Skip to main content

Advertisement

SpringerLink
Log in

Neuronal Biomarkers in Predicting Neurodevelopmental Outcome in Term Babies with Perinatal Asphyxia

  • Original Article
  • Published:
The Indian Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Objective

To assess whether serum levels of neuronal biomarkers (S100 calcium-binding protein B and Neuron specific enolase) correlate with the neurodevelopmental outcome of term neonates at 18 mo who had hypoxic ischemic encephalopathy and underwent therapeutic hypothermia.

Methods

This randomized controlled trial was conducted in a tertiary care teaching hospital, south India. There were 162 term infants with moderate to severe hypoxic ischemic encephalopathy who were randomized into 2 groups (Group A and B). Neonates in Group A and B received normothermia and therapeutic hypothermia respectively. Serum levels of neuronal biomarkers were estimated at 0, 24 (±1) and 72 (±1) h after birth using sandwich ELISA in both groups. All neonates were carefully monitored till discharge. Infants who survived the neonatal period were followed up in the high risk clinic for 18 mo and neurodevelopmental assessment was done using Developmental Assessment Scale for Indian Infants (DASII). Neurodevelopmental outcomes between the two groups were compared using Chi square test and neuronal biomarker levels between the groups were compared using Mann Whitney test.

Results

The baseline maternal and neonatal characteristics in both groups were comparable. There was statistically insignificant lesser mortality in therapeutic hypothermia group compared to normothermia group with Risk Ratio (RR): 0.82 (28.2% vs. 34.5%, 95% CI: 0.52–1.29, p = 0.38). Among the survivors, children in therapeutic hypothermia group had better motor and mental scores compared to those in normothermia group at 18 mo. There was no significant correlation between S100B and Neuron specific enolase levels and neurodevelopmental outcome.

Conclusions

Serum levels of neuronal biomarkers (S100B and Neuron specific enolase) do not correlate with the long term neurodevelopmental outcome among these infants.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Kurinczuk JJ, White-Koning M, Badawi N. Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum Dev. 2010;86:329–38.

    Article  Google Scholar 

  2. Shankaran S. Current status of hypothermia for hypoxemic ischemia of the newborn. Indian J Pediatr. 2014;81:578–84.

    Article  Google Scholar 

  3. Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev. 2013;1:CD003311.

    Google Scholar 

  4. Bhat BV, Adhisivam B. Therapeutic cooling for perinatal asphyxia-Indian experience. Indian J Pediatr. 2014;81:585–91.

    Article  Google Scholar 

  5. Bhat BV, Adhisivam B. Therapeutic hypothermia in hypoxic-ischemic encephalopathy. Indian J Pediatr. 2015;82:105–6.

    Article  Google Scholar 

  6. Goncalves CA, Leite MC, Nardin P. Biological and methodological features of the measurement of S100B, a putative marker of brain injury. Clin Biochem. 2008;41:755–63.

    Article  CAS  Google Scholar 

  7. Kaiser E, Kuzmits R, Pregant P, Burghuber O, Worofka W. Clinical biochemistry of neuron-specific enolase. Clin Chim Acta. 1989;183:13–31.

    Article  CAS  Google Scholar 

  8. Massaro N, Chang T, Kadom N, Tsuchida T, Scafidi J, Glass P. Biomarkers of brain injury in neonatal encephalopathy treated with hypothermia. J Pediatr. 2012;161:434–40.

    Article  CAS  Google Scholar 

  9. Celtik C, Acunas B, Oner N, Pala O. Neuron-specific enolase as a marker of the severity and outcome of hypoxic ischemic encephalopathy. Brain Dev. 2004;26:398–402.

  10. Bharadwaj SK, Bhat BV. Therapeutic hypothermia using gel packs for term neonates with hypoxic ischaemic encephalopathy in resource-limited settings: a randomized controlled trial. J Trop Pediatr. 2012;58:382–8.

    Article  Google Scholar 

  11. Thomas N, Abiramalatha T, Bhat V, et al. Phase changing material for therapeutic hypothermia in neonates with hypoxic ischemic encephalopathy - a multi-centric study. Indian Pediatr. 2018;55:201–5.

    Article  Google Scholar 

  12. Phatak P. Developmental assessment scales for Indian infants (DASII) – revised Baroda norms manual. 1997.

  13. Bharadwaj SK, Bhat BV, Vickneswaran V, Adhisivam B, Bobby Z, Habeebullah S. Oxidative stress, antioxidant status and neurodevelopmental outcome in neonates born to pre-eclamptic mothers. Indian J Pediatr. 2018;85:351–7.

    Article  Google Scholar 

  14. Pauliah SS, Shankaran S, Wade A, Cady EB, Thayyil S. Therapeutic hypothermia for neonatal encephalopathy in low- and middle-income countries: a systematic review and meta-analysis. PLoS One. 2013;8:e58834.

    Article  CAS  Google Scholar 

  15. Graham EM, Everett AD, Delpech JC, Northington FJ. Blood biomarkers for evaluation of perinatal encephalopathy: state of the art. Curr Opin Pediatr. 2018;30:199–203.

