Birth defects research. Part A, Clinical and molecular teratology最新文献

{"title":"Letter to the editor interpreting trends in the context of previous evidence.","authors":"R. Kirby","doi":"10.1002/bdra.23565","DOIUrl":"https://doi.org/10.1002/bdra.23565","url":null,"abstract":"","PeriodicalId":8983,"journal":{"name":"Birth defects research. Part A, Clinical and molecular teratology","volume":"100 1","pages":"1042"},"PeriodicalIF":0.0,"publicationDate":"2016-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80595271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changing of the guards: EMA warning on paternal use of mycophenolate mofetil: An unnecessary and insufficiently substantiated precaution","authors":"Per Damkier, Anneke Passier, Lotte Bo Petersen, Gro Havnen, Andreas James Thestrup Pedersen","doi":"10.1002/bdra.23556","DOIUrl":"10.1002/bdra.23556","url":null,"abstract":"On October 23, 2015, the European Medicines Agency (EMA) issued a press release and subsequently recommended a change to the Summary of Product Characteristics (SmPC) for mycophenolate mofetil (MMF) (EMA, 2015a,b). This specifically addressed pregnancy related issues and the wording in SmPC sections 4.4 (Special warnings and precautions for use) and 4.6 (Pregnancy and lactation) (EMA, 2015b). A Direct Healthcare Professional Communication from the manufacturer followed the EMA press release (Roche, 2015). The new warnings and precautions now for the first time included a specific statement on paternal exposure before conception, stating that: “Sexually active men are recommended to use condoms during treatment and for at least 90 days after cessation of treatment” (EMA, 2015b). The rationale or supporting evidence behind these recommendations is not presented. The FDA SmPC does not hold a similar warning (FDA, 2016). These are very strong measures called upon by a regulatory authority that in effect mean that renal transplant recipients receiving MMF de facto cannot (or at the very least are strongly advised not to) father a child. Complying with EMA precautions, planned fatherhood would require substituting MMF with a different immunosuppressant drug such as azathioprine; this would not be without risk of organ rejection or serious adverse reactions. We believe these precautionary measures are unsubstantiated by any meaningful level of evidence, and we believe they introduce unnecessary concerns to clinicians and organ transplant recipients planning fatherhood as well as parents-to-be who conceived during paternal use of MMF. In our respective Drug and Teratology Information Services across three European countries, we have received many calls from confused clinicians and worried male renal transplant recipients planning fatherhood. These include questions about termination of pregnancy in case of paternal exposure. MMF is a well-documented human teratogen following first trimester in utero exposure, and appropriate precautions are suggested in the SmPC (Anderka et al., 2009; Hoeltzenbein et al., 2012; EMA, 2015b). The amount of human data relating to paternal exposure is moderate but quite reassuring, and does not suggest a level of risk that justifies the EMAwarnings and precautions. The United States National Transplantation Pregnancy Registry (NTPR) identified 205 pregnancies fathered by 152 transplant recipients who received MMF at the estimated time of conception (Jones et al., 2013). Among 194 live births, the rates of malformations, miscarriages and prematurity were 3.1% (no specific pattern), 6.8% and 11%, respectively. All of these observations are well with the expected range. The NTPR has since collected 70 additional cases with no signs of adverse fetal outcome (personal communication, Michael J. Moritz, NTPR, December 2015). A Norwegian study, reported 2463 male organ transplant recipients who fathered 4614 children before transpla","PeriodicalId":8983,"journal":{"name":"Birth defects research. Part A, Clinical and molecular teratology","volume":"106 10","pages":"860-861"},"PeriodicalIF":0.0,"publicationDate":"2016-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdra.23556","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90868824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acardiac twin pregnancies part III: Model simulations","authors":"Martin J.C. van Gemert,&nbsp;Michael G. Ross,&nbsp;Peter G.J. Nikkels,&nbsp;Jeroen P.H.M. van den Wijngaard","doi":"10.1002/bdra.23559","DOIUrl":"https://doi.org/10.1002/bdra.23559","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Acardiac monochorionic twins lack cardiac function but grow by passive perfusion of the pump twin's deoxygenated arterial blood through placental arterioarterial (AA) and venovenous (VV) anastomoses and by hypoxia-mediated neovascularization. Pump twins therefore must continuously increase their cardiac output which may cause heart failure. Our aims were: to adapt our twin-twin transfusion syndrome model for acardiac twin pregnancies, to simulate pump and acardiac twin development, and to examine the model for early prognostic markers of pump twin survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used an infinite acardiac placental resistance, based on placental dye injection studies and simulations, suggesting the AA-Acardiac-VV series resistance determines the pump twin's excess cardiac output. Pump and acardiac development were expressed by the pump's excess cardiac output versus its normal value, represented by pump/acardiac umbilical venous diameter (UVD) ratios.