Prenatal nitrate exposure from diet and drinking water and timing of puberty in sons and daughters: A nationwide cohort study
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Background: In Western countries, age at pubertal development has declined during the last century in girls, and probably also in boys. No studies have investigated whether nitrate, a widespread environmental exposure with teratogenic and hormone disrupting properties, might affect timing of puberty. Objectives: We investigated if prenatal exposure to nitrate from drinking water and diet was associated with timing of puberty. Methods: This cohort study included 15,819 children born from 2000 to 2003 within the Danish National Birth Cohort. Self-reported information on current status of various pubertal milestones was provided every six months by a questionnaire from 11 years of age until 18 years or full maturity, whichever came first. Maternal nitrate intake from diet (mg/day) was derived from a mid-pregnancy food frequency questionnaire and individual level nitrate exposure from drinking water (mg/L) was derived using measurements from Danish public waterworks. Adjusted average differences in months in age at attaining several pubertal milestones as well as the average age difference in age at attaining all the milestones were estimated separately for diet and water using a regression model for interval-censored data. C- and E-vitamin, red meat and processed meat intake were explored as potential effect modifiers in sub-analyses. Results: No strong associations were observed between prenatal exposure to nitrate and timing of puberty in children. However, sons born of mothers with a nitrate concentration in drinking water at their residential address of > 25 mg/L (half of the World Health Organisation (WHO) guideline value) compared with ≤ 1 mg/L showed a tendency towards earlier age at pubertal development with an average age difference of −1.2 months (95 % confidence interval,−3.0;0.6) for all the pubertal milestones combined. Discussion: Studies including more highly exposed children are needed before the current WHO drinking water guideline value for nitrate can be considered safe concerning pubertal development.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 107659 |
| Tidsskrift | Environment International |
| Vol/bind | 170 |
| Antal sider | 15 |
| ISSN | 0160-4120 |
| DOI | |
| Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
This study has been supported by the Graduate School of Health, Aarhus University and The Health Foundation (19-B-0075).
Funding Information:
The drinking water database has been established by grants from United States National Institute of Environmental Health Sciences (R01 ES027823-01A1) and BERTHA - the Danish Big Data Centre for Environment and Health funded by the Novo Nordisk Foundation Challenge Programme (grant NNF17OC0027864). 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 have 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), The 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). Access to data from DNBC can be obtained. The procedure for application for data access is available at the website: https://www.dnbc.dk/access-to-dnbc-data. The graphical abstract was created with BioRender.com. The DNBC is approved by the Danish Data Protection Agency and the Committee on Health Research Ethics. The DNBC participants provided informed consent at enrolment. This study was registered by the Danish Data Protection Agency (2016-051-000001, rec no 1643) and approved by the Steering Committee of the DNBC (Ref. no. 2018-27).
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 have 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), The 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 drinking water database has been established by grants from United States National Institute of Environmental Health Sciences (R01 ES027823-01A1) and BERTHA - the Danish Big Data Centre for Environment and Health funded by the Novo Nordisk Foundation Challenge Programme (grant NNF17OC0027864).
Publisher Copyright:
© 2022 The Authors
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