title: Efficacy and safety of histamine-2 receptor antagonists.
abstract: OBJECTIVE
  Histamine-2 receptor antagonists (H2RAs) are frequently used in the treatment of gastroesophageal reflux disease (GERD) in children; however, their efficacy and safety is questionable.
  
  
  OBJECTIVE
  To systematically review the literature to assess the efficacy and safety of H2RAs in pediatric GERD.
  
  
  METHODS
  PubMed, EMBASE, and the Cochrane database were searched for randomized clinical trials investigating the efficacy and safety of H2RAs in pediatric GERD. Two reviewers independently extracted data from the included articles. The quality of the evidence was assessed using the Grades of Recommendations, Assessment, Development, and Evaluation approach. When possible, infants and children were analyzed separately.
  
  
  RESULTS
  Eight studies with a total of 276 children (0-15 years of age) were included. Compared with the placebo, H2RAs were more effective in the reduction of symptoms in terms of histologic healing and increasing gastric pH and had a larger overall treatment effect. In infants, H2RAs were only more effective in terms of histologic healing. Comparing H2RAs with antacids, H2RAs were more effective in symptom reduction in only 1 study. H2RAs compared with proton pump inhibitors were not significantly different in any of the outcome measures. For safety analysis, data were not reported in a quantitative manner and for all outcomes, the quality of evidence was very low.
  
  
  CONCLUSIONS
  Evidence to support the efficacy and safety of H2RAs in infants and children is limited and of poor quality. Well-designed placebo-controlled trials are needed before thorough conclusions can be drawn.
authors.affiliation: Department of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Rachel
authors.initials: R
authors.lastname: van der Pol
authors.affiliation: Dutch Cochrane Centre, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Miranda
authors.initials: M
authors.lastname: Langendam
authors.affiliation: Department of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Marc
authors.initials: M
authors.lastname: Benninga
authors.affiliation: Department of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Michiel
authors.initials: M
authors.lastname: van Wijk
authors.affiliation: Department of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Merit
authors.initials: M
authors.lastname: Tabbers
mesh_terms: D000293:Adolescent; D000863:Antacids / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005764:Gastroesophageal Reflux / Q000188:drug therapy* / Q000473:pathology; D006635:Histamine H2 Antagonists / Q000627:therapeutic use*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007223:Infant; D007231:Infant, Newborn; D054328:Proton Pump Inhibitors / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000863:Antacids; D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors