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Therapeutic Hypothermia in Neonatal Hypoxic-Ischemic Encephalopathy


Purpose of Review

Therapeutic hypothermia reduces death or disability in term and near-term infants with moderate-severe hypoxic-ischemic encephalopathy. Nevertheless, many infants still survive with disability, despite hypothermia, supporting further research in to ways to further improve neurologic outcomes.

Recent Findings

Recent clinical and experimental studies have refined our understanding of the key parameters for hypothermic neuroprotection, including timing of initiation, depth, and duration of hypothermia, and subsequent rewarming rate. However, important knowledge gaps remain. There is encouraging clinical evidence from a small phase II trial that combined treatment of hypothermia with recombinant erythropoietin further reduces risk of disability but definitive studies are still needed.


In conclusion, recent studies suggest that current protocols for therapeutic hypothermia are near-optimal, and that the key to better neurodevelopmental outcomes is earlier diagnosis and initiation of hypothermia after birth. Further research is essential to find and evaluate ways to further improve outcomes after hypoxic-ischemic encephalopathy, including add-on therapies for therapeutic hypothermia and preventing pyrexia during labor and delivery.

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Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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The authors’ work reported in this review has been supported by grants from the Health Research Council of New Zealand, New Zealand Lottery Grants Board, the Auckland Medical Research Foundation, the Neurological Foundation of New Zealand, the Norwegian Research Council, and the Moulton Foundation UK.

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Correspondence to Alistair J. Gunn.

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Conflict of Interest

Laura Bennet, Joanne Davidson, Simerdeep Dhillon, Marianne Thoresen, Guido Wassink and Kelly Zhou each declare no potential conflicts of interest. Alistair J. Gunn reports a US patent 6,986,783 issued. Patent held by the University of Auckland.

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Wassink, G., Davidson, J.O., Dhillon, S.K. et al. Therapeutic Hypothermia in Neonatal Hypoxic-Ischemic Encephalopathy. Curr Neurol Neurosci Rep 19, 2 (2019).

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  • Neonatal encephalopathy
  • Therapeutic hypothermia
  • Neonatal neuroprotection
  • Fetal sheep
  • Erythropoietin
  • Neonatal examination