Birth Defects Research. Part A, Clinical And Molecular Teratology[JOURNAL]
Sun
200 papers
Genetic association of the glycine cleavage system genes and myelomeningocele.
Shah RH, Northrup H, Hixson JE … +2 more , Morrison AC, Au KS
Birth Defects Res A Clin Mol Teratol · 2016 Oct · PMID 27620832 · Full text
BACKGROUND: 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 fol...
BACKGROUND: 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. METHODS: 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 AMT 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). RESULTS: We identified six novel, heterozygous variants in the AMT 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 AMT gene and one in the GLDC gene. No novel variants in the exons of the other two GCS genes (DLD and GCSH) were identified. CONCLUSION: 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.
Prevalence and descriptive epidemiology of esophageal atresia in the Russian Federation.
Demikova NS, Vydrych YV, Podolnaya MA … +2 more , Lapina AS, Asanov AY
Birth Defects Res A Clin Mol Teratol · 2016 Oct · PMID 27601140 · Publisher ↗
BACKGROUND: This study examined the prevalence of esophageal atresia (EA) and the relationship between EA and demographic factors in the Russian Federation. METHODS: Data were obtained from a population-based congenital...
BACKGROUND: This study examined the prevalence of esophageal atresia (EA) and the relationship between EA and demographic factors in the Russian Federation. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
Congenital abnormalities in newborns of women with pregestational diabetes: A time-trend analysis, 1994 to 2009.
Agha MM, Glazier RH, Moineddin R … +1 more , Booth G
Birth Defects Res A Clin Mol Teratol · 2016 Oct · PMID 27511615 · Publisher ↗
BACKGROUND: 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 aci...
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Environmental factors in the etiology of isolated and nonisolated esophageal atresia in a Chinese population: A case-control study.
Feng Y, Chen R, Li X … +1 more , Mo X
Birth Defects Res A Clin Mol Teratol · 2016 Oct · PMID 27494675 · Publisher ↗
BACKGROUND: Esophageal atresia (EA) is a common birth defect that occurs with tracheoesophageal fistula (TEF), although etiological studies on EA/TEF have produced inconsistent results. METHODS: The aim of this study was...
BACKGROUND: Esophageal atresia (EA) is a common birth defect that occurs with tracheoesophageal fistula (TEF), although etiological studies on EA/TEF have produced inconsistent results. METHODS: 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. RESULTS: The results of this case-control study suggest that lower maternal education (p < 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. CONCLUSION: 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.
Inhibition of the 3-hydroxy-3-methyl-glutaryl-CoA reductase induces orofacial defects in zebrafish.
Signore IA, Jerez C, Figueroa D … +4 more , Suazo J, Marcelain K, Cerda O, Colombo Flores A
Birth Defects Res A Clin Mol Teratol · 2016 Oct · PMID 27488927 · Publisher ↗
BACKGROUND: 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 defect...
BACKGROUND: 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. METHODS: We used zebrafish hmgcrb 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 in situ hybridization using known craniofacial markers. Also, we visualized neural crest cell migration in a transgenic fish. RESULTS: 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 gli1 in ventral brain, oral ectoderm, and pharyngeal endoderm in mutants and in late atorvastatin-treated embryos. CONCLUSION: 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.
Effects of thyroxine exposure on the Twist 1 +/- phenotype: A test of gene-environment interaction modeling for craniosynostosis.
Durham EL, Howie RN, Black L … +6 more , Bennfors G, Parsons TE, Elsalanty M, Yu JC, Weinberg SM, Cray JJ
Birth Defects Res A Clin Mol Teratol · 2016 Oct · PMID 27435288 · Full text
BACKGROUND: Craniosynostosis, the premature fusion of one or more of the cranial sutures, is estimated to occur in 1:1800 to 2500 births. Genetic murine models of craniosynostosis exist, but often imperfectly model human...
