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

Objective: Antibiotic use during pregnancy may affect asthma risk in offspring. However, studies show conflicting results, and the observed association could be confounded by unmeasured covariates. We aimed to assess the association accounting for possible confounding factors. Methods: A population-based cohort study and sibling study using data from Danish national registers, which comprised 411,883 liveborn singletons during 2005–2011. The children were followed from 5 years of age until the first onset of asthma, emigration, death, or Dec 31, 2016, whichever came first. Maternal antibiotic use, infections, and asthma in the children were defined by data from the National Patient Register and Prescription Registry. We estimated hazard ratios (HRs) of asthma using proportional Cox regression models. Results: Approximately 36.5% of pregnant women redeemed at least one antibiotic prescription. Antibiotic use during pregnancy was associated with childhood asthma in cohort analyses (HR=1.23, 95% confidence interval (CI): 1.20–1.26), but not in sibling analyses (HR= 0.97, 95% CI: 0.91–1.03). In cohort analyses, the risk of offspring asthma was 1.16 (95% CI: 1.13–1.20) for antibiotics used for urogenital infections, 1.19 (95% CI: 1.10–1.29) for respiratory infections, 1.26 (95% CI: 1.14–1.39) for ear or eye infections, and 1.01 (95% CI: 0.75–1.35) for skin infections, respectively. All these associations disappeared in the sibling analyses. Conclusion: Prenatal exposure to antibiotic use during pregnancy is not associated with asthma in children. The association observed by previous studies could be due to familial confounding.