Prognostic values of serum neuronal biomarkers NSE and protein S-100 in acute period of severe hypoxic-ischemic encephalopathy in term infants

Authors

  • Denys Surkov Communal institution "Dnepropetrovsk Regional Children's Clinical Hospital of Dnepropetrovsk Regional Council" Kosmichna str., 13, Dnipro, Ukraine, 49100, Ukraine https://orcid.org/0000-0002-6456-8493

DOI:

https://doi.org/10.15587/2519-4798.2018.143413

Keywords:

caspases, biomarkers, protein S-100, NSE, hypoxia, ischemia, reperfusion, hypothermia, encephalopathy, newborns

Abstract

It remains unclear if the serum concentrations of neuron-specific enolase (NSE) and protein S-100 correlate with severity and possible complications of hypoxic ischemic encephalopathy (HIE) as well as monitoring parameters of cerebral perfusion and central hemodynamics in term newborns.

The aim of research. To determine diagnostic and predictable values of NSE and protein S-100 in acute period of severe hypoxic-ischemic encephalopathy in neonates.

Materials and methods. Data of 89 term infants with Apgar score at birth of seven or less and Sarnat stage II-III was collected during ≤72 hours of life. The correlation between NSE, S-100 and Glasgow Coma Scale, seizures, confirmed by the aEEG, the unwanted development of neurological complications such as cerebral leukomalacia, and the short-term clinical results were analyzed.

Result. In acute period of HIE the concentration of serum neuronal biomarkers S-100 and NSE proteins substantially exceeds the reference values for the first hours after labor and exceeds the normal range until the 5th day of life. The dynamics of these data significantly changes during this period. Mostly diagnostically and prognostically significant the measurement of biomarkers was on the 3rd day of treatment, immediately after the end of the therapeutic hypothermia, at the beginning of rewarming and brain reperfusion, when both indicators were most closely correlated with the assessment of the GCS: NSE (r=-0.3; p=0.002 ) and S-100 (r=-0.3; p=0.003). The value of S-100 on day 1 correlating with the following unwanted development of leukomalacia is above 1.8 μg/L (p=0.002), which is more than 3 times higher from the reference level of 0.51 μg/L given by Simon-Pimmel J. (2017) for term newborns.

Conclusion. The evaluation of the serum concentrations of protein S-100 and neuron-specific enolase in the acute period of hypoxic ischemic encephalopathy in the term newborns has a significant diagnostic and predictable value and correlates with the severity and short-term clinical results of HIE

Author Biography

Denys Surkov, Communal institution "Dnepropetrovsk Regional Children's Clinical Hospital of Dnepropetrovsk Regional Council" Kosmichna str., 13, Dnipro, Ukraine, 49100

