Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Quantitative EEG and prediction of outcome in neonatal encephalopathy: a review

Abstract

Electroencephalogram (EEG) is an important biomarker for neonatal encephalopathy (NE) and has significant predictive value for brain injury and neurodevelopmental outcomes. Quantitative analysis of EEG involves the representation of complex EEG data in an objective, reproducible and scalable manner. Quantitative EEG (qEEG) can be derived from both a limited channel EEG (as available during amplitude integrated EEG) and multi-channel conventional EEG. It has the potential to enable bedside clinicians to monitor and evaluate details of cortical function without the necessity of continuous expert input. This is particularly useful in NE, a dynamic and evolving condition. In these infants, continuous, detailed evaluation of cortical function at the bedside is a valuable aide to management especially in the current era of therapeutic hypothermia and possible upcoming neuroprotective therapies. This review discusses the role of qEEG in newborns with NE and its use in informing monitoring and therapy, along with its ability to predict imaging changes and short and long-term neurodevelopmental outcomes.

Impact

  • Quantitative representation of EEG data brings the evaluation of continuous brain function, from the neurophysiology lab to the NICU bedside and has a potential role as a biomarker for neonatal encephalopathy.

  • Clinical and research applications of quantitative EEG in the newborn are rapidly evolving and a wider understanding of its utility is valuable.

  • This overview summarizes the role of quantitative EEG at different timepoints, its relevance to management and its predictive value for short- and long-term outcomes in neonatal encephalopathy.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Lee, A. C. et al. Intrapartum-related neonatal encephalopathy incidence and impairment at regional and global levels for 2010 with trends from 1990. Pediatr. Res. 74, 50–72 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  2. Sarnat, H. B. & Sarnat, M. S. Neonatal encephalopathy following fetal distress: a clinical and electroencephalographic study. Arch. Neurol. 33 https://doi.org/10.1001/archneur.1976.00500100030012 (1976).

  3. Azzopardi, D. V. et al. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N. Engl. J. Med. 361, 1349–1358 (2009).

    Article  CAS  PubMed  Google Scholar 

  4. Weeke, L. C. Role of EEG background activity, seizure burden and MRI in predicting neurodevelopmental outcome in full-term infants with hypoxic-ischaemic encephalopathy in the era of therapeutic hypothermia. Eur. J. Paediatr. Neurol. 20 https://doi.org/10.1016/j.ejpn.2016.06.003 (2016).

  5. Ouwehand, S. et al. Predictors of outcomes in hypoxic-ischemic encephalopathy following hypothermia: a meta-analysis. Neonatology 117, 411–427 (2020).

    Article  CAS  PubMed  Google Scholar 

  6. Peeples, E. S. et al. Predictive models of neurodevelopmental outcomes after neonatal hypoxic-ischemic encephalopathy. Pediatrics 147, e2020022962 (2021).

    Article  PubMed  Google Scholar 

  7. del Río, R. et al. Amplitude integrated electroencephalogram as a prognostic tool in neonates with hypoxic-ischemic encephalopathy: a systematic review. PLoS ONE 11, e0165744 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Toole, J. M. O. & Boylan, G. B. NEURAL: quantitative features for newborn EEG using Matlab. http://arxiv.org/abs/1704.05694 (2017).

  9. Finn, D., O’Toole, J. M., Dempsey, E. M. & Boylan, G. B. EEG for the assessment of neurological function in newborn infants immediately after birth. Arch. Dis. Child Fetal Neonatal Ed. 104, F510–F514 (2019).

    Article  PubMed  Google Scholar 

  10. Paul, K., Krajča, V., Roth, Z., Melichar, J. & Petránek, S. Comparison of quantitative EEG characteristics of quiet and active sleep in newborns. Sleep Med. 4, 543–552 (2003).

    Article  PubMed  Google Scholar 

  11. Suppiej, A. et al. Spectral analysis highlight developmental EEG changes in preterm infants without overt brain damage. Neurosci. Lett. 649, 112–115 (2017).

    Article  CAS  PubMed  Google Scholar 

  12. Gavrisheva, N. V. & Gavrishev, A. A. Nonlinear dynamics methods for neonatal EEG differentiation. Biomed. Eng. 55, 294–296 (2021).

    Article  Google Scholar 

  13. Greene, B. R. et al. A comparison of quantitative EEG features for neonatal seizure detection. Clin. Neurophysiol. 119, 1248–1261 (2008).

