Castori M, Bottillo I, Morlino S
… +5 more, Barone C, Cascone P, Pediatric Craniofacial Malformation (PECRAM) Study Group, Grammatico P, Laino L
Birth Defects Res A Clin Mol Teratol
· 2016 Jan · PMID 26663529
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BACKGROUND: Campomelic dysplasia and acampomelic campomelic dysplasia (ACD) are allelic disorders due to heterozygous mutations in or around SOX9. Translocations and deletions involving the SOX9 5' regulatory region are...BACKGROUND: Campomelic dysplasia and acampomelic campomelic dysplasia (ACD) are allelic disorders due to heterozygous mutations in or around SOX9. Translocations and deletions involving the SOX9 5' regulatory region are rare causes of these disorders, as well as Pierre Robin sequence (PRS) and 46,XY gonadal dysgenesis. Genotype-phenotype correlations are not straightforward due to the complex epigenetic regulation of SOX9 expression during development. METHODS: We report a three-generation pedigree with a novel ∼1 Mb deletion upstream of SOX9 and including KCNJ2 and KCNJ16, and ascertained for dominant transmission of PRS. RESULTS: Further characterization of the family identified subtle appendicular anomalies and a variable constellation of axial skeletal features evocative of ACD in several members. Affected males showed learning disability. CONCLUSION: The identified deletion was smaller than all other chromosome rearrangements associated with ACD. Comparison with other reported translocations and deletions involving this region allowed further refining of genotype-phenotype correlations and an update of the smallest regions of overlap associated with the different phenotypes. Intrafamilial variability in this pedigree suggests a phenotypic continuity between ACD and PRS in patients carrying mutations in the SOX9 5' regulatory region.
Cura F, Böhmer AC, Klamt J
… +8 more, Schünke H, Scapoli L, Martinelli M, Carinci F, Nöthen MM, Knapp M, Ludwig KU, Mangold E
Birth Defects Res A Clin Mol Teratol
· 2016 Feb · PMID 26648166
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BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (nsCL/P) is one of the most common congenital malformations in humans. Its average global incidence is 1.7 per 1000 live births, with wide variation accordi...BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (nsCL/P) is one of the most common congenital malformations in humans. Its average global incidence is 1.7 per 1000 live births, with wide variation according to geographical location and ethnicity. Its etiology involves both genetic and environmental factors. The aim of the present study was to confirm genetic association of a selection of 15 candidate nsCL/P loci using an independent sample of the Italian population. METHODS: At least one single-nucleotide polymorphism (SNP) for each locus was genotyped in 380 nuclear trios. RESULTS: Transmission disequilibrium analysis revealed significant associations for three variants at two loci (8q24 and 1p22). Two SNPs at 8q24 showed the strongest level of association, the rs987525 (PTDT = 6.81 × 10(-6) ; homozygous relative risk = 3.60 [95% confidence interval, 2.12-6.13]), and the rs17241253 (PTDT = 1.03 × 10(-5) ; homozygous relative risk = 3.75 [95% confidence interval, 2.10-6.67]). Four additional loci (at 1q32, 3q12, 8q21, and 10q25) achieved nominally significant p-values. Two SNPs at 1p36 achieved p-values of < 0.1. The present data suggest that 6 of the 15 analyzed nsCL/P risk loci contribute significantly to nsCL/P risk in the Italian population. These include the 1p22 locus, which previous research has implicated predominantly in Asian populations. CONCLUSION: Different loci, including 8q24 and 1p22 have been found associated with nsCL/P in multiple populations. Further efforts are needed to identify causative variants and transfer knowledge to clinical application, such as personal genetic risk assessment.
