NEW YORK (Reuters Health) - There is little high-quality evidence to support the efficacy and safety of histamine-2 receptor antagonists (H2RAs) for pediatric gastroesophageal reflux disease (GERD), researchers said today.
With studies published to date, it's hard to draw any conclusions regarding the efficacy and safety of H2RAs in pediatric GERD, Dr. Rachel van der Pol and colleagues from the Academic Medical Center in Amsterdam conclude in an August 18 online paper in JAMA Pediatrics.
GERD is relatively common in infants and children, affecting as much as 3.3% of the pediatric population. Yet clinicians "still struggle with the management of GERD," note the co-authors of a linked commentary.
"With a growing body of literature that illustrates a lack of efficacy and alarming adverse effects, there is increasing reason to limit the empirical use of acid suppression therapy in children," write Dr. Alexandra Menchise and Dr. Mitchell Cohen of Cincinnati Children's Hospital Medical Center in Ohio.
Dr. van der Pol and colleagues did a systematic review of eight randomized controlled trials of H2RAs involving 276 infants and children age 0 to 15 years with GERD. Ranitidine was investigated in three studies, cimetidine in two studies, famotidine in two studies and nizatidine in one study.
Overall, HR2As were more effective than placebo in reducing signs and symptoms of GERD in terms of histologic healing and increasing gastric pH and had a "larger overall treatment effect," the team reports.
Few of the studies reported results for infants and children separately. In those that did, 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 one study. Comparing H2RAs with proton pump inhibitors, there were no significant differences in any of the outcome measures.
The reviewers caution, however, that the quality of the available evidence is "very low owing to the high risk of bias, small sample sizes, and the clinical heterogeneity of the studies. Therefore, positive results regarding the efficacy of H2RAs should be interpreted with caution."
As is the case for efficacy, they found it hard to draw firm conclusions on safety because safety data in the reviewed studies were not quantitatively reported. Although generally safe, H2RAs have been associated with necrotizing enterocolitis, community-acquired pneumonia, and gastrointestinal infections, Dr. van der Pol and colleagues point out.
"We know that H2RAs decrease acid secretion by inhibiting histamine-2 receptors on gastric parietal cells and that H2RAs can cause irritability, headache, somnolence, and other adverse effects," Dr. Menchise and Dr. Cohen add in their editorial.
They say evidence supporting the effectiveness of H2RAs and PPIs in raising gastric pH is "undoubtedly strong but evidence supporting the efficacy for symptom treatment is not."
They add, "Emerging data suggest acid reduction carries increased risk of both respiratory and gastrointestinal infections in children, possibly related to a change in microbiome. According to the Hippocratic Oath, it is our duty as physicians to prescribe regimens for the good of our patients and to do no harm. It is becoming clearer that in many circumstances, prescribing acid-reducing medication in infants is doing no good and increasing the risk of harm."
Dr. van der Pol and colleagues say it is "startling that in a disorder as common as pediatric GERD, pharmacological therapy lacks a firm scientific base for its efficacy and safety."
"Considering the previously reported safety issues in newborns, H2RAs should be prescribed with great caution and only if acid-induced GERD has been confirmed," they conclude.
A related paper in JAMA Pediatrics today suggests a mechanism behind the link between acid suppression therapy and increased risk of upper and lower respiratory tract infections: changes in gastric and lung microflora brought on by acid suppression.
This cross-sectional study included 48 children on acid-suppression therapy and 51 children not on acid-suppression therapy.
Dr. Rachel Rosen of Boston Children's Hospital and colleagues found that 46% of children on acid suppression had gastric bacterial overgrowth compared with 18% of untreated children (p=0.003). Streptococcus, Veillonella, Dermabacter and Rothia were all more common in the gastric fluid of treated children. The researchers also observed changes in lung microflora with acid suppression.
While further study is needed, Dr. Rosen and colleagues say acid suppression therapy "may need to be limited in patient at risk for infections."
SOURCE: http://bit.ly/1v9ExTE, http://bit.ly/1yShk8M and http://bit.ly/1AsONsX
JAMA Pediatr 2014.
Reuters Health Information © 2014
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