    Article  CAS  PubMed  Google Scholar 

  14. van ’t Westende, C. et al. Neonatal quantitative electroencephalography and long‐term outcomes: a systematic review. Dev. Med. Child Neurol. 64, 413–420 (2022).

    Article  PubMed  Google Scholar 

  15. Raurale, S. A. et al. Grading hypoxic-ischemic encephalopathy in neonatal EEG with convolutional neural networks and quadratic time–frequency distributions. J. Neural Eng. 18, 046007 (2021).

    Article  PubMed Central  Google Scholar 

  16. Vesoulis, Z. A. et al. WU-NEAT: a clinically validated, open-source MATLAB toolbox for limited-channel neonatal EEG analysis. Comput. Methods Prog. Biomed. 196, 105716 (2020).

    Article  Google Scholar 

  17. Bakheet, D., Alotaibi, N., Konn, D., Vollmer, B. & Maharatna, K. Prediction of cerebral palsy in newborns with hypoxic-ischemic encephalopathy using multivariate EEG analysis and machine learning. IEEE Access 9, 137833–137846 (2021).

    Article  Google Scholar 

  18. Korotchikova, I., Stevenson, N. J., Walsh, B. H., Murray, D. M. & Boylan, G. B. Quantitative EEG analysis in neonatal hypoxic ischaemic encephalopathy. Clin. Neurophysiol. 122, 1671–1678 (2011).

    Article  CAS  PubMed  Google Scholar 

  19. Moghadam, S. M. et al. An automated bedside measure for monitoring neonatal cortical activity: a supervised deep learning-based electroencephalogram classifier with external cohort validation. Lancet Digit. Health 4, e884–e892 (2022).

    Article  CAS  PubMed  Google Scholar 

  20. Delorme, A. & Makeig, S. EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis. J. Neurosci. Methods 134, 9–21 (2004).

    Article  PubMed  Google Scholar 

  21. Pavel, A. M. et al. A machine-learning algorithm for neonatal seizure recognition: a multicentre, randomised, controlled trial. Lancet Child Adolesc. Health 4, 740–749 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Pavel, A. M. et al. Machine learning for the early prediction of infants with electrographic seizures in neonatal hypoxic‐ischemic encephalopathy. Epilepsia 64, 456–468 (2023).

    Article  PubMed  Google Scholar 

  23. Lacan, L. et al. Quantitative approach to early neonatal EEG visual analysis in hypoxic-ischemic encephalopathy severity: bridging the gap between eyes and machine. Neurophysiol. Clin. 51, 121–131 (2021).

    Article  PubMed  Google Scholar 

  24. Stevenson, N. J. An automated system for grading EEG abnormality in term neonates with hypoxic-ischaemic encephalopathy. https://hollis.harvard.edu/primo-explore/fulldisplaydocid=TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3605495&vid=HVD2&search_scope=everything&tab=everything&lang=en_US&context=PC (2013).

  25. Garvey, A. A. et al. Multichannel EEG abnormalities during the first 6 h in infants with mild hypoxic–ischaemic encephalopathy. Pediatr. Res. 90, 117–124 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  26. Conway, J. M., Walsh, B. H., Boylan, G. B. & Murray, D. M. Mild hypoxic ischaemic encephalopathy and long term neurodevelopmental outcome—a systematic review. Early Hum. Dev. 120 https://doi.org/10.1016/j.earlhumdev.2018.02.007 (2018).

  27. Jain, S. V. et al. Prediction of neonatal seizures in hypoxic-ischemic encephalopathy using electroencephalograph power analyses. Pediatr. Neurol. 67, 64–70.e2 (2017).

    Article  PubMed  Google Scholar 

  28. Sansevere, A. J. et al. Seizure prediction models in the neonatal intensive care unit. J. Clin. Neurophysiol. Publ. Am. Electroencephalogr. Soc. 36, 186–194 (2019).

    Google Scholar 

  29. McKee, J. L. et al. Leveraging electronic medical record-embedded standardised electroencephalogram reporting to develop neonatal seizure prediction models: a retrospective cohort study. Lancet Digit. Health 5, e217–e226 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Bell, A. H., McClure, B. G. & Hicks, E. M. Power spectral analysis of the EEG of term infants following birth asphyxia. Dev. Med. Child Neurol. 32, 990–998 (1990).

