Abstract
This study explored the association between exposure to acetaminophen during pregnancy and pubertal development using data from 15,822 boys and girls in the longitudinal Puberty Cohort, nested within the Danish National Birth Cohort. Use of acetaminophen was reported 3 times during pregnancy and 6 months postpartum. In total, 54% of mothers indicated use at least once during pregnancy. Between 2012 and 2017, sons and daughters provided information on a wide range of pubertal milestones—including Tanner stages, axillary hair growth, and age at menarche or voice break and first ejaculation—every 6 months from 11 years of age until full sexual maturation. Data were analyzed using a regression model for interval-censored data, providing adjusted mean monthly differences in age at attaining the pubertal milestones according to intrauterine cumulative (weeks) and trimester-specific acetaminophen exposure. Our results suggested a tendency towards slightly earlier attainment of almost all studied markers of female pubertal development with increasing number of weeks of exposure (i.e., about 1.5–3 months earlier age at pubic hair, axillary hair, and acne development comparing unexposed with those prenatally exposed for more than 12 weeks). Male pubertal development had no strong association with acetaminophen exposure.
Highlights
This study explored the association between exposure to acetaminophen during pregnancy and pubertal development using data from 15,822 boys and girls in the longitudinal Puberty Cohort, nested within the Danish National Birth Cohort
Our results suggested a tendency towards slightly earlier attainment of almost all studied markers of female pubertal development with increasing number of weeks of exposure
Results from our population-based cohort study suggest that intrauterine exposure to acetaminophen might be associated with slightly earlier attainment of almost all studied female markers of pubertal development, most pronounced for pubic hair growth, axillary hair growth, and occurrence of acne, but with wide confidence intervals
Summary
This study explored the association between exposure to acetaminophen during pregnancy and pubertal development using data from 15,822 boys and girls in the longitudinal Puberty Cohort, nested within the Danish National Birth Cohort. Acetaminophen, known as paracetamol, is being used at least once by more than 50% of pregnant women in some countries [2,3,4] It is considered safe by the general public and remains a first choice for treatment for fever and pain during pregnancy [5]. It remains largely unknown to what extent a potential endocrine programming disruption of intrauterine exposure to acetaminophen might affect long-term reproductive health, such as age at puberty timing. To our knowledge, this is the first study on puberty timing, and we hypothesize that intrauterine exposure to acetaminophen alters the timing of markers of male and female pubertal development
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