Gastrointestinal Effects of Caffeine in Preterm Infants - a Systematic Review and Bayesian Meta-Analysis

Abstract

INTRODUCTION: Caffeine is widely used in preterm infants to prevent or treat apnea of prematurity. Adverse gastrointestinal effects of caffeine at usual doses have not been thoroughly researched in preterm infants. We present a systematic review and meta-analysis that summarizes the results of trials on the gastrointestinal effects of caffeine in preterm infants. METHODS: We searched MEDLINE, Web of Science, Scopus, and clinicaltrials.gov up to April 21st, 2023. We included randomised controlled trials assessing caffeine versus placebo in preterm neonates and reporting gastrointestinal side effects. Risk of bias was assessed using the Cochrane Risk of Bias tool. We performed a Bayesian meta-analysis to estimate the pooled odds ratio (OR) of gastrointestinal side effects comparing caffeine against placebo. RESULTS: Nine trials involving 2,746 preterm infants were analyzed. Seven trials assessing necrotizing enterocolitis and four trials assessing feeding intolerance in our meta-analysis found no differences between caffeine versus placebo, ([OR]=1.007, 95%CrI=[0.021;5.462]) and (OR=1.266, 95%CrI=[0.064;28.326]), respectively. Four trials assessed the outcomes spontaneous intestinal perforation, constipation, and gastrointestinal disorder (composite outcome: gastroesophageal regurgitation or dilated bowel loops), age at oral feeding, and cholestasis syndrome, and found no differences between groups. One trial assessed the outcomes gastroesophageal symptoms and duration of tube feeding in days and found that caffeine was associated with a reduced burden of gastroesophageal reflux symptoms at two weeks of life (p< 0.05), but not at term. CONCLUSIONS: According to this systematic review and meta-analysis, the use of caffeine at usual doses in preterm infants did not result in significant gastrointestinal adverse effects.