Lactate combined with lymphocyte counts as useful predictors for the severity and prognosis of necrotizing enterocolitis: a retrospective cohort study

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Abstract
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. 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. Severe NEC exhibited significantly lower lymphocytes (1.58 vs. 3.71 × 109/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). 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.
Funding Information
  • Guangdong Yiyang Foundation Project (JZ2022001)
  • Natural Science Foundation of Guangdong Province (2022A1515012548)

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