Proton Pump Inhibitors (PPI), H2 Blocker Use, and Risk of Inflammatory Bowel Disease (IBD) in Children

BACKGROUND

Previous longitudinal and cross-sectional studies have shown that changes in the composition of the gut microbiota are associated with IBD. Thus, it is plausible that drugs that alter the microbiome may increase the risk of future IBD. Previous studies have examined the association of Proton Pump Inhibitors (PPIs) and H2-receptor antagonists (H2 blockers) with changes in the microbiome. Some evidence suggests that use of PPIs and H2 blockers may provoke disease flares in individuals with established IBD; however, no studies have investigated the relationship of PPIs and H2 blockers with risk of developing IBD in children. The objective of this study was to determine the relation between PPI and H2 blocker use and pediatric-onset IBD.

METHODS

We conducted a nested case-control study of 285 Kaiser Permanente Northern California members, age ≤21 years who were diagnosed with IBD from 1996 to 2016. We used data from the electronic health record to identify cases and controls from inpatient and outpatient data. Four controls were matched to each case on age, race, and membership status at the case’s index date. Both cases and controls had at least five years of continuous membership prior to the index date. Disease risk scores (DRS) were computed for each subject. Odds ratios (RR) and 95% confidence intervals were calculated using conditional logistic regression models adjusted for DRS.

RESULTS

The mean age of the children was 15.1 ± 2.6 years and 49.5% were female. During the study period, 6 cases and 6 controls were prescribed PPIs and 10 cases and 28 controls were prescribed H2 blockers (5 children were prescribed both). The odds ratios for the association of receipt of at least one prescription of PPI or H2 blocker with risk of subsequent IBD was 3.6 (95% CI 1.1 to 11.7) for PPIs and 1.6 (95% CI 0.7 to 3.7) for H2 blockers.

CONCLUSION

There appears to be a considerable difference in risk associated with PPIs compared to H2 blockers. Many of the children in this study did not have symptoms consistent with FDA-approved indications for PPI use, highlighting need for appropriate prescribing patterns. These findings have implications for clinical treatment of children with gastrointestinal symptoms and warrants further investigation in a larger cohort. This study adds to the growing body of evidence for prudent use of PPIs by providing evidence of an association between childhood use of PPIs and future IBD diagnoses.