BACKGROUND: Craniosynostosis, the premature fusion of one or more of the cranial sutures, is estimated to occur in 1:1800 to 2500 births. Genetic murine models of craniosynostosis exist, but often imperfectly model human patients. Case, cohort, and surveillance studies have identified excess thyroid hormone as an agent that can either cause or exacerbate human cases of craniosynostosis. METHODS: Here we investigate the influence of in utero and in vitro exogenous thyroid hormone exposure on a murine model of craniosynostosis, Twist 1 +/-. RESULTS: By 15 days post-natal, there was evidence of coronal suture fusion in the Twist 1 +/- model, regardless of exposure. With the exception of craniofacial width, there were no significant effects of exposure; however, the Twist 1 +/- phenotype was significantly different from the wild-type control. Twist 1 +/- cranial suture cells did not respond to thyroxine treatment as measured by proliferation, osteogenic differentiation, and gene expression of osteogenic markers. However, treatment of these cells did result in modulation of thyroid associated gene expression. CONCLUSION: Our findings suggest the phenotypic effects of the genetic mutation largely outweighed the effects of thyroxine exposure in the Twist 1 +/- model. These results highlight difficultly in experimentally modeling gene-environment interactions for craniosynostotic phenotypes. Birth Defects Research (Part A) 106:803-813, 2016. © 2016 Wiley Periodicals, Inc.
Letter to the editor interpreting trends in the context of previous evidence.
Kirby RS
Birth Defects Res A Clin Mol Teratol · 2016 Dec · PMID 27731923 · Publisher ↗
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Diprosopus: Systematic review and report of two cases.
Bidondo MP, Groisman B, Tardivo A … +6 more , Tomasoni F, Tejeiro V, Camacho I, Vilas M, Liascovich R, Barbero P
Birth Defects Res A Clin Mol Teratol · 2016 Dec · PMID 27704687 · Publisher ↗
BACKGROUND: Diprosopus is a subtype of symmetric conjoined twins with one head, facial duplication and a single trunk. Diprosopus is a very rare congenital anomaly. METHODS: This is a systematic review of published cases...
BACKGROUND: Diprosopus is a subtype of symmetric conjoined twins with one head, facial duplication and a single trunk. Diprosopus is a very rare congenital anomaly. METHODS: This is a systematic review of published cases and the presentation of two new cases born in Argentina. We estimated the prevalence of conjoined twins and diprosopus using data from the National Network of Congenital Anomalies of Argentina (RENAC). RESULTS: The prevalence of conjoined twins in RENAC was 19 per 1,000,000 births (95% confidence interval, 12-29). Diprosopus prevalence was 2 per 1,000,000 births (95% confidence interval, 0.2-6.8). In the systematic review, we identified 31 diprosopus cases. The facial structures more frequently duplicated were nose and eyes. Most frequent associated anomalies were: anencephaly, duplication of cerebral hemispheres, craniorachischisis, oral clefts, spinal abnormalities, congenital heart defects, diaphragmatic hernia, thoracic and/or abdominal visceral laterality anomalies. One of the RENAC cases and three cases from the literature had another discordant nonmalformed twin. CONCLUSION: The conjoined twins prevalence was similar to other studies. The prevalence of diprosopus was higher. The etiology is still unknown. The presence of visceral laterality anomalies may indicate the link between diprosopus and the alteration or duplication of the primitive node in the perigastrulation period (12-15 days postfertilization). Pregnancies of more than two embryos may be a risk factor for diprosopus. Given the low prevalence of this defect, it would be useful to perform studies involving several surveillance systems and international consortiums. Birth Defects Research (Part A), 2016. © 2016 Wiley Periodicals, Inc. Birth Defects Research (Part A) 106:993-1007, 2016. © 2016 Wiley Periodicals, Inc.
Acardiac twin pregnancies part III: Model simulations.
van Gemert MJ, Ross MG, Nikkels PG … +1 more , Wijngaard JP
Birth Defects Res A Clin Mol Teratol · 2016 Dec · PMID 27629527 · Publisher ↗
BACKGROUND: 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 hy...
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Birth defects and neonatal morbidity caused by teratogen exposure after the embryonic period.
Scheuerle AE, Aylsworth AS
Birth Defects Res A Clin Mol Teratol · 2016 Nov · PMID 27511745 · Publisher ↗
BACKGROUND: Pharmaceutical pregnancy exposure registries seek to evaluate temporal associations between drug exposures and adverse outcomes, particularly congenital anomalies. These registries record observed association...
