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Background: Risk factors for birth defects are frequently investigated using data limited to liveborn infants. By conditioning on survival, results of such studies may be distorted by selection bias, also described as "livebirth bias." However, the implications of livebirth bias on risk estimation remain poorly understood.Objectives: We sought to quantify livebirth bias and to investigate the conditions under which it arose.Methods: We used data on 3994 birth defects cases and 11 829 controls enrolled in the National Birth Defects Prevention Study to compare odds ratio (OR) estimates of the relationship between three established risk factors (antiepileptic drug use, smoking, and multifetal pregnancy) and four birth defects (anencephaly, spina bifida, omphalocele, and cleft palate) when restricted to livebirths as compared to among livebirths, stillbirths, and elective terminations. Exposures and birth defects represented varying strengths of association with livebirth; all controls were liveborn. We performed a quantitative bias analysis to evaluate the sensitivity of our results to excluding terminated and stillborn controls.Results: Cases ranged from 33% liveborn (anencephaly) to 99% (cleft palate). Smoking and multifetal pregnancy were associated with livebirth among anencephaly (crude OR [cOR] 0.61 and cOR 3.15, respectively) and omphalocele cases (cOR 2.22 and cOR 5.22, respectively). For analyses of the association between exposures and birth defects, restricting to livebirths produced negligible differences in estimates except for anencephaly and multifetal pregnancy, which was twofold higher among livebirths (adjusted OR [aOR] 4.93) as among all pregnancy outcomes (aOR 2.44). Within tested scenarios, bias analyses suggested that results were not sensitive to the restriction to liveborn controls.Conclusions: Selection bias was generally limited except for high mortality defects in the context of exposures strongly associated with livebirth. Findings indicate that substantial livebirth bias is unlikely to affect studies of risk factors for most birth defects. [ABSTRACT FROM AUTHOR]

Objective: Maternal risk factors for pregnancy outcomes are known to vary by employment status. We evaluated whether pre-pregnancy diet quality varies by occupation in a population-based sample.Design: We analysed interview data from 7341 mothers in a national case-control study of pregnancy outcomes. Self-reported job(s) held during the 3 months before pregnancy were classified using Standard Occupational Classification (SOC) codes. Usual diet in the year before conception was assessed with a semi-quantitative FFQ and evaluated using the Diet Quality Index for Pregnancy (DQI-P). Using logistic regression, we calculated adjusted OR and 95 % CI to estimate associations between low diet quality (defined as the lowest quartile of DQI-P scores) and occupation types.Setting: The National Birth Defects Prevention Study: Arkansas, California, Georgia, Iowa, Massachusetts, North Carolina, New Jersey, New York, Texas, Utah.Participants: Employed mothers of infants born between 1997 and 2011.Results: No occupation was strongly associated with low diet quality. Moderate but relatively imprecise associations were observed for women employed in management (OR: 1·3; 95 % CI: 1·1, 1·7); arts, design, entertainment, sports and media (OR: 1·4; 95 % CI: 0·9, 2·1); protective service (OR 1·3; 95 % CI: 0·7, 2·5) and farming, fishing, and forestry occupations (OR: 0·5; 95 % CI: 0·2, 1·1).Conclusions: Our analyses suggest that women in certain occupations may have lower diet quality in the months before pregnancy. Further research is needed to determine whether certain occupations could benefit from interventions to improve diet quality in the workplace for women of reproductive age. [ABSTRACT FROM AUTHOR]

Background: Approximately 1 in 2000 infants is born with a limb deficiency in the US. Research has shown that women's periconceptional diet and use of vitamin supplements can affect risk of birth defects. We investigated whether maternal consumption of nutritional antioxidants was associated with occurrence of transverse limb deficiency (TLD) and longitudinal limb deficiencies (LLD).Methods: We analysed case-control data from mothers and their singleton infants with TLD (n = 566), LLD (n = 339), or no malformation (controls; n = 9384) in the National Birth Defects Prevention Study (1997-2009). Using a modified food frequency, we estimated usual pre-pregnancy antioxidant consumption by total fruit and vegetable consumption (in grams) grouped into tertiles, and cumulative antioxidant score (ranging from 1 to 10) based on consumption of three antioxidants: beta-carotene, lycopene, and lutein. We estimated odds ratios (OR) adjusted for maternal age, race/ethnicity, education, smoking, alcohol use, body mass index, and total energy.Results: Compared to women in the lowest tertile of fruit and vegetable consumption, women in the highest tertile were less likely to have infants with TLD (OR 0.74, 95% CI 0.57, 0.96) or LLD (OR 0.82, 95% CI 0.59, 1.13). Compared to the lowest antioxidant consumption score of 1, those with the highest score of 10 had ORs of 0.68 (95% CI 0.48, 0.95) for TLD and 0.77 (95% CI 0.50, 1.17) for LLD.Conclusions: Dietary intake of antioxidants was associated with reduced odds of limb deficiencies. These findings add further evidence for women's periconceptional diet reducing occurrence of some birth defects. [ABSTRACT FROM AUTHOR]

