Maternal antibiotic use during pregnancy and asthma in children: population-based cohort study and sibling design.

Antibiotic use during pregnancy may affect asthma risk in offspring. However, epidemiological studies yielded conflicting findings, with an observed association possibly confounded by shared familial factors. We sought to assess the association between maternal antibiotic use during pregnancy and childhood asthma in the offspring, by accounting for time-stable familial factors.We conducted a population-based cohort study and sibling study using data from Danish nationwide registers, which comprised 407 804 liveborn singletons from 2005 to 2011. Antibiotic use during pregnancy was defined as at least one antibiotic prescription filled by the mother from 1 month prior to pregnancy up until delivery, identified in the National Prescription Registry. First-time asthma in the offspring was determined by hospital treatment or asthma medication treatment after age 5 years. We estimated hazard ratios (HRs) of asthma using Cox regression in the population-based cohort and stratified Cox regression in the sibling cohort.Approximately 36.5% of pregnant women redeemed antibiotic prescriptions. Antibiotic use during pregnancy was associated with childhood asthma in cohort analyses (HR 1.21, 95% CI 1.18-1.24), but not in sibling analyses (HR 0.96, 95% CI 0.90-1.03). In the population-based analyses, higher risks of asthma were seen with longer duration of maternal antibiotic use, a higher number of prescriptions and prescriptions of multiple types of antibiotics. All these associations disappeared in the sibling analyses.The associations observed by previous studies for prenatal exposure to antibiotics and offspring asthma risk are likely to be due to confounding factors shared within families.