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Gastrointestinal effects of caffeine in preterm infants: a systematic review and Bayesian meta-analysis
Beatriz Gama1, Madalena von Hafe2, Rafael Vieira3,4
1Department of Gynecology-Obstetrics and Pediatrics, Universidade do Porto Faculdade de Medicina, Porto, Portugal.
Insights
Caffeine use in preterm infants for apnea of prematurity is not linked to significant gastrointestinal issues. This review found no increased risk of necrotizing enterocolitis or feeding intolerance with caffeine treatment.
Area of Science:
- Neonatal Medicine
- Pharmacology
- Gastroenterology
Background:
- Caffeine citrate is a standard treatment for apnea of prematurity.
- Gastrointestinal (GI) adverse effects of caffeine in neonates require further investigation.
Approach:
- Systematic review and Bayesian meta-analysis of randomized controlled trials (RCTs) involving preterm infants treated with caffeine versus placebo.
- Searched major databases up to April 2023 for trials reporting GI side effects.
- Assessed risk of bias using the Cochrane Risk of Bias tool.
Key Points:
- Analysis of 9 trials with 2746 infants found no significant difference in necrotizing enterocolitis or feeding intolerance between caffeine and placebo groups.
- No increased risk observed for spontaneous intestinal perforation, constipation, or other composite GI disorders.
- Caffeine showed a potential reduction in gastro-oesophageal reflux symptoms at 2 weeks post-treatment.
Conclusions:
- Current evidence suggests that standard doses of caffeine are safe regarding gastrointestinal adverse effects in preterm infants.
- The findings support the continued use of caffeine for apnea of prematurity without significant GI concerns.
Objective:
Caffeine is widely used in preterm infants to prevent or treat apnoea of prematurity. Adverse gastrointestinal effects of caffeine have not been thoroughly researched in preterm infants. With this systematic review and meta-analysis, we aim to summarise the results of trials on the gastrointestinal effects of caffeine in preterm infants.
Design:
We searched MEDLINE, Web of Science, Scopus and ClinicalTrials.gov up to 21 April 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. A Bayesian meta-analysis was performed to estimate the pooled OR of gastrointestinal side effects.
Results:
Nine trials involving 2746 preterm infants were analysed. Seven trials assessing necrotising enterocolitis and four trials assessing feeding intolerance in our meta-analysis found no differences between caffeine and placebo (OR=1.007 (95% credible interval 0.021, 5.462), I2=97.4%, and OR=1.266 (95% credible interval 0.064, 28.326), I2=84.8%, respectively). Four trials assessed the outcomes spontaneous intestinal perforation, constipation, gastrointestinal disorder (composite outcome: gastro-oesophageal regurgitation or dilated bowel loops), age at oral feeding and cholestasis syndrome and found no differences between groups. One trial assessed the outcomes gastro-oesophageal symptoms and duration of tube feeding and found that caffeine was associated with a reduced burden of gastro-oesophageal reflux symptoms at 2 weeks (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 does not seem to be associated with significant gastrointestinal adverse effects.
