Proton pump inhibitors have been increasingly used in young children, but they may increase the risk of infection, either by alteration of the gastric microbiota or direct action on the immune system. A nationwide cohort study was undertaken to investigate the association between proton pump inhibitor use and serious infections in young children.

The study population included all children identified from a national health registry born between 2010 and 2018 who received first-time treatment for gastroesophageal reflux disease or other gastric acid-related disorders. Treatment was with proton pump inhibitors, histamine 2 receptor antagonists, or antacids or alginate. Follow-up began at the index date (the first date the medication was dispensed) and continued to whichever came first: occurrence of serious infection, loss to follow-up, death, or December 2019.

Of the total study population of 1,262,424 children, 606,645 received proton pump inhibitors. Proton pump inhibitor exposure over time was associated with an increased risk of serious infections overall and at specific sites, including the digestive tract; lower respiratory tract; kidneys or urinary tract; musculoskeletal system; nervous system; and ear, nose, and throat sphere. Proton pump inhibitor exposure over time was associated with higher risks of both bacterial and viral infections. Children with and without a history of severe prematurity or chronic illness were at increased risk for infection as a result of proton pump inhibitor exposure. The risk of infection gradually decreased after discontinuation of proton pump inhibitors but remained elevated for several months.

The authors note several limitations of the study, including that the national registry didn't provide information about the indication for treatment, breastfeeding or social interactions, and the use of proton pump inhibitors over the counter or while children were hospitalized.