(181) Acid Suppressive Medication and The Incidence of Chronic Childhood Immunological Diseases: A Scoping Review

Publication Number: 1226

Background: Acid suppressive drugs are used widely in pregnancy and early childhood, but their long-term safety remain unclear. Acid suppressive drugs disrupt the microbiome, and growing evidence links microbiome disruption to the development of immune-mediated disease.

Objectives: To characterize the literature on prenatal and childhood exposure to proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) and incident pediatric allergic or autoimmune diseases.

Methods: In this scoping review, we searched PubMed, Scopus, and Web of Science to identify relevant studies from 2001-2020 written in English. Eligible studies included prenatal or childhood exposure to PPIs and/or H2RAs and the risk of new pediatric immunologic disease diagnosis in humans. Two authors independently screened studies, first by title/abstract screen and second by full-text review; discrepancies were reconciled by consensus. One author abstracted descriptive meta-data and summary results; data were confirmed by a second author.

Results: Of 2,458 citations screened, 20 papers were eligible for inclusion. Most published studies (17) were from Europe or the USA. Cohort studies were most common (11), followed by case-control (4), case-crossover (2), systematic reviews (2), and cross-sectional (1). Median sample size was 11,277 (3,452, 154,237). Most studies (16) were performed within electronic databases; 3 studies’ data were self-reported. Overall, 18 papers reported on both PPI and H2RA use, 2 on PPIs, and none solely on H2RAs; the majority (13) examined prenatal exposure, 7 examined childhood exposure, and 1 both. Most papers (16) focused on allergic outcomes (most commonly asthma or atopic dermatitis); 4 studies examined gastrointestinal diseases (eosinophilic esophagitis or inflammatory bowel disease). In all but 1 study, positive associations were reported between prenatal or early childhood exposure to PPIs and/or H2RA and incident pediatric immunologic diseases; a dose-response relationship was tested and present in just 2 studies. Commonly reported limitations were unmeasured confounding, including confounding by indication, and protopathic bias.

Conclusions: Most studies identified in this scoping review reported positive associations between prenatal or early childhood exposure to acid suppressive drugs and incident pediatric immunologic diseases, particularly asthma and other allergic diseases. Few studies have examined autoimmune disease outcomes, and concerns for residual confounding were common. Further research will help clarify the nature and magnitude of immunologic risks from early exposure to acid suppressive drugs, to inform shared decision-making and clinical guidelines on PPI/H2RA usage during pregnancy and early childhood.