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Proton pump inhibitors (PPIs) are ineffective in reducing gastroesophageal reflux disease (GERD) symptoms in infants, and placebo-controlled trials in older children are lacking, according to the results of a systematic review reported online April 4 and will appear in the May print issue of Pediatrics.

"Use of ...PPIs for the treatment of ...GERD in children has increased enormously," write Rachel J. van der Pol, MD, from the Department of Pediatric Gastroenterology and Nutrition at Emma Children's Hospital AMC in Amsterdam, the Netherlands, and colleagues. "However, effectiveness and safety of PPIs for pediatric GERD are under debate."

The investigators searched PubMed, EMBASE, and the Cochrane Database of Systematic Reviews for studies of PPIs in children aged 0 to 18 years with GERD. Inclusion criteria were randomized controlled trials and crossover studies investigating the efficacy and safety of PPIs, with reported outcomes including reduction in GERD symptoms, gastric pH, histologic abnormalities, and adverse events.

Data from children aged 0 to 17 years were included from 12 identified studies. For reduction of GERD symptoms among infants, PPIs were more effective in 1 study (vs hydrolyzed formula), ineffective in 2 studies, and equally effective in 2 studies (vs placebo). Compared with alginates, ranitidine, or a different PPI dosage, PPIs were equally effective for children and adolescents.

In 4 studies reporting on gastric acidity, PPIs were more effective in infants and children than placebo, alginates, or ranitidine. Three studies showed that PPIs were comparable to ranitidine or alginates for reducing histologic abnormalities. Six studies showed no differences in treatment-related adverse events for PPIs vs placebo or a different PPI dosage.

"PPIs are not effective in reducing GERD symptoms in infants," the review authors write. "Placebo-controlled trials in older children are lacking. Although PPIs seem to be well tolerated during short-term use, evidence supporting the safety of PPIs is lacking."

Limitations of this review include statistical and clinical heterogeneity of the included studies, precluding a pooled analysis with a fixed- or random-effect model. Also, there were few well-designed randomized, placebo-controlled trials with high methodologic quality, and sample sizes were often small.

"[P]hysicians should be careful when prescribing PPIs, medications that are not approved for infants and have potential adverse effects, unless there is documented disease or with careful monitoring," the review authors write.

"Large, well-designed, placebo-controlled, randomized trials with well-chosen end points are necessary to evaluate the effect and safety of PPIs in the entire pediatric age range. Furthermore, we recommend more pathophysiological research on symptom genesis to be able to clearly define homogeneous patient groups and to enable the development of a therapy to tackle this growing health care problem."

Two of the study authors have disclosed various financial relationships with AstraZeneca. The other study authors have disclosed no relevant financial relationships.

Pediatrics. Published onine April 4, 2011. Abstract

Related Link
The Children's Digestive Health and Nutrition Foundation provides information about GERD in Infants on their Web site along with links for downloadable parent guides in English and Spanish.

Clinical Context

In North America, 12.3% of infants and 1% of other pediatric age groups are diagnosed with GERD. Symptoms of GERD are usually nonspecific and may vary from regurgitation to excessive crying and respiratory tract symptoms. For mild infant GERD, treatment entails parental guidance and education combined with feed thickeners and/or positioning therapy. In older children and adolescents, dietary and behavioral changes frequently reduce symptoms significantly. Treatment with pharmacotherapy consists of antisecretory agents and PPIs. Use of PPIs for the treatment of GERD in children has increased enormously. However, the effectiveness and safety of PPIs for pediatric GERD are under debate.

The aim of this systematic review was to determine the effectiveness and safety of PPIs in children with GERD.

Study Highlights

• The authors performed a search in PubMed, EMBASE, and the Cochrane Database of Systematic Reviews for randomized controlled trials and crossover studies investigating the efficacy and safety of PPIs in children aged 0 to 18 years with GERD for reduction in GERD symptoms, gastric pH, histologic aberrations, and reported adverse events.
• 2 reviewers independently screened all abstracts of identified systematic reviews for eligibility.
• 12 studies from Europe, Australia, and North America were included, with data from 895 children aged 0 to 17 years. 10 studies were randomized controlled trials, and 2 were crossover trials.
• The reviewers initially agreed on 85.8% of the quality items. However, because of the heterogeneity among the included studies regarding the participants, interventions, and outcome measures, a meta-analysis was not possible.
• Results demonstrated that for infants, PPIs were more effective in 1 study (vs hydrolyzed formula), was not effective in 2 studies, and was equally effective in 2 studies (vs placebo) for the reduction of GERD symptoms.
• For children and adolescents, PPIs were equally effective (vs alginates, ranitidine, or a different PPI dosage).
• For gastric acidity, in infants and children, PPIs were more effective (vs placebo, alginates, or ranitidine) in 4 studies.
• For reduction of histologic aberrations, PPIs showed no difference (vs ranitidine or alginates) in 3 studies.
• Adverse effects tend to be of mild to moderate nature; headache is the most frequently reported treatment-related adverse event. 6 studies reported no differences in treatment-related adverse events (vs placebo or a different PPI dosage).

Clinical Implications

• For mild infant GERD, treatment entails parental guidance and education combined with feed thickeners and/or positioning therapy. In older children and adolescents, dietary and behavioral changes frequently reduce symptoms of GERD significantly.
• PPIs are not effective in reducing GERD symptoms in infants. Although PPIs seem to be well tolerated during short-term use, evidence supporting the safety of PPIs is lacking in children and adolescents.

CME Test

1       A 2-month-old boy presents to your office for a routine well-child examination. For the past month, his mother is concerned that he usually vomits after each feed. You suspect the child has mild GERD. All of the following methods are appropriate initial treatment options for this patient except:

①        Parental guidance

②        Pharmacotherapy

③        Feeding thickening

④        Positioning therapy

2       According to this study by van der Pol and colleagues, PPIs were more effective in reducing which of the following conditions?

①        GERD symptoms in infants

②        GERD symptoms in children and adolescents

③        Gastric acidity

④         Histologic aberrations

解答：

1.A 2-month-old boy presents to your office for a routine well-child examination. For the past month, his mother is concerned that he usually vomits after each feed. You suspect the child has mild GERD. All of the following methods are appropriate initial treatment options for this patient except:

Answer: Pharmacotherapy

For mild infant GERD, parental guidance and education combined with feed thickeners and/or positioning will often suffice. Pharmacotherapy may be indicated for infants crying and distressed behavior.

2.According to this study by van der Pol and colleagues, PPIs were more effective in reducing which of the following conditions?

Answer: Gastric acidity

For gastric acidity, in infants and children, PPIs were more effective (vs placebo, alginates, or ranitidine) in 4 studies.