Birth Defects Res A Clin Mol Teratol
· 2015 Dec · PMID 26470995
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BACKGROUND: Ethanol is a teratogen affecting numerous regions of the developing nervous system. The present study was undertaken to ascertain whether ethanol independently disrupts distinct signaling pathways or rather d...BACKGROUND: Ethanol is a teratogen affecting numerous regions of the developing nervous system. The present study was undertaken to ascertain whether ethanol independently disrupts distinct signaling pathways or rather disrupts interactive pathways that regulate development of ethanol-sensitive tissues. METHODS: Zebrafish embryos were exposed to ethanol in the absence or presence of aldh1a3 or Shh morpholino oligonucleotides (MOs), which disrupt retinoic acid (RA) or sonic hedgehog (Shh) function, respectively. Morphological analysis of ocular or midbrain-hindbrain boundary (MHB) development was conducted, and the ability to rescue ethanol and MO-induced phenotypes was assessed. In situ hybridization was used to analyze Pax6a expression during ocular development. RESULTS: Chronic ethanol exposure, or combined ethanol and MO treatment, results in perturbed MHB formation and microphthalmia. While RA can rescue the MHB phenotype following ethanol combined with either MO, Shh mRNA is unable to rescue the disrupted MHB with combined ethanol and aldh1a3 MO treatment. RA also is unable to rescue microphthalmia induced by ethanol and Shh MO. CONCLUSION: These studies demonstrate that while reduction of either RA or Shh signaling produces the same disruption of MHB or ocular development, that can be phenocopied using ethanol combined with either MO, RA overexpression can only rescue disrupted MHB, but not microphthalmia, in combined subthreshold Shh MO and ethanol. Our data suggest that MHB development may involve crosstalk between RA and Shh signaling, while ocular development depends on RA and Shh signaling that both are targets of ethanol in fetal alcohol spectrum disorders but do not depend on a mechanism involving crosstalk.
Figueiredo JC, Ly S, Magee KS
… +17 more, Ihenacho U, Baurley JW, Sanchez-Lara PA, Brindopke F, Nguyen TH, Nguyen V, Tangco MI, Giron M, Abrahams T, Jang G, Vu A, Zolfaghari E, Yao CA, Foong A, DeClerk YA, Samet JM, Magee W
Birth Defects Res A Clin Mol Teratol
· 2015 Oct · PMID 26466527
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BACKGROUND: Several lifestyle and environmental exposures have been suspected as risk factors for oral clefts, although few have been convincingly demonstrated. Studies across global diverse populations could offer addit...BACKGROUND: Several lifestyle and environmental exposures have been suspected as risk factors for oral clefts, although few have been convincingly demonstrated. Studies across global diverse populations could offer additional insight given varying types and levels of exposures. METHODS: We performed an international case-control study in the Democratic Republic of the Congo (133 cases, 301 controls), Vietnam (75 cases, 158 controls), the Philippines (102 cases, 152 controls), and Honduras (120 cases, 143 controls). Mothers were recruited from hospitals and their exposures were collected from interviewer-administered questionnaires. We used logistic regression modeling to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Family history of clefts was strongly associated with increased risk (maternal: OR = 4.7; 95% CI, 3.0-7.2; paternal: OR = 10.5; 95% CI, 5.9-18.8; siblings: OR = 5.3; 95% CI, 1.4-19.9). Advanced maternal age (5 year OR = 1.2; 95% CI, 1.0-1.3), pregestational hypertension (OR = 2.6; 95% CI, 1.3-5.1), and gestational seizures (OR = 2.9; 95% CI, 1.1-7.4) were statistically significant risk factors. Lower maternal (secondary school OR = 1.6; 95% CI, 1.2-2.2; primary school OR = 2.4, 95% CI, 1.6-2.8) and paternal education (OR = 1.9; 95% CI, 1.4-2.5; and OR = 1.8; 95% CI, 1.1-2.9, respectively) and paternal tobacco smoking (OR = 1.5, 95% CI, 1.1-1.9) were associated with an increased risk. No other significant associations between maternal and paternal factors were found; some environmental factors including rural residency, indoor cooking with wood, chemicals and water source appeared to be associated with an increased risk in adjusted models. CONCLUSION: Our study represents one of the first international studies investigating risk factors for clefts among multiethnic underserved populations. Our findings suggest a multifactorial etiology including both maternal and paternal factors.
