Serum Neuron-Specific Enolase and Lactate Predict Hypoxic-Ischemic Encephalopathy in Asphyxiated Neonates: A Retrospective Cohort Study
DOI:
https://doi.org/10.70088/7mvee730Keywords:
Perinatal Asphyxia, Hypoxic-ischemic encephalopathy, Neuron-specific enolase, Lactate, NeonateAbstract
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.References
J. J. Kurinczuk, M. White-Koning, and N. Badawi, "Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy," Early Hum. Dev., vol. 86, no. 6, pp. 329–338, 2010.
J. J. Volpe, Neurology of the Newborn, 1st ed. Philadelphia, PA: W.B. Saunders, 1981, pp. 1–648.
X. Qin, J. Cheng, Y. Zhong, et al., "Mechanism and treatment related to oxidative stress in neonatal hypoxic-ischemic encephalopathy," Front. Mol. Neurosci., vol. 12, p. 88, 2019.
T. W. Pin, B. Eldridge, and M. P. Galea, "A review of developmental outcomes of term infants with post-asphyxia neonatal encephalopathy," Eur. J. Paediatr. Neurol., vol. 13, no. 3, pp. 224–234, 2009.
C. E. Ahearne, G. B. Boylan, and D. M. Murray, "Short and long term prognosis in perinatal asphyxia: An update," World J. Clin. Pediatr., vol. 5, no. 1, pp. 67–74, 2016.
M. van Handel, H. Swaab, L. S. de Vries, et al., "Long-term cognitive and behavioral consequences of neonatal encephalopathy following perinatal asphyxia: A review," Eur. J. Pediatr., vol. 166, no. 7, pp. 645–654, 2007.
R. C. Vannucci, "Hypoxic-ischemic encephalopathy," Am. J. Perinatol., vol. 17, no. 3, pp. 113–120, 2000.
M. Douglas-Escobar and M. D. Weiss, "Hypoxic-ischemic encephalopathy: A review for the clinician," JAMA Pediatr., vol. 169, no. 4, pp. 397–403, 2015.
Y. F. Tu, P. M. Wu, W. H. Yu, et al., "Lactate predicts neurological outcomes after perinatal asphyxia in post-hypothermia era: A prospective cohort study," Life (Basel), vol. 11, no. 11, 2021.
H. B. Sarnat and M. S. Sarnat, "Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study," Arch. Neurol., vol. 33, no. 10, pp. 696–705, 1976.
I. Caramelo, M. Coelho, M. Rosado, et al., "Biomarkers of hypoxic-ischemic encephalopathy: A systematic review," World J. Pediatr., vol. 19, no. 6, pp. 505–548, 2023.
L. Chalak, "New horizons in mild hypoxic-ischemic encephalopathy: A standardized algorithm to move past conundrum of care," Clin. Perinatol., vol. 49, no. 1, pp. 279–294, 2022.
L. Chalak, S. Latremouille, I. Mir, et al., "A review of the conundrum of mild hypoxic-ischemic encephalopathy: Current challenges and moving forward," Early Hum. Dev., vol. 120, pp. 88–94, 2018.
L. C. Weeke, F. Groenendaal, K. Mudigonda, et al., "A novel magnetic resonance imaging score predicts neurodevelopmental outcome after perinatal asphyxia and therapeutic hypothermia," J. Pediatr., vol. 192, pp. 33–40, 2018.
M. Rutherford, C. Malamateniou, A. McGuinness, et al., "Magnetic resonance imaging in hypoxic-ischaemic encephalopathy," Early Hum. Dev., vol. 86, no. 6, pp. 351–360, 2010.
M. Douglas-Escobar and M. D. Weiss, "Biomarkers of hypoxic-ischemic encephalopathy in newborns," Front. Neurol., vol. 3, p. 144, 2012.
R. Authifa, P. Gohiya, and J. Shrivastava, "Correlation of arterial lactate and pH with the immediate outcome of term asphyxiated neonates," Cureus, vol. 17, no. 3, p. e80093, 2025.
C. Mooney, D. O'Boyle, M. Finder, et al., "Predictive modelling of hypoxic ischaemic encephalopathy risk following perinatal asphyxia," Heliyon, vol. 7, no. 7, p. e07411, 2021.
H. Z. Huang, X. F. Hu, X. H. Wen, et al., "Serum neuron-specific enolase, magnetic resonance imaging, and electrophysiology for predicting neurodevelopmental outcomes of neonates with hypoxic-ischemic encephalopathy: A prospective study," BMC Pediatr., vol. 22, no. 1, p. 290, 2022.
L. Zhang, C. Wang, Q. Jia, et al., "The significance of glycemic variability in conjunction with lactate metabolism levels in the clinical assessment of neonatal hypoxic-ischemic encephalopathy," Sci. Rep., vol. 15, no. 1, p. 29072, 2025.
T. Hurley, F. Quirke, A. Branagan, et al., "Systematic review of terminology, definitions, and eligibility criteria in trials of neonatal encephalopathy, hypoxic-ischemic encephalopathy, and perinatal asphyxia," Pediatr. Res., 2026.
"Executive summary: Neonatal encephalopathy and neurologic outcome, second edition. Report of the American College of Obstetricians and Gynecologists' Task Force on Neonatal Encephalopathy," Obstet. Gynecol., vol. 123, no. 4, pp. 896–901, 2014.
H. Gohatre, R. K. Kulkarni, D. Ambike, et al., "Comparison of modified Sarnat staging and Thompson score in neonatal hypoxic-ischemic encephalopathy," Cureus, vol. 18, no. 2, p. e104350, 2026.
E. von Elm, D. G. Altman, M. Egger, et al., "The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: Guidelines for reporting observational studies," Lancet, vol. 370, no. 9596, pp. 1453–1457, 2007.
Y. Li, J. L. Wisnowski, L. Chalak, et al., "Mild hypoxic-ischemic encephalopathy (HIE): Timing and pattern of MRI brain injury," Pediatr. Res., vol. 92, no. 6, pp. 1731–1736, 2022.
M. Machie, L. Weeke, L. S. de Vries, et al., "MRI score ability to detect abnormalities in mild hypoxic-ischemic encephalopathy," Pediatr. Neurol., vol. 116, pp. 32–38, 2021.
B. H. Walsh, J. Neil, J. Morey, et al., "The frequency and severity of magnetic resonance imaging abnormalities in infants with mild neonatal encephalopathy," J. Pediatr., vol. 187, pp. 26–33, 2017.
A. R. Horn, S. Pillay, and S. C. Velaphi, "Neonatal encephalopathy due to suspected hypoxic-ischaemic encephalopathy," World J. Pediatr., vol. 21, no. 9, pp. 853–86, 2025.
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Yincong Chen, Yanling Lu, Yueqin Ding, Kuihuan Tan, Huixue Lu, Zhifeng Chen (Author)
This work is licensed under a Creative Commons Attribution 4.0 International License.
