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.