Birth Defects Res A Clin Mol Teratol
· 2015 Dec · PMID 26408417
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BACKGROUND: While it is known that cadmium-exposed embryonic cells have increased activation of c-Jun N-terminal kinase (JNK), the role of this stress signaling pathway in the embryotoxic response is not clear. Thus, the...BACKGROUND: While it is known that cadmium-exposed embryonic cells have increased activation of c-Jun N-terminal kinase (JNK), the role of this stress signaling pathway in the embryotoxic response is not clear. Thus, the effects of modification of the transcription factor c-Jun, one of the downstream targets of JNK, on cadmium-induced embryotoxicity were investigated in primary cultures of mouse embryo limb bud cells. METHODS: Cultures of limb bud cells harvested on day 11 of gestation were pretreated with antisense oligonucleotides (ASO) to c-Jun to reduce its expression, and then incubated with cadmium in the form of cadmium chloride. Toxicity was measured through assessments of cell proliferation and differentiation, while the effectiveness of the ASO in reducing c-Jun was assessed through Western blotting using phosphorylation-specific antibodies. RESULTS: When cells were treated with ASO c-Jun, the total amounts of c-Jun and also cadmium-induced c-Jun activation were diminished. Cadmium-induced cytotoxicity, indicated by reduced cell numbers and differentiation, was found to decrease when cells were exposed to the antisense oligonucleotides to c-Jun. In addition, limb cell numbers and differentiation were also enhanced by exposure to ASO in the absence of cadmium. CONCLUSION: The JNK pathway, and particularly the downstream effector c-Jun, appears to play an important role in regulating cell survival and differentiation in mouse embryo limb bud cells both in the presence and absence of the toxic metal cadmium.
Christensen KE, Deng L, Bahous RH
… +2 more, Jerome-Majewska LA, Rozen R
Birth Defects Res A Clin Mol Teratol
· 2015 Dec · PMID 26408344
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BACKGROUND: A single nucleotide polymorphism (SNP) in the synthetase domain of the trifunctional folate-dependent enzyme MTHFD1 (c.1958G>A, R653Q) has been linked to adverse pregnancy outcomes, neural tube defects, and p...BACKGROUND: A single nucleotide polymorphism (SNP) in the synthetase domain of the trifunctional folate-dependent enzyme MTHFD1 (c.1958G>A, R653Q) has been linked to adverse pregnancy outcomes, neural tube defects, and possibly congenital heart defects. Maternal folate deficiency may also modify the risk associated with these disorders. We recently established a mouse model with a mild deficiency of 10-formyltetrahydrofolate synthetase activity in MTHFD1 (Mthfd1S(+/-) mice) to investigate disorders associated with SNPs in this gene. The effect of synthetase deficiency on embryonic heart development has not yet been examined. METHODS: Female Mthfd1S(+/+) and (+/-) mice were placed on control and folate-deficient diets for 6 weeks before mating to Mthfd1S(+/-) males. Embryos and placentae were collected at embryonic day 14.5. Embryos were evaluated for congenital heart defects by histological examination. RESULTS: Embryonic Mthfd1S(+/-) genotype was associated with an increased incidence of heart defects, primarily ventricular septal defects. Other markers of embryonic development (crown-rump length, embryonic weight, embryonic delay, placental weight, and thickness of the ventricular myocardium) were not affected by embryonic genotype. Maternal genotype and diet did not have a significant effect on these outcomes. CONCLUSION: Deficiency of the MTHFD1 10-formyltetrahydrofolate synthetase activity in embryos is associated with increased incidence of congenital heart defects.
Birth Defects Res A Clin Mol Teratol
· 2015 Nov · PMID 26408207
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BACKGROUND: The prevalence of gastroschisis, a birth defect of the abdominal wall, has been increasing in several areas around the world. Suggested risk factors for gastroschisis include maternal age, race/ethnicity, nat...BACKGROUND: The prevalence of gastroschisis, a birth defect of the abdominal wall, has been increasing in several areas around the world. Suggested risk factors for gastroschisis include maternal age, race/ethnicity, nativity, body mass index, and socioeconomic status. METHODS: Data for cases of gastroschisis and live births were taken from the Texas Birth Defects Registry and Texas vital records for deliveries between 1999 and 2011. Prevalence by subgroups over time was calculated for: infant sex, maternal age, race/ethnicity, nativity, education, parity, plurality, body mass index, and payer type. Stratified, adjusted, and interaction analyses of the trends were conducted using Poisson regression. A joinpoint trend analysis was also conducted for each subgroup. RESULTS: A total of 2,549 gastroschisis cases and 4,970,979 live births were delivered in 1999 to 2011, for an overall prevalence of 5.13 cases per 10,000 live births (95% confidence interval = 4.93-5.33). On average, the prevalence increased 4.8% each year; this overall time trend was statistically significant (p-value < 0.0001). The time trend remained significant after adjusting for all variables, except payer type. The stratified analysis showed the increasing time trend was significant in many of the subgroups. However, there were no significant differences in the magnitude of the time trends between subgroups according to the interaction analysis. CONCLUSION: This study confirms the increasing prevalence of gastroschisis over the time period 1999 to 2011 in Texas. The results suggest that no population subgroups are experiencing a significantly different increase in gastroschisis prevalence over time than others.