BACKGROUND: 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. METHODS: The six-digit-code list was used to determine anomalies that might result from medication exposures limited to the fetal period. RESULTS: 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. CONCLUSION: 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.
Association between IRF6 and 8q24 polymorphisms and nonsyndromic cleft lip with or without cleft palate: Systematic review and meta-analysis.
Wattanawong K, Rattanasiri S, McEvoy M … +2 more , Attia J, Thakkinstian A
Birth Defects Res A Clin Mol Teratol · 2016 Sep · PMID 27511269 · Full text
BACKGROUND: 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). METHODS: Data extraction was indepen...
BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.
A 2015 global update on folic acid-preventable spina bifida and anencephaly.
Arth A, Kancherla V, Pachón H … +3 more , Zimmerman S, Johnson Q, Oakley GP
Birth Defects Res A Clin Mol Teratol · 2016 Jul · PMID 27418029 · Publisher ↗
BACKGROUND: Spina bifida and anencephaly are two major neural tube defects. They contribute substantially to perinatal, neonatal, infant, and under-five mortality and life-long disability. To monitor the progress toward...
BACKGROUND: Spina bifida and anencephaly are two major neural tube defects. They contribute substantially to perinatal, neonatal, infant, and under-five mortality and life-long disability. To monitor the progress toward the total prevention of folic acid-preventable spina bifida and anencephaly (FAP SBA), we examined their global status in 2015. METHODS: Based on existing data, we modeled the proportion of FAP SBA that are prevented in the year 2015 through mandatory folic acid fortification globally. We included only those countries with mandatory fortification that added at least 1.0 ppm folic acid as a fortificant to wheat and maize flour, and had complete information on coverage. Our model assumed mandatory folic acid fortification at 200 μg/day is fully protective against FAP SBA, and reduces the rate of spina bifida and anencephaly to a minimum of 0.5 per 1000 births. RESULTS: Our estimates show that, in 2015, 13.2% (35,500 of approximately 268,700 global cases) of FAP SBA were prevented in 58 countries through mandatory folic acid fortification of wheat and maize flour. Most countries in Europe, Africa, and Asia were not implementing mandatory fortification with folic acid. CONCLUSION: Knowledge that folic acid prevents spina bifida and anencephaly has existed for 25 years, yet only a small fraction of FAP SBA is being prevented worldwide. Several countries still have 5- to 20-fold epidemics of FAP SBA. Implementation of mandatory fortification with folic acid offers governments a proven and rapid way to prevent FAP SBA-associated disability and mortality, and to help achieve health-related Sustainable Development Goals. Birth Defects Research (Part A) 106:520-529, 2016. © 2016 Wiley Periodicals, Inc.
What is standing in the way of complete prevention of folate preventable neural tube defects?
Mills JL, Dimopoulos A, Bailey RL
Birth Defects Res A Clin Mol Teratol · 2016 Jul · PMID 27418028 · Full text
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Further evidence for deletions in 7p14.1 contributing to nonsyndromic cleft lip with or without cleft palate.
Klamt J, Hofmann A, Böhmer AC … +13 more , Hoebel AK, Gölz L, Becker J, Zink AM, Draaken M, Hemprich A, Scheer M, Schmidt G, Martini M, Knapp M, Mangold E, Degenhardt F, Ludwig KU
Birth Defects Res A Clin Mol Teratol · 2016 Sep · PMID 27384521 · Publisher ↗
BACKGROUND: Nonsyndromic cleft with or without cleft palate (nsCL/P) is a common birth defect. Although genome-wide association studies (GWAS) have identified numerous risk variants, a considerable fraction of the geneti...
