Nitrate in drinking water and risk of birth defects: Findings from a cohort study of over one million births in Denmark

Background: A few studies have reported an increased risk of birth defects (BD) with maternal exposure to nitrate in drinking water. We examined this association in a large cohort study with well-characterized exposure. Methods: Danish singletons liveborn to Danish-born parents from 1991–2013 were identified using civil and patient registries (n=1,018,914). Exposure to nitrate was estimated using a spatial model based on national data linked with individual addresses. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression. Findings: In total, 33,182 cases of BD were identified. Nitrate concentrations were generally well below US and EU standards. We observed an exposure-response relationship (p=0·004) between nitrate during pregnancy and eye BD, and increased risk in the highest exposure group (≥25 mg/L nitrate) (OR: 1·29; 95% CI: 1·00, 1·66). An interaction was observed between maternal age and continuous nitrate exposure for nervous system BD (p