Cross-over trial of treatment for bradycardia attributed to gastroesophageal reflux in preterm infants.
OBJECTIVE
To determine whether anti-reflux medications reduce bradycardia episodes attributed to clinically suspected gastroesophageal reflux (GER).


METHODS
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.
Wheatley
Eva
E
Department of Pediatrics, Division of Neonatology, University of Texas Health Science Center, Houston, TX, USA.
Kennedy
Kathleen A
KA
D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D001919:Bradycardia / Q000209:etiology / Q000517:prevention & control*; D018592:Cross-Over Studies; D005260:Female; D005764:Gastroesophageal Reflux / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008787:Metoclopramide / Q000627:therapeutic use*; D011899:Ranitidine / Q000627:therapeutic use*
D000897:Anti-Ulcer Agents; D011899:Ranitidine; D008787:Metoclopramide