Abstract
BACKGROUND: Necrotizing enterocolitis (NEC) lacks useful biomarkers for early risk stratification. Despite evidence of lactate metabolism and immune dysregulation in NEC pathogenesis, their synergistic diagnostic potential remains underexplored. METHOD: This retrospective cohort study analyzed 118 neonates with NEC (2017-2022), stratified into two subgroups: mild NEC (Bell's stage ≤ IIa, n = 59) and severe NEC (Bell's stage ≥ IIb, n = 59). Threshold effects, multivariable logistic regression, and mediation analysis were employed to assess nonlinear relationships and biomarker interaction. RESULTS: Severe NEC exhibited significantly lower lymphocytes (1.58 vs. 3.71 × 10(9)/L, p < 0.001), increased mechanical ventilation requirements (89.8% vs. 39.0%, p < 0.001), and elevated lactate levels (6.4 mmol/L vs. 2.8 mmol/L, p < 0.001). Multivariable regression identified lactate (OR 3.84, p < 0.001) and lymphocytes (OR 0.33, p = 0.021) as independent severity predictors. Threshold analysis showed nonlinear correlations of lactate with NEC severity, surgical intervention, and mortality (turning point: 6.1, 6.4, and 5.4 mmol/L), each 1 mmol/L lactate increase above threshold raised mortality risk 1.7-fold (OR 1.70, p = 0.022). Lymphocytes exhibited significant indirect mediation in combined lactate-NEC evaluation (7.79%, p = 0.008). The lactate-lymphocyte combination achieved useful prognostic accuracy (AUC = 0.96, sensitivity = 89.8%, specificity = 89.8%), outperforming lactate alone (AUC = 0.93, sensitivity = 91.5%, specificity = 81.4%; p < 0.001). CONCLUSION: Combined lactate and lymphocytes enhance risk stratification and prognostic accuracy in NEC, bridge metabolic and immune pathways, and offer clinical utility for guiding early interventions in high-risk neonates with NEC.