharmaceuticals and illicit drugs or ChemSpider. This hidden target screening approach led to the detection of numerous compounds including the illicit drug cocaine and its metabolite benzoylecgonine and the pharmaceuticals carbamazepine, gemfibrozil and losartan. The compounds found using both approaches were combined, and isotopic pattern and retention time prediction were used to filter out false positives. The remaining potential positives were reanalysed in MS/MS mode and their product ions were compared with literature and/or mass spectral libraries. The inclusion of the chemical database ChemSpider led to the tentative identification of several metabolites, including paraxanthine, theobromine, theophylline and carboxylosartan, as well as the pharmaceutical phenazone. The first three of these compounds are isomers and they were subsequently distinguished based on their product ions and predicted retention times. This work has shown that the use deconvolution tools facilitates non-target screening and enables the identification of a higher number of compounds. - Highlights: • A hidden target non-target screening method is utilised using two databases • Two software (MsXelerator and Sieve 2.1) used for both methods • 22 compounds tentatively identified following MS/MS reinjection • More information gleaned from this combined approach than individually

  7. Fragment-Based Screening of a Natural Product Library against 62 Potential Malaria Drug Targets Employing Native Mass Spectrometry

    Science.gov (United States)

    2018-01-01

    Natural products are well known for their biological relevance, high degree of three-dimensionality, and access to areas of largely unexplored chemical space. To shape our understanding of the interaction between natural products and protein targets in the postgenomic era, we have used native mass spectrometry to investigate 62 potential protein targets for malaria using a natural-product-based fragment library. We reveal here 96 low-molecular-weight natural products identified as binding partners of 32 of the putative malarial targets. Seventy-nine (79) fragments have direct growth inhibition on Plasmodium falciparum at concentrations that are promising for the development of fragment hits against these protein targets. This adds a fragment library to the published HTS active libraries in the public domain. PMID:29436819

  8. Hemothorax in the newborn

    International Nuclear Information System (INIS)

    Oppermann, H.C.; Wille, L.

    1980-01-01

    Twenty cases of hemothorax in newborns are reviewed in detail. This unusual cause of acute respiratory distress within the neonatal period was observed in 14 males and 6 females. Most of the patients were fullterm newborns. As causal factors hemorrhagic disease of the newborn (vitamin K deficiency), disseminated intravascular coagulation, arteriovenous malformations and pleural/vascular rupture are considered. The time of occurrence of bleeding symptoms ranged from 1 to 28 days of life. Sixteen out of 20 patients survived without sequelae, but in 4 cases the outcome was lethal. (orig.) [de

  9. Target analysis of primary aromatic amines combined with a comprehensive screening of migrating substances in kitchen utensils by liquid chromatography-high resolution mass spectrometry.

    Science.gov (United States)

    Sanchis, Yovana; Coscollà, Clara; Roca, Marta; Yusà, Vicent

    2015-06-01

    An analytical strategy including both the quantitative target analysis of 8 regulated primary aromatic amines (PAAs), as well as a comprehensive post-run target screening of 77 migrating substances, was developed for nylon utensils, using liquid chromatography-orbitrap-high resolution mass spectrometry (LC-HRMS) operating in full scan mode. The accurate mass data were acquired with a resolving power of 50,000 FWHM (scan speed, 2 Hz), and by alternating two acquisition events, ESI+ with and without fragmentation. The target method was validated after statistical optimization of the main ionization and fragmentation parameters. The quantitative method presented appropriate performance to be used in official monitoring with recoveries ranging from 78% to 112%, precision in terms of Relative Standard Deviation (RSD) was less than 15%, and the limits of quantification were between 2 and 2.5 µg kg(-1). For post-target screening, a customized theoretical database was built for food contact material migrants, including bisphenols, phthalates, and other amines. For identification purposes, accurate exact mass (<5 ppm) and some diagnostic ions including fragments were used. The strategy was applied to 10 real samples collected from different retailers in the Valencian Region (Spain) during 2014. Six out of eight target PAAs were detected in at least one sample in the target analysis. The most frequently detected compounds were 4,4'-methylenedianiline and aniline, with concentrations ranging from 2.4 to 19,715 µg kg(-1) and 2.5 to 283 µg kg(-1), respectively. Two phthalates were identified and confirmed in the post-run target screening analysis. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Suspect screening of large numbers of emerging contaminants in environmental waters using artificial neural networks for chromatographic retention time prediction and high resolution mass spectrometry data analysis.

    Science.gov (United States)

    Bade, Richard; Bijlsma, Lubertus; Miller, Thomas H; Barron, Leon P; Sancho, Juan Vicente; Hernández, Felix

    2015-12-15

    The recent development of broad-scope high resolution mass spectrometry (HRMS) screening methods has resulted in a much improved capability for new compound identification in environmental samples. However, positive identifications at the ng/L concentration level rely on analytical reference standards for chromatographic retention time (tR) and mass spectral comparisons. Chromatographic tR prediction can play a role in increasing confidence in suspect screening efforts for new compounds in the environment, especially when standards are not available, but reliable methods are lacking. The current work focuses on the development of artificial neural networks (ANNs) for tR prediction in gradient reversed-phase liquid chromatography and applied along with HRMS data to suspect screening of wastewater and environmental surface water samples. Based on a compound tR dataset of >500 compounds, an optimized 4-layer back-propagation multi-layer perceptron model enabled predictions for 85% of all compounds to within 2min of their measured tR for training (n=344) and verification (n=100) datasets. To evaluate the ANN ability for generalization to new data, the model was further tested using 100 randomly selected compounds and revealed 95% prediction accuracy within the 2-minute elution interval. Given the increasing concern on the presence of drug metabolites and other transformation products (TPs) in the aquatic environment, the model was applied along with HRMS data for preliminary identification of pharmaceutically-related compounds in real samples. Examples of compounds where reference standards were subsequently acquired and later confirmed are also presented. To our knowledge, this work prese