Postnatal Bisphenol A exposure and risk of precocious puberty in children: updated systematic review and meta-analysis.

Abstract

<h4>Background</h4>Precocious puberty (PP), defined as the development of secondary sexual characteristics before age eight in girls or nine in boys, has shown a rising prevalence globally. Bisphenol A (BPA), an endocrine-disrupting chemical commonly found in plastics, has been suggested to influence pubertal timing, but epidemiological evidence remains inconsistent. This systematic review and meta-analysis aimed to evaluate the association between postnatal BPA exposure and early pubertal onset in children.<h4>Methods</h4>Following PRISMA 2020 guidelines, PubMed, Embase, Scopus, Web of Science, and Cochrane were searched for observational studies published between 2000 and 2024. Eligible studies assessed postnatal BPA exposure using validated analytical methods (e.g., LC-MS/MS) and reported associations with central precocious puberty (CPP) or related early pubertal outcomes. Risk of bias was evaluated using the Newcastle-Ottawa Scale, and random-effects meta-analysis was used to pool odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity, publication bias, and certainty of evidence were assessed via I², Egger's test, and GRADE.<h4>Results</h4>Nine studies comprising 5,549 participants, predominantly girls were included, of which nine provided data for meta-analysis. Higher postnatal BPA exposure was observationally associated with increased odds of early pubertal onset (pooled OR = 4.45, 95% CI: 1.69-11.72), with a heterogeneity of (I² = 92%).Associations were stronger among girls and in studies using LC-MS/MS. Dose-response analyses, based on three studies, suggested a 14% increase in odds per 1 μg/L BPA increment and should be interpreted cautiously. Evidence in boys was limited and inconclusive.<h4>Conclusion</h4>Postnatal BPA exposure shows a consistent observational association with early pubertal onset in girls. These findings should not be interpreted as evidence of causality. The results are primarily applicable to girls and should not be extrapolated to boys, given the limited male data. Cross-sectional studies provide supportive evidence only and do not establish temporal relationships.<h4>Systematic trial registration</h4>PROSPERO, identifier: CRD420251168575.