ABSTRACT
BACKGROUND: Recent studies suggest that the use of acid suppressants in early childhood may increase the risk of allergic diseases. OBJECTIVE: To systematically review and synthesize associations between the childhood use of acid suppressants and development of allergic diseases. METHODS: PubMed, Embase, The Cochrane Library, and Scopus were searched using a systematic search strategy. We included observational or interventional studies that looked at the use of acid suppressants in the pediatric population, in association with allergic outcomes such as asthma, atopic dermatitis, allergic rhinitis, allergic conjunctivitis, and food allergies. Key data were extracted and risk of bias was evaluated according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and a PROSPERO-registered protocol. Maximally adjusted estimates were pooled using mixed-effects models, and heterogeneity was measured using I2. Further subgroup and sensitivity analyses were conducted. Overall quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations framework. RESULTS: This review included 5 observational studies from 1977 records with low-to-moderate risk of bias. Childhood acid-suppressant use was associated with significantly increased hazards of asthma (hazard ratio [HR] = 1.44, 95% confidence interval [CI] = 1.31-1.58), atopic dermatitis (HR = 1.12, 95% CI = 1.10-1.14), and allergic rhinitis (HR = 1.40, 95% CI = 1.24-1.58). These associations were adjusted for confounders such as demographics, parental educational level, and use of antibiotics. Overall quality of evidence was low. CONCLUSIONS: Childhood use of acid suppressants may increase the risk of incident asthma, atopic dermatitis, and allergic rhinitis. However, larger studies such as randomized controlled trials are needed to determine causality. These drugs should be used judiciously in pediatric patients, and more stringent guidelines should be advocated.