S124 Antibiotic Exposure Before 2 Years of Age is Associated With Increased Risk of Pediatric IBD in a Norwegian Nation-Wide Study

Abstract

Background: The incidence of pediatric IBD (PIBD) rises. This development is likely related to environmental factors that cause disturbances in the gut microbiota. The infant’s microbiome is shaped among other factors by exposure to the maternal microbiome and reaches adult diversity around 3 years age. Antibiotics impact the developing microbiome. Earlier studies have shown an association between PIBD and postnatal antibiotic exposure but lack information on prenatal antibiotic exposure and potential confounders. Thus, the primary aim of this study was to determine whether prenatal antibiotic exposure and antibiotics the first 2 years of life are independently associated with subsequent PIBD, before a mature and stabilized gut microbiome is established. Methods: We conducted a nationwide register-based cohort study using data from the Norwegian Patient Registry to identify children with pediatric IBD <18 years born from 2004 to 2012. Dispensed antibiotics were retrieved from the Norwegian Prescription Database, and the Medical Birth Registry of Norway and Statistics Norway contributed with potential confounding factors. The unique personal ID number given to all new-born in Norway was used to connect the registers. All children were followed until December 31, 2020. We analyzed whether use of pre- and postnatal antibiotics until 2 years of age were associated with subsequent IBD by logistic regression adjusted for potential confounders. Results: The study-population included 536,821 children; 758 were classified as PIBD cases distributed as: 403 (53%) Crohn`s Disease, 243 (32%) Ulcerative Colitis and 112 (15%). IBD Unclassified. The IBD cases included 423 boys and 335 girls with a male predominance among the CD cases (2.2: 1). In the main analysis, sex-adjusted odds ratio (aOR) for developing IBD when exposed to antibiotics before 2 years of age compared to no exposure was 1.40 (95% CI: 1.21-1.61). After adjustment for prenatal antibiotic exposure the aOR was 1.39 (95% 1.20-1.59). Further adjustments for potential confounders as mode of delivery, preeclampsia, birthweight and gestational age, season of birth and maternal age, education, smoking, and parity did not change the OR estimates more than +/- 0.01. We found the strongest association for ≥2 courses of antibiotic exposures (aOR 2.14 (95% 1.34-3.43) and for broad-spectrum AB (aOR 2.36 95%CI: 1.45-3.83) compared to no exposure. This association was driven by the CD cases (aOR 1.59 with 95%CI: 1.31-1.94 P<0.01) while no significant association to antibiotic exposure was observed for the UC cases (aOR 1.12 95%CI: 0.87-1.44 P=0.89). Antibiotic exposure during the last trimester was associated with offspring PIBD (aOR 1.23 95%CI: 1.01-1.51), but this association was borderline significant after adjustment for postnatal antibiotic exposure (P = 0.07). Conclusion(s): In a nation-wide, register-based study from Norway, children exposed to antibiotics before 2 years of age were 1.4 -fold more likely to develop IBD before the age 18 years than controls. This association was found for CD only and was robust to adjustments for prenatal antibiotic exposures and other potential confounders.