BACKGROUND: Nonsyndromic cleft with or without cleft palate (nsCL/P) is a common birth defect. Although genome-wide association studies (GWAS) have identified numerous risk variants, a considerable fraction of the genetic heritability remains unknown. The aim of the present study was to replicate a previous finding that de novo deletions in a 62 kb region of chromosome 7p14 are a risk factor for nsCL/P, using an independent cohort. METHODS: Data from a published case-control GWAS cohort of 399 patients and 1318 controls were used. Copy number variant (CNV) detection in the 62 kb candidate region of 7p14 was performed using QuantiSNP. Putative CNVs in probands were verified and validated by quantitative polymerase chain reaction. Segregation analyses were performed in family members for whom DNA was available. RESULTS: Within the 62 kb candidate region, a deletion of 7.4 kb showed association with nsCL/P (13/387 cases, 20/1300 controls, plowest = 0.024, odds ratio = 2.22). In all families with a sporadic case (n = 3), the deletion occurred de novo. In multiplex families, both incomplete segregation and incomplete penetrance were observed. CONCLUSION: The present data support the hypothesis that deletions at 7p14 are a common risk factor for nsCL/P. Genome-wide CNV analyses in nsCL/P cohorts are warranted to explore the functional relevance of these deletions and their contribution to nsCL/P, and to determine exact breakpoints. Birth Defects Research (Part A) 106:767-772, 2016. © 2016 Wiley Periodicals, Inc.
In utero exposure to venlafaxine, a serotonin-norepinephrine reuptake inhibitor, increases cardiac anomalies and alters placental and heart serotonin signaling in the rat.
Laurent L, Huang C, Ernest SR … +3 more , Berard A, Vaillancourt C, Hales BF
Birth Defects Res A Clin Mol Teratol · 2016 Dec · PMID 27384265 · Publisher ↗
BACKGROUND: Human studies are inconsistent with respect to an association between treatment with selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRI/SNRIs) and an increase in the incidence of conge...
BACKGROUND: Human studies are inconsistent with respect to an association between treatment with selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRI/SNRIs) and an increase in the incidence of congenital heart defects. Here we tested the hypothesis that in utero exposure to venlafaxine, a highly prescribed SNRI, increases the incidence of fetal heart defects and alters placental and fetal heart serotonin signaling in the rat. METHODS: Timed-pregnant Sprague Dawley rats were gavaged daily with venlafaxine hydrochloride (0, 3, 10, 30, or 100 mg/kg/day) from gestation day 8 to 20. On gestation day 21, fetuses were examined for external and internal malformations; placentas and fetal hearts were collected for the analysis of gene expression. RESULTS: Venlafaxine had no effect on the number of live fetuses, fetal body weights, or external morphology in the absence of maternal toxicity. However, venlafaxine significantly increased the placental index (fetal body/placental weight ratio) and the incidence of fetal cardiac anomalies. Venlafaxine exposure decreased placental expression of the serotonin transporter (SERT/Slc6a4) at the transcript and protein levels. In contrast, venlafaxine increased SERT expression in the hearts of female, but not male, fetuses. Expression of the serotonin 2B receptor (5-HT /Htr2b) and of fibroblast growth factor 8 was induced in fetal hearts. CONCLUSION: In utero venlafaxine exposure altered the placental index and induced fetal cardiac anomalies in rats. We propose that the increased incidence of cardiac anomalies is mediated through alterations in serotonin signaling in the placenta and fetal heart. Birth Defects Research (Part A), 2016. © 2016 Wiley Periodicals, Inc. Birth Defects Research (Part A) 106:1044-1055, 2016. © 2016 Wiley Periodicals, Inc.
A novel 2q14.1q14.3 deletion involving GLI2 and RNU4ATAC genes associated with partial corpus callosum agenesis and severe intrauterine growth retardation.
Goumy C, Gay-Bellile M, Salaun G … +11 more , Kemeny S, Eymard-Pierre E, Biard M, Pebrel-Richard C, Vanlieferinghen P, Francannet C, Tchirkov A, Laurichesse H, Rouzade C, Gouas L, Vago P
Birth Defects Res A Clin Mol Teratol · 2016 Sep · PMID 27346851 · Publisher ↗
BACKGROUND: Microdeletions encompassing chromosome bands 2q14.1q14.3 are rare. To date, eight reports of relatively large deletions of this region (∼20 Mb) but only two small deletions (<6 Mb) have been reported. These d...