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>UVD ratios distinguish between AA-VV anastomoses that do and do not cause hydropic pump twins. Pump twins can handle relative larger acardiac perfusion at later than earlier gestation. Both VV and acardiac resistances are significantly smaller than the AA resistance, based on respectively clinical data and acardiac blood volumetric growth.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our simulations support clinical results which show that UVD ratios aid in the prediction of pump twin risk. The AA anastomosis controls the future of both the pump and the acardiac. Correlation between acardiac size and pump twin risk is secondary to the AA size but remains clinically usable. These factors may aid in the development of methods for pump twin prognosis and the promotion of selective clinical interventions.Birth Defects Research (Part A), 2016.© 2016 Wiley Periodicals, Inc. Birth Defects Research (Part A) 106:1008–1015, 2016. © 2016 Wiley Periodicals, Inc.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8983,"journal":{"name":"Birth defects research. Part A, Clinical and molecular teratology","volume":"106 12","pages":"1008-1015"},"PeriodicalIF":0.0,"publicationDate":"2016-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdra.23559","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91840956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic association of the glycine cleavage system genes and myelomeningocele","authors":"Rita H. Shah,&nbsp;Hope Northrup,&nbsp;James E. Hixson,&nbsp;Alanna C. Morrison,&nbsp;Kit Sing Au","doi":"10.1002/bdra.23552","DOIUrl":"10.1002/bdra.23552","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neural tube defects (NTDs) are one of the most common congenital birth defects, with myelomeningocele (MM) being the most severe form compatible with life. Recent studies show a link between mitochondrial folate one carbon metabolism and NTDs by means of the glycine cleavage system (GCS). We hypothesize that single nucleotide polymorphisms and novel variants in the coding regions of the GCS genes increase the risk for MM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>DNA was obtained from 96 subjects with MM born before the United States mandated folic acid fortification of grains in 1998. Primers were designed for polymerase chain reaction amplification and sequencing of all exons in the <i>AMT</i> gene, one of four genes in the GCS, followed by identification of single nucleotide polymorphisms and novel variants. An additional 252 MM subjects underwent whole exome sequencing to examine all four GCS genes (aminomethyltransferase, glycine dehydrogenase, glycine cleavage system protein-H, and dihydrolipoamide dehydrogenase).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified six novel, heterozygous variants in the <i>AMT</i> gene with three predicted to be deleterious to AMT function (p.Val7Leu, p.Pro251Arg, and p.Val380Met). Five extremely rare, known heterozygous variants were found in the <i>AMT</i> gene and one in the <i>GLDC</i> gene. No novel variants in the exons of the other two GCS genes (<i>DLD</i> and <i>GCSH</i>) were identified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We identified novel and rare, known variants in two of the four GCS genes that may contribute to the development of MM. Consistent with previous findings, the current study provides additional support that genetic variations in GCS genes contribute to the risk of NTDs. Birth Defects Research (Part A) 106:847–853, 2016. © 2016 Wiley Periodicals, Inc.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8983,"journal":{"name":"Birth defects research. Part A, Clinical and molecular teratology","volume":"106 10","pages":"847-853"},"PeriodicalIF":0.0,"publicationDate":"2016-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdra.23552","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90061486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and descriptive epidemiology of esophageal atresia in the Russian Federation","authors":"Nataliya S. Demikova,&nbsp;Yulia V. Vydrych,&nbsp;Marina A. Podolnaya,&nbsp;Aleksandra S. Lapina,&nbsp;Aliy Yu. Asanov","doi":"10.1002/bdra.23553","DOIUrl":"10.1002/bdra.23553","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>This study examined the prevalence of esophageal atresia (EA) and the relationship between EA and demographic factors in the Russian Federation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data were obtained from a population-based congenital malformations registry across 14 years (2000–2013) in 24 regions of the Russian Federation and included cases of EA among live births and stillbirths.