Early-life exposures associated with antibiotic use and risk of subsequent Crohn's disease

Objective. An inappropriate immune response to normal bowel flora is implicated in the etiology of Crohn's disease. Tolerance to bowel flora develops in infancy, so factors disrupting normal patterns of bowel colonization may increase the risk of Crohn's disease. The aim of this study was to test the hypothesis that antibiotic therapy between birth and age 5 years may disrupt the pattern of bowel colonization and increase the risk of Crohn's disease. Material and methods. Some 1098 patients with Crohn's disease and 6550 controls matched by delivery unit, year of birth, sex, and born between 1973 and 1997 were identified through the Swedish population registers. Seven inpatient diagnoses between birth and age 5 years associated with antibiotic therapy were identified by prospectively recorded data. Results. Of the seven diagnoses, only pneumonia and otitis media were sufficiently common for use in the analyses. Pneumonia and otitis media were not independent of each other in their association with Crohn's disease and the more important association was with pneumonia. Pneumonia by age 5 years was statistically significantly associated with both pediatric- and adult Crohn's disease, with odds ratios (and 95% CI) of 2.74 (1.04-7.21) and 4.94 (1.83-13.23), respectively. Pneumonia after age 5 years was not statistically significantly associated with Crohn's disease. Conclusions. Pneumonia prior to age 5 years, but not later, was associated with subsequent Crohn's disease and this may represent either susceptibility or causation. The results are consistent with early exposures influencing immune function, such as through disruption of bowel colonization, and thus increasing the risk of Crohn's disease.