Prenatal nitrosatable prescription drug intake, drinking water nitrate, and the risk of stillbirth: a register- and population-based cohort of Danish pregnancies, 1997–2017

Abstract Background Nitrosatable drugs commonly prescribed during pregnancy can react with nitrite to form N-nitroso compounds which have been associated with an increased risk of stillbirth. Whether maternal residential drinking water nitrate modifies this association is unknown. We investigated, i...

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Autores principales:	Anne Marie Ladehoff Thomsen, Cecilia Høst Ramlau-Hansen, Jörg Schullehner, Ninna Hinchely Ebdrup, Zeyan Liew, Vanessa Coffman, Leslie Stayner, Birgitte Hansen, Jørn Olsen
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Nitrosatable drug Amine Amide N-nitroso compounds Stillbirth Drinking water nitrate Industrial medicine. Industrial hygiene RC963-969 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/e65edac846484f298f0b2f36ac0cbc27
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spelling	oai:doaj.org-article:e65edac846484f298f0b2f36ac0cbc272021-11-21T12:33:09ZPrenatal nitrosatable prescription drug intake, drinking water nitrate, and the risk of stillbirth: a register- and population-based cohort of Danish pregnancies, 1997–201710.1186/s12940-021-00805-z1476-069Xhttps://doaj.org/article/e65edac846484f298f0b2f36ac0cbc272021-11-01T00:00:00Zhttps://doi.org/10.1186/s12940-021-00805-zhttps://doaj.org/toc/1476-069XAbstract Background Nitrosatable drugs commonly prescribed during pregnancy can react with nitrite to form N-nitroso compounds which have been associated with an increased risk of stillbirth. Whether maternal residential drinking water nitrate modifies this association is unknown. We investigated, if household drinking water nitrate was associated with stillbirth, and if it modified the association between nitrosatable prescription drug intake and the risk of stillbirth. Methods We conducted an individual-level register- and population-based cohort study using 652,810 women with the first recorded singleton pregnancy in the Danish Medical Birth Registry between 1997 and 2017. Nitrosatable drug exposure was recorded by use of the Danish National Patient Registry defined as women with a first redeemed prescription of a nitrosatable drug the first 22 weeks of pregnancy. The reference group was women with no redeemed prescription of a nitrosatable drug in this period. The average individual drinking water nitrate concentration level (mg/L) was calculated in the same period. We categorized nitrosatable drugs as secondary amines, tertiary amines, and amides. Cox hazard regression was used to estimate crude and adjusted hazard ratios with 95% confidence intervals for stillbirth stratified into five categories of nitrate concentrations: ≤1 mg/L, > 1- ≤ 2 mg/L, > 2- ≤ 5 mg/L, > 5- ≤ 25 mg/L, and > 25 mg/L. Results Drinking water nitrate exposure in the population was not associated with the risk of stillbirth. Among 100,244 women who had a nitrosatable prescription drug redeemed ≤22 weeks of pregnancy of pregnancy, 418 (0.42%) had a stillbirth compared to 1993 stillbirths (0.36%) among 552,566 referent women. Women with any nitrosatable prescription drug intake and > 1- ≤ 2 mg/L nitrate concentration had an increased risk of stillbirth [adjusted hazard ratio 1.55 (95% confidence interval, 1.15–2.09)] compared with referent women. In the stratified analyses, the highest risk of stillbirth was found among women with secondary amine intake and > 25 mg/L nitrate concentrations [adjusted hazard ratio 3.11 (95% CI, 1.08–8.94)]. Conclusions The association between nitrosatable prescription drug intake and the risk of stillbirth may depend on the level of nitrate in household drinking water. Evaluations of the effect of nitrosatable drug intake on perinatal outcomes might consider nitrate exposure from drinking water.Anne Marie Ladehoff ThomsenCecilia Høst Ramlau-HansenJörg SchullehnerNinna Hinchely EbdrupZeyan LiewVanessa CoffmanLeslie StaynerBirgitte HansenJørn OlsenBMCarticleNitrosatable drugAmineAmideN-nitroso compoundsStillbirthDrinking water nitrateIndustrial medicine. Industrial hygieneRC963-969Public aspects of medicineRA1-1270ENEnvironmental Health, Vol 20, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Nitrosatable drug Amine Amide N-nitroso compounds Stillbirth Drinking water nitrate Industrial medicine. Industrial hygiene RC963-969 Public aspects of medicine RA1-1270
