Randomized Clinical Trial of Metoclopramide as Prophylaxis of Gastroesophageal Reflux Disease in Preterm Infants

Background: Gastroesophageal reflux (GER) is more frequent in premature infants. Metoclopramide was introduced routinely in premature babies followed in ambulatory care by the Colombian Kangaroo Mother Care program (KMCP), based on a 2004 Cochrane review. Aim: Because of the recent controversy on the use of metoclopramide in children, this study was conducted to evaluate the effectiveness and safety of metoclopramide given as GER disease (GERD) prophylaxis. Methods: A randomized clinical trial was conducted between April 2017 and January 2019 in 466 premature infants discharged home and followed at a KMCP. Double-blind allocation to metoclopramide versus placebo was performed, 0.2 mg/kg three times daily, administered 15 min before feeding, up to term. Exclusion criteria were oxygen dependency, any perinatal neurological problem or parent’s participation refusal. The incidence of GERD symptoms and adverse events that could be associated with the use of metoclopramide were recorded by parents weekly (e.g., emesis, cyanosis or apnea, post-prandial crying episodes, extrapyramidal symptoms, tremor, and drowsiness). Results: A total of 466 subjects were recruited, most of them late preterm. The groups’ baseline characteristics were similar. Median duration of the intervention was approximately 3 weeks, at which time most patients were at term. In the longitudinal mixed effects analysis, we did not find clinically significant differences in GERD-related symptoms between groups, either in minor or severe side effects. Conclusion: Results show absence of effectiveness in the systematic use of metoclopramide as prophylaxis of GERD symptoms in premature infants. Additionally, no adverse effects attributable to the drug were found. ClinicalTrials.gov: NCT02907632; September 20, 2016. Retrospectively registered.