Fetal and Early Life Antibiotics and Risk of Pediatric Inflammatory Bowel Disease: A Population-based Nationwide Register Study

Objective To assess whether antibiotic exposure prenatally and before two years of age are associated with subsequent pediatric inflammatory bowel disease (PIBD), as earlier studies diverge substantially in risk estimations or do not include prenatal exposure. Methods We performed a register-based cohort study including all children in Norway born 2004-2012 until study end December 31, 2020. Exposures were defined as dispensed antibiotics to mothers during pregnancy and to children before two years of age. Main outcome was ICD-10 code registrations consistent with PIBD. Results Among 536 819 children 797 PIBD cases were identified.The adjusted odds ratio (aOR) for developing PIBD if exposed to antibiotics before two years of age compared to no exposure was 1.33 (95% CI 1.15–1.53), adjusted for sex and prenatal antibiotic exposure. An adjustment for maternal smoking during pregnancy increased the aOR to 1.42 (1.22–1.66), but with minimal changes after further adjustments for potential confounders related to pregnancy, birth, or socioeconomic status. A dose-response association was observed in those receiving more than two antibiotic courses (aOR 1.47, 1.25–1.73), and with higher effect estimates for broad-spectrum antibiotics (aOR 2.57, 1.82–3.63). Antibiotic exposure during pregnancy was numerically but not significantly associated with offspring PIBD (aOR 1.15, 0.99–1.34). Conclusions Children exposed to antibiotics before two years of age were more likely to develop pediatric IBD than controls. Exposure prenatally to maternal antibiotics was numerically but not statistically significant associated to subsequent PIBD.