Prenatal exposure to nitrosatable drugs and timing of puberty in sons and daughters: A nationwide cohort study.
Nitrate
Nitrosatable drugs
Pregnancy
Prenatal
Puberty
Journal
International journal of hygiene and environmental health
ISSN: 1618-131X
Titre abrégé: Int J Hyg Environ Health
Pays: Germany
ID NLM: 100898843
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
23
06
2023
revised:
12
09
2023
accepted:
03
10
2023
medline:
27
10
2023
pubmed:
12
10
2023
entrez:
11
10
2023
Statut:
ppublish
Résumé
N-nitroso compounds (NOCs) can be formed by endogenous reactions between nitrosatable drugs and nitrite. Animal studies have found that several NOCs are teratogenic, and epidemiological studies report associations between prenatal exposure to nitrosatable drugs and adverse birth outcomes. It is unknown whether prenatal exposure to nitrosatable drugs is harmful to the child's reproductive health, including pubertal development. We investigated whether prenatal exposure to nitrosatable drugs was associated with timing of puberty and whether nitrate, nitrite and antioxidant intake modified any association. The population-based Danish National Birth Cohort (DNBC) Puberty Cohort, which includes 15,819 children, was used to investigate the association between prenatal exposure to nitrosatable drugs and timing of puberty. Around gestational week 11 and gestational week 18, mothers provided information about drug use during pregnancy. The children's self-reported information on onset of pubertal milestones was collected every six months from 11 years of age and throughout puberty. To investigate potential effect modification by nitrite, nitrate and antioxidant intake, information on these factors was obtained from a food frequency questionnaire completed by the mothers in gestational week 25, and information on nitrate concentration in maternal drinking water at her residential address was obtained from monitoring data from public waterworks. Data were analysed using a multivariable regression model for interval-censored data estimating difference in months in timing of puberty between exposure groups. A total of 2,715 children were prenatally exposed to nitrosatable drugs. We did not find an association between prenatal exposure to nitrosatable drugs and timing of puberty. This finding was supported by null-findings in the following sub-analyses investigating: 1. subtypes of nitrosatable drugs (secondary and tertiary amines and amides), 2. dose-dependency (duration of drug intake), 3. effect modification by maternal intake of nitrate, nitrite, and antioxidants. 4. confounding by indication. Prenatal exposure to nitrosatable drugs was not associated with timing of puberty. Nitrosatable drugs are commonly used drugs in pregnancy, and further research is needed to allow firm conclusions on the potential effect of prenatal exposure to nitrosatable drugs on the child's reproductive health.
Sections du résumé
BACKGROUND
N-nitroso compounds (NOCs) can be formed by endogenous reactions between nitrosatable drugs and nitrite. Animal studies have found that several NOCs are teratogenic, and epidemiological studies report associations between prenatal exposure to nitrosatable drugs and adverse birth outcomes. It is unknown whether prenatal exposure to nitrosatable drugs is harmful to the child's reproductive health, including pubertal development.
OBJECTIVES
We investigated whether prenatal exposure to nitrosatable drugs was associated with timing of puberty and whether nitrate, nitrite and antioxidant intake modified any association.
METHODS
The population-based Danish National Birth Cohort (DNBC) Puberty Cohort, which includes 15,819 children, was used to investigate the association between prenatal exposure to nitrosatable drugs and timing of puberty. Around gestational week 11 and gestational week 18, mothers provided information about drug use during pregnancy. The children's self-reported information on onset of pubertal milestones was collected every six months from 11 years of age and throughout puberty. To investigate potential effect modification by nitrite, nitrate and antioxidant intake, information on these factors was obtained from a food frequency questionnaire completed by the mothers in gestational week 25, and information on nitrate concentration in maternal drinking water at her residential address was obtained from monitoring data from public waterworks. Data were analysed using a multivariable regression model for interval-censored data estimating difference in months in timing of puberty between exposure groups.
RESULTS
A total of 2,715 children were prenatally exposed to nitrosatable drugs. We did not find an association between prenatal exposure to nitrosatable drugs and timing of puberty. This finding was supported by null-findings in the following sub-analyses investigating: 1. subtypes of nitrosatable drugs (secondary and tertiary amines and amides), 2. dose-dependency (duration of drug intake), 3. effect modification by maternal intake of nitrate, nitrite, and antioxidants. 4. confounding by indication.
CONCLUSIONS
Prenatal exposure to nitrosatable drugs was not associated with timing of puberty. Nitrosatable drugs are commonly used drugs in pregnancy, and further research is needed to allow firm conclusions on the potential effect of prenatal exposure to nitrosatable drugs on the child's reproductive health.
Identifiants
pubmed: 37820420
pii: S1438-4639(23)00162-1
doi: 10.1016/j.ijheh.2023.114271
pii:
doi:
Substances chimiques
Nitrites
0
Nitrates
0
Antioxidants
0
Nitroso Compounds
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
114271Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.