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.

  • Comment
  • Published:

The predictive role of brain magnetic resonance imaging in neonates with hypoxic-ischemic encephalopathy

Pediatric Research volume 95, pages 601–602 (2024)Cite this article

The article by Wu et al.1 reported on how neonatal neuroimaging correlates with neurodevelopmental outcomes in infants with hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia. The study comprised a large cohort of neonates who were recruited to the multicenter randomized controlled High-Dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial2 and underwent a harmonized neuroimaging protocol within a narrow time window. The modified intention to treat analysis enabled the investigators to include 500 infants with presumed HIE in the final analysis, making it the largest study on the subject matter to date. As the authors point out, it is important to determine the best neuroimaging biomarkers of neurodevelopmental outcomes in infants with HIE to improve our ability to counsel families. However, we would like to raise several concerns in regard to the use of the injury classification, which reported substantial overlap between normal, mild, and moderate categories for predicting outcome, and the conclusion that in the absence of severe brain injury, MRI does not accurately predict neurodevelopmental outcomes.

When brain MRI is used for prognostication, not all anatomical areas are weighted equally and injury to particular regions of the brain requires special attention for identifying infants who are at risk of long-term neurodevelopmental impairments (NDI). The scoring system developed by Trivedi et al.3 used in the present study takes into account the extent of injury in the basal ganglia and thalami regions of the brain; however, there is much less representation of white matter areas, which could lead to underestimation of extensive white matter injury. Additionally, involvement of the descending corticospinal tract fibers puts the infant at high risk of developing motor deficits but injury to the cerebral peduncles is not specifically quantified in the study, instead, the brainstem is assessed broadly; also co-existing conditions such as parenchymal white matter hemorrhages, cerebral sinovenous thrombosis, and intraventricular hemorrhage are not taken into account, all of which may be additional risk factors for adverse neurodevelopmental outcomes.4 Although MR spectroscopy was assessed separately in the present study, this is also not included in the Trivedi scoring system; neither is an evaluation of particular anatomical areas such as the hippocampus and optic radiations, which may also have neurodevelopmental implications.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Data availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

References

  1. Wu, Y. W. et al. How well does neonatal neuroimaging correlate with neurodevelopmental outcomes in infants with hypoxic-ischemic encephalopathy? Pediatr. Res. https://doi.org/10.1038/s41390-023-02510-8, 1–8 (2023).

  2. Wu, Y. W. et al. Trial of erythropoietin for hypoxic-ischemic encephalopathy in newborns. N. Engl. J. Med. 387, 148–159 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Trivedi, S. B. et al. A validated clinical MRI injury scoring system in neonatal hypoxic-ischemic encephalopathy. Pediatr. Radio. 47, 1491–1499 (2017).

    Article  Google Scholar 

  4. Martinez-Biarge, M., Diez-Sebastian, J., Rutherford, M. A. & Cowan, F. M. Outcomes after central grey matter injury in term perinatal hypoxic-ischaemic encephalopathy. Early Hum. Dev. 86, 675–682 (2010).

    Article  PubMed  Google Scholar 

  5. Langeslag, J. F. et al. Outcome prediction and inter-rater comparison of four brain magnetic resonance imaging scoring systems of infants with perinatal asphyxia and therapeutic hypothermia. Neonatology 119, 311–319 (2022).

    Article  CAS  PubMed  Google Scholar 

  6. Thoresen, M. et al. MRI combined with early clinical variables are excellent outcome predictors for newborn infants undergoing therapeutic hypothermia after perinatal asphyxia. EclinicalMedicine 36, 100885 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Weeke, L. C. et al. A novel magnetic resonance imaging score predicts neurodevelopmental outcome after perinatal asphyxia and therapeutic hypothermia. J. Pediatr. 192, 33–40 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Ni Bhroin, M. et al. Relationship between MRI scoring systems and neurodevelopmental outcome at two years in infants with neonatal encephalopathy. Pediatr. Neurol. 126, 35–42 (2022).

    Article  PubMed  Google Scholar 

  9. Martinez-Biarge, M. et al. White matter and cortical injury in hypoxic-ischemic encephalopathy: antecedent factors and 2-year outcome. J. Pediatr. 161, 799–807 (2012).

    Article  PubMed  Google Scholar 

  10. Harteman, J. C. et al. Diffusion-weighted imaging changes in cerebral watershed distribution following neonatal encephalopathy are not invariably associated with an adverse outcome. Dev. Med. Child. Neurol. 55, 642–653 (2013).

    Article  PubMed  Google Scholar 

  11. Parmentier, C. E. J., de Vries, L. S. & Groenendaal, F. Magnetic resonance imaging in (near-)term infants with hypoxic-ischemic encephalopathy. Diagnostics (Basel) 12, 645 (2022).

    Article  PubMed  Google Scholar 

  12. Martinez-Biarge, M. et al. Predicting motor outcome and death in term hypoxic-ischemic encephalopathy. Neurology 76, 2055–2061 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

Funding

None.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Division of Neonatology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

    Mehmet N. Cizmeci

  2. Department of Pediatrics, Hammersmith Hospital, Imperial College, London, UK

    Miriam Martinez-Biarge

  3. Division of Neonatal Neurology, Hammersmith Hospital, Imperial College, London, UK

    Frances M. Cowan

  4. Division of Neonatal Neuroscience, Bristol University, Bristol, UK

    Frances M. Cowan

Authors
  1. Mehmet N. Cizmeci
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Miriam Martinez-Biarge
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Frances M. Cowan
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

M.N.C. drafted the manuscript, made revisions suggested by the authors, and approved the final version of the manuscript. M.M.-B. critically reviewed, and approved the final version of the manuscript for publication. F.M.C. critically reviewed, and approved the final version of the manuscript for publication.

Corresponding author

Correspondence to Mehmet N. Cizmeci.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

Patient consent is not required.

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

Cizmeci, M.N., Martinez-Biarge, M. & Cowan, F.M. The predictive role of brain magnetic resonance imaging in neonates with hypoxic-ischemic encephalopathy. Pediatr Res 95, 601–602 (2024). https://doi.org/10.1038/s41390-023-02732-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41390-023-02732-w

This article is cited by

Search

Advanced search

Quick links