The association of early life exposure to antibiotics and the development of asthma, eczema and atopy in a birth cohort: confounding or causality?

BACKGROUND: In general, studies reporting positive associations between antibiotic exposure and respiratory and allergic disease have been unable to determine the nature of this association. OBJECTIVE: To examine the association between antibiotic exposure in infancy and the development of asthma, eczema and atopy in early childhood. METHODS: In a birth cohort study, we collected reported antibiotic exposure before 3 months and before 15 months along with outcomes (wheeze, asthma, eczema, rash, inhaler use) at 15 months (n=1011) and 4 years (n=986). Atopy was measured using skin prick tests at 15 months. RESULTS: We found significant univariate associations of antibiotic exposure before 3 months with asthma developing between birth and 15 months [OR 2.32 (95% CI 1.45-3.69)]. After adjustment for chest infections, this association reduced (OR=1.58, 95% CI 0.96-2.60) becoming marginally significant (P=0.07). A marginally significant association of antibiotics with atopy (OR=1.44, 95% CI 0.96-2.14) in the univariate analysis also reduced after adjustment for chest infections (OR=1.36, 95% CI 0.91-2.05). There was no effect of antibiotic exposure before 15 months on asthma developing after 15 months and present between 3 and 4 years (OR=1.35 95% CI 0.85-2.14). Antibiotic exposure before 3 months was not associated with eczema and rash developing between birth and 15 months but exposure before 15 months was related to eczema [OR 1.83 (95% CI 1.10-3.05)] and rash [OR 1.61 (95% CI 1.02-2.53)] developing after 15 months and remaining present at 4 years. These effects reduced in the multivariate analysis. CONCLUSIONS: Our findings suggest that the effect of antibiotics on respiratory disease may be due to confounding by chest infections at an early age when asthma may be indistinguishable from infection.