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.

  • Article
  • Published:

Therapeutic hypothermia for hypoxic-ischemic encephalopathy after perinatal sentinel events: less brain injury on MRI and improved neurodevelopmental outcome at 18–36 months

Journal of Perinatology volume 40, pages 633–639 (2020)Cite this article

Subjects

Abstract

Objective

To study the association between perinatal sentinel events (PSE) and brain MRI/neurodevelopmental outcomes in neonates with hypoxic-ischemic encephalopathy (HIE) receiving therapeutic hypothermia (TH).

Design

This is a retrospective single-center study. Data collection included perinatal history, brain MRI, and neurodevelopmental outcome.

Results

Out of the 182 neonates, 53 (29%) neonates had PSE and 129 (71%) neonates did not have PSE. Neonates with PSE had more normal MRIs (76%) compared with neonates without PSE (55%), p = 0.01. PSE was associated with favorable motor (p = 0.02), language outcome (p = 0.03), and trend to better cognitive scores (p = 0.13). In PSE, favorable motor outcome persisted (OR for impairment 0.15 (0.003–0.84), p = 0.03) after adjusting for the degree of encephalopathy and brain MRI injury. Injury on brain MRI despite TH after PSE was associated with unfavorable neurodevelopmental outcome (p < 0.001).

Conclusion

Neonates with HIE receiving TH after PSE had less severe injury on brain MRI after rewarming, and improved motor and language outcomes at 18–36 months.

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

Similar content being viewed by others

Data availability

The datasets used and/or analyzed during this study are available from the corresponding author on reasonable request.

References

  1. Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005;353:1574–84.

    Article  CAS  Google Scholar 

  2. Azzopardi DV, Strohm B, Edwards AD, Dyet L, Halliday HL, Juszczak E, et al. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med. 2009;361:1349–58.

    Article  CAS  Google Scholar 

  3. Jacobs SE, Morley CJ, Inder TE, Stewart MJ, Smith KR, McNamara PJ, et al. Whole-body hypothermia for term and near-term newborns with hypoxic-ischemic encephalopathy: a randomized controlled trial. Arch Pediatr Adolesc Med. 2011;165:692–700.

    Article  Google Scholar 

  4. Badawi N, Kurinczuk JJ, Keogh JM, Alessandri LM, O’Sullivan F, Burton PR, et al. Intrapartum risk factors for newborn encephalopathy: the Western Australian case-control study. BMJ. 1998;317:1554–8.

    Article  CAS  Google Scholar 

  5. Locatelli A, Incerti M, Paterlini G, Doria V, Consonni S, Provero C, et al. Antepartum and intrapartum risk factors for neonatal encephalopathy at term. Am J Perinatol. 2010;27:649–54.

    Article  Google Scholar 

  6. Martinez-Biarge M, Madero R, González A, Quero J, García-Alix A. Perinatal morbidity and risk of hypoxic-ischemic encephalopathy associated with intrapartum sentinel events. Am J Obstet Gynecol. 2012;206:148.e141–7.

    Article  Google Scholar 

  7. Martinez-Biarge M, Diez-Sebastian J, Wusthoff CJ, Mercuri E, Cowan FM. Antepartum and intrapartum factors preceding neonatal hypoxic-ischemic encephalopathy. Pediatrics. 2013;132:e952–9.

    Article  Google Scholar 

  8. Novak CM, Eke AC, Ozen M, Burd I, Graham EM. Risk factors for neonatal hypoxic-ischemic encephalopathy in the absence of sentinel events. Am J Perinatol. 2019;36:27–33.

    Article  Google Scholar 

  9. Gunn AJ, Gunn TR, de Haan HH, Williams CE, Gluckman PD. Dramatic neuronal rescue with prolonged selective head cooling after ischemia in fetal lambs. J Clin Invest. 1997;99:248–56.

    Article  CAS  Google Scholar 

  10. Gunn AJ, Gunn TR, Gunning MI, Williams CE, Gluckman PD. Neuroprotection with prolonged head cooling started before postischemic seizures in fetal sheep. Pediatrics. 1998;102:1098–106.

    Article  CAS  Google Scholar 

  11. Kasdorf E, Grunebaum A, Perlman JM. Subacute hypoxia-ischemia and the timing of injury in treatment with therapeutic hypothermia. Pediatr Neurol. 2015;53:417–21.

    Article  Google Scholar 

  12. de Vries LS, Groenendaal F. Patterns of neonatal hypoxic-ischaemic brain injury. Neuroradiology. 2010;52:555–66.

    Article  Google Scholar 

  13. Shankaran S, Laptook AR, McDonald SA, Hintz SR, Barnes PD, Das A. et al. Acute perinatal sentinel events, neonatal brain injury pattern, and outcome of infants undergoing a trial of hypothermia for neonatal hypoxic-ischemic encephalopathy. J Pediatr. 2017;180:275–8.

