Prenatal Exposure to Acid-Suppressive Medications and Incident Risk of Inflammatory Bowel Disease in Children

Importance: Acid-suppressive medications, including proton pump inhibitors (PPIs) and H2 receptor antagonists (H2RAs), are commonly used during pregnancy; however, concerns have emerged about their potential impact on gut and immune development in children. Objective: To examine the association between prenatal exposure to acid-suppressive medications and the risk of inflammatory bowel disease (IBD), including Crohn disease (CD) and ulcerative colitis (UC). Design, Setting, and Participants: This nationwide cohort study assessed mother-child pairs from the National Health Insurance Service of South Korea identified between January 1, 2009, and December 31, 2017, with follow-up through December 31, 2023. Offspring exposed to acid-suppressive medications were matched 1:3 to those who were unexposed. Exposure: Prenatal exposure to 1 or more prescriptions for PPIs or H2RAs. Main outcomes and Measures: Incident risk of IBD, UC, and CD in children. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with corresponding 95% CIs. Subgroup analysis was conducted by medication type, timing of exposure, prescription count, maternal gastrointestinal history, and sibling comparisons (to control for shared familial factors). Results: After 1:3 PS matching, 1 837 916 mother-child pairs were included (mean [SD] maternal age, 32.1 [4.7] years; 913 260 [49.7%] female infants). Prenatal exposure to acid-suppressive medications was associated with an elevated risk of IBD (HR, 1.08; 95% CI, 1.01 to 1.15), with a significant association observed for CD (1.10; 95% CI, 1.02 to 1.19) but not for UC (1.04; 95% CI, 0.93 to 1.17). There was no evidence of difference in absolute risk differences (RD) for IBD (RD, 0.41 per 1000 children; 95% CI, -0.97 to 1.79), CD (RD, 0.51; 95% CI, -0.98 to 2.00), and UC (RD, 0.21; 95% CI, -1.56 to 1.97). In sibling comparison analyses, no significant associations were observed for IBD (HR, 1.06; 95% CI, 0.88-1.27), CD (1.03; 95% CI, 0.84-1.27), or UC (1.10; 95% CI, 0.78-1.55). Conclusions and Relevance: In this cohort study, offspring exposed to acid-suppressive medications during pregnancy with sibling analyses showed no clear association with adverse outcomes. These findings suggest that in clinical settings, the minimal potential risk to the offspring should be carefully balanced against the therapeutic need for acid-suppressive treatment during pregnancy, supporting use when clinically indicated.