PhD, Head of Department

Department of Anaesthesiology and Intensive Care for Newborns

References

  1. Wyckoff, M. H., Aziz, K., Escobedo, M. B., Kapadia, V. S., Kattwinkel, J., Perlman, J. M. et. al. (2015). Part 13: Neonatal Resuscitation: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation, 132 (18), 543–560. doi: http://doi.org/10.1161/cir.0000000000000267
  2. Tagin, M., Abdel-Hady, H., Rahman, S., Azzopardi, D. V., Gunn, A. J. (2015). Neuroprotection for Perinatal Hypoxic Ischemic Encephalopathy in Low- and Middle-Income Countries. The Journal of Pediatrics, 167 (1), 25–28. doi: http://doi.org/10.1016/j.jpeds.2015.02.056
  3. Chiang, M.-C., Ashraf, Q. M., Ara, J., Mishra, O. P., Delivoria-Papadopoulos, M. (2007). Mechanism of caspase-3 activation during hypoxia in the cerebral cortex of newborn piglets. Neuroscience Letters, 421 (1), 67–71. doi: http://doi.org/10.1016/j.neulet.2007.05.024
  4. Kaur, C., Rathnasamy, G., Ling, E.-A. (2013). Roles of Activated Microglia in Hypoxia Induced Neuroinflammation in the Developing Brain and the Retina. Journal of Neuroimmune Pharmacology, 8 (1), 66–78. doi: http://doi.org/10.1007/s11481-012-9347-2
  5. Glass, H. C. (2014). Neonatal seizures: advances in mechanisms and management. Clinics in Perinatology, 41 (1), 177–190. doi: http://doi.org/10.1016/j.clp.2013.10.004
  6. Gerner, G. J., Burton, V. J., Poretti, A., Bosemani, T., Cristofalo, E., Tekes, A. et. al. (2015). Transfontanellar duplex brain ultrasonography resistive indices as a prognostic tool in neonatal hypoxic-ischemic encephalopathy before and after treatment with therapeutic hypothermia. Journal of Perinatology, 36 (3), 202–206. doi: http://doi.org/10.1038/jp.2015.169
  7. Chalak, L. F., Sánchez, P. J., Adams-Huet, B., Laptook, A. R., Heyne, R. J., Rosenfeld, C. R. (2014). Biomarkers for Severity of Neonatal Hypoxic-Ischemic Encephalopathy and Outcomes in Newborns Receiving Hypothermia Therapy. The Journal of Pediatrics, 164 (3), 468–474. doi: http://doi.org/10.1016/j.jpeds.2013.10.067
  8. Douglas-Escobar, M., Weiss, M. D. (2012). Biomarkers of hypoxic-ischemic encephalopathy in newborns. Frontiers in Neurology, 3, 144. doi: http://doi.org/10.3389/fneur.2012.00144
  9. Qian, J., Zhou, D., Wang, Y.-W. (2008). Umbilical artery blood S100β protein: a tool for the early identification of neonatal hypoxic-ischemic encephalopathy. European Journal of Pediatrics, 168 (1), 71–77. doi: http://doi.org/10.1007/s00431-008-0711-4
  10. Chiesa, C., Pellegrini, G., Panero, A., De Luca, T., Assumma, M., Signore, F., Pacifico, L. (2003). Umbilical cord interleukin-6 levels are elevated in term neonates with perinatal asphyxia. European Journal of Clinical Investigation, 33 (4), 352–358. doi: http://doi.org/10.1046/j.1365-2362.2003.01136.x
  11. Douglas-Escobar, M., Yang, C., Bennett, J., Shuster, J., Theriaque, D., Leibovici, A. et. al. (2010). A Pilot Study of Novel Biomarkers in Neonates With Hypoxic-Ischemic Encephalopathy. Pediatric Research, 68 (6), 531–536. doi: http://doi.org/10.1203/pdr.0b013e3181f85a03
  12. Massaro, A. N., Chang, T., Kadom, N., Tsuchida, T., Scafidi, J., Glass, P. et. al. (2012). Biomarkers of Brain Injury in Neonatal Encephalopathy Treated with Hypothermia. The Journal of Pediatrics, 161 (3), 434–440. doi: http://doi.org/10.1016/j.jpeds.2012.02.047
  13. Massaro, A. N., Chang, T., Baumgart, S., McCarter, R., Nelson, K. B., Glass, P. (2014). Biomarkers S100B and Neuron-Specific Enolase Predict Outcome in Hypothermia-Treated Encephalopathic Newborns. Pediatric Critical Care Medicine, 15 (7), 615–622. doi: http://doi.org/10.1097/pcc.0000000000000155
  14. Chaparro-Huerta, V., Flores-Soto, M. E., Merin Sigala, M. E., Barrera de León, J. C., Lemus-Varela, M. de L., Torres-Mendoza, B. M. de G., Beas-Zárate, C. (2017). Proinflammatory Cytokines, Enolase and S-100 as Early Biochemical Indicators of Hypoxic-Ischemic Encephalopathy Following Perinatal Asphyxia in Newborns. Pediatrics & Neonatology, 58 (1), 70–76. doi: http://doi.org/10.1016/j.pedneo.2016.05.001
  15. Beloborodova, N. V., Dmitriyeva, I. B., Chernevskaya, E. A. (2011). Diagnostic Value of S100B Protein in Critical Conditions. General Reanimatology, 7 (6), 72–76. doi: http://doi.org/10.15360/1813-9779-2011-6-72
  16. Abbasoglu, A., Sarialioglu, F., Yazici, N., Bayraktar, N., Haberal, A., Erbay, A. (2015). Serum Neuron-specific Enolase Levels in Preterm and Term Newborns and in Infants 1–3 Months of Age. Pediatrics & Neonatology, 56 (2), 114–119. doi: http://doi.org/10.1016/j.pedneo.2014.07.005
  17. Zaigham, M., Lundberg, F., Olofsson, P. (2017). Protein S100B in umbilical cord blood as a potential biomarker of hypoxic-ischemic encephalopathy in asphyxiated newborns. Early Human Development, 112, 48–53. doi: http://doi.org/10.1016/j.earlhumdev.2017.07.015
  18. Simon-Pimmel, J., Lorton, F., Masson, D., Bouvier, D., Hanf, M., Gras-Le Guen, C. (2017). Reference ranges for serum S100B neuroprotein specific to infants under four months of age. Clinical Biochemistry, 50 (18), 1056–1060. doi: http://doi.org/10.1016/j.clinbiochem.2017.08.014
  19. Elstad, M., Whitelaw, A., Thoresen, M. (2011). Cerebral Resistance Index is less predictive in hypothermic encephalopathic newborns. Acta Paediatrica, 100 (10), 1344–1349. doi: http://doi.org/10.1111/j.1651-2227.2011.02327.x

Published

2018-10-01

How to Cite

Surkov, D. (2018). Prognostic values of serum neuronal biomarkers NSE and protein S-100 in acute period of severe hypoxic-ischemic encephalopathy in term infants. ScienceRise: Medical Science, (6 (26), 32–41. https://doi.org/10.15587/2519-4798.2018.143413

Issue

Section

Medical Science