Table 9.

Key evidence summary of AST-associated side effects in children

Potential risk	Evidence summary
Dysbiosis	PPIs alter the microbiome in the oral cavity, gut, and lungs, leading to adverse outcomes such as necrotizing enterocolitis, late-onset sepsis in premature infants, CDI, asthma, obesity, and SIBO134
CDI	In a population-based, nested case-control study, PPIs had significantly higher odds (OR, 21.5) of CDI in pediatric patients as compared with H2RAs (OR, 2.64)135 PPI use is an independent risk factor for severe CDI in children136
Serious infections in children	A nationwide cohort study carried out on over 1.2 million children demonstrated a 34% increased risk of serious infections in children on PPI therapy137 Elevated risk of infection was observed throughout the body, including the GI tract, ear, nose, throat, lower respiratory tract, urinary tract, and nervous system137 Both bacterial and viral infections were more common in children receiving PPIs137
Hospitalization in children with oropharyngeal dysphagia	In a retrospective cohort study, the use of PPIs in pediatric patients suffering from oropharyngeal dysphagia with evidence of aspiration was associated with an increased risk of hospitalization (IRR, 1.77) and longer hospital stay (IRR, 2.51)138
HA-AKI	In a multicenter retrospective cohort study involving 42,232 hospitalized children, PPI use showed a significantly higher risk of HA-AKI compared with nonusers and H2RAs, with odds ratios of 1.37 and 1.24, respectively91
Fracture	A retrospective cohort analysis showed that early exposure to AST is associated with an increased risk of childhood fractures, with a higher risk associated with PPIs (HR, 1.23) than H2RAs (1.04)139 A nationwide cohort study including 115,933 pairs of children demonstrated that PPI use is linked to a slightly elevated risk of fracture of varying types (HR, 1.1)140
Asthma	A nationwide cohort study that included 80,870 pairs of children and adolescents showed that those on PPI therapy had a significantly higher incidence rate of asthma (HR, 1.57)141

AST, acid suppression therapy; CDI, Clostridium difficile infection; GI, gastrointestinal; H2RA, H2-receptor antagonist; HA-AKI, hospital-acquired acute kidney injury; HR, hazard ratio; IRR, incidence rate ratio; PPI, proton pump inhibitor; SIBO, small intestine bacterial overgrowth