Current Pharmacological Management of Gastro-Esophageal Reflux in Children

Abstract

Gastro-esophageal reflux (GER) is a common phenomenon, characterized by the regurgitation of the gastric contents into the esophagus. Gastro-esophageal reflux disease (GERD) is the term applied when GER is associated with sequelae or faltering growth. The main aims of treatment are to alleviate symptoms, promote normal growth, and prevent complications. Medical treatments for children include (i) altering the viscosity of the feeds with alginates; (ii) altering the gastric pH with antacids, histamine H(2) receptor antagonists, and proton pump inhibitors; and (iii) altering the motility of the gut with prokinetics, such as metoclopramide and domperidone. Our aim was to systematically review the evidence base for the medical treatment of gastro-oesophageal reflux in children. We searched PubMed, AdisOnline, MEDLINE, and EMBASE, and then manually searched reviews from the past 5 years using the key words 'gastro-esophageal' (or 'gastroesophageal'), 'reflux', 'esophagitis', and 'child$' (or 'infant') and 'drug$' or 'therapy'. Articles included were in English and had an abstract. We used the levels of evidence adopted by the Centre for Evidence-Based Medicine in Oxford to assess the studies for all reported outcomes that were meaningful to clinicians making decisions about treatment. This included the impact of clinical symptoms, pH study profile, and esophageal appearance at endoscopy. Five hundred and eight articles were reviewed, of which 56 papers were original, relevant clinical trials. These were assessed further. Many of the studies considered had significant methodological flaws, although based on available evidence the following statements can be made. For infant GERD, ranitidine and omeprazole and probably lansoprazole are safe and effective medications, which promote symptomatic relief, and endoscopic and histological healing of esophagitis. Gaviscon(R) Infant sachets are safe and can improve symptoms of reflux. There is less evidence to support the use of domperidone or metoclopramide. More evidence is needed before other anti-reflux medications can be recommended. For older children, acid suppression is the mainstay of treatment. The largest evidence base supports the early use of H(2) receptor antagonists or proton pump inhibitors.

Esophageal impedance baselines in infants before and after placebo and proton pump inhibitor therapy

“…PPI therapy is proven effective for healing esophagitis in adults (13)(14)(15), for reducing acid exposure in infants (16)(17)(18) and is suggested to heal erosive esophagitis in 89% of children (19). However PPIs have not been proven to relieve symptoms of GERD in infants (20)(21)(22).…”

Question 1: Does the use of ranitidine increase the risk of NEC in preterm infants?

“…A meta-analysis by Tighe et al reported that ranitidine and omeprazole are safe and effective medications which promote symptomatic relief and histological evidence of benefit in infant with GERD 11. However no similar studies have been conducted in preterm babies.…”

Drugs Acting on the Gut: Prokinetics, Antispasmodics, Laxatives

“…The most commonly reported adverse event was diarrhea. Two systematic reviews of pediatric GERD treatments did not recommend the use of domperidone in this patient population due to lack of data showing its ef fi cacy [ 7,8 ] . Oral domperidone in neonates is associated with prolonged QTc interval in patients ³ 32 weeks of gestation [ 9 ] .…”