Acid-suppressive medication and incidence of chronic childhood immune-mediated diseases: A scoping review

Abstract

Background: Use of acid-suppressive medications (ASMs), for example, proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs), has been rising along with the incidence of pediatric immune-mediated diseases (IMDs). We conducted a scoping review to characterize the literature about prenatal or pediatric exposure to ASMs in relation to incident pediatric IMDs.

Methods: Electronic searches were conducted to identify studies from 2001 to 2023 on (a) prenatal or pediatric exposure to PPIs and/or H2RAs and (b) the risk of developing chronic IMDs during childhood. Eligible studies after title/abstract and full-text screening underwent data abstraction.

Results: Of 26 eligible studies, 11 focused on prenatal ASM exposure and 16 on pediatric exposure. Asthma was the most commonly investigated outcome (16 studies), followed by other allergic diseases (8), eosinophilic esophagitis (3), inflammatory bowel disease (2), and other autoimmune diseases (2). Positive associations between ASM exposure and pediatric IMD outcomes emerged in all but two recent studies, which reported null or negative associations with allergic diseases. The strength of associations was similar across exposure times (prenatal/pediatric), medications (PPIs/H2RAs), and outcomes. Dose-response relationships were often present (7/11 studies). Reported effects by trimester and age of exposure varied. Commonly reported limitations were residual confounding, exposure misclassification, and outcome misclassification.

Conclusion: In summary, prenatal or pediatric exposure to PPIs and/or H2RAs has frequently, but not exclusively, been associated with the development of asthma, other allergic diseases, and chronic gastrointestinal IMDs. However, concerns remain about confounding and other sources of bias. Prescribers and families should be aware of these possible risks of ASMs.

Keywords: allergic rhinitis; asthma; child; eosinophilic esophagitis; histamine H2 antagonists; immune system diseases; infant; inflammatory bowel disease; pregnancy; proton pump inhibitors.

Figure 1:

PRISMA-ScR Flow Chart; depicting the flow of data through phases of the review. Note that Robinson et al’s prospective cohort study was replaced with an updated analysis after the second literature search.