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Balancing therapeutic benefits and hidden risks of proton pump inhibitors in pediatric practice: a narrative review and update

Clin Exp Pediatr > Epub ahead of print
DOI: https://doi.org/10.3345/cep.2025.02761    [Epub ahead of print]
Published online February 25, 2026.
Balancing therapeutic benefits and hidden risks of proton pump inhibitors in pediatric practice: a narrative review and update
Maria Rogalidou  , Alexandra Papadopoulou 
Division of Gastroenterology & Hepatology, First Pediatrics Department, National and Kapodistrian University of Athens, “Agia Sofia” Children’s Hospital, Athens, Greece
Correspondence: 
Maria Rogalidou, Email: rogalidoum@yahoo.com
Received: 20 November 2025   • Revised: 28 December 2025   • Accepted: 30 December 2025
Abstract
Proton pump inhibitors (PPIs) are drugs whose main effect is catalytic and long-lasting suppression of gastric acid secretion, with an anti-inflammatory effect. The main indications for PPIs use include the treatment of gastroesophageal reflux disease, peptic ulcer disease, functional dyspepsia, Barrett esophagus, eosinophilic esophagitis, and hypersecretory diseases such as gastrinoma and Zollinger-Ellison syndrome. Their contribution to eradication therapy for Helicobacter pylori is also important. However, the long-term use of PPIs has been associated with various adverse drug reactions and complications, such as the development of fundic gland polyposis, atrophic gastritis, gastric cancer, vitamin B12 deficiency, hypomagnesemia, osteoporosis/ fractures, changes in the microbiome, increased risk of infection, necrotizing enterocolitis, renal injury, and other conditions. Thus, administration of PPIs should be based on scientific evidence of their efficacy and safety. Their long-term administration should be cautious, and continuation reassessed frequently. Caution should be exercised when administering PPIs to neonates and infants. This narrative review and update aims to summarize and critically evaluate the current evidence, based on the most recent clinical guidelines, regarding the use of PPIs in children, with a focus on their indications, efficacy, safety, and limitations.
Key Words: Proton pump inhibitors, Gastroesophageal reflux disease, Indications in childhood, Adverse drug reactions, Side effects


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