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  • Clinical Research Article
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Seizures after initiation of rewarming in cooled infants with hypoxic ischaemic encephalopathy

Pediatric Research volume 95, pages 752–757 (2024)Cite this article

Abstract

Background

Seizures after initiation of rewarming from therapeutic hypothermia for neonatal encephalopathy are well recognised but not easy to predict.

Methods

A secondary analysis was performed of NEOLEV2 trial data, a multicentre randomised trial of levetiracetam versus phenobarbital for neonatal seizures. Enrolled infants underwent continuous video EEG (cEEG) monitoring. The trial data were reviewed for 42 infants with seizures during therapeutic hypothermia and 118 infants who received therapeutic hypothermia but had no seizures on cEEG.

Results

Overall, 112 of 160 (70%) had cEEG monitoring continued until rewarming was completed. Of the 42 infants with prior seizures, there were 30 infants with valid cEEG available and seizures occurred following the initiation of rewarming in 8 (26.6%). For the 118 seizure-naive infants, 82 (69.5%) continued cEEG until either rewarming was completed or 90 h of age and none had documented seizures.

Conclusion

Overall, just over a quarter of infants with prior seizures had cEEG evidence of at least one seizure in the 24 h after initiation of rewarming but no seizure-naive infant had cEEG evidence of seizure(s) on rewarming. Critically, by reporting the two groups separately, the data can provide guidance on the duration of EEG monitoring.

Impact

  • Infants with hypoxic ischaemic encephalopathy who have cEEG evidence of seizures during therapeutic hypothermia have a significant risk of further seizures on rewarming.

  • For infants with hypoxic ischaemic encephalopathy but no cEEG evidence of seizures during therapeutic hypothermia, there is very little risk of de novo seizures.

  • Ongoing work utilising large cohorts may generate EEG criteria that refine estimates of risk for rewarming seizures.

  • Based on current experience, if seizures have occurred during therapeutic hypothermia for hypoxic ischaemic encephalopathy, the EEG monitoring should be continued during rewarming and for 12 h thereafter to minimise the risk of missing an event.

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Fig. 1: Seizure burden per day for the whole cohort during receipt of therapeutic hypothermia.
Fig. 2: Flow diagram to illustrate the selection of infants from NEOLEV2 study cohort who had seizures during TH.

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Data availability

The data that support the findings of this study are not publicly available due to privacy considerations of the research participants. However, some data items are potentially available via the corresponding author, upon reasonable request.

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Acknowledgements

We acknowledge the work of all the NEOLEV2 investigators and particularly the neurophysiologists Mark Nespeca, Jeff Gold, Sonya Wang, Neggy Rismanchi, Rachel Kuperman, Minh Le, Andrew Mower and Emma Macdonald-Laurs.

Funding

The NEOLEV2 study was funded by the US Food and Drug Administration Orphan Products Division (1 RO1FD004147). M.R.B. has research time supported by a Health Research Council, Clinical Practitioner Research Fellowship (20/030). S.L.D. was funded by Starship Foundation for time reviewing EEGs.

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Authors and Affiliations

  1. Newborn Service, Auckland City Hospital, Auckland, New Zealand

    Malcolm R. Battin

  2. Paediatric Neurology, Starship Hospital, Auckland, New Zealand

    Suzanne L. Davis & Cynthia Sharpe

  3. Pediatric Neurology, UCSF Benioff Children’s Hospital, Oakland, CA, USA

    Marisa Gardner

  4. Neonatology, UCSF Benioff Children’s Hospital, Oakland, CA, USA

    Priscilla Joe

  5. Neonatology, Sharp Mary Birch Hospital for Women and Newborns, San Diego, CA, USA

    Maynard Rasmussen

  6. Department of Neurosciences and Pediatrics, University of California, San Diego, CA, USA

    Richard Haas

Authors
  1. Malcolm R. Battin
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  3. Marisa Gardner
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  5. Maynard Rasmussen
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  7. Cynthia Sharpe
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Contributions

M.R.B., S.L.D. and C.S. conceptualised the study. R.H. and C.S. conceptualised the NEOLEV2 trial. S.L.D. reviewed the EEG traces. M.R.B. performed the initial analyses with input from C.S. and S.L.D. M.R.B. drafted the initial manuscript. All authors contributed to the interpretations of the data and analyses, provided input on the manuscript and approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.

Corresponding author

Correspondence to Malcolm R. Battin.

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Competing interests

M.R.B., S.L.D., M.G., P.J., M.R. and R.H. have indicated they have no potential conflicts of interest to disclose. C.S. has done consulting work for Sun Pharmaceuticals.

Consent to participate

Consent was obtained from parents of all children enrolled in the trial, including infants who were monitored but did not receive trial medication.

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Battin, M.R., Davis, S.L., Gardner, M. et al. Seizures after initiation of rewarming in cooled infants with hypoxic ischaemic encephalopathy. Pediatr Res 95, 752–757 (2024). https://doi.org/10.1038/s41390-023-02863-0

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