Global incidence of Necrotizing Enterocolitis: a systematic review and Meta-analysis

Background Necrotizing Enterocolitis (NEC) is a major cause of morbidity and mortality in the Neonatal Intensive Care Unit (NICU), yet the global incidence of NEC has not been systematically evaluated. We conducted a systematic review and meta-analysis of cohort studies reporting the incidence of NEC in infants with Very Low Birth Weight (VLBW). Methods The databases searched included PubMed, MEDLINE, the Cochrane Library, EMBASE and grey literature. Eligible studies were cohort or population-based studies of newborns including registry data reporting incidence of NEC. Incidence were pooled using Random Effect Models (REM), in the presence of substantial heterogeneity. Additional, bias adjusted Quality Effect Models (QEM) were used to get sensitivity estimates. Subgroup analysis and meta-regression were used to explore the sources of heterogeneity. Funnel plots as appropriate for ratio measures were used to assess publication bias. Results A systematic and comprehensive search of databases identified 27 cohort studies reporting the incidence of NEC. The number of neonate included in these studies was 574,692. Of this 39,965 developed NEC. There were substantial heterogeneity between studies (I-2 = 100%). The pooled estimate of NEC based on REM was 7.0% (95% CI: 6.0-8.0%). QEM based estimate (6.0%; 95% CI: 4.0-9.0%) were also similar. Funnel plots showed no evidence of publication bias. Although, NEC estimates are similar across various regions, some variation between high and low income countries were noted. Meta regression findings showed a statistically significant increase of NEC over time, quantified by the publication year. Conclusion Seven out of 100 of all VLBW infants in NICU are likely to develop NEC. However, there were considerable heterogeneity between studies. High quality studies assessing incidence of NEC along with associated risk factors are warranted.