Prenatal antibiotic exposure and risk of attention-deficit/hyperactivity disorder: a population-based cohort study

BACKGROUND: Abnormal microbiota composition induced by prenatal exposure to antibiotics has been proposed as a potential contributor to the development of attention-deficit/hyperactivity disorder (ADHD). We examined the association between prenatal antibiotic exposure and risk of ADHD. METHODS: We conducted a population-based retrospective cohort study of children born in Manitoba, Canada, between 1998 and 2017 and their mothers. We defined exposure as the mother having filled 1 or more antibiotic prescriptions during pregnancy. The outcome was diagnosis of ADHD in the offspring, as identified in administrative databases. We estimated hazard ratios (HRs) using Cox proportional hazards regression in the overall cohort, in a separate cohort matched on high-dimensional propensity scores and in a sibling cohort. RESULTS: In the overall cohort, consisting of 187 605 children, prenatal antibiotic dispensation was associated with increased risk of ADHD (HR 1.22, 95% confidence interval [CI] 1.18-1.26). Similar results were observed in the matched cohort of 129 674 children (HR 1.20, 95% CI 1.15-1.24) but not in the sibling cohort (HR 1.06, 95% CI 0.99-1.13). Two negative-control analyses indicated a positive association with ADHD despite the lack of a reasonable biological mechanism, which suggested that the observed association between prenatal antibiotic dispensation and risk of ADHD was likely due to confounding. INTERPRETATION: In our study, prenatal antibiotic exposure was not associated with increased risk of ADHD in children. Although the risk was higher in the overall and matched cohorts, it was likely overestimated because of unmeasured confounding. Future studies are warranted to examine other factors affecting microbiota composition in association with risk of ADHD.
Attention-deficit/hyperactivity disorder (ADHD) is a neuro-developmental disorder (1,2) that is associated with many long-term adverse health and social outcomes, such as comorbid depression and anxiety, drug abuse, motor vehicle collisions [...]