PURPOSE OF THE STUDY.
The goal of this study was to investigate the association between exposure to antibiotics in fetal and early life and asthma in childhood, adjusting for confounding variables.
The study included a population of 493 785 Swedish children born to women pregnant between July 2005 and December 2010 identified from the Medical Birth Register, including 180 894 who were eligible for sibling analyses.
Key outcome and exposure data were collected from national demographic and health registries. Exposure to antibiotic use was categorized into the following 3 groups: any antibiotics; antibiotics for respiratory infections; and antibiotics for urinary tract or skin and soft tissue infections. Asthma diagnosis was defined as having both an asthma diagnosis and receipt of asthma medications. The association between antibiotic exposure and asthma was investigated with multivariate Cox proportional hazard regression models, and a stratified proportional hazards model conditional on sibling group was used to adjust for shared factors within families.
Overall, 6% of the children in the study were defined as having asthma. In total, 20% of the children in the full cohort had been exposed to antibiotics in fetal life, and at least 1 prescription of any antibiotic during childhood was filled for 62% of children. Antibiotic exposure in fetal life was associated with an increased risk of asthma in multivariate cohort analyses (hazard ratio 1.28, 95% confidence interval 1.25–1.32), but not in sibling analyses (0.99, 0.92–1.07). In multivariate cohort analyses, antibiotics used to treat respiratory infections in childhood were associated with a more pronounced increased risk of asthma (4.12, 3.78–4.50) than antibiotics used for urinary tract and skin infections (1.54, 1.24–1.92). In sibling analyses, the excess risks after exposures to antibiotics for respiratory infections decreased (2.36, 1.78–3.13) and disappeared for antibiotics for urinary tract and skin infections (0.85, 0.47–1.55).
Previous positive associations between exposure to antibiotics in fetal and early life and subsequent childhood asthma could have been caused by shared familial factors, in addition to confounding by respiratory infections.
This study uses the breadth of administrative data available in Sweden to investigate the association between antibiotics and childhood asthma, taking familial factors into account. Earlier studies are conflicting with systematic reviews highlighting that the association between antibiotic exposure and asthma could be caused by bias. This study corroborates the potential for reverse causation and confounding by indication; the latter implies that the association is confounded by a third factor (such as respiratory infection) that could both explain the indication for antibiotic use and act as a risk factor for asthma.
- Copyright © 2015 by the American Academy of Pediatrics