Van Zutphen AR, Bell EM, Browne ML
… +4 more, Lin S, Lin AE, Druschel CM, National Birth Defects Prevention Study
Birth Defects Res A Clin Mol Teratol
· 2015 Nov · PMID 26408052
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BACKGROUND: Asthma affects 4% to 8% of pregnant women and studies suggest maternal asthma, particularly when uncontrolled, may be associated with adverse reproductive outcomes. METHODS: We examined self-reported asthma m...BACKGROUND: Asthma affects 4% to 8% of pregnant women and studies suggest maternal asthma, particularly when uncontrolled, may be associated with adverse reproductive outcomes. METHODS: We examined self-reported asthma medication use and the risk of congenital heart defects (CHD) in the National Birth Defects Prevention Study, a multi-center, population-based case-control study of selected major structural defects. We evaluated maternal use of bronchodilators and anti-inflammatories during the periconceptional period (1 month before conception through the first 3 pregnancy months) among 7638 infants with CHDs and 8106 nonmalformed controls with estimated delivery dates from 1997 to 2007. We used logistic regression to estimate odds ratios and 95% confidence intervals for 20 types of CHDs. RESULTS: Among asthma medications reported during the periconceptional period among controls, albuterol accounted for 85.1% of all bronchodilator use, and fluticasone, prednisone, and montelukast accounted for 46.1%, 15.6%, and 14.9% of anti-inflammatory use, respectively. Of the women who reported bronchodilators during the periconceptional period, 71.1% reported use throughout pregnancy and only 29.4% reported concurrent use of an anti-inflammatory. We observed one statistically significant association between maternal bronchodilator use only and anomalous pulmonary venous return (odds ratio 2.3, 95% confidence interval 1.1-4.8) among numerous comparisons. CONCLUSION: We did not observe statistically significant associations between the reported use of asthma medications during pregnancy and most specific types of CHDs. Despite limitations in our inability to evaluate asthma status and severity, our study suggests that maternal asthma medication use does not substantially, if at all, increase the risk of CHDs.
Birth Defects Res A Clin Mol Teratol
· 2016 Jan · PMID 26407522
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BACKGROUND: The National Children's Study (NCS) Vanguard Study began enrollment in January 2009 as an initial pilot study for a planned large-scale, longitudinal U.S. cohort study of the effect of environmental influence...BACKGROUND: The National Children's Study (NCS) Vanguard Study began enrollment in January 2009 as an initial pilot study for a planned large-scale, longitudinal U.S. cohort study of the effect of environmental influences on child health and development, with biological and environmental sample collection conducted in seven locations from April 2009 to October 2010. We sought to determine rates of consent for, and success of collection of, maternal and paternal biospecimens before and during pregnancy in the NCS Vanguard Study. METHODS: Samples of blood, saliva, vaginal swabs, urine, hair, and nails were collected before and during pregnancy. All specimens were sent to a central repository for processing, storage, and quality assessment. RESULTS: Of 780 pregnant women asked to consent to sample collection, 773 (>99%) agreed, and of 295 nonpregnant women, 292 (99%) agreed. Of 440 fathers asked to consent to sample collection, 435 (99%) agreed. Frequency of successful collection of biospecimens varied depending on sample and visit type. In descending order, the ranges over all visit types of the proportion of expected samples successfully collected from women were: urine, 92.5 to 95.7%; hair, 89.6 to 92.5%; vaginal swab, 84.2 to 88.5%; blood, 74.9 to 78.5%; 2-day saliva, 65.8 to 81.6%; and nails, 76.4 to 76.7%. For fathers, rates were highest for urine (94.9%) and lowest for hair (63.0%). CONCLUSION: High rates of consent for and collection of a wide variety of biospecimens can be achieved in prospective epidemiologic cohort studies of pregnant women. Ease of sample collection may be a primary factor influencing successful biospecimen collection.
