Prenatal exposure to nitrate from drinking water and markers of fetal growth restriction: A population-based study of nearly one million Danish-born children

BACKGROUND: High levels of nitrate (NO3⁻) in drinking water cause methemoglobinemia in infants; however, few studies have examined the potential effects of low-level exposure on fetal growth, and the results have been inconsistent. OBJECTIVES: We sought to assess the association between maternal exposure to nitrate in drinking water during pregnancy and offspring size at birth in a nationwide study of full-term (≥37 wk gestation) live-born singletons. METHODS: We estimated maternal nitrate exposure for 898,206 births in Denmark during 1991–2011 by linkage of individual home address(es) with nitrate data from the national monitoring database. Maternal address during pregnancy, infant size at birth [i.e., birth weight, low birth weight (LBW), body length, and birth head circumference] and covariates were compiled from the Danish Civil Registration System, the Danish Medical Birth Register, and The Integrated Database for Longitudinal Labor Market Research. Linear and logistic models with generalized estimating equations were used to account for multiple births to an individual. Nitrate exposure was modeled using five categories and as a log-transformed continuous variable. RESULTS: There was evidence of a decreasing trend in models for term birth weight using categorical or continuous measures of exposure. Modeling exposure continuously, a difference of −9:71 g (95% confidence interval: −14:60, −4:81) was predicted at 25 mg/L (half the value of the European Union drinking water standard) compared with 0 mg/LNO3⁻. Body length also decreased as nitrate concentrations increased in categorical and continuous models. There was little evidence of an association between NO3⁻ and head circumference or LBW. DISCUSSION: Although the estimated effects were small, our findings for live singleton births to Danish-born parents suggest that maternal intake of nitrate from drinking water may reduce term birth weight and length, which are markers of intrauterine growth. However, there was little evidence for an association between nitrate and head circumference or LBW. Future studies in other populations and with data on dietary sources of nitrate are encouraged to confirm or refute these findings.