Maternal periconceptional exposure to drinking water disinfection by-products and neural tube defects in offspring
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Background: Epidemiological research for associations between maternal periconceptional exposure to disinfection by-products (DBPs) in drinking water and neural tube defects (NTDs) in offspring is inconclusive.
Methods: Population-based, maternal interview reports of drinking water sources and consumption from the National Birth Defects Prevention Study were linked with public water system monitoring data near homes and workplaces. Maternal drinking water DBP concentrations of NTD case and control children delivered during January 2000-December 2005 were analyzed. DBPs available for analysis included total trihalomethanes (TTHMs), the five most common haloacetic acids combined (HAA5), and individual TTHM and HAA5 species. Maternal periconceptional (one month before pregnancy through first pregnancy month) exposure was categorized as unexposed, any exposure, and exposed to <1/2 or ≥1/2 the Maximum Contaminant Levels or Maximum Contaminant Level Goals for public water systems where available and non-zero. Associations between DBPs and all NTDs combined and selected subtypes were estimated using mixed effects logistic regression models including maternal race/ethnicity and education as fixed effects and study site as a random intercept; covariates were identified from a directed acyclic graph.
Results: Overall, 201 case and 1346 control children were eligible for analyses. Adjusted odds ratio (aOR) estimates from 0.9-1.7 were observed for all NTDs combined, with positive estimates (aORs ≥1.3) observed for TTHM, HAA5, chloroform, bromodichloromethane, monochloroacetic acid, dichloroacetic acid, and trichloroacetic acid; those for any exposure to dichloroacetic acid and trichloroacetic acid were statistically significant. For anencephaly, estimates (aORs 0.9-3.0) were similar to or increased for these DBPs and dibromoacetic acid but similar or reduced for remaining DBPs. For spina bifida, estimates (aORs 1.0-1.4) were similar or reduced; none were statistically significant.
Conclusions: Examination of associations between maternal DBP exposures and all NTDs and selected subtypes showed positive associations with several DBPs, with some reaching statistical significance for all NTDs combined and anencephaly.