Birth Defects Res A Clin Mol Teratol
· 2015 Nov · PMID 26397383
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BACKGROUND: Interpregnancy interval is a risk factor for various adverse birth outcomes including birth defects. We investigated the relationship between interpregnancy interval and birth defects. METHODS: We conducted a...BACKGROUND: Interpregnancy interval is a risk factor for various adverse birth outcomes including birth defects. We investigated the relationship between interpregnancy interval and birth defects. METHODS: We conducted a retrospective cohort study using linked data from Nevada Birth Outcomes Monitoring System and birth certificate data for 124,341 singleton live births, of which 4641 infants had 7192 birth defects, among Nevada resident women between 2006 and 2011. We used logistic regression to assess factors independently associated with birth defects. RESULTS: Women who had an interpregnancy interval of 36 months or more, adjusted odds ratio (AOR) = 1.16, 95% confidence interval [CI], 1.01-1.33, were more likely to have an infant with a birth defect compared with women with an interpregnancy interval of 18 to 23 months. Other independent risk factors for birth defects included male infants, AOR = 1.34, 95% CI, 1.26-1.42; maternal age (30-34 years) and advanced maternal age (35 years and older), AOR = 1.10, 95% CI, 1.01-1.19 and AOR = 1.29, 95% CI, 1.18-1.42, respectively; being a Black woman, AOR = 1.46, 95% CI, 1.32-1.61; three and four or more previous births, AOR = 1.12, 95% CI, 1.02-1.23 and AOR = 1.24, 95% CI, 1.11-1.38, respectively; smoking, AOR = 1.23, 95% CI, 1.10-1.38; and prescription drug use, AOR = 1.14, 95% CI, 1.07-1.21. CONCLUSION: A long interpregnancy interval is an independent risk factor for birth defects. It may be helpful for maternal and child health programs and health care providers to highlight the deleterious effects of a long interpregnancy interval.
Birth Defects Res A Clin Mol Teratol
· 2015 Dec · PMID 26390016
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BACKGROUND: Folate receptor autoantibodies in women have been associated with neural tube pregnancy and in children with cerebral folate deficiency syndrome and autism. These autoantibodies have been implicated in blocki...BACKGROUND: Folate receptor autoantibodies in women have been associated with neural tube pregnancy and in children with cerebral folate deficiency syndrome and autism. These autoantibodies have been implicated in blocking folate transport to the fetus and to the brain in infants. METHODS: We report a woman with multiple pregnancy related complications who was diagnosed with autoantibodies to the folate receptor alpha. RESULTS: A treatment strategy with folate supplementation and reducing the antibody titer proved effective in normal pregnancy outcome. CONCLUSION: This long-term follow up of a subject with folate receptor autoantibodies is a first report of its kind and describes treatment strategy to prevent pregnancy related complications due to folate receptor autoantibodies.
Birth Defects Res A Clin Mol Teratol
· 2016 Feb · PMID 26389802
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BACKGROUND: Fetal exposure to maternal ingestion of warfarin is known to produce certain dysmorphic features in the neonate, known as fetal warfarin syndrome (FWS). There is a general consensus that maternal intake of wa...BACKGROUND: Fetal exposure to maternal ingestion of warfarin is known to produce certain dysmorphic features in the neonate, known as fetal warfarin syndrome (FWS). There is a general consensus that maternal intake of warfarin at a daily dose of 5 mg or less is safe both for the infant and the mother. METHODS: We report four cases of FWS born to mothers with rheumatic heart disease on warfarin prophylaxis during pregnancy at a dose less than 5 mg/day. RESULTS: Along with typical facial features of FWS and multiple epiphyseal stippling in skeletal x-ray, Case 1 had Dandy-Walker malformation and Case 2 had laryngo-tracheomalacia and patent ductus arteriosus. CONCLUSION: We emphasize the need for optimizing the choice and dosage schedule of anticoagulants during pregnancy, least harmful for the mother and her developing fetus.