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The total number of births was 6,478,706. There were 1317 cases of isolated EA, resulting in a rate of 2.03 (95% confidence interval [CI], 1.92–2.15) per 10,000 births or 1 case per 4926 births. There were differences in the prevalence of EA among regional registries of the Russian Federation. The prevalence of EA during the study period was stable. 57.3% of all cases were cases of EA with tracheo-esophageal fistula (compared with 42.7% of cases without fistula). The male/female sex ratio was 1.3. The relative risk of EA was higher for live births with birth weight less than 3000 g (relative risk [RR] = 2.58 (95% CI, 2.36–2.82), for older maternal age (RR = 1.47 (95% CI, 1.24–1.75), for males (RR = 1.09; 95% CI, 1.03–1.17), and for the first gravidity (RR = 1.17; 95% CI, 1.09–1.25).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> CONCLUSION</h3>\u0000 \u0000 <p>In this study, the prevalence of EA across different regions of the Russian Federation was analyzed. The prevalence of EA in the period under study remained stable, and the relative risk of EA was associated with maternal age, birth weight and gravidity. Birth Defects Research (Part A) 106:854–859, 2016. © 2016 Wiley Periodicals, Inc.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8983,"journal":{"name":"Birth defects research. Part A, Clinical and molecular teratology","volume":"106 10","pages":"854-859"},"PeriodicalIF":0.0,"publicationDate":"2016-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdra.23553","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34713579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between IRF6 and 8q24 polymorphisms and nonsyndromic cleft lip with or without cleft palate: Systematic review and meta-analysis","authors":"Kachin Wattanawong,&nbsp;Sasivimol Rattanasiri,&nbsp;Mark McEvoy,&nbsp;John Attia,&nbsp;Ammarin Thakkinstian","doi":"10.1002/bdra.23540","DOIUrl":"10.1002/bdra.23540","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>We conducted a systematic review and meta-analysis of interferon regulatory factor 6 and 8q24 polymorphisms with nonsyndromic cleft lip with/without cleft palate (NSCL/P).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data extraction was independently performed by two reviewers. Genotypic effects of four polymorphisms from 31 studies were pooled separately by ethnicity using a mixed-effect logit model with accounting for heterogeneity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>For rs2235371, AA and GA carried, respectively, 51% (95% confidence interval [CI], 37%–61%) and 42% (95% CI, 32%–50%) lower risks of NSCL/P than GG genotypes in Asians, but these genotypes were not significant in Caucasians. For rs2013162, only AA was significant, that is, carried 0.65 (95% CI, 0.52–0.82) times lower odds than CC in Caucasians but not for Asians. For rs642961, AA and GA genotypes, respectively, carried 2.47 (95% CI, 1.41–4.35) and 1.40 (95% CI, 1.12–1.75) times higher odds in Asian, and 2.03 (95% CI, 1.52–2.71) and 1.58 (95% CI, 1.37–1.82) times higher odds in Caucasians compare with GG genotypes. For rs987525, AA and CA genotypes carried 2.27 (95% CI, 1.43–3.60) and 1.34 (95% CI, 1.02–1.77) times higher odds in Asian, and 5.25 (95% CI, 3.98–6.91) and 2.13 (95% CI–1.82, 2.49) times higher odds in Caucasians, and 1.42 (95% CI, 1.10–1.82) and 1.28 (95% CI, 1.09–1.50) times higher odds in mixed ethnicities compared with CC genotypes. These variant effects remained significant based on applying Bonferroni corrected-thresholds, except in the mixed ethnicity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We show robust variant effects in NSCL/P. Considering them with other genes and risk factors might be useful to improve prediction of NSCL/P occurrence. Birth Defects Research (Part A) 106:773–788, 2016. © 2016 The Authors Birth Defects Research Part A: Clinical and Molecular Teratology Published by Wiley Periodicals, Inc.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8983,"journal":{"name":"Birth defects research. Part A, Clinical and molecular teratology","volume":"106 9","pages":"773-788"},"PeriodicalIF":0.0,"publicationDate":"2016-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdra.23540","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34745515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Congenital abnormalities in newborns of women with pregestational diabetes: A time-trend analysis, 1994 to 2009","authors":"Mohammad M. Agha,&nbsp;Richard H. Glazier,&nbsp;Rahim Moineddin,&nbsp;Gillian Booth","doi":"10.1002/bdra.23548","DOIUrl":"10.1002/bdra.23548","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The main objective of the current study is to examine the trend of congenital abnormalities among children born by women with and without diabetes, and to explore the impact of food fortification by folic acid on the rate of birth defects among these two groups of mothers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>All children born alive in Ontario, Canada, during 1994 to 2009 and their mothers were included in study. Diagnosis of pregestational diabetes among mothers was identified using Diabetes registry, and diagnosis of birth defects among children were identified using hospital records.