What is the association between common medications (indomethacin, ibuprofen and acetaminophen) and spontaneous intestinal perforations in premature infants? A systematic review protocol

Abstract

Background: Spontaneous intestinal perforation (SIP) affects very low birth weight preterm neonates and accounts for 44% of gastrointestinal perforations. Commonly used medications such as indomethacin, ibuprofen and acetaminophen for PDA closure, increases the risk of intestinal perforation. Unfortunately, the majority of the data combine SIP with those affected by necrotizing enterocolitis (NEC) despite them being separate entities. This systematic review aims to explore the association between the use of common medications and SIP in the premature infant cohort independently from NEC. Methods: Our study will focus on preterm infants with exposure to either indomethacin, ibuprofen or acetaminophen where SIP is a reported outcome. A health science librarian will search Medline and Medline in Process via OVID, Embase Classic + Embase via OVID, the LILACS database, the ScIELO database and the Cochrane Library including EBM Reviews - Cochrane Central Register of Controlled Trials. Search dates for each database will be from their respective dates of inception to March 2022. All articles will undergo screening by two independent reviewers, and if selected, data extraction with risk of bias assessment by two independent reviewers. A third reviewer will settle any disagreements that may occur. Incidence of SIP will be measured as a proportion. Individual proportions will be pooled using a random effects logistic regression model. The comparative incidence of SIP by treatment group will be measured using the odds ratio. Odds ratios will be pooled using the DerSimonian and Laird random effects model for meta-analysis. PROSPERO Registration: CRD42017058603