Prenatal and/or childhood acid-suppressive medication use and risk of serious infections in children: A retrospective analysis of Taiwanese medical claims data

Recent studies suggest an increased risk of serious infections associated with proton pump inhibitor (PPI) use in young children, but no study simultaneously examined the impact of acid-suppressive medication (ASM) use during pregnancy and childhood on infection risk in children. This study aimed to investigate the associations between prenatal and/or childhood exposure to ASMs and serious infections in children. A national cohort study was conducted based on the entire medical claims data in Taiwan, comparing prenatal and/or childhood exposure to PPIs or histamine-2 receptor antagonists (H2RAs) with antacid exposure in an active-comparator design. We quantified the risks of hospitalization for overall serious infection and specific infections, including sepsis, acute bronchiolitis or bronchitis, pneumonia, acute gastroenteritis, pyelonephritis, cellulitis or soft-tissue infection, meningitis or encephalitis, and septic arthritis or osteoarthritis, among children with prenatal and/or childhood exposure to PPIs or H2RAs. Adjusted hazard ratios (AHRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazard models. Among 195,377 mother-child pairs prenatally exposed to PPIs or H2RAs (13.39% of the prenatal cohort) and 1,263,741 pairs exposed to antacids, prenatal exposure to PPIs or H2RAs was associated with an increased risk of overall serious infection compared with antacid exposure (AHR: 1.09; 95% CI: 1.06–1.12), as well as specific infections, including sepsis (AHR: 1.21; 95% CI: 1.03–1.12), acute bronchiolitis or bronchitis (AHR: 1.07; 95% CI: 1.03–1.11), pneumonia (AHR: 1.10; 95% CI: 1.04–1.15), acute gastroenteritis (AHR: 1.12; 95% CI: 1.06–1.18), and pyelonephritis (AHR: 1.10; 95% CI: 1.02–1.19). Subgroup analyses demonstrated consistent results for PPI and H2RA exposure when analyzed separately. Childhood exposure to PPIs or H2RAs was also associated with increased risks of serious infections, with the highest risks generally observed among children exposed during both prenatal and childhood periods (AHR 1.12 for overall serious infection; AHR 1.62 for sepsis; AHR 1.29 for acute bronchiolitis or bronchitis; AHR 1.06 for pneumonia; AHR 1.30 for acute gastroenteritis; and AHR 1.24 for pyelonephritis). This nationwide cohort study provides real-world evidence of an association between prenatal and childhood exposure to PPIs or H2RAs and an increased risk of serious infections in children.