Background: We examined a large number of variables to generate new hypotheses regarding a wider range of risk factors for anophthalmia/microphthalmia using data mining.Methods: Data were from the National Birth Defects Prevention Study, a multicentre, case-control study from 10 centres in the United States. There were 134 cases of "isolated" and 87 "nonisolated" (with other major birth defects) of anophthalmia/microphthalmia and 11 052 nonmalformed controls with delivery dates October 1997-December 2011. Using random forest, a data mining procedure, we compared the two case types with controls for 201 variables. Variables considered important ranked by random forest were included in a multivariable logistic regression model to estimate odds ratios and 95% confidence intervals.Results: Predictors for isolated cases included paternal race/ethnicity, maternal intake of certain nutrients and foods, and childhood health problems in relatives. Using regression, inverse associations were observed with greater maternal education and with increasing intake of folate and potatoes. Odds were slightly higher with greater paternal education, for increased intake of carbohydrates and beans, and if relatives had a childhood health problem. For nonisolated cases, predictors included paternal race/ethnicity, maternal intake of certain nutrients, and smoking in the home the month before conception. Odds were higher for Hispanic fathers and smoking in the home and NSAID use the month before conception.Conclusions: Results appear to support previously hypothesised risk factors, socio-economic status, NSAID use, and inadequate folate intake, and potentially provide new areas such as passive smoking pre-pregnancy, and paternal education and ethnicity, to explore for further understanding of anophthalmia/microphthalmia. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether better diet quality in mothers is associated with lower risk for major non-syndromic congenital heart defects in their children.Design: Multicentre population-based case-control study, the National Birth Defects Prevention Study.Setting: Ten sites in the USA.Participants: Mothers of babies with major non-syndromic congenital heart defects (n=9885) and mothers with unaffected babies (n=9468) with estimated date of delivery from 1997 to 2009.Main Outcome Measures: Adjusted ORs for specific major congenital heart defects by quartiles of maternal diet quality in the year before pregnancy, assessed by the Diet Quality Index for pregnancy (DQI-P) and the Mediterranean Diet Score. Quartile 1 (Q1) reflecting the worst diet quality and Q4 the best diet quality.Results: Better diet quality was associated with reduced risk for some conotruncal and atrial septal heart defects. For DQI-P, estimated risks reductions (Q4 vs Q1) for conotruncal defects were 37% for tetralogy of Fallot (OR 0.63, 95% CI 0.49 to 0.80) and 24% overall (OR 0.76, 95% CI 0.64 to 0.91); and for septal defects, 23% for atrial septal defects (OR 0.77, 95% CI 0.63 to 0.94) and 14% overall (OR 0.86, 95% CI 0.75 to 1.00). Risk reductions were weaker or minimal for most other major congenital heart defects.Conclusions: Better diet quality is associated with a reduced occurrence of some conotruncal and septal heart defects. This finding suggests that a reduction in certain cardiac malformations may be an additional benefit of improved maternal diet quality, reinforcing current preconception care recommendations. [ABSTRACT FROM AUTHOR]

Objectives: To describe maternal exposure to tobacco in the three months before conception and throughout pregnancy, examine risk factors associated with tobacco exposure in pregnancy and smoking cessation, assess use of pharmacotherapy for smoking cessation and evaluate birth outcomes by smoking status.Design: A cohort of women from a multi-site United States study were asked retrospectively about their exposure to tobacco.Population: The study population was comprised of 4,667 mothers of non-malformed control infants who participated in the National Birth Defects Prevention Study from 1997 to 2003.Methods: Using computer-assisted telephone interview responses from this population-based sample, we assessed patterns of maternal smoking and exposure to environmental tobacco smoke (ETS) as well as use of pharmacotherapy for quitting smoking during pregnancy.Results: Overall, 961 (20.6%) mothers reported any smoking and 1,401 (30.0%) reported any exposure to ETS at home or work during the three months before conception through pregnancy. Of the 961 smokers, 512 (53.3%) reportedly quit smoking before or during pregnancy, including 379 (74% of quitters) in the first trimester, and 420 (43.7%) continued to smoke throughout the pregnancy. Only 2.1% of smokers reportedly used pharmacotherapy to quit smoking anytime from three months before conception through pregnancy. Low birthweight and preterm delivery rates were lowest among offspring of non-smokers and highest in offspring of those who continued to smoke throughout pregnancy.Conclusions: About one-half of mothers who reported preconceptional smoking quit before or during pregnancy. Use of pharmacotherapy to quit smoking during pregnancy was not common. [ABSTRACT FROM AUTHOR]

