Is it GERD or typical spit up? PPI use in young children may increase risk of serious infections

Proton pump inhibitors (PPIs) are one of the main treatments for gastroesophageal reflux disease (GERD), as they effectively reduce gastric acid secretion. In infants, it is often difficult to distinguish between GERD and uncomplicated gastroesophageal reflux (spitting up). Gastroesophageal reflux affects up to 70% of infants aged three to four months and resolves spontaneously by 12 months. Uncomplicated gastroesophageal reflux does not require PPI treatment. PPI use is growing among young children in most high-income countries. For example, in France, 6.1% of children younger than two years of age used PPIs in 2019, compared to 3.6% in 2010. PPIs have been associated with various adverse effects, including bone fractures, acute kidney injury, allergy, asthma and inflammatory bowel diseases in children. They have also been suspected of leading to infections through pH modification or a direct action on the immune system. Data on the risk of PPI-related infections in young children are scarce. To examine this issue, a nationwide cohort study in France investigated the association between PPI use and serious infections in young children. The study used data from the Mother-Child EPI-MERES Register built from the French Health Data System. All children born during 2010 through 2018 who received a medication (PPI, histamine-2 receptor antagonist or antacid/alginate) for GERD or other gastric acid-related disorder were included in the study. Children were followed up until hospital admission for serious infection, loss of follow-up or death, or until the end of 2019, whichever came first. The main outcome was the first occurrence of any serious infection requiring hospitalization. Serious infections were classified according to body site (digestive tract; ear, nose and throat; lower respiratory tract; kidneys or urinary tract; skin; musculoskeletal system; and nervous system) and by pathogen (viral or bacterial). Results showed the following: The study included 1,262,424 children (median follow-up of 3.8 years). Of these children, 606,645 received a PPI (53.4% male; median age at index date, 88 days). Another 655,779 children did not receive a PPI (52.2% male; median age at index date, 82 days). PPI exposure was associated with an increased risk of serious infections overall (adjusted hazard ratio [aHR], 1.34; 95% CI, 1.32–1.36). Increased risks were also seen for digestive tract infections (aHR, 1.52; 95% CI, 1.48–1.55); ear, nose and throat infections (aHR, 1.47; 95% CI, 1.41–1.52); lower respiratory tract infections (aHR, 1.22; 95% CI, 1.19–1.25); kidney or urinary tract infections (aHR, 1.20; 95% CI, 1.15–1.25); and nervous system infections (aHR, 1.31; 95% CI, 1.11–1.54). PPI use was associated with increased risks for both bacterial infections (aHR, 1.56; 95% CI, 1.50–1.63) and viral infections (aHR, 1.30; 95% CI, 1.28–1.33). The authors comment that to their knowledge, this is the first study investigating the risk of serious infections associated with PPI use in young children that included an assessment of infection at various body sites. In their study, PPI use was associated with an increased risk of serious infections in young children overall. More specifically, PPI use was associated with an increased risk of infections of the digestive tract, ear/nose/throat, lower respiratory tract, kidneys/urinary tract and nervous system. As well, the study found an increased risk for both bacterial and viral infections. The authors caution that PPIs should not be used in the pediatric population without a clear therapeutic indication. Reference 1. Lassalle M, Zureik M, Dray-Spira R. Proton pump inhibitor use and risk of serious infections in young children. JAMA Pediatr 2023. Published online August 14, 2023. (accessed August 17, 2023).

Is it GERD or typical spit up? PPI use in young children may increase risk of serious infections

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