TY - JOUR

T1 - Prenatal exposure to tap water containing nitrate and the risk of small-for-gestational-age

T2 - A nationwide register-based study of Danish births, 1991–2015

AU - Jensen, Anja Søndergaard

AU - Coffman, Vanessa R.

AU - Schullehner, Jörg

AU - Trabjerg, Betina B.

AU - Pedersen, Carsten B.

AU - Hansen, Birgitte

AU - Olsen, Jørn

AU - Pedersen, Marie

AU - Stayner, Leslie T.

AU - Sigsgaard, Torben

N1 - Publisher Copyright: © 2023 The Author(s)

PY - 2023

Y1 - 2023

N2 - Background: Prenatal nitrate exposure from household tap water has been associated with increased risk of fetal growth restriction, preterm birth, birth defects, and childhood cancer. We aim to examine the association between maternal consumption of drinking-water nitrate during pregnancy and small-for-gestational-age (SGA) in a nationwide study of Danish-born children, as only one prior study has examined this association. Methods: We linked individual-level household estimates of nitrate in tap water and birth registry data to all live singleton Danish births during 1991–2015 from Danish-born parents where the mother resided in Denmark throughout the pregnancy. Exposure was both binned into four categories and modeled as an ln-transformed continuous variable. SGA was defined as the bottom 10% of births by birth weight per sex and gestational week. Multiple logistic regression models with generalized estimating equations were used to account for siblings born to the same mother while controlling for relevant confounders. Results: In the cohort of 1,078,892 births, the median pregnancy nitrate exposure was 1.9 mg/L nitrate. Compared to the reference group (≤2 mg/L), we found an increased risk of SGA in the second category (>2–5 mg/L) (OR = 1.04, 95% CI: 1.03–1.06) and third category (>5–25 mg/L) (OR = 1.02, 95% CI: 1.00–1.04) but not in the highest (>25 mg/L). There was strong (p = 0.002) evidence of an increase in SGA with nitrate in the model with continuous exposure (OR = 1.02, 95% CI: 1.01–1.04 per 10-fold increase in nitrate). Results were robust when restricting to households with nitrate levels at or below the current Danish and European Union regulatory drinking water standard (50 mg/L nitrate). Conclusions: Our findings suggest that exposure from nitrate in household tap water, even below current regulatory standards, may increase risk of SGA, raising concerns of whether current allowable nitrate levels in drinking water protect children from SGA.

AB - Background: Prenatal nitrate exposure from household tap water has been associated with increased risk of fetal growth restriction, preterm birth, birth defects, and childhood cancer. We aim to examine the association between maternal consumption of drinking-water nitrate during pregnancy and small-for-gestational-age (SGA) in a nationwide study of Danish-born children, as only one prior study has examined this association. Methods: We linked individual-level household estimates of nitrate in tap water and birth registry data to all live singleton Danish births during 1991–2015 from Danish-born parents where the mother resided in Denmark throughout the pregnancy. Exposure was both binned into four categories and modeled as an ln-transformed continuous variable. SGA was defined as the bottom 10% of births by birth weight per sex and gestational week. Multiple logistic regression models with generalized estimating equations were used to account for siblings born to the same mother while controlling for relevant confounders. Results: In the cohort of 1,078,892 births, the median pregnancy nitrate exposure was 1.9 mg/L nitrate. Compared to the reference group (≤2 mg/L), we found an increased risk of SGA in the second category (>2–5 mg/L) (OR = 1.04, 95% CI: 1.03–1.06) and third category (>5–25 mg/L) (OR = 1.02, 95% CI: 1.00–1.04) but not in the highest (>25 mg/L). There was strong (p = 0.002) evidence of an increase in SGA with nitrate in the model with continuous exposure (OR = 1.02, 95% CI: 1.01–1.04 per 10-fold increase in nitrate). Results were robust when restricting to households with nitrate levels at or below the current Danish and European Union regulatory drinking water standard (50 mg/L nitrate). Conclusions: Our findings suggest that exposure from nitrate in household tap water, even below current regulatory standards, may increase risk of SGA, raising concerns of whether current allowable nitrate levels in drinking water protect children from SGA.

KW - Drinking water

KW - Logistic regression

KW - Nitrate

KW - Severe small for gestational age

KW - Small for gestational age (SGA)

KW - Tap water

U2 - 10.1016/j.envint.2023.107883

DO - 10.1016/j.envint.2023.107883

M3 - Journal article

C2 - 37001213

AN - SCOPUS:85151247104

VL - 174

JO - Environment international

JF - Environment international

SN - 0160-4120

M1 - 107883

ER -