1. Gaines, Chloe PhD, RN, FNP-BC

Article Content

This article is a summary/review of the below article:


Tighe, M., Afzal, N. A., Bevan, A., Hayen, A., Munro, A., & Beattie, R. M. (2014). Pharmacological treatment of children with gastro-oesophageal reflux. Cochrane Database of Systematic Reviews. Issue 11. Art. No.: CD008550. doi: 10.1002/14651858.CD008550.pub2.



Gastro-esophageal reflux (GER), a common physiological process, is defined as the passage of gastric contents into the esophagus with or without regurgitation and vomiting occurring several times per day in healthy infants, children, and adults. In healthy individuals, most episodes of GER occur after eating and cause few or no symptoms. In contrast, gastro-esophageal reflux disease (GERD) is present when reflux of gastric contents causes troublesome symptoms and/or complications (Vandenplas & Rudolph, 2009).


Reflux episodes occur during transient relaxations of the lower esophageal sphincter (LES) permitting gastric contents to flow into the esophagus. In infants with physiological GER or GERD, common symptoms can include regurgitation, and vomiting, which are usually self-limiting and do not need treatment. Infants with GERD have more troublesome symptoms, such as significant distress, or other sequelae such as weight loss. Children may complain of pain, heartburn, and weight loss.


Infants with physiological GER may benefit from conservative management such as reassurance regarding benign outlook and feeding advice. Pediatric patients with GERD may be offered feed changes, pharmacologic therapy, and surgery. This review summarizes pharmacological treatments of children with gastro-oesophageal reflux which include proton pump inhibitors, H2 antagonists, prokinetics, compound alginate preparations, and antispasmodics.



This Cochrane review aims to provide a robust analysis of currently available pharmacological interventions used to treat children with GER by assessing all outcomes indicating benefit or harm.



The major goals of treatment of children with GER are to alleviate symptoms, promote normal growth and prevent complications. The authors considered and evaluated all randomized controlled trials (RCTs) related to pharmacological agents used for treating GER symptoms. The population included all children (birth to 16 years) with GER associated with troublesome symptoms or complications. The authors also performed analysis based on two groups: infants younger than 12 months of age and children between 12 months and 16 years of age. Two authors searched four databases and the ongoing trials registry. Unpublished studies were hand searched. Studies assessing pharmacological treatments for children with co-existent conditions such as asthma that predispose to GERD were excluded.



The summary of main results was discussed with respect to each class of medications (i.e., proton pump inhibitors, H2 antagonists, prokinetics, compound alginate preparations, and antispasmodics).


Proton pump inhibitors

Moderate evidence, obtained within the limitations of study design as discussed, suggests that PPIs are efficacious, particularly in older children with GERD, and evidence of their efficacy in infants with GERD is weak. Less evidence shows significant improvement in symptoms with increasing doses, but increasing the dose may increase the risk of side effects. The risk of side effects was less prominent for omeprazole and lansoprazole than for pantoprazole. No evidence has been found for the use of PPIs in functional reflux. Further studies assessing the long-term impact/safety profile of PPIs are recommended.


H2 antagonists

With so few RCTs and no appropriate head-to-head comparisons against PPIs, meta-analysis to further investigate the effects of treatment was not possible. Ranitidine appears to be efficacious and safe in children over one year of age; RCTs evaluating the use of ranitidine in infants were not identified. Cimetidine and nizatidine also improved symptoms and signs of GERD in older children and infants. No RCTs evaluated the use of H2 antagonists in functional reflux. Further data are called for, with a recommendation for head-to-head trials against PPIs, given the current high usage of H2 antagonists for GERD.



Evidence for the efficacy of domperidone in GER is very poor in older children, infants and neonates as the result of limitations in study design and length of follow-up and this evidence is too weak to permit recommendations. No evidence of efficacy was identified in children with neurodisability.


Compound alginate preparations

Weak evidence suggests that Gaviscon Infant(R) improves symptoms in infants, including those with functional reflux, but further research is recommended including follow-up to a specified age.



A single study showed improvement in acid reflux and transient lower oesophageal sphincter relaxations in children treated with baclofen, but this was a short-duration (two-hour) trial, and no other studies are available in this group; applicability of this study is difficult, and further double-blind RCTs are recommended to evaluate the effects of baclofen in reducing GER, particularly in children with neurodisability, who are often prescribed baclofen for concomitant spasticity.



The systematic review authors concluded that there is evidence to support the use of PPIs and Gaviscon Infant(R) in infants with GERD; however, further studies are recommended. Studies of omeprazole and lansoprazole in infants with functional GER have demonstrated variable benefit. For older children, there is moderate evidence to support the use of PPIs and some evidence to support the use of H2 antagonists in older children with GERD. Further RCT's are recommended because of a lack of independent placebo-controlled and head-to-head trials. No robust RCT evidence is available to support the use of domperidone, and further studies on prokinetics are recommended, including assessments of erythromycin.


No robust RCT evidence has been found regarding treatment of preterm babies with GER/GERD or children with neurodisabilities. Initiation of RCTs with common endpoints is recommended, given the frequency of treatment and the use of multiple anti-reflux agents in these children.


Implications for Practice

Children often present in primary health care clinics with gastro-oesophageal reflux symptoms and parents seek resolutions to their child's symptoms from the provider. As GER and GERD are diagnosed clinically, the primary care provider must perform a detailed health assessment and provide a management plan which often includes pharmacological treatments for those with GERD.


This is the first systematic review that assesses the medical evidence for commonly prescribed pharmacological treatments of GERD in children and infants using Cochrane methodology. Of the treatments reviewed, there is moderate evidence that PPIs are efficacious in older children with GERD and weak evidence of their efficacy in infants with GERD, but weak evidence of absence of efficacy in infants with GER was found. Some evidence was also found to support the efficacy of H2 antagonists in children with GERD. There is no effective evidence to allow recommendations to support treatment with prokinetics. Weak evidence also suggests that Gavison Infant improves symptoms in infants with functional GER. However, the provider must prescribe with caution because further research of these pharmacological treatments is recommended.




Vandenplas Y., Rudolph C. D. (2009). Pediatric gastroesophageal reflux clinical practice guidelines: Joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). Journal of Pediatric Gastroenterology and Nutrition, 49, 498-547. [Context Link]