spellingShingle	Nitrosatable drug Amine Amide N-nitroso compounds Stillbirth Drinking water nitrate Industrial medicine. Industrial hygiene RC963-969 Public aspects of medicine RA1-1270 Anne Marie Ladehoff Thomsen Cecilia Høst Ramlau-Hansen Jörg Schullehner Ninna Hinchely Ebdrup Zeyan Liew Vanessa Coffman Leslie Stayner Birgitte Hansen Jørn Olsen Prenatal nitrosatable prescription drug intake, drinking water nitrate, and the risk of stillbirth: a register- and population-based cohort of Danish pregnancies, 1997–2017
description	Abstract Background Nitrosatable drugs commonly prescribed during pregnancy can react with nitrite to form N-nitroso compounds which have been associated with an increased risk of stillbirth. Whether maternal residential drinking water nitrate modifies this association is unknown. We investigated, if household drinking water nitrate was associated with stillbirth, and if it modified the association between nitrosatable prescription drug intake and the risk of stillbirth. Methods We conducted an individual-level register- and population-based cohort study using 652,810 women with the first recorded singleton pregnancy in the Danish Medical Birth Registry between 1997 and 2017. Nitrosatable drug exposure was recorded by use of the Danish National Patient Registry defined as women with a first redeemed prescription of a nitrosatable drug the first 22 weeks of pregnancy. The reference group was women with no redeemed prescription of a nitrosatable drug in this period. The average individual drinking water nitrate concentration level (mg/L) was calculated in the same period. We categorized nitrosatable drugs as secondary amines, tertiary amines, and amides. Cox hazard regression was used to estimate crude and adjusted hazard ratios with 95% confidence intervals for stillbirth stratified into five categories of nitrate concentrations: ≤1 mg/L, > 1- ≤ 2 mg/L, > 2- ≤ 5 mg/L, > 5- ≤ 25 mg/L, and > 25 mg/L. Results Drinking water nitrate exposure in the population was not associated with the risk of stillbirth. Among 100,244 women who had a nitrosatable prescription drug redeemed ≤22 weeks of pregnancy of pregnancy, 418 (0.42%) had a stillbirth compared to 1993 stillbirths (0.36%) among 552,566 referent women. Women with any nitrosatable prescription drug intake and > 1- ≤ 2 mg/L nitrate concentration had an increased risk of stillbirth [adjusted hazard ratio 1.55 (95% confidence interval, 1.15–2.09)] compared with referent women. In the stratified analyses, the highest risk of stillbirth was found among women with secondary amine intake and > 25 mg/L nitrate concentrations [adjusted hazard ratio 3.11 (95% CI, 1.08–8.94)]. Conclusions The association between nitrosatable prescription drug intake and the risk of stillbirth may depend on the level of nitrate in household drinking water. Evaluations of the effect of nitrosatable drug intake on perinatal outcomes might consider nitrate exposure from drinking water.
format	article
author	Anne Marie Ladehoff Thomsen Cecilia Høst Ramlau-Hansen Jörg Schullehner Ninna Hinchely Ebdrup Zeyan Liew Vanessa Coffman Leslie Stayner Birgitte Hansen Jørn Olsen
author_facet	Anne Marie Ladehoff Thomsen Cecilia Høst Ramlau-Hansen Jörg Schullehner Ninna Hinchely Ebdrup Zeyan Liew Vanessa Coffman Leslie Stayner Birgitte Hansen Jørn Olsen
author_sort	Anne Marie Ladehoff Thomsen
title	Prenatal nitrosatable prescription drug intake, drinking water nitrate, and the risk of stillbirth: a register- and population-based cohort of Danish pregnancies, 1997–2017
title_short	Prenatal nitrosatable prescription drug intake, drinking water nitrate, and the risk of stillbirth: a register- and population-based cohort of Danish pregnancies, 1997–2017
title_full	Prenatal nitrosatable prescription drug intake, drinking water nitrate, and the risk of stillbirth: a register- and population-based cohort of Danish pregnancies, 1997–2017
title_fullStr	Prenatal nitrosatable prescription drug intake, drinking water nitrate, and the risk of stillbirth: a register- and population-based cohort of Danish pregnancies, 1997–2017
title_full_unstemmed	Prenatal nitrosatable prescription drug intake, drinking water nitrate, and the risk of stillbirth: a register- and population-based cohort of Danish pregnancies, 1997–2017
title_sort	prenatal nitrosatable prescription drug intake, drinking water nitrate, and the risk of stillbirth: a register- and population-based cohort of danish pregnancies, 1997–2017
publisher	BMC
publishDate	2021
url	https://doaj.org/article/e65edac846484f298f0b2f36ac0cbc27
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Prenatal nitrosatable prescription drug intake, drinking water nitrate, and the risk of stillbirth: a register- and population-based cohort of Danish pregnancies, 1997–2017

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