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A Review of Histamine-2 Receptor Antagonist and Proton Pump Inhibitor Therapy for Gastroesophageal Reflux Disease in Neonates and Infants

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Abstract

Proton pump inhibitors (PPI) and histamine-2 receptor antagonists (H2RA) are commonly used medications in neonates and infants for the treatment of gastroesophageal reflux disease (GERD), especially in neonatal intensive care units (NICUs). A literature review was conducted to evaluate the efficacy and safety of histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) in preterm neonates, term neonates, and infants. A total of 27 studies were included in this review. Antacid medications in studies have consistently shown positive pharmacodynamic effects, including increasing gastric pH, reducing the reflux index, and reducing the number of acidic reflux events. The benefit found in placebo-controlled trials are limited exclusively to these surrogate outcomes. The actual clinically salient outcomes which H2RAs and PPIs are used for, such as reduction in GERD symptoms, especially irritability and improved feed tolerance and weight gain, have consistently shown no clinical benefit. H2RAs and PPIs appear to be extremely well tolerated by the neonatal and infant populations, which would mimic our experience with these medications in our unit. The available data from large, retrospective cohort and case-control studies paint a much more concerning picture regarding the potential for an increased risk in the development of allergies, anaphylactic reactions, necrotizing enterocolitis (NEC), other nosocomial infections, and lower respiratory tract infections. Given the risks associated with and lack of clinical effectiveness of both H2RAs and PPIs, use of these medications should be limited to specific clinical situations. Further studies are required to determine whether antacid pharmacologic therapy might benefit certain neonates and infants, such as those with complex medical issues.

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  1. BC Children’s and Women’s Hospital, Pharmacy, Vancouver, BC, Canada

    Jason Tan, Sonia Jeffries & Roxane Carr

  2. University of British Columbia, Faculty of Pharmaceutical Sciences, Vancouver, BC, Canada

    Jason Tan & Roxane Carr

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Tan, J., Jeffries, S. & Carr, R. A Review of Histamine-2 Receptor Antagonist and Proton Pump Inhibitor Therapy for Gastroesophageal Reflux Disease in Neonates and Infants. Pediatr Drugs 25, 557–576 (2023). https://doi.org/10.1007/s40272-023-00580-z

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