Drinking water nitrate and risk of pregnancy loss: a nationwide cohort study

TY - JOUR

T1 - Drinking water nitrate and risk of pregnancy loss

T2 - a nationwide cohort study

AU - Ebdrup, Ninna Hinchely

AU - Schullehner, Jörg

AU - Knudsen, Ulla Breth

AU - Liew, Zeyan

AU - Thomsen, Anne Marie Ladehoff

AU - Lyngsø, Julie

AU - Bay, Bjørn

AU - Arendt, Linn Håkonsen

AU - Clemmensen, Pernille Jul

AU - Sigsgaard, Torben

AU - Hansen, Birgitte

AU - Ramlau-Hansen, Cecilia Høst

PY - 2022/9

Y1 - 2022/9

N2 - BACKGROUND: Nitrate contamination is seen in drinking water worldwide. Nitrate may pass the placental barrier. Despite suggestive evidence of fetal harm, the potential association between nitrate exposure from drinking water and pregnancy loss remains to be studied. We aimed to investigate if nitrate in drinking water was associated with the risk of pregnancy loss.METHODS: We conducted a nationwide cohort study of 100,410 pregnancies (enrolled around gestational week 11) in the Danish National Birth Cohort (DNBC) during 1996-2002. Spontaneous pregnancy losses before gestational week 22 were ascertained from the Danish National Patient Registry and DNBC pregnancy interviews. Using the national drinking water quality-monitoring database Jupiter, we estimated the individual and time-specific nitrate exposure by linking geocoded maternal residential addresses with water supply areas. The nitrate exposure was analyzed in spline models using a log-transformed continuous level or classified into five categories. We used Cox proportional hazards models to estimate associations between nitrate and pregnancy loss and used gestational age (days) as the time scale, adjusting for demographic, health, and lifestyle variables.RESULTS: No consistent associations were found when investigating the exposure as a categorical variable and null findings were also found in trimester specific analyses. In the spline model using the continuous exposure variable, a modestly increased hazard of pregnancy loss was observed for the first trimester at nitrate exposures between 1 and 10 mg/L, with the highest. adjusted hazard ratio at 5 mg/L of nitrate of 1.16 (95% CI: 1.01, 1.34). This trend was attenuated in the higher exposure ranges.CONCLUSION: No association was seen between drinking water nitrate and the risk of pregnancy loss when investigating the exposure as a categorical variable. When we modelled the exposure as a continuous variable, a dose-dependent association was found between drinking water nitrate exposure in the first trimester and the risk of pregnancy loss. Very early pregnancy losses were not considered in this study, and whether survival bias influenced the results should be further explored.

AB - BACKGROUND: Nitrate contamination is seen in drinking water worldwide. Nitrate may pass the placental barrier. Despite suggestive evidence of fetal harm, the potential association between nitrate exposure from drinking water and pregnancy loss remains to be studied. We aimed to investigate if nitrate in drinking water was associated with the risk of pregnancy loss.METHODS: We conducted a nationwide cohort study of 100,410 pregnancies (enrolled around gestational week 11) in the Danish National Birth Cohort (DNBC) during 1996-2002. Spontaneous pregnancy losses before gestational week 22 were ascertained from the Danish National Patient Registry and DNBC pregnancy interviews. Using the national drinking water quality-monitoring database Jupiter, we estimated the individual and time-specific nitrate exposure by linking geocoded maternal residential addresses with water supply areas. The nitrate exposure was analyzed in spline models using a log-transformed continuous level or classified into five categories. We used Cox proportional hazards models to estimate associations between nitrate and pregnancy loss and used gestational age (days) as the time scale, adjusting for demographic, health, and lifestyle variables.RESULTS: No consistent associations were found when investigating the exposure as a categorical variable and null findings were also found in trimester specific analyses. In the spline model using the continuous exposure variable, a modestly increased hazard of pregnancy loss was observed for the first trimester at nitrate exposures between 1 and 10 mg/L, with the highest. adjusted hazard ratio at 5 mg/L of nitrate of 1.16 (95% CI: 1.01, 1.34). This trend was attenuated in the higher exposure ranges.CONCLUSION: No association was seen between drinking water nitrate and the risk of pregnancy loss when investigating the exposure as a categorical variable. When we modelled the exposure as a continuous variable, a dose-dependent association was found between drinking water nitrate exposure in the first trimester and the risk of pregnancy loss. Very early pregnancy losses were not considered in this study, and whether survival bias influenced the results should be further explored.

KW - Abortion, Spontaneous/chemically induced

KW - Cohort Studies

KW - Drinking Water/adverse effects

KW - Drinking water nitrate

KW - Female

KW - Humans

KW - Nitrates/adverse effects

KW - Nitrogen Oxides

KW - Nitrosatable drug exposure

KW - Placenta

KW - Pregnancy

KW - Pregnancy loss

KW - Cohort study

UR - http://www.scopus.com/inward/record.url?scp=85138143685&partnerID=8YFLogxK

U2 - 10.1186/s12940-022-00897-1

DO - 10.1186/s12940-022-00897-1

M3 - Journal article

C2 - 36114546

SN - 1476-069X

VL - 21

JO - Environmental Health: A Global Access Science Source

JF - Environmental Health: A Global Access Science Source

IS - 1

M1 - 87

ER -