BACKGROUND: Microdeletions encompassing chromosome bands 2q14.1q14.3 are rare. To date, eight reports of relatively large deletions of this region (∼20 Mb) but only two small deletions (<6 Mb) have been reported. These deletions can cause a variable phenotype depending on the size and location of the deletion. Cognitive disability, facial dysmorphism, and postnatal growth retardation are the most common phenotypic features. CASE: We report on a novel 5.8 Mb deletion of 2q14.1q14.3 identified by array comparative genomic hybridization in a fetus with severe intrauterine growth retardation and partial agenesis of the corpus callosum. The deletion contained 24 coding genes including STEAP3, GLI2, and RNU4ATAC and was inherited from the mild affected mother. A sibling developmental delay and similar dysmorphic facial features was found to have inherited the same deletion. CONCLUSION: This case emphasizes the variable expressivity of the 2q14 microdeletion and reinforces the hypothesis that agenesis of corpus callosum, microcephaly, developmental delay, and distinctive craniofacial features may be part of the phenotypic spectrum characterizing the affected patients. We suggest that GLI2 is a dosage-sensitive gene that may be responsible for the agenesis of corpus callosum observed in the proband. Birth Defects Research (Part A) 106:793-797, 2016. © 2016 Wiley Periodicals, Inc.
Age range for inclusion affects ascertainment by birth defects registers.
Gibson CS, Scott H, Haan E … +1 more , Scheil W
Birth Defects Res A Clin Mol Teratol · 2016 Sep · PMID 27324669 · Publisher ↗
BACKGROUND: The South Australian Birth Defects Register (SABDR) has collected the date of diagnosis of notified birth defects since the 2005 birth year cohort. This study aims to document the age at diagnosis for each of...
BACKGROUND: The South Australian Birth Defects Register (SABDR) has collected the date of diagnosis of notified birth defects since the 2005 birth year cohort. This study aims to document the age at diagnosis for each of the main diagnostic categories of birth defects, to produce a profile of when defects are diagnosed. METHODS: Deidentified data were extracted from the SABDR for birth years 2005 to 2007. Each birth defect was assigned to a mutually exclusive date of diagnosis category (termination/stillbirth; neonatal [birth-28 days]; 1 month-1 year; 1-2 years; 2-3 years; 3-4 years; 4-5 years; unspecified). Each defect was also grouped according to the International Classification of Diseases Ninth edition-British Paediatric Association major diagnostic categories (nervous, cardiovascular, respiratory, gastrointestinal, urogenital, musculoskeletal, chromosomal, metabolic, hematological/immune, other). RESULTS: There were 6419 defects identified in 3676 individuals, and 98.6% of defects had a diagnosis date recorded. Terminations of pregnancy/stillbirths accounted for 20.3% of defects notified, and a further 46.7% of defects were diagnosed within the neonatal period. A total of 81.5% of defects were diagnosed by 1 year of age. An additional 17.2% of defects were diagnosed between the ages of 1 and 5 years. There were wide differences in age at diagnosis between the major diagnostic categories. CONCLUSION: This study highlights the value of birth defect registers collecting information about birth defects from terminations of pregnancy, stillbirths, and live births up to a child's fifth birthday. Reviewing diagnosis date provides insight into the pattern of diagnosis of different birth defects. This provides valuable information to medical specialists and researchers regarding the interpretation of information from birth defect data collections. Birth Defects Research (Part A) 106:761-766, 2016. © 2016 Wiley Periodicals, Inc.
Abstracts from the 13th EUROCAT SCIENTIFIC SYMPOSIUM: Advancing congenital anomaly research through collaboration, 16-17 June 2016, Milan, Italy.
Birth Defects Res A Clin Mol Teratol · 2016 Jun · PMID 27301564 · Publisher ↗
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Use of azathioprine and corticosteroids during pregnancy and birth outcome in women diagnosed with inflammatory bowel disease.
Plauborg AV, Hansen AV, Garne E
Birth Defects Res A Clin Mol Teratol · 2016 Jun · PMID 27301563 · Publisher ↗
BACKGROUND: The aim of this study was to describe prescription patterns for azathioprine and corticosteroids for pregnant women with inflammatory bowel diseases (IBD) before, during, and after pregnancy and to describe p...
