Nitrate in drinking water and pregnancy outcomes: A narrative review of epidemiological evidence and proposed biological mechanisms

Abstract

There is emerging evidence of an association between nitrate contamination in drinking water and adverse pregnancy outcomes. Few studies have discussed the evidence in the context of plausible biological mechanisms. We performed a narrative review of the current evidence investigating associations between nitrate in drinking water and the risk of adverse pregnancy outcomes with a focus on congenital anomalies (CA) and preterm birth (PTB). We also reviewed evidence and discuss several biological mechanisms that may explain the observed associations. We reviewed cohort and case-control epidemiological studies assessing associations between maternal nitrate exposure and adverse pregnancy outcomes published until January 2023. Three plausible mechanisms may explain how maternal exposure to nitrate may impact pregnancy outcomes, which include the formation of N-nitroso compounds (NOC), thyroid dysfunction and oxidative stress. For CA, seven studies were included (two cohort and five case-control studies). The strongest associations observed in epidemiological studies were for neural tube defects. Inconsistent positive and negative associations were observed for anomalies of the limb, eye, ear, face and neck. Of the four PTB studies (all cohort studies), three of the largest cohort studies observed associations between PTB with nitrate levels >5 mg/L while one small cohort study did not. Emerging epidemiological evidence has observed a potential increased risk of adverse pregnancy outcomes with elevated maternal nitrate exposure in drinking water. There are also plausible biological mechanisms to support this association. However, the current evidence lacks homogeneity and additional longitudinal evidence with robust exposure asssessments is required. Given the increasing concentrations of nitrate contamination in drinking water in many countries, and the adverse effects observed at concentrations below the current regulatory standard, a further precautionary approach should be adopted until futher evidence emerges.