Enteral feeding during cyclooxygenase inhibitor treatment for patent ductus arteriosus: A systematic review

BACKGROUND: This study evaluated the effect of modifying enteral feeding during cyclooxygenase inhibitor (COXI) treatment on patent ductus arteriosus (PDA) in preterm infants. METHODS: We searched MEDLINE, EMBASE, CENTRAL, CINAHL, and ICHUUSHI databases for randomized and nonrandomized controlled trials, checked the references lists and major clinical trials. Non-human and non-English studies were excluded. Evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation. Preterm infants born before 37 weeks of gestation are treated with COXIs for PDA, including indomethacin and ibuprofen. The primary outcomes were the composite outcome of necrotizing enterocolitis (NEC) or gastrointestinal perforation and its components (NEC and gastrointestinal perforation). RESULTS: Two randomized controlled trials (n = 303) and one retrospective cohort study (n = 261) were included (total: n = 564). No significant differences were observed in the composite gastrointestinal outcome (risk ratio [RR]: 1.10, 95% confidence interval [CI]: 0.51-2.37; 1 study, 177 infants, very low certainty of evidence [CoE]), NEC (RR: 1.01, 95% CI: 0.47-2.15; 2 studies, 300 infants, very low CoE), or gastrointestinal perforation (RR: 1.94, 95% CI: 0.25-14.81; 2 studies, 300 infants, very low CoE) between discontinuation and continuation of enteral feeding. Discontinuation of enteral feeding resulted in a significantly lower rate of surgical closure for PDA compared to continuation (RR: 0.56, 95% CI: 0.37-0.86; 1 study, 177 infants, low CoE). CONCLUSIONS: Neither discontinuation nor continuation of enteral feeding significantly affected the composite gastrointestinal outcome and its components (NEC and gastrointestinal perforation).