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The prevalence of births among diabetic mothers increased by almost 200% during the study period. Among children born to mothers with diabetes, the prevalence for all anomalies combined was approximately 47% higher and for various cardiac and central nervous system anomalies up to a three- to fivefold higher than those born to nondiabetic mothers. While the rate of birth defects in both groups observed a considerable decline after food fortification in 1999, but the gap between two groups remained unchanged over time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>While the prevalence of birth defects among diabetic pregnancies is still considerably higher that nondiabetic pregnancies, results of the current study indicate a declining trend in the prevalence of some congenital abnormalities among babies born to both diabetic and nondiabetic mothers after 1999. We need to be more aggressive in implementing preventive measures, including a national diabetes plan or the proposed universal policy of supra-dietary folic acid supplementation for women with diabetes who are of reproductive age. Birth Defects Research (Part A) 106:831–839, 2016. © 2016 Wiley Periodicals, Inc.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8983,"journal":{"name":"Birth defects research. Part A, Clinical and molecular teratology","volume":"106 10","pages":"831-839"},"PeriodicalIF":0.0,"publicationDate":"2016-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdra.23548","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34359250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Birth defects and neonatal morbidity caused by teratogen exposure after the embryonic period","authors":"Angela E. Scheuerle,&nbsp;Arthur S. Aylsworth","doi":"10.1002/bdra.23555","DOIUrl":"10.1002/bdra.23555","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pharmaceutical pregnancy exposure registries seek to evaluate temporal associations between drug exposures and adverse outcomes, particularly congenital anomalies. These registries record observed associations that may or may not be causally-related to the exposure. Most major congenital malformations (i.e., structural birth defects) result from abnormal development during embryogenesis. A standardized catalog of defects of concern (colloquially the “BPA Codes”) is used both in public health surveillance programs and pregnancy exposure registries. There are, however, some anomalies that cause significant morbidity and mortality for which isolated second or third trimester exposures may be pathogenically significant. There currently exists no standardized list of defects for which exposure limited to the fetal period may be problematic.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The six-digit-code list was used to determine anomalies that might result from medication exposures limited to the fetal period.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Defects with documented first trimester pathogenesis (e.g., anencephaly, heterotaxy) were eliminated from consideration, as were chromosomal and single gene disorders (e.g., trisomy 21, achondroplasia). The remaining defects include the following: (1) those that are known to or could reasonably originate or manifest after the embryonic period (e.g., porencephaly, cataracts); (2) those for which pathogenesis is unclear or variable enough that exposure at any gestational age might be considered relevant (e.g., club foot, microcephaly); and (3) those that include some component of abnormal growth (e.g., hemihyperplasia). “Unspecified” defects (e.g., “abnormality of the leg”) were included by default because there is insufficient information to assume first trimester embryogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The final result is a list of major and minor anomalies in 11 organ system categories that may be caused by teratogen exposure during the fetal period. Birth Defects Research (Part A) 106:935–939, 2016. © 2016 Wiley Periodicals, Inc.