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Abstract: Background: Maternal exposure to drinking water disinfection byproducts (DBP)s may contribute to orofacial cleft (OFC) development, but studies are sparse and beset with limitations. Methods: Population‐based, maternal interview reports of drinking water filtration and consumption for 680 OFC cases (535 isolated) and 1826 controls were linked with DBP concentration data using maternal residential addresses and public water system monitoring data. Maternal individual‐level exposures to trihalomethanes (THM)s and haloacetic acids (HAA)s (µg/L of water consumed) were estimated from reported consumption at home, work, and school. Compared to no exposure, associations with multisource maternal exposure <1/2 or ≥1/2 the Maximum Contaminant Levels (MCL)s for total THMs (TTHM)s and HAAs (HAA5) or Maximum Contaminant Level Goals (MCLG)s for individual THMs and HAAs (if non‐zero) were estimated for all OFCs and isolated OFCs, cleft palate (CP), and cleft lip ± cleft palate (CL/P) using logistic regression analyses. Results: Compared to controls, associations were near or below unity for maternal TTHM, HAA5, and individual THM exposures with all OFCs and isolated OFCs, CP, and CL/P. Associations also were near or below unity for individual HAAs with statistically significant, inverse associations observed with each OFC outcome group except CL/P. Conclusions: This study examined associations for maternal reports of drinking water filtration and consumption and maternal DBP exposure from drinking water with OFCs in offspring. Associations observed were near or below unity and mostly nonsignificant. Continued, improved research using maternal individual‐level exposure data will be useful in better characterizing these associations. [ABSTRACT FROM AUTHOR]

Introduction: We examined the association of biliary atresia with maternal dietary intake, using National Birth Defects Prevention Study (NBDPS) data from 152 cases and 11,112 nonmalformed controls born 1997–2011. Methods: NBDPS is a multisite, population‐based case‐control study. Exposure data were from maternal telephone interviews, which included a food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were generated from logistic regression models that included nutritional factors as continuous variables and were adjusted for energy intake only or energy intake plus covariates (maternal race‐ethnicity, education, age, prepregnancy body mass index, vitamin/mineral supplement intake, conception during summer). Models included a quadratic term for the nutrient if p < 0.10. ORs reflect odds of having biliary atresia for nutrient values at the 75th compared to 25th percentile values of each nutrient, based on distributions among controls. Results: ORs for which the 95% CI excluded 1.00 were energy‐adjusted ORs for calcium (0.63), protein (0.65), riboflavin (0.71), and diet quality index (0.69), and fully adjusted ORs for calcium (0.68) and vitamin E (0.72). ORs that were fully adjusted for covariates tended to be closer to 1.0 than ORs adjusted only for energy intake. ORs for the other studied nutrients had 95% CIs that included 1.00. Conclusions: NBDPS is the first study to include detailed information on maternal dietary intake and risk of biliary atresia. Our results suggest reduced risks associated with some nutrients, which may provide etiologic clues but should be interpreted with caution given the small number of cases and novelty of the investigation. [ABSTRACT FROM AUTHOR]

Background: Folic acid fortification significantly reduced the prevalence of neural tube defects (NTDs) in the United States. The popularity of “low carb” diets raises concern that women who intentionally avoid carbohydrates, thereby consuming fewer fortified foods, may not have adequate dietary intake of folic acid. Methods: To assess the association between carbohydrate intake and NTDs, we analyzed data from the National Birth Defects Prevention Study from 1,740 mothers of infants, stillbirths, and terminations with anencephaly or spina bifida (cases), and 9,545 mothers of live born infants without a birth defect (controls) conceived between 1998 and 2011. Carbohydrate and folic acid intake before conception were estimated from food frequency questionnaire responses. Restricted carbohydrate intake was defined as ≤5th percentile among controls. Odds ratios were estimated with logistic regression and adjusted for maternal race/ethnicity, education, alcohol use, folic acid supplement use, study center, and caloric intake. Results: Mean dietary intake of folic acid among women with restricted carbohydrate intake was less than half that of other women (p < .01), and women with restricted carbohydrate intake were slightly more likely to have an infant with an NTD (AOR = 1.30, 95% CI: 1.02, 1.67). Conclusions: This is the first study to examine the association between carbohydrate intake and NTDs among pregnancies conceived postfortification. We found that women with restricted carbohydrate intake were 30% more likely to have an infant with anencephaly or spina bifida. However, more research is needed to understand the pathways by which restricted carbohydrate intake might increase the risk of NTDs. [ABSTRACT FROM AUTHOR]

Background: We previously explored associations between nutrients including folate and other macro and micronutrients and risks of anophthalmia or microphthalmia in the National Birth Defects Prevention Study. In the current study, we expand those previous results with larger sample sizes and conduct analyses with an additional diet quality index using more recent data. Methods: The National Birth Defects Prevention Study is a population‐based, multicenter case‐control study of over 30 major birth defects, with estimated due dates from October 1997 to December 2011. Cases were 224 infants diagnosed with anophthalmia or microphthalmia. Controls were 11,109 live‐born, nonmalformed infants randomly selected by each study center. Mothers completed a standardized, computer‐assisted telephone interview between 6 weeks and 24 months after delivery. Mothers responded to a shortened food frequency questionnaire, assessing their nutrient intake for the year before pregnancy, and questions about periconceptional (2 months before to 2 months after conception) vitamin supplement use. Nutrient intake quartiles were based on the intake among controls. Results: Among vitamin supplement users, odds of anophthalmia/microphthalmia were decreased for women with intake levels in the highest quartile of folate (0.56, 95% confidence interval [CI] 0.32–0.98), magnesium (0.42, 95% CI 0.22–0.82), and vitamin E (0.50, 95% CI 0.29–0.89). Among women not reporting vitamin supplement use, the odds were significantly increased for beta‐carotene (2.5, 95% CI 1.10–5.68) and decreased for retinol (0.37, 95% CI 0.19–0.73). Conclusions: In this expanded analysis, we observed associations for a few nutrients, specifically forms of vitamin A. However, the heterogeneity of results by form and vitamin use necessitates further inquiry. [ABSTRACT FROM AUTHOR]

Background: Cigarette smoking is a well‐studied risk factor for orofacial clefts (OFCs). Little is known about which constituents in cigarette smoke contribute to this teratogenicity in humans. One constituent, cadmium, has been associated with OFCs in animal studies; in humans, the role of maternal cadmium exposure on OFCs, independent of cigarette smoke, is unclear. In particular, the relation between maternal occupational cadmium exposure and OFCs is largely unexplored. Methods: Using data from a large, population‐based case‐control study, we compared expert rater assessed maternal occupational cadmium exposure from self‐reported occupational histories during the period 1 month before through 3 months after conception between OFC cases (n = 1,185) and unaffected controls (n = 2,832). Multivariable logistic regression analyses were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals for any (yes/no) and cumulative (no, low, high exposure) occupational cadmium exposures and all OFCs, cleft lip ± cleft palate (CL/P) and cleft palate (CP). Results: Overall, 45 mothers (cases = 13, controls = 32) were rated as having occupational cadmium exposure. Comparing all OFCs to controls, we observed inverse, nonsignificant aORs for any or low exposure, and positive, nonsignificant aORs for high exposure. Where data were available, aORs for CL/P and CP tended to parallel those for all OFCs. Conclusion: To our knowledge, this is the first study to specifically examine maternal occupational cadmium exposure and OFCs, using expert rater exposure assessment. The small numbers of exposed mothers observed, however, led to imprecise estimates. Continued research using more detailed occupational exposure assessment and increased sample sizes is recommended. [ABSTRACT FROM AUTHOR]