Purpose: To examine the prevalence of, and factors associated with, atypical antipsychotic use among U.S. pregnant women, and potential associations between early pregnancy atypical antipsychotic use and risk for 14 birth defects.Methods: We analyzed data from the National Birth Defects Prevention Study (1997-2011), a U.S. population-based case-control study examining risk factors for major structural birth defects.Results: Atypical antipsychotic use during pregnancy was more common among women with pre-pregnancy obesity, and women who reported illicit drug use before and during pregnancy, smoking during pregnancy, alcohol use during pregnancy, or use of other psychiatric medications during pregnancy. We observed elevated associations (defined as a crude odds ratio [cOR] ≥2.0) between early pregnancy atypical antipsychotic use and conotruncal heart defects (6 exposed cases; cOR: 2.3, 95% confidence interval [CI]: 0.9-6.1), and more specifically Tetralogy of Fallot (3 exposed cases; cOR: 2.5, 95% CI: 0.7-8.8), cleft palate (4 exposed cases, cOR: 2.5, 95% CI: 0.8-7.6), anorectal atresia/stenosis (3 exposed cases, cOR: 2.8, 95% CI: 0.8-9.9), and gastroschisis (3 exposed cases, cOR: 2.1, 95% CI: 0.6-7.3).Conclusions: Our findings support the close clinical monitoring of pregnant women using atypical antipsychotics. Women treated with atypical antipsychotics generally access healthcare services before pregnancy; efforts to reduce correlates of atypical antipsychotic use might improve maternal and infant health in this population. [ABSTRACT FROM AUTHOR]

Objective: To estimate the risk of stillbirth (fetal death at 20 weeks of gestation or more) associated with specific birth defects.Methods: We identified a population-based retrospective cohort of neonates and fetuses with selected major birth defects and without known or strongly suspected chromosomal or single-gene disorders from active birth defects surveillance programs in nine states. Abstracted medical records were reviewed by clinical geneticists to confirm and classify all birth defects and birth defect patterns. We estimated risks of stillbirth specific to birth defects among pregnancies overall and among those with isolated birth defects; potential bias owing to elective termination was quantified.Results: Of 19,170 eligible neonates and fetuses with birth defects, 17,224 were liveborn, 852 stillborn, and 672 electively terminated. Overall, stillbirth risks ranged from 11 per 1,000 fetuses with bladder exstrophy (95% CI 0-57) to 490 per 1,000 fetuses with limb-body-wall complex (95% CI 368-623). Among those with isolated birth defects not affecting major vital organs, elevated risks (per 1,000 fetuses) were observed for cleft lip with cleft palate (10; 95% CI 7-15), transverse limb deficiencies (26; 95% CI 16-39), longitudinal limb deficiencies (11; 95% CI 3-28), and limb defects due to amniotic bands (110; 95% CI 68-171). Quantified bias analysis suggests that failure to account for terminations may lead to up to fourfold underestimation of the observed risks of stillbirth for sacral agenesis (13/1,000; 95% CI 2-47), isolated spina bifida (24/1,000; 95% CI 17-34), and holoprosencephaly (30/1,000; 95% CI 10-68).Conclusion: Birth defect-specific stillbirth risk was high compared with the U.S. stillbirth risk (6/1,000 fetuses), even for isolated cases of oral clefts and limb defects; elective termination may appreciably bias some estimates. These data can inform clinical care and counseling after prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: To compare the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and/or opioids to the use of acetaminophen without NSAIDs or opioids with respect to associations with birth defects.Methods: We used data from the National Birth Defects Prevention Study (1997-2011). Exposure was self-reported maternal analgesic use from the month before through the third month of pregnancy (periconceptional). Adjusted odds ratios (aORs) were calculated to examine associations with 16 birth defects.Results: Compared to acetaminophen, mothers reporting NSAIDs were significantly more likely to have offspring with gastroschisis, hypospadias, cleft palate, cleft lip with cleft palate, cleft lip without cleft palate, anencephaly, spina bifida, hypoplastic left heart syndrome, pulmonary valve stenosis, and tetralogy of Fallot (aOR range, 1.2-1.6). Opioids were associated with tetralogy of Fallot, perimembranous ventricular septal defect, and ventricular septal defect with atrial septal defect (aOR range, 1.8-2.3), whereas use of both opioids and NSAIDs was associated with gastroschisis, cleft palate, spina bifida, hypoplastic left heart syndrome, and pulmonary valve stenosis (aOR range, 2.0-2.9).Conclusions: Compared to periconceptional use of acetaminophen, selected birth defects occurred more frequently among infants of women using NSAIDs and/or opioids. However, we could not definitely determine whether these risks relate to the drugs or to indications for treatment. [ABSTRACT FROM AUTHOR]