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8983,"journal":{"name":"Birth defects research. Part A, Clinical and molecular teratology","volume":"106 11","pages":"935-939"},"PeriodicalIF":0.0,"publicationDate":"2016-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdra.23555","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34359694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmental factors in the etiology of isolated and nonisolated esophageal atresia in a Chinese population: A case–control study","authors":"Yu Feng,&nbsp;Runsen Chen,&nbsp;Xiaonan Li,&nbsp;Xuming Mo","doi":"10.1002/bdra.23550","DOIUrl":"10.1002/bdra.23550","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Esophageal atresia (EA) is a common birth defect that occurs with tracheoesophageal fistula (TEF), although etiological studies on EA/TEF have produced inconsistent results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The aim of this study was to examine the association between environmental factors during pregnancy and the risk of EA/TEF in a Chinese population. Cases of isolated EA and nonisolated EA and unaffected controls were identified between July 2005 and November 2015, and face-to-face questionnaires concerning exposure to environmental factors were administered to the birth mothers of 130 cases and 400 controls. The adjusted odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the association between environmental factors and the risk of EA/TEF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results of this case–control study suggest that lower maternal education (p &lt; 0.0001), maternal binge drinking (OR = 2.63; 95% CI, 1.05–6.6) and pickled food consumption (OR = 2.04; 95% CI, 1.31–3.71) during pregnancy increase the risk of EA in offspring, while maternal folic acid supplementation (OR = 0.45; 95% CI, 0.29–0.71) is significantly associated with a decreased risk of EA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These results suggest a role for environmental exposures in the etiology of EA/TEF; however, further studies are needed to replicate the observed associations. Birth Defects Research (Part A) 106:840–846, 2016. © 2016 Wiley Periodicals, Inc.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8983,"journal":{"name":"Birth defects research. Part A, Clinical and molecular teratology","volume":"106 10","pages":"840-846"},"PeriodicalIF":0.0,"publicationDate":"2016-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdra.23550","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34625884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of the 3-hydroxy-3-methyl-glutaryl-CoA reductase induces orofacial defects in zebrafish","authors":"Iskra A. Signore,&nbsp;Carolina Jerez,&nbsp;Diego Figueroa,&nbsp;José Suazo,&nbsp;Katherine Marcelain,&nbsp;Oscar Cerda,&nbsp;Alicia Colombo Flores","doi":"10.1002/bdra.23546","DOIUrl":"10.1002/bdra.23546","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Orofacial clefts (OFCs) are common birth defects, which include a range of disorders with a complex etiology affecting formation of craniofacial structures. Some forms of syndromic OFCs are produced by defects in the cholesterol pathway. The principal enzyme of the cholesterol pathway is the 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR). Our aim is to study whether defects of HMGCR function would produce orofacial malformation similar to those found in disorders of cholesterol synthesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used zebrafish <i>hmgcrb</i> mutants and HMGCR inhibition assay using atorvastatin during early and late stages of orofacial morphogenesis in zebrafish. To describe craniofacial phenotypes, we stained cartilage and bone and performed <i>in situ</i> hybridization using known craniofacial markers. Also, we visualized neural crest cell migration in a transgenic fish.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our results showed that mutants displayed loss of cartilage and diminished orofacial outgrowth, and in some cases palatal cleft. Late treatments with statin show a similar phenotype. Affected-siblings displayed a moderate phenotype, whereas early-treated embryos had a minor cleft. We found reduced expression of the downstream component of Sonic Hedgehog-signaling <i>gli1</i> in ventral brain, oral ectoderm, and pharyngeal endoderm in mutants and in late atorvastatin-treated embryos.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results suggest that HMGCR loss-of-function primarily affects postmigratory cranial neural crest cells through abnormal Sonic Hedgehog signaling, probably induced by reduction in metabolites of the cholesterol pathway. Malformation severity correlates with the grade of HMGCR inhibition, developmental stage of its disruption, and probably with availability of maternal lipids. Together, our results might help to understand the spectrum of orofacial phenotypes found in cholesterol synthesis disorders. Birth Defects Research (Part A) 106:814–830, 2016. © 2016 Wiley Periodicals, Inc.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8983,"journal":{"name":"Birth defects research. Part A, Clinical and molecular teratology","volume":"106 10","pages":"814-830"},"PeriodicalIF":0.0,"publicationDate":"2016-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdra.23546","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34633578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}