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
N1 - Funding Information:
Follow-up of mothers and children has been supported by the Danish Medical Research Council (SSVF 0646, 271-08-0839/06-066023, O602-01042B, 0602-02738B), the Lundbeck Foundation (195/04, R100-A9193), Innovation Fund Denmark 0603-00294B (09-067124), the Nordea Foundation (02-2013-2014), Aarhus Ideas (AU R9-A959-13-S804), University of Copenhagen Strategic Grant (IFSV 2012), and the Danish Council for Independent Research (DFF – 4183-00594 and DFF—4183-00152).
Funding Information:
Horsens Hospital, the Health Research Foundation of the Central Denmark Region, Aarhus University, Aase and Ejnar Danielsen’s Foundation, Merck and Ferring funded this work. The funders had no impact on design or study conduct.
Funding Information:
The Danish National Birth Cohort was established with a significant grant from the Danish National Research Foundation. Additional support was obtained from the Danish Regional Committees, the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth Defects Foundation, the Health Foundation and other minor grants. The DNBC Biobank has been supported by the Novo Nordisk Foundation and the Lundbeck Foundation. Follow-up of mothers and children has been supported by the Danish Medical Research Council (SSVF 0646, 271-08-0839/06-066023, O602-01042B, 0602-02738B), the Lundbeck Foundation (195/04, R100-A9193), Innovation Fund Denmark 0603-00294B (09-067124), the Nordea Foundation (02-2013-2014), Aarhus Ideas (AU R9-A959-13-S804), University of Copenhagen Strategic Grant (IFSV 2012), and the Danish Council for Independent Research (DFF – 4183-00594 and DFF—4183-00152).
Funding Information:
The Danish National Birth Cohort was established with a significant grant from the Danish National Research Foundation. Additional support was obtained from the Danish Regional Committees, the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth Defects Foundation, the Health Foundation and other minor grants. The DNBC Biobank has been supported by the Novo Nordisk Foundation and the Lundbeck Foundation.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
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 - Cohort study
KW - Drinking water nitrate
KW - Nitrosatable drug exposure
KW - Pregnancy loss
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 - Article
C2 - 36114546
AN - SCOPUS:85138143685
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 -
