Unfortunately, most of the available studies do not make this distinction in their subjects. Also, available data primarily regard formula-fed infants, and are insufficient to make recommendations for breastfed infants. Esophageal pH probe monitoring is the gold standard for measuring reflux in research; however, its correlation with symptoms is questionable and it is infrequently used in clinical practice.3 Therefore, recommendations are focused primarily on treating only clinically-evident reflux (emesis and regurgitation).
Five small RCTs studied the practice of using formula thickeners (TABLES 1 AND 2). In 1 study, formula thickened with rice cereal decreased emesis episodes.4 Two studies of carob bean gum–thickened formula vs plain formula yielded conflicting results.5,6 In the study showing improvement with carob bean gum, the parents were not blinded to the treatment, which may have led to bias favoring the treatment.5 An uncontrolled, comparative trial of carob bean gum vs rice cereal suggested superiority of carob bean gum as a thickener, although both treatments yielded improvement.7 Carob bean gum is available in the UK as a powder (Instant Carobel) but is not widely available in the US.
Three trials studied the effects of other conservative therapies such as positional changes and pacifiers on reflux measured by pH probe; unfortunately, none assessed clinical outcomes such as emesis or regurgitation.3 Reflux by pH probe was worsened in a trial studying the infant seat for positioning. In the trial studying elevating the head of the bed to 30° in the prone position, reflux measured by pH probe was also unchanged; prone positioning is no longer recommended due to the risk of Sudden Infant Death Syndrome (SIDS).8 The trial of pacifier use showed improvement of reflux by pH probe when used in the seated position, but worsening in the prone position. Since pH probe does not necessarily reflect clinical symptoms, the utility of the information from these studies is limited.
Only 1 trial of drugs used to treat infant reflux measured clinical symptoms. This large manufacturer-sponsored RCT found that sodium alginate9 significantly reduced emesis episodes in treated infants. Sodium alginate is marketed in the UK as Gaviscon Infant. While this trial included breastfed infants, it did not report the numbers of breastfed infants in the 2 treatment groups or present data separately for breastfed infants. Small RCTs of metoclopramide10 and omeprazole11 show significant improvement in reflux index measured by pH probe. However, metoclopramide yielded no improvement in symptom counts, and the omeprazole study resulted in no differences in “cry-fuss time” between treatment groups.
Recommendations from others
The North American Society for Pediatric Gastroenterology and Nutrition recommends thickening agents or a trial of hypoallergenic formula for vomiting infants.2 They caution against prone positioning and favor proton pump inhibitors over H2 blockers for symptomatic relief and healing of esophagitis. They found insufficient evidence to recommend surgery over medication.
Clinical Commentary
Lack of age-appropriate RCTs make evidence-based treatment difficult
Alfreda L. Bell, MD
Kelsey-Seybold Clinic, Houston, Tex
Gastroesophageal reflux, defined as the passage of gastric contents into the esophagus, is one of the most common gastroesophageal problems in infants. GERD is a pathological process in infants manifested by poor weight gain, signs of esophagitis, persistent respiratory symptoms or complications, and changes in neurologic behavior. Gastroesophageal reflux generally resolves within the first year of life, as the lower esophageal sphincter mechanism matures. Traditionally, these infants have been managed conservatively with feeding schedule modifications, thickened feeds, changes in positions after feeding, and formula changes. Depending on the history and clinical presentation of an infant with GERD, more detailed evaluation and treatment may be necessary.
As per the North American Society for Pediatric Gastroenterology and Nutrition, if an upper gastrointestinal series has ruled out anatomic causes of gastroesophageal reflux, and nonpharmacologic interventions have failed, an acid suppressive agent is usually the first line of therapy. The lack of age-appropriate case definitions and randomized controlled trials, however, make it difficult for those practitioners who treat infants to have a evidence-based protocol for managing GERD.