Prenatal or Early-Life Exposure to Antibiotics and Risk of Childhood Asthma: A Systematic Review

CONTEXT: The increasing prevalence of childhood asthma has been associated with low microbial exposure as described by the hygiene hypothesis.

OBJECTIVE: We sought to evaluate the evidence of association between antibiotic exposure during pregnancy or in the first year of life and risk of childhood asthma.

METHODS: PubMed was systematically searched for studies published between 1950 and July 1, 2010. Those that assessed associations between antibiotic exposure during pregnancy or in the first year of life and asthma at ages 0 to 18 years (for pregnancy exposures) or ages 3 to 18 years (for first-year-of-life exposures) were included. Validity was assessed according to study design, age at asthma diagnosis, adjustment for respiratory infections, and consultation rates.

RESULTS: For exposure in the first year of life, the pooled odds ratio (OR) for all studies (N = 20) was 1.52 (95% confidence interval [CI]: 1.30–1.77). Retrospective studies had the highest pooled risk estimate for asthma (OR: 2.04 [95% CI: 1.83–2.27]; n = 8) compared with database and prospective studies (OR: 1.25 [95% CI: 1.08–1.45]; n = 12). Risk estimates for studies that adjusted for respiratory infections (pooled OR: 1.16 [95% CI: 1.08–1.25]; n = 5) or later asthma onset (pooled OR for asthma at or after 2 years: OR: 1.16 [95% CI: 1.06–1.25]; n = 3) were weaker but remained significant. For exposure during pregnancy (n = 3 studies), the pooled OR was 1.24 (95% CI: 1.02–1.50).

CONCLUSIONS: Antibiotics seem to slightly increase the risk of childhood asthma. Reverse causality and protopathic bias seem to be possible confounders for this relationship.