BACKGROUND: Necrotizing enterocolitis (NEC) is a leading gastrointestinal condition in preterm infants, characterized by significant morbidity and mortality. Early recognition of risk factors is crucial for its prevention and prediction. This study focuses on identifying factors that contribute to the development of NEC in neonates. METHODS: A case-control study that looked back at 144 newborns hospitalized to a Wuhan hospital between January 2010 and March 2023 for NEC was carried out. Over the same period, another 144 children without NEC were identified and selected as the non-NEC group for comparison, following a 1:1 pairing ratio. The relevant data from these two groups of newborns were compared. Univariate analysis was conducted using T-tests or χ RESULTS: A total of 288 neonates (144 NEC and 144 non-NEC) were enrolled. The independent risk variables for NEC, as shown by the multivariate logistic regression analysis (p <
0.05), were Small for Gestational Age (SGA), neonatal sepsis, neonatal hyperbilirubinemia, and non-human milk (HM) feeding. Furthermore, ROC (receiver operating characteristic) analysis showed that the AUC (area under the curve) of the Logistic regression model predicting the effect of neonatal necrotizing enterocolitis was 0.746, suggesting a high level of discriminative ability in differentiating efficacy. This model can be instrumental in facilitating early identification of infants prone to developing NEC in clinical settings. CONCLUSION: In conclusion, the risk factors associated with newborn NEC include SGA, neonatal sepsis, and non-HM feeding. Newborn hyperbilirubinemia may potentially serve as a protective factor against NEC.