PPI Use Raises Risk of Infections in Pediatric Population: JAMA

Proton pump inhibitor use surged the risk of serious infections among young children. The infections of the digestive tract, ENT sphere, lower respiratory tract, kidneys or urinary tract, and nervous system infections with both bacterial and viral infections have increased with the use of proton pump inhibitors. 

The study was published in the JAMA Pediatrics on August 14, 2023. 

Proton pump inhibitors (PPIs) effectively reduce gastric acid secretion and are one of the main treatments for gastroesophageal reflux disease (GERD). Uncomplicated gastroesophageal reflux like the physiological process of spitting up in infants that resolves spontaneously does not require PPIs. PPIs may alter the microbiota of the gut or act directly on the immune system leading to infections. As there is limited research on the association between PPIs and infections, researchers from France conducted a nationwide study to assess the associations between PPI use and serious infections in children, overall, and by infection site and pathogen. 

Based on the Mother-Child EPI-MERES Register built from the French Health Data System (SNDS), the study was carried out by including all children born between January 1, 2010, and December 31, 2018, who received treatments like PPIs, histamine 2 receptor antagonists, or antacids/alginate for gastroesophageal reflux disease or other gastric acid–related disorders. Children were followed up from the index date which was the first date of dispersion of any of these medications until admission to the hospital for serious infection, loss of follow-up, death, or December 31, 2019. 

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 healthcare utilization. 

Findings: 

• The study population comprised 12,62,424 children, including 6,06,645 who received PPI (323 852 male [53.4%]; median [IQR] age at index date, 88 [44-282] days) and 655 779 who did not receive PPI (342 454 male [52.2%]; median [IQR] age, 82 [44-172] days).
• The median [IQR] follow-up, was 3.8 [1.8-6.2] years. 
• PPI exposure was associated with an increased risk of overall serious infections.
• Increased risks were also observed for infections in the digestive tract; ear, nose, and throat sphere; lower respiratory tract; kidneys or urinary tract; and nervous system and for both bacterial and viral infections. 

Thus, this is the first study that investigated the risk of infections associated with PPIs in young children for various sites and pathogens even with and without a history of severe prematurity or chronic illness. Further research is needed to investigate the dose, duration, and persistence of risk after treatment withdrawal. 

Further reading: Lassalle M, Zureik M, Dray-Spira R. Proton Pump Inhibitor Use and Risk of Serious Infections in Young Children. JAMA Pediatr. Published online August 14, 2023. doi:10.1001/jamapediatrics.2023.2900