Nitrate contamination in drinking water and adverse reproductive and birth outcomes: a systematic review and meta-analysis

Exposure to low levels of nitrate in drinking water may have adverse reproductive effects. We reviewed evidence about the association between nitrate in drinking water and adverse reproductive outcomes published to November 2022. Randomized trials, cohort or case–control studies published in English that reported the relationship between nitrate intake from drinking water and the risk of perinatal outcomes were included. Random-effect models were used to pool data. Three cohort studies showed nitrate in drinking water is associated with an increased risk of preterm birth (odds ratio for 1 mg/L NO 3 -N increased (OR 1 ) = 1.01, 95% CI 1.00, 1.01, I 2 = 23.9%, 5,014,487 participants; comparing the highest versus the lowest nitrate exposure groups pooled OR (OR p ) = 1.05, 95% CI 1.01, 1.10, I 2 = 0%, 4,152,348 participants). Case–control studies showed nitrate in drinking water may be associated with the increased risk of neural tube defects OR 1 = 1.06, 95% CI 1.02, 1.10; 2 studies, 2196 participants; I 2 = 0%; and OR p = 1.51, 95% CI 1.12, 2.05; 3 studies, 1501 participants; I 2 = 0%). The evidence for an association between nitrate in drinking water and risk of small for gestational age infants, any birth defects, or any congenital heart defects was inconsistent. Increased nitrate in drinking water may be associated with an increased risk of preterm birth and some specific congenital anomalies. These findings warrant regular review as new evidence becomes available.