BACKGROUND: The aim of this study was to describe prescription patterns for azathioprine and corticosteroids for pregnant women with inflammatory bowel diseases (IBD) before, during, and after pregnancy and to describe pregnancy outcomes. METHODS: A cohort composed of all singleton pregnancies in Danish registries from 1996 to 2009 was divided by maternal IBD status: Crohn's disease (CD, n = 827), ulcerative colitis (UC, N = 1361), or no IBD diagnosis (background population, n = 814,231). The number of women with a prescription for azathioprine, local and systemic steroids within a 3-month period was computed for each of the pregnancy trimesters and the year before and after pregnancy. Outcomes of interest were stillbirth, perinatal mortality, low birth weight (LBW), preterm birth, and small for gestational age (SGA). RESULTS: Number of prescriptions for azathioprine decreased just before and during pregnancy and increased after birth. Number of prescriptions for local and systemic corticosteroids decreased approximately 30% compared with before pregnancy and increased in the second trimester. There was an increased risk among mothers with IBD of LBW (adjusted odds ratio [adjOR]: CD: 2.25 [95% confidence interval {CI}, 1.74-2.91], UC: 1.81 [95% CI, 1.42-2.30]), preterm birth (adjOR: CD: 2.54 [95% CI, 2.04-3.15], UC: 1.86 [95% CI, 1.52-2.27]), and SGA (adjOR: CD: 1.99 [95% CI, 1.26-3.15], UC: 1.80 [95% CI, 1.18-2.75]). CONCLUSION: Use of azathioprine and corticosteroids was often reduced or discontinued before or during early pregnancy followed by an increased use of corticosteroids later in pregnancy. Women diagnosed with IBD and with prescriptions for azathioprine and/or corticosteroids, have an increased risk of LBW, pre-term birth, and SGA. Birth Defects Research (Part A) 106:494-499, 2016. © 2016 Wiley Periodicals, Inc.
Absence of prenatal ultrasound surveillance: Data from the Portuguese congenital anomalies registry.
Correia S, Machado A, Braz P … +2 more , Rodrigues AP, Matias-Dias C
Birth Defects Res A Clin Mol Teratol · 2016 Jun · PMID 27301562 · Publisher ↗
BACKGROUND: In Portugal, prenatal care guidelines advocate two prenatal ultrasound scans for all pregnant women. Not following this recommendation is considered inadequate prenatal surveillance. The National Registry of...
BACKGROUND: In Portugal, prenatal care guidelines advocate two prenatal ultrasound scans for all pregnant women. Not following this recommendation is considered inadequate prenatal surveillance. The National Registry of Congenital Anomalies (RENAC in Portuguese) is an active population-based registry and an important instrument for the epidemiological surveillance of congenital anomalies (CA) in Portugal. Regarding pregnancies with CA, this study aims to describe the epidemiology of absent prenatal ultrasound scans and factors associated with this inadequate surveillance. METHODS: A cross-sectional comparative study from 2008 to 2013 was carried out using data from RENAC. Associations of nonuptake of prenatal ultrasound screening with socio-demographic health behaviors and obstetric history data were evaluated using multiple logistic regression. Potential confounders were investigated and included if they changed the crude odds ratio estimate by at least 10% after adjustment by the Mantel-Haenszel method. The statistical significance level was set at 5%. RESULTS: Overall, 6090 notifications of congenital anomalies were reported to RENAC, and 2% of the pregnant women reported no prenatal ultrasound screening surveillance. These women were on average aged 30.0 years, and 52.8% had no professional occupation. The odds of not performing an ultrasound scan during their pregnancy increased 2.47 times with lack of professional activity, 4.67 times in non-Caucasian women, and decreased 46% for any previous miscarriage. CONCLUSION: For pregnant women who did not receive an ultrasound screening examination during pregnancy, the strongest statistically associated factors were professional occupation, ethnicity, and number of miscarriages in previous gestations. Birth Defects Research (Part A) 106:489-493, 2016. © 2016 Wiley Periodicals, Inc.
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