Background: Antibiotics have been associated with attention deficit/hyperactivity disorder (ADHD), but evidence is inconsistent.

Purpose: To assess whether use of systemic antibiotics during pregnancy and in the first five years of life increases the risk of childhood ADHD.

Methods: We conducted a nationwide, population-based retrospective cohort study using linked administrative data for the period 2005-2021, and including live births (n=315,789) from October 2005 to December 2010. Maternal and childhood antibiotic-use was defined as ≥1 antibiotic dispensing during pregnancy and at age 0-5 years, respectively. ADHD was identified using ICD-10-AM diagnostic codes (F90.X) or by ≥2 dispensing’s of Atomoxetine within a 12‑month period. Children were followed until diagnosis, death, migration, or end of study, whichever occurred first. Cox proportional hazards regression was used adjusted for relevant sociodemographic and perinatal covariates.

Results: Overall, 30% of mothers were dispensed ≥1 antibiotic during pregnancy, and 96% of children received ≥1 antibiotic in the first five years. In total, 1,110 ADHD cases were identified. Both maternal and early childhood antibiotic-use were associated with an increased risk of ADHD: HR=1.61, 95% CI 1.41–1.83 and HR=4.02, 95% CI 2.00–8.07, respectively.  A clear dose-response relationship was observed, particularly for early-childhood exposure (0-5 years), with markedly elevated risk (HR=5.58, 95% CI 2.76–11.28) among children receiving ≥13 courses. Higher risks were observed for penicillin’s, macrolides, cephalosporins, and other antibiotics, but not for tetracyclines; associations were strongest for broad-spectrum antibiotics. Findings were consistent across alternative ADHD case definitions.

Conclusions: Exposure to antibiotics during pregnancy and especially in early childhood was associated, in a dose-dependent manner, with an increased risk of ADHD.