TY - JOUR

T1 - Prenatal Exposure to Nitrate from Drinking Water and Markers of Fetal Growth Restriction

T2 - A Population-Based Study of Nearly One Million Danish-Born Children

AU - Coffman, Vanessa R

AU - Jensen, Anja Søndergaard

AU - Trabjerg, Betina B

AU - Pedersen, Carsten B

AU - Hansen, Birgitte

AU - Sigsgaard, Torben

AU - Olsen, Jørn

AU - Schaumburg, Inger

AU - Schullehner, Jörg

AU - Pedersen, Marie

AU - Stayner, Leslie T

PY - 2021

Y1 - 2021

N2 - BACKGROUND: High levels of nitrate ( NO 3 - ) 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 / L   NO 3 - . Body length also decreased as nitrate concentrations increased in categorical and continuous models. There was little evidence of an association between NO 3 - 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. https://doi.org/10.1289/EHP7331.

AB - BACKGROUND: High levels of nitrate ( NO 3 - ) 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 / L   NO 3 - . Body length also decreased as nitrate concentrations increased in categorical and continuous models. There was little evidence of an association between NO 3 - 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. https://doi.org/10.1289/EHP7331.

U2 - 10.1289/EHP7331

DO - 10.1289/EHP7331

M3 - Journal article

C2 - 33539179

VL - 129

JO - Environmental Health Perspectives

JF - Environmental Health Perspectives

SN - 0091-6765

IS - 2

M1 - 27002

ER -