Prenatal and early-life antibiotic use and risk of childhood asthma: A retrospective cohort study

Background: Although associations between antibiotic exposure in infants and asthma development are reported, few studies have examined the effects of prenatal exposure to antibiotics. We evaluated this association considering the antibiotic types using a large-scale claim database in Japan. Methods: This retrospective study using health insurance administrative claim data in Japan included children born between January 2005 and September 2014. We constructed 2 cohorts: initial cohort, with information on children's mothers, and sibling cohort, with at least one sibling. Cox proportional hazard regression and sibling-matched cohort analyses were performed to determine the association between exposure to antibiotics in utero or the first year of life and asthma development until age 6. Results: In the initial cohort, antibiotic exposure during the foetal period was associated with early asthma development (until age 3; HR: 1.18, 95% CI: 1.08-1.30). However, this association disappeared after 3years. The association between antibiotic exposure in the first year of life and asthma was stronger in early (HR: 2.43, 95% CI: 2.20-2.69) than later (HR: 1.23, 95% CI: 1.11-1.36) life. In the sibling cohort, we observed positive associations between foetal exposure and asthma by adjusting for familial factors (HR: 1.34, 95% CI: 1.05-1.72), which remained during the first year of life (HR: 1.62, 95% CI: 1.27-2.07). Conclusions: Exposure to antibiotics during the first year of life was associated with childhood asthma even after adjusting for familial factors. However, a weak association was observed between prenatal antibiotic exposure and asthma development.