Proton Pump Inhibitor Use and Risk of Serious Infections in Young Children

Abstract

Importance: Proton pump inhibitor (PPI) use may lead to infections through alteration of the microbiota or direct action on the immune system. However, only a few studies were conducted in children, with conflicting results. Objective: To assess the associations between PPI use and serious infections in children, overall and by infection site and pathogen. Design, Setting, and Participants: This nationwide cohort study was based on the Mother-Child EPI-MERES Register built from the French Health Data System (SNDS). We included all children born between January 1, 2010, and December 31, 2018, who received a treatment for gastroesophageal reflux disease or other gastric acid-related disorders, namely PPIs, histamine 2 receptor antagonists, or antacids/alginate. The index date was defined as the first date any of these medications was dispensed. Children were followed up until admission to the hospital for serious infection, loss of follow-up, death, or December 31, 2019. Exposure: PPI exposure over time. Main Outcomes and Measures: Associations between serious infections and PPI use were estimated by adjusted hazard ratios (aHRs) and 95% CIs using Cox models. PPI use was introduced as time-varying. A 30-day lag was applied to minimize reverse causality. Models were adjusted for sociodemographic data, pregnancy characteristics, child comorbidities, and health care utilization. Results: The study population comprised 1262424 children (median [IQR] follow-up, 3.8 [1.8-6.2] years), including 606645 who received PPI (323852 male [53.4%]; median [IQR] age at index date, 88 [44-282] days) and 655779 who did not receive PPI (342454 male [52.2%]; median [IQR] age, 82 [44-172] days). PPI exposure was associated with an increased risk of serious infections overall (aHR, 1.34; 95% CI, 1.32-1.36). Increased risks were also observed for infections in the digestive tract (aHR, 1.52; 95% CI, 1.48-1.55); ear, nose, and throat sphere (aHR, 1.47; 95% CI, 1.41-1.52); lower respiratory tract (aHR, 1.22; 95% CI, 1.19-1.25); kidneys or urinary tract (aHR, 1.20; 95% CI, 1.15-1.25); and nervous system (aHR, 1.31; 95% CI, 1.11-1.54) and for both bacterial (aHR, 1.56; 95% CI, 1.50-1.63) and viral infections (aHR, 1.30; 95% CI, 1.28-1.33). Conclusions and Relevance: In this study, PPI use was associated with increased risks of serious infections in young children. Proton pump inhibitors should not be used without a clear indication in this population..