    Article  Google Scholar 

  16. Massaro AN, Chang T, Baumgart S, McCarter R, Nelson KB, Glass P. Biomarkers S100B and neuron-specific enolase predict outcome in hypothermia-treated encephalopathic newborns. Pediatr Crit Care Med. 2014;15:615–22.

    Article  Google Scholar 

  17. Nagdyman N, Komen W, Ko HK, Muller C, Obladen M. Early biochemical indicators of hypoxic-ischemic encephalopathy after birth asphyxia. Pediatr Res. 2001;49:502–6.

    Article  CAS  Google Scholar 

  18. Nagdyman N, Grimmer I, Scholz T, Muller C, Obladen M. Predictive value of brain- specific proteins in serum for neurodevelopmental outcome after birth asphyxia. Pediatr Res. 2003;54:270–5.

    Article  CAS  Google Scholar 

  19. Roka A, Kelen D, Halasz J, Beko G, Azzopardi D, Szabo M. Serum S100B and neuron- specific enolase levels in normothermic and hypothermic infants after perinatal asphyxia. Acta Paediatr. 2012;101:319–23.

    Article  CAS  Google Scholar 

  20. Massaro AN, Jeromin A, Kadom N, et al. Serum biomarkers of MRI brain injury in neonatal hypoxic ischemic encephalopathy treated with whole-body hypothermia: a pilot study. Pediatr Crit Care Med. 2013;14:310–7.

    Article  Google Scholar 

  21. Douglas-Escobar M, Yang C, Bennett J, et al. A pilot study of novel biomarkers in neonates with hypoxic-ischemic encephalopathy. Pediatr Res. 2010;68:531–6.

    Article  CAS  Google Scholar 

  22. Chalak LF, Sanchez PJ, Adams-Huet B, Laptook AR, Heyne RJ, Rosenfeld CR. Biomarkers for severity of neonatal hypoxic-ischemic encephalopathy and outcomes in newborns receiving hypothermia therapy. J Pediatr. 2014;164:468–74.

    Article  CAS  Google Scholar 

  23. Douglas-Escobar MV, Heaton SC, Bennett J, et al. UCH- L1 and GFAP serum levels in neonates with hypoxic-ischemic encephalopathy: a single center pilot study. Front Neurol. 2014;5:273.

    Article  Google Scholar 

  24. Thorngren-Jerneck K, Alling C, Herbst A, Amer-Wahlin I, Marsal K. S100 protein in serum as a prognostic marker for cerebral injury in term newborn infants with hypoxic ischemic encephalopathy. Pediatr Res. 2004;55:406–12.

    Article  CAS  Google Scholar 

  25. Liu F, Yang S, Du Z, Guo Z. Dynamic changes of cerebral-specific proteins in full-term newborns with hypoxic-ischemic encephalopathy. Cell Biochem Biophys. 2013;66:389–96.

    Article  CAS  Google Scholar 

  26. Ennen CS, Huisman TA, Savage WJ, et al. Glial fibrillary acidic protein as a biomarker for neonatal hypoxic-ischemic encephalopathy treated with whole-body cooling. Am J Obstet Gynecol. 2011;205:251.

    Article  CAS  Google Scholar 

  27. Alshweki A, Pérez-Muñuzuri A, López-Suárez O, Baña A, Couce ML, Wane D. Relevance of urinary S100B protein levels as a short-term prognostic biomarker in asphyxiated infants treated with hypothermia. Medicine. 2017;96:e8453.

    Article  CAS  Google Scholar 

  28. Massaro AN, Wu YW, Bammler TK, et al. Plasma biomarkers of brain injury in neonatal hypoxic-ischemic encephalopathy. J Pediatr. 2018;194:67–75.e1.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neonatology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, 605006, India

    R. Christina Catherine, B. Vishnu Bhat, B. Adhisivam & Shruthi K. Bharadwaj

  2. Department of Pediatrics and Neonatology, AVMC, Kirumampakkam, Puducherry, 607402, India

    B. Vishnu Bhat

  3. Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India

    Vickneshwaran Vinayagam

  4. Department of Preventive & Social Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India

    Palanivel Chinnakali

Authors
  1. R. Christina Catherine
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. Vishnu Bhat
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. Adhisivam
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shruthi K. Bharadwaj
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Vickneshwaran Vinayagam
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Palanivel Chinnakali
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

RCC: helped in data collection; BVB: designed and supervised study and edited manuscript; BA: helped in designing study, data analysis and drafting manuscript; SKB: helped in data collection and clinical management; VV: helped in biomarker assay; PC: data analysis. BVB is the guarantor for this paper.

Corresponding author

Correspondence to B. Vishnu Bhat.

Ethics declarations

Conflict of Interest

None.

Source of Funding

Department of Biotechnology, Government of India (Grant No. BT/PR8717/MED/97/141/2013).

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Catherine, R.C., Bhat, B.V., Adhisivam, B. et al. Neuronal Biomarkers in Predicting Neurodevelopmental Outcome in Term Babies with Perinatal Asphyxia. Indian J Pediatr 87, 787–792 (2020). https://doi.org/10.1007/s12098-020-03283-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12098-020-03283-2

Keywords

Search

Navigation