Meta-analysis of the association between prenatal antibiotic exposure and risk of childhood attention-deficit/hyperactivity disorder.

Background: Studies examining the association between maternal antibiotic use during pregnancy and the risk of childhood attention-deficit/hyperactivity disorder (ADHD) have yielded inconsistent results. This meta-analysis synthesizes available evidence to establish a more comprehensive understanding of this association. Methods: Observational studies published through October 2, 2024, were systematically searched from Cochrane Library, EMBASE, Web of Science, and PubMed databases. The Newcastle-Ottawa Scale was used to assess the quality of the included studies, and statistical analyses were performed using Stata version 15.0. Results: Nine studies encompassing 6,180,434 participants were included. Prenatal antibiotic exposure was associated with an increased risk of childhood ADHD (HR = 1.15; 95 % CI = 1.09–1.22, P < 0.0001; OR = 1.28; 95 % CI = 1.21–1.35, P < 0.001). Both mid-pregnancy (HR = 1.11; 95 % CI = 1.02–1.22, P = 0.282) and late-pregnancy (HR = 1.07; 95 % CI = 1.02–1.12, P = 0.521) antibiotic exposure was associated with an increased risk of ADHD. Repeated antibiotic exposures was associated with an increased risk further (twice: HR = 1.13; 95 % CI = 1.10–1.16, P = 0.856; ≥3 times: HR = 1.21; 95 % CI = 1.17–1.24, P = 0.166). Conclusion: This analysis identified a link between maternal antibiotic use during pregnancy and an increased risk of childhood ADHD. Large-scale, multicenter, well-designed prospective studies are needed to confirm these findings and adjust for potential confounders in evaluating the relationship between prenatal antibiotic exposure and childhood ADHD. © 2025 Elsevier B.V.