Age of onset of necrotising enterocolitis (NEC) and focal intestinal perforation (FIP) in very preterm and low birthweight infants: a systematic review

ObjectiveReview of age of onset of necrotising enterocolitis (NEC) and focal intestinal perforation (FIP) in very preterm (≤32 weeks) and/or very low birthweight (VLBW, ≤1500 g) infants.DesignPreregistered review undertaken according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses in July 2021 and updated October 2021.Data sourcesMEDLINE/ PubMed, Embase, CINAHL and Cochrane Central Register of Controlled Trials.EligibilityEligible studies reported age of onset of NEC and/or FIP in randomised controlled trials of >200 or observational studies of >500 infants.Data extraction and synthesisTitles/abstracts were screened; eligible articles underwent data extraction. Age of onset as day of life (DOL) and/or corrected gestational age (CGA) were extracted alongside study information, such as NEC definition, included population, intervention, location and dates studied. Weighted means were used to compare onset by birth gestation, study type, NEC definition, trial intervention, location and dates studied. Comparison was done by Mann-Whitney U test or one-way analysis of variance.ResultsOf the 747 screened studies 188 were eligible. Removal of duplicates, studies without onset data and ineligible populations left 10 RCTs and 14 observational studies contributing 51 NEC cohorts; 49 reported onset DOL and 14 CGA. 2984 cases of NEC had average DOL onset of 16.7 (15.5 in RCTs, 16.9 in observational studies), and CGA onset of 30.1 weeks. Gestation did not impact DOL onset. No other demographic feature impacted NEC onset. Few studies included data on FIP.ConclusionsAverage onset of NEC in exclusively very preterm/very low birthweight infants is in the third week of life and unlike in cohorts including more mature or heavier infants is not impacted by birth gestation.