Serum Neuron-Specific Enolase and Lactate Predict Hypoxic-Ischemic Encephalopathy in Asphyxiated Neonates: A Retrospective Cohort Study

Background: Hypoxic-ischemic encephalopathy (HIE) is one of the most severe complications of perinatal asphyxia, which is related to high mortality and permanent neurological impairments. Current clinical tools for early identification of at-risk infants lack sensitivity and objectivity, underscoring the urgent need for accessible biomarkers that can guide timely intervention. Methods: This retrospective cohort study was conducted at the Tenth Affiliated Hospital of Southern Medical University from 2020 to 2025. The study cohort consisted of 57 neonates with perinatal asphyxia. 28 of the infants had the diagnosis of HIE and 29 of the infants didn't have the diagnosis of HIE. Clinical characteristics, laboratory parameters, and Weeke MRI scores were compared between the two groups, and multivariable logistic regression analysis identified independent risk factors for HIE. Results: Compared with controls, the HIE group showed higher elevations in serum NSE (median 73.15 vs 45.80 ng/mL, P < 0.0001) and blood lactate (mean 11.63 ± 2.702 vs 8.800 ± 3.453 mmol/L, P = 0.0014). Multivariable analysis confirmed both NSE (aOR = 1.047, 95% CI: 1.013–1.082, P = 0.007) and lactate (aOR = 1.280, 95% CI: 1.015–1.614, P = 0.037) as independent predictors of HIE, with a Nagelkerke R2 of 0.486. Conclusions: Serum NSE measured at 24–72 hours and blood lactate measured within the first hour postpartum were independent factors associated with HIE in asphyxiated neonates. NSE, as a direct marker of neuronal injury, may serve as a valuable early biomarker for risk stratification.