The impact of the route of administration on the efficacy and safety of the drug therapy for patent ductus arteriosus in premature infants: a systematic review and meta-analysis

Background This systematic review and meta-analysis aims to explore the potential impact of the route of administration on the efficacy of therapies and occurrence of adverse events when administering medications to premature infants with patent ductus arteriosus (PDA). Method The protocol for this review has been registered with PROSPERO (CRD 42022324598). We searched relevant studies in PubMed, Embase, Cochrane, and the Web of Science databases from March 26, 1996, to January 31, 2022. Results A total of six randomized controlled trials (RCTs) and five observational studies were included for analysis, involving 630 premature neonates in total. Among these infants, 480 were in the ibuprofen group (oral vs. intravenous routes), 78 in the paracetamol group (oral vs. intravenous routes), and 72 in the ibuprofen group (rectal vs. oral routes). Our meta-analysis revealed a significant difference in the rate of PDA closure between the the initial course of oral ibuprofen and intravenous ibuprofen groups (relative risk (RR) = 1.27, 95% confidence interval (CI) [1.13–1.44]; P