Nasri K, Ben Fradj MK, Touati A
… +9 more, Aloui M, Ben Jemaa N, Masmoudi A, Elmay MV, Omar S, Feki M, Kaabechi N, Marrakchi R, Gaigi SS
Birth Defects Res A Clin Mol Teratol
· 2015 Dec · PMID 26386249
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BACKGROUND: This study was conducted to determine whether low folate and vitamin B12 levels, as well as high homocysteine levels in pregnant women are associated with neural tube defects (NTDs) in Tunisia. METHODS: A tot...BACKGROUND: This study was conducted to determine whether low folate and vitamin B12 levels, as well as high homocysteine levels in pregnant women are associated with neural tube defects (NTDs) in Tunisia. METHODS: A total of 75 NTDs pregnancies and 75 matched controls were included in the study. Their vitamin B12, folate, and red blood cell folate concentrations were measured using a radio-immunoassay kit and total homocysteine concentrations were determined using a fluorescent polarization immunoassay. RESULTS: Vitamin B12 and folate concentrations were lower in NTD-affected pregnant women than in controls (respectively, p = 0.009 and p < 0.001). Total homocysteine concentration was significantly higher in the NTDs group than in controls (p = 0.008). In the case group, the folate levels were positively related with vitamin B12 levels (r = 0.54; p < 0.001) and negatively correlated with total homocysteine levels (r = -0.19; p = 0.04). Besides, red blood cell folate levels were positively correlated with folate levels (r = 0.24; p = 0.02) and negatively correlated with total homocysteine levels (r = -0.37; p = 0.001). CONCLUSION: Lower concentrations of folate and vitamin B12 are related to the increased risk of NTDs. Both folate and vitamin B12 intake insufficiency could contribute to the increased risk of NTDs. A dietary supplement, combining folate and vitamin B12, might be an effective measure to decrease the NTDs incidence in Tunisia.
Wang M, De Marco P, Merello E
… +3 more, Drapeau P, Capra V, Kibar Z
Birth Defects Res A Clin Mol Teratol
· 2015 Dec · PMID 26368655
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BACKGROUND: Neural tube defects (NTDs) are among the most common congenital defects affecting approximately 1 in 1000 live births in North America. Their etiology is complex including environmental and genetic factors. D...BACKGROUND: Neural tube defects (NTDs) are among the most common congenital defects affecting approximately 1 in 1000 live births in North America. Their etiology is complex including environmental and genetic factors. Defects in the planar cell polarity (PCP) signaling pathway have been strongly associated with NTDs in animal models and human cohorts. Protein tyrosine kinase 7 (Ptk7) was shown to cause a very severe form of NTDs called craniorachischisis in a mouse model and genetically interacts with a core PCP member Vangl2 where double heterozygotes suffer from spina bifida. In this study, we examined the role of PTK7 in human NTDs to determine whether variants at this gene predispose to these defects. METHODS: We sequenced the coding region and the exon-intron junctions of PTK7 in a cohort of 473 patients affected with various forms of open and closed NTDs. Novel and rare variants(<1%) were genotyped in a cohort of 473 individuals. Their pathogenic effect was predicted in silico and functionally in an overexpression assay in a well-established zebrafish model. RESULTS: We identified in our cohort 6 rare variants, 3 of which were absent in public databases. One variant, p.Gly348Ser, acted as a hypermorph when overexpressed in the zebrafish model. CONCLUSION: We detected potentially pathogenic PTK7 variants in 1.1% of our NTD cohort. Our findings implicate PTK7 as a risk factor for NTDs and provide additional evidence for a pathogenic role of PCP signaling in these malformations.
