To systematically review and meta-analyse longitudinal studies on antibiotic use and subsequent development of wheeze and/or asthma in the light of study quality, outcome measurement, reverse causation (wheezing or asthmatic symptoms themselves have caused the prescription of antibiotics) and confounding-by- indication (respiratory tract infections that lead to antibiotic use may be the underlying cause triggering later development of asthma symptoms).
Studies were identified through Pubmed, Medline and Embase searches up to November 1st 2010 and by perusing reference lists. Only English-language papers and studies with a longitudinal observational design were included. Study quality was assessed using the Newcastle-Ottawa scale.
We identified 21 longitudinal studies. The effect of antibiotic use on wheeze/asthma risk varied between studies. Eighteen studies were eligible for meta-analysis, showing a pooled odds ratio of 1.27 (95% confidence interval 1.12–1.43) for wheeze/asthma. When we eliminated studies with possible reverse causation and confounding-by-indication, the pooled risk estimate in the nine remaining studies was attenuated to an odds ratio of 1.12 (0.98–1.26).
Definition of wheeze or asthma and age at follow-up differed widely between studies. Three studies focussed on wheeze/asthma beyond the age of 5–6 years with the presence of active symptoms and/or medication showing a pooled odds ratio of 1.08 (0.93–1.23) which was dominated by one large study.
Heterogeneity of disease definition, reverse causation and confounding-by-indication lead to overestimation of the association between antibiotic use and the subsequent development of wheeze/asthma. The association was weak when fully adjusted for these types of bias.