    Article  Google Scholar 

  14. Okereafor A, Allsop J, Counsell SJ, Fitzpatrick J, Azzopardi D, Rutherford MA, et al. Patterns of brain injury in neonates exposed to perinatal sentinel events. Pediatrics. 2008;121:906–14.

    Article  Google Scholar 

  15. Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol. 1976;33:696–705.

    Article  CAS  Google Scholar 

  16. Barkovich AJ, Hajnal BL, Vigneron D, Sola A, Partridge JC, Allen F, et al. Prediction of neuromotor outcome in perinatal asphyxia: evaluation of MR scoring systems. AJNR Am J Neuroradiol. 1998;19:143–9.

    CAS  PubMed  Google Scholar 

  17. Bayley N. Manual for the Bayley Scales of infant and toddler development. 3rd ed. San Antonio, TX: Harcourt Assessment; 2006.

    Google Scholar 

  18. West CR, Curr L, Battin MR, Harding JE, McCowan LM, Belgrave S, et al. Antenatal antecedents of moderate or severe neonatal encephalopathy in term infants-a regional review. Aust N. Z J Obstet Gynaecol. 2005;45:207–10.

    Article  Google Scholar 

  19. Nelson KB, Bingham P, Edwards EM, Horbar JD, Kenny MJ, Inder T, et al. Antecedents of neonatal encephalopathy in the vermont oxford network encephalopathy registry. Pediatrics. 2012;130:878–86.

    Article  Google Scholar 

  20. Sarkar S, Donn SM, Bapuraj JR, Bhagat I, Dechert RE, Barks JD. The relationship between clinically identifiable intrapartum sentinel events and short-term outcome after therapeutic hypothermia. J Pediatr. 2011;159:726–30.

    Article  Google Scholar 

  21. 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;CD003311.

  22. Shah PS, Perlman M. Time courses of intrapartum asphyxia: neonatal characteristics and outcomes. Am J Perinatol. 2009;26:39–44.

    Article  Google Scholar 

  23. Shankaran S, Laptook AR, Pappas A, McDonald SA, Das A, Tyson JE, et al. Effect of depth and duration of cooling on death or disability at age 18 months among neonates with hypoxic-ischemic encephalopathy: a randomized clinical trial. JAMA. 2017;318:57–67.

    Article  Google Scholar 

  24. Thoresen M, Tooley J, Liu X, Jary S, Fleming P, Luyt K, et al. Time is brain: starting therapeutic hypothermia within three hours after birth improves motor outcome in asphyxiated newborns. Neonatology. 2013;104:228–33.

    Article  Google Scholar 

  25. Mcintyre S, Badawi N, Blair E, Nelson KB. Does aetiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy influence the outcome of treatment? Dev Med Child Neurol. 2015;57(Suppl 3):2–7.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

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

    Beate Grass, Amr El Shahed, Linh G. Ly, Vann Chau, Diane Wilson & Hilary Whyte

  2. Department of Pediatrics, Mansoura University, Mansoura, Egypt

    Amr El Shahed

  3. Department of Pediatrics, University of Toronto, Toronto, ON, Canada

    Linh G. Ly & Hilary Whyte

  4. Neonatal Neuroscience Team, The Hospital for Sick Children, Toronto, ON, Canada

    Vann Chau

  5. Department of Diagnostic Imaging, The Hospital for Sick Children, Toronto, ON, Canada

    Helen M. Branson & Susan Blaser

  6. CV Data Management Centre, The Hospital for Sick Children, Toronto, ON, Canada

    Kyle Runeckles

Authors
  1. Beate Grass
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amr El Shahed
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Linh G. Ly
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vann Chau
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Helen M. Branson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Susan Blaser
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kyle Runeckles
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Diane Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hilary Whyte
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

BG and AES made the conception and design of the study; they were responsible for acquisition of data, data analysis and interpretation, search and review of literature, and drafting of this paper. LGL, VC, HMB, SB, and DW helped with the acquisition of data, data interpretation, and critical review of this paper. KR performed all statistical analyses of the study and critically revised the paper. HW supervised conception and design of the study, data analysis and interpretation, search and review of literature, and critical review of this paper. All authors have read and approved the final paper.

Corresponding author

Correspondence to Beate Grass.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval and consent to participate

Data collection and evaluation for this study were approved by the Research and Ethics Board (REB) at The Hospital for Sick Children, Toronto, Canada, REB file number: 1000041535. Consent for publication is entailed in the approval. Written consent for the standard medical care given to the neonate as described in this observational study was obtained from the parents.

Additional information

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

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Grass, B., El Shahed, A., Ly, L.G. et al. Therapeutic hypothermia for hypoxic-ischemic encephalopathy after perinatal sentinel events: less brain injury on MRI and improved neurodevelopmental outcome at 18–36 months. J Perinatol 40, 633–639 (2020). https://doi.org/10.1038/s41372-020-0602-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-020-0602-8

This article is cited by

Search

Advanced search

Quick links