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Prenatal exposure to antibiotics and timing of puberty in sons and daughters: A population-based cohort study
Anne Gaml-Sørensen1, Nis Brix1, Andreas Ernst2
1Department of Public Health, Research Unit for Epidemiology, Aarhus University, Bartholins Allé 2, 8000, Aarhus C., Denmark.
Insights
Prenatal antibiotic exposure in mothers did not impact the timing of puberty in their children. This large cohort study found no significant association between antibiotic use during pregnancy and pubertal development milestones in sons or daughters.
Area of Science:
- Reproductive Health
- Pediatric Endocrinology
- Pharmacology
Background:
- Prenatal exposure to antibiotics is common, raising concerns about potential effects on child development.
- Pubertal timing is a sensitive indicator of developmental trajectories, influenced by various environmental factors.
- Understanding the impact of in utero exposures is crucial for long-term health outcomes.
Purpose of the Study:
- To investigate the association between prenatal antibiotic exposure and the timing of pubertal development in both sons and daughters.
- To analyze trimester-specific and overall pregnancy antibiotic exposure effects on pubertal milestones.
- To assess potential associations using a robust statistical approach with an active comparator sub-analysis.
Main Methods:
- A population-based cohort study of 15,638 children born in Denmark (2000-2003).
- Maternal antibiotic use data collected during pregnancy; children followed from age 11 for pubertal milestones (Tanner stages, acne, voice break, menarche, etc.).
- Multivariable censored time-to-event regression models were used, adjusting for confounders, with combined estimates for overall pubertal timing.
Main Results:
- Maternal antibiotic use during pregnancy occurred in 21.1% of cases.
- No significant association was found between prenatal antibiotic exposure and the timing of individual pubertal milestones.
- Adjusted combined estimates showed minimal, non-significant differences in pubertal timing for exposed sons (-0.4 months) and daughters (-0.1 months).
Conclusions:
- Prenatal exposure to antibiotics was not associated with earlier or later pubertal timing in children.
- Findings were consistent across trimester-specific analyses and an active comparator sub-analysis.
- This study suggests that antibiotic use during pregnancy does not alter the timing of sexual maturation.
Objective:
To investigate if prenatal exposure to antibiotics is associated with earlier timing of pubertal development in sons and daughters.
Study Design:
This population-based cohort study is based upon the Puberty Cohort and includes a sample of 15,638 children born 2000-2003 in Denmark. Information on maternal use of antibiotics was collected around gestational week 30 and 6 months postpartum. The children were followed-up half-yearly from 11 years of age and throughout sexual maturation providing information on Tanner stages, acne and axillary hair, in addition to voice break and first ejaculation in sons and menarche in daughters. Due to the half-yearly collection of data on pubertal timing, the data was censored and therefore analysed using a multivariable censored time-to-event regression model. We examined both prenatal exposure to antibiotics at any time in pregnancy and trimester-specific prenatal exposure to antibiotics and pubertal timing, adjusting for maternal baseline socioeconomic and lifestyle characteristics. Mean age differences for the pubertal milestones between exposure groups were estimated. A combined estimate for overall pubertal timing was calculated based on combining all pubertal milestones into one model for sons and daughters, using Huber-White robust variance estimation which handles the risk of type 1 errors due to multiple testing of correlated outcomes. An active comparator approach with restriction to women reporting to have a urinary tract infection (cystitis) treated with either penicillin or sulfonamides was employed in a sub-analysis.
Results:
The prevalence of any maternal use of antibiotics in pregnancy was 21.1 %. There was no association between prenatal exposure to antibiotics and timing of pubertal development for the individual milestones. The adjusted combined estimate for pubertal timing in sons prenatally exposed to antibiotics at any point in pregnancy was -0.4 (95 % confidence interval (CI): -1.2; 0.4) months compared to unexposed sons. The adjusted combined estimate for pubertal timing in daughters prenatally exposed to antibiotics at any point in pregnancy was -0.1 (95 % CI: -0.9; 0.7) months compared to unexposed daughters. Both the trimester-specific analyses and the active comparator analysis revealed similar results.
Conclusion:
Prenatal exposure to antibiotics was not associated with pubertal timing.
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