Lopez KN, Marengo LK, Canfield MA
… +2 more, Belmont JW, Dickerson HA
Birth Defects Res A Clin Mol Teratol
· 2015 Nov · PMID 26333177
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BACKGROUND: Heterotaxy syndrome (HTX) is a constellation of defects including abnormal organ lateralization and often including congenital heart defects. HTX has widely divergent population-based estimates of prevalence,...BACKGROUND: Heterotaxy syndrome (HTX) is a constellation of defects including abnormal organ lateralization and often including congenital heart defects. HTX has widely divergent population-based estimates of prevalence, racial and ethnic predominance, and mortality in current literature. METHODS: The objective of this study was to use a population-based registry to investigate potential racial and ethnic disparities in HTX. Using the Texas Birth Defects Registry, we described clinical features and mortality of HTX among infants delivered from 1999 to 2006. We calculated birth prevalence and crude prevalence (cPR) ratios for infant sex, maternal diabetes, and sociodemographic factors. RESULTS: A total of 353 HTX cases were identified from 2,993,604 births (prevalence ratio = 1.18 per 10,000 live births. HTX prevalence was approximately 70% higher among infants of Hispanic and non-Hispanic black mothers and 28% higher among female infants (cPR = 1.28; 95% confidence interval,1.04-1.59). There was a twofold higher female preponderance for infants of mothers who were non-Hispanic white or black. Mothers with diabetes were three times more likely to have a child with HTX compared with nondiabetics (cPR = 3.13; 95% confidence interval, 2.12-4.45). Among nondiabetics, HTX cases were 86% more likely to have a Hispanic mother and 72% a non-Hispanic black mother. First-year mortality for live born children with HTX was 30.9%. CONCLUSION: This study represents one of the largest population-based studies of HTX to date, with a novel finding of higher rates of HTX among Hispanic infants of mostly Mexican origin, as well as among female infants of only non-Hispanic white and black mothers. These findings warrant further investigation.
Mody SK, Farala JP, Wu J
… +2 more, Felix R, Chambers C
Birth Defects Res A Clin Mol Teratol
· 2015 Oct · PMID 26306028
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BACKGROUND: The aim of this study is to investigate contraceptive usage among women prescribed or currently taking a category D or X medication using the electronic medical record. METHODS: This is a retrospective study...BACKGROUND: The aim of this study is to investigate contraceptive usage among women prescribed or currently taking a category D or X medication using the electronic medical record. METHODS: This is a retrospective study assessing contraceptive usage among women prescribed category D or X medications. We obtained access to the electronic medical records of women seen in an academic Family Medicine Department between April 2011 and April 2012 who were prescribed a category D or X medication. Information was abstracted regarding the specific category D or X medication, demographics, sexual activity, sexual partner gender, and contraceptive usage. RESULTS: There were a total of 610 women included in this study. Among the 610 women, 72 (11.8%) of women had documentation that they were not asked about their sexual activity. Sexual activity with men was documented in 407 of the 610 women (66.7%). Of these 407 women, 132 (32.4%) had no contraceptive method documented. Among the women using contraception, the most common method used was oral contraception. CONCLUSION: According to data obtained from the electronic medical record, women who are taking a category D or X medication are not always asked about sexual activity. Contraception usage among women taking category D or X medications and who were sexually active with men was similar to the general population. Contraception usage should be better in this population given the risk of an unintended pregnancy includes fetal exposure to a potential teratogen. The electronic medical record creates an opportunity for an intervention to increase contraception utilization in this population.
Bu L, Chen Q, Wang H
… +11 more, Zhang T, Hetmanski JB, Schwender H, Parker M, Chou YH, Yeow V, Chong SS, Zhang B, Jabs EW, Scott AF, Beaty TH
Birth Defects Res A Clin Mol Teratol
· 2015 Oct · PMID 26278207
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BACKGROUND: The forkhead box F2 gene (FOXF2) located in chromosome 6p25.3 has been shown to play a crucial role in palatal development in mouse and rat models. To date, no evidence of linkage or association has been repo...BACKGROUND: The forkhead box F2 gene (FOXF2) located in chromosome 6p25.3 has been shown to play a crucial role in palatal development in mouse and rat models. To date, no evidence of linkage or association has been reported for this gene in humans with oral clefts. METHODS: Allelic transmission disequilibrium tests were used to robustly assess evidence of linkage and association with nonsyndromic cleft lip with or without cleft palate for nine single nucleotide polymorphisms (SNPs) in and around FOXF2 in both Asian and European trios using PLINK. RESULTS: Statistically significant evidence of linkage and association was shown for two SNPs (rs1711968 and rs732835) in 216 Asian trios where the empiric P values with permutation tests were 0.0016 and 0.005, respectively. The corresponding estimated odds ratios for carrying the minor allele at these SNPs were 2.05 (95% confidence interval = 1.41, 2.98) and 1.77 (95% confidence interval = 1.26, 2.49), respectively. CONCLUSION: Our results provided statistical evidence of linkage and association between FOXF2 and nonsyndromic cleft lip with or without cleft palate.