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It is difficult to predict the risk of mortality in necrotizing enterocolitis (NEC). This study aimed at identifying risk factors for severe NEC (Bell stage III) and mortality in preterm children with NEC. In this multicenter retrospective study, we analyzed multiple data from 157 premature children with confirmed NEC in the period from January 2007 to October 2018. We performed univariate, multivariate, stepwise logistic regression, and receiver operator characteristics (ROC) analyses. We were able to demonstrate that low Apgar scores (notably at 1' and 5'), low hemoglobin concentration (Hgb), and high lactate level at disease onset and during disease correlated with NEC severity and mortality (P < 0.05, respectively). Severe NEC was related to congenital heart disease (CHD - OR 2.6, CI95% 1.2-5.8, P 0.015) and patent ductus arteriosus (PDA - OR 3.3, CI95% 1.6-6.9, P 0.0012), whereas death was related to the presence of PDA (OR 5.5, CI95% 2.3-14, P < 0.001).Conclusion: Low Apgar scores, low Hgb, high lactate levels, and the presence of CHD or PDA correlated with severe NEC or mortality in children with NEC. What is Known: • It remains difficult to predict which infant that suffers from necrotizing enterocolitis at risk of death. • Several clinical and laboratory parameters tools to predict fatal outcome in NEC. What is New: • The following laboratory parameters were associated with the risk of death from NEC: Hemoglobin concentration, base excess and lactate level. • The following clinical variables were associated with the risk of death from NEC: Apgar scores, as well as the presence of congenital heart disease and patent ductus arteriosus., (© 2021. The Author(s).)