Does Antibiotic Exposure During Infancy Lead to Development of Asthma? A Systemic Review and Metaanalysis

Marra F, Lynd L, Coombes M, et al. Chest . 2006;129:610–618 PURPOSE OF THE STUDY. To determine the association between antibiotic exposure in the first year of life and the development of childhood asthma by conducting a meta-analysis. METHODS. A search of all available electronic databases (Medline, Embase, EBM databases, Web of Science, PapersFirst, ProceedingsFirst, and the Cochrane database) for the period between January 1966 and September 2004 was performed. Studies included populations receiving at least 1 prescription for an antibiotic during the first year of life. The primary outcome was the development of physician-diagnosed asthma between the ages of 1 and 18 years. Only studies published in English and those that reported odds ratios (ORs) were included. RESULTS. Review of 2042 references yielded 8 studies that met criteria; 4 were retrospective, and 4 were prospective. The studies were reported between 1999 and 2004 and included sample sizes between 263 and 21 129 children. All retrospective studies used questions from the International Study of Asthma and Allergies in Childhood survey. Five studies were used to determine if there was a dose-response relationship between the number of antibiotic courses received and the risk of childhood asthma. These 5 studies included 27 167 children and 3392 asthma cases. The pooled OR for the 8 studies was 2.05 (95% confidence interval [CI]: 1.41–2.99). The association between antibiotic use in the first year of life and asthma was significantly higher in the retrospective studies (OR: 2.82; 95% CI: 2.07–3.85) than in the prospective studies (OR: 1.12; 95% CI: 0.88–1.42). The overall OR for the dose-response association of antibiotic use in the first year of life and asthma was 1.16 (95% CI: 1.05–1.28), but there was a trend toward a stronger association in the retrospective studies than in the prospective studies. CONCLUSIONS. Meta-analysis of the impact of antibiotics in the first year of life revealed a possible increase in later development of asthma in childhood on the basis of only the retrospective study results. Additional study is needed to determine a causal relationship. REVIEWER COMMENTS. This meta-analysis was the first to address the question of whether antibiotic use in the first year of life is associated with subsequent development of asthma. On the basis of the analysis, exposure to at least 1 antibiotic in the first year of life seems to be a risk factor for the development of childhood asthma; however, when the analysis was stratified by the subtypes of studies (prospective versus retrospective), only the pooled results from the retrospective studies yielded a positive association. All of the 95% CIs for the prospective studies crossed 1.00, which brings into question the association between exposure to antibiotics in the first year of life and the subsequent development of childhood asthma. Additional large-scale, prospective studies will be needed to confirm or refute the association.