Objective-To determine whether anti-reflux medications reduce bradycardia episodes attributed to clinically suspected gastroesophageal reflux (GER).Study design-We conducted a masked trial comparing metoclopramide, 0.2 mg/kg/dose q 6 hours, and ranitidine, 2 mg/kg/dose q 8 hours, with saline placebo. Each infant served as his own control. Preterm infants having >3 bradycardia episodes per 2 days were eligible if the clinician intended to begin anti-reflux medications for bradycardia attributed to GER.Results-The mean (SD) birth weight was 1238 (394) g and gestational age was 29 (3) weeks. Eighteen infants were enrolled at 35 (22) days of age. There were 4.6 (3.1) and 3.6 (2.7) bradycardia episodes per day in the drug and placebo periods, respectively. The mean difference (drug minus placebo) was 0.94 (95% CI, 0.04 to 1.95) (P = .04 by t test). There was a decrease in bradycardia episodes over time (P < .001 by nonparametric repeated-measures analysis of variance).Conclusions-Anti-reflux medications did not reduce, and may have increased, bradycardia episodes in preterm infants with GER. Because there was an improvement of bradycardia episodes over time, unrelated to treatment, unmasked therapeutic trials of medications are likely to lead to misleading conclusions.Gastroesophageal reflux (GER), commonly defined as the involuntary passage of gastric contents into the esophagus, has been reported to occur in more than 85% of preterm infants. 1 In some infants, GER can be severe enough to cause gastroesophageal reflux disease (GERD), which results in malnutrition, esophagitis, or respiratory disease. 2 Claims have been made since the 1970s that apnea in preterm infants could be caused by GER. 3,4 Apnea and bradycardia are very common in preterm infants; episodes frequently occur during and after feeding when GER is also frequent. 5 Apnea and bradycardia occurring around feedings might be causally related to GER by the mechanism of refluxate traveling up the esophagus, blocking the airway, and causing an obstructive apnea and subsequent bradycardia. Another proposed mechanism to link these events is the laryngeal chemoreflex, which causes respiratory pauses and airway closure immediately after regurgitation to the upper airway. 6 However, numerous observational studies have failed to demonstrate a temporal relationship between GER events and apnea. 7 Common diagnostic approaches to GER include the upper gastrointestinal series (UGI) and the pH probe study. The UGI, which consists of radiographs taken after contrast material is infused or swallowed into the stomach, is neither sensitive nor specific for the diagnosis of GER. 8 The pH probe study, which is the traditional gold standard for diagnosing GERD,The authors declare no potential conflicts of interest, real or perceived. There have been no prospective randomized trials of treatment for GERD in preterm infants with or without apnea and bradycardia. The purpose of our study was to determine whether anti-reflux medications reduce bradycardia attributed to ...