Analysis of risk factors for necrotizing enterocolitis in premature infants and clinical significance of serum SMOX and ACR

Abstract Background: This study aimed to identify risk factors for NEC in preterm infants and evaluate the predictive utility of serum spermine oxidase (SMOX) and acrolein (ACR) levels for the early detection of NEC. Methods: A nested case–control study was conducted among preterm infants with a gestational age of <34 weeks who were admitted to the Neonatal Department of the Children’s Hospital of Soochow University within 24 hours after birth between October 2021 and October 2023. Thirty-two infants who subsequently developed NEC (Bell stage II or higher) were included in the NEC group, while 32 gestational age-matched preterm infants without NEC were randomly selected as controls. For each infant in the NEC group, one gestational age-matched control without NEC was selected using a 1:1 matching strategy, based on admission date, gestational age (±1 week), and birth weight (±200 g). Serum SMOX and ACR concentrations were measured on postnatal days 1,7, 14, and 28. Multivariable logistic regression analysis was performed to identify independent risk factors for NEC. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive performance of SMOX and ACR. A combined prediction model incorporating clinical risk factors and serum biomarkers was subsequently established. Results: A total of 64 preterm infants were included, with a mean gestational age of 29.1 ± 2.0 weeks and a mean birth weight of 1223.0 ± 298.6 g. Compared with the control group, the NEC group had significantly higher rates of respiratory distress syndrome, sepsis, blood transfusion, and fluid overload during the first three postnatal days (all P < 0.05), and the proportion of infants who received early enteral feeding was significantly lower (P < 0.05). Serum SMOX concentrations on postnatal day 14 were higher in the NEC group than in the control group (249.2 ± 71.2 vs. 194.0 ± 52.9 U/mL, P < 0.05), whereas lower concentrations were observed on day 28 (213.2 ± 60.2 vs. 246.0 ± 63.9 U/mL, P < 0.05). Serum ACR concentrations were higher in the NEC group on both postnatal days 14 and 28 (66.1 ± 13.3 vs. 58.8 ± 12.7 pg/mL and 71.1 ± 15.8 vs. 58.7 ± 14.5 pg/mL, respectively; both P < 0.05). Multivariable logistic regression identified sepsis, fluid overload during the first three postnatal days, and elevated SMOX and ACR levels on postnatal day 14 as independent risk factors for NEC. A prediction model incorporating these variables yielded an area under the ROC curve (AUC) of 0.870 (95% CI: 0.780–0.960), with a sensitivity of 81.3% and a specificity of 90.3%. The Hosmer–Lemeshow goodness-of-fit test showed no evidence of poor calibration (P = 0.165). Internal validation using 1,000 bootstrap resamples yielded a 95% confidence interval of 0.787–0.961. The calibration curve showed agreement between predicted and observed probabilities of NEC. Conclusion: Sepsis and high fluid overload within three days after admission are independent risk factors for NEC in preterm infants <34 weeks of gestation. SMOX and ACR demonstrate good predictive value for NEC, and combined monitoring of these markers may improve the accuracy of NEC prediction and diagnosis.