    Article  CAS  PubMed  Google Scholar 

  31. Abend, N. S. et al. EEG monitoring during therapeutic hypothermia in neonates, children, and adults. Am. J. Electroneurodiagnostic Technol. 51, 141–164 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Nash, K. B. et al. Video-EEG monitoring in newborns with hypoxic-ischemic encephalopathy treated with hypothermia. Neurology 76, 556–562 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Hamelin, S., Delnard, N., Cneude, F., Debillon, T. & Vercueil, L. Influence of hypothermia on the prognostic value of early EEG in full-term neonates with hypoxic ischemic encephalopathy. Neurophysiol. Clin. Neurophysiol. 41, 19–27 (2011).

    Article  CAS  Google Scholar 

  34. Hathi, M. et al. Quantitative EEG in babies at risk for hypoxic ischemic encephalopathy after perinatal asphyxia. J. Perinatol. 30, 122–126 (2010).

    Article  CAS  PubMed  Google Scholar 

  35. Burnsed, J., Quigg, M., Zanelli, S. & Goodkin, H. P. Clinical severity, rather than body temperature, during the rewarming phase of therapeutic hypothermia affect quantitative EEG in neonates with hypoxic ischemic encephalopathy. J. Clin. Neurophysiol. 28, 10–14 (2011).

    Article  PubMed  Google Scholar 

  36. Birca, A. et al. Rewarming affects EEG background in term newborns with hypoxic–ischemic encephalopathy undergoing therapeutic hypothermia. Clin. Neurophysiol. 127, 2087–2094 (2016).

    Article  PubMed  Google Scholar 

  37. Matic, V. et al. Improving reliability of monitoring background EEG dynamics in asphyxiated infants. IEEE Trans. Biomed. Eng. 63, 973–983 (2016).

    Article  PubMed  Google Scholar 

  38. Kota, S. et al. Prognostic value of continuous electroencephalogram delta power in neonates with hypoxic-ischemic encephalopathy. J. Child Neurol. 35, 517–525 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Kim, K. Y., Lee, J. Y., Moon, J. U., Eom, T. H. & Kim, Y. H. Comparative analysis of background EEG activity based on MRI findings in neonatal hypoxic-ischemic encephalopathy: a standardized, low-resolution, brain electromagnetic tomography (sLORETA) study. BMC Neurol. 22, 204 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Dereymaeker, A. et al. Automated EEG background analysis to identify neonates with hypoxic-ischemic encephalopathy treated with hypothermia at risk for adverse outcome: a pilot study. Pediatr. Neonatol. 60, 50–58 (2019).

    Article  PubMed  Google Scholar 

  41. Dunne, J. M. et al. Automated electroencephalographic discontinuity in cooled newborns predicts cerebral MRI and neurodevelopmental outcome. Arch. Dis. Child Fetal Neonatal Ed. 102, F58–F64 (2017).

    Article  PubMed  Google Scholar 

  42. Zhang, Q., Hu, Y., Dong, X. & Feng, X. Clinical significance of electroencephalography power spectrum density and functional connection analysis in neonates with hypoxic‐ischemic encephalopathy. Int. J. Dev. Neurosci. 81, 142–150 (2021).

    Article  PubMed  Google Scholar 

  43. Alotaibi, N., Bakheet, D., Konn, D., Vollmer, B. & Maharatna, K. Cognitive outcome prediction in infants with neonatal hypoxic-ischemic encephalopathy based on functional connectivity and complexity of the electroencephalography signal. Front. Hum. Neurosci. 15, 795006 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  44. Dixon, B., Reis, C., Ho, W., Tang, J. & Zhang, J. Neuroprotective strategies after neonatal hypoxic ischemic encephalopathy. Int. J. Mol. Sci. 16, 22368–22401 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

Each of the authors listed have contributed significantly to this manuscript and met the Pediatric Research authorship requirements as elaborated below. Sriya Roychaudhuri: substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; drafting the article; final approval of the version to be published. Katie Hannon: drafting the article and final approval of the version to be published. John Sunwoo: substantial contributions to conception and design along with analysis and interpretation of previously published data; revising it critically for important intellectual content; and final approval of the version to be published. Aisling A. Garvey: drafting segments of the manuscript and revising it critically for important intellectual content; and final approval of the version to be published. Mohamed El-Dib: substantial contributions to conception and design, analysis and interpretation of data; drafting and revising the article critically for important intellectual content; final approval of the version to be published.

Corresponding author

Correspondence to Mohamed El-Dib.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

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

Consent statement As this is a review article, patient consent was not required.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Roychaudhuri, S., Hannon, K., Sunwoo, J. et al. Quantitative EEG and prediction of outcome in neonatal encephalopathy: a review. Pediatr Res 96, 73–80 (2024). https://doi.org/10.1038/s41390-024-03138-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41390-024-03138-y

Search

Quick links