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Therapeutic hypothermia initiated within 6 hours of birth is associated with reduced brain injury on MR biomarkers in mild hypoxic-ischaemic encephalopathy: a non-randomised cohort study
  1. Paolo Montaldo1,
  2. Peter J Lally1,
  3. Vânia Oliveira1,
  4. Ravi Swamy1,
  5. Josephine Mendoza1,
  6. Gaurav Atreja2,
  7. Ujwal Kariholu2,
  8. Vijayakumar Shivamurthappa2,
  9. Natasha Liow2,
  10. Justinas Teiserskas2,
  11. Russell Pryce3,
  12. Aung Soe3,
  13. Seetha Shankaran4,
  14. Sudhin Thayyil1
  1. 1 Centre for Perinatal Neuroscience, Imperial College London, London, UK
  2. 2 Neonatal Unit, Imperial Healthcare NHS Trust, London, UK
  3. 3 Oliver Fisher Neonatal Unit, Medway NHS Hospital Foundation Trust, Gillingham, UK
  4. 4 Perinatal-Neonatal Medicine, Wayne State University, Detroit, Michigan, USA
  1. Correspondence to Dr Sudhin Thayyil, Department of Paediatrics, Centre for Perinatal Neuroscience, Imperial College London, London W12 0HS, UK; s.thayyil{at}


Objective To examine the effect of therapeutic hypothermia on MR biomarkers and neurodevelopmental outcomes in babies with mild hypoxic-ischaemic encephalopathy (HIE).

Design Non-randomised cohort study.

Setting Eight tertiary neonatal units in the UK and the USA.

Patients 47 babies with mild HIE on NICHD neurological examination performed within 6 hours after birth.

Interventions Whole-body cooling for 72 hours (n=32) or usual care (n=15; of these 5 were cooled for <12 hours).

Main outcome measures MRI and MR spectroscopy (MRS) within 2 weeks after birth, and a neurodevelopmental outcome assessment at 2 years.

Results The baseline characteristics in both groups were similar except for lower 10 min Apgar scores (p=0.02) in the cooled babies. Despite this, the mean (SD) thalamic NAA/Cr (1.4 (0.1) vs 1.6 (0.2); p<0.001) and NAA/Cho (0.67 (0.08) vs 0.89 (0.11); p<0.001) ratios from MRS were significantly higher in the cooled group. Cooled babies had lower white matter injury scores than non-cooled babies (p=0.02). Four (27%) non-cooled babies with mild HIE developed seizures after 6 hours of age, while none of the cooled babies developed seizures (p=0.008). Neurodevelopmental outcomes at 2 years were available in 40 (85%) of the babies. Adverse outcomes were seen in 2 (14.3%) non-cooled babies, and none of the cooled babies (p=0.09).

Conclusions Therapeutic hypothermia may have a neuroprotective effect in babies with mild HIE, as demonstrated by improved MRS biomarkers and reduced white matter injury on MRI. This may warrant further evaluation in adequately powered randomised controlled trials.

  • neonatology
  • neurology

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  • Contributors PM acquired and analysed the data, performed neurodevelopmental outcome assessments and wrote the first draft of the manuscript. PJL acquired and analysed the MR spectroscopy data and wrote the first draft of the manuscript. NL, JT, RP, RS, VO, JM, GA, UK, VS and AS supported the data acquisition and interpretation. SS assisted in designing the study and interpretation of the data. ST conceived the idea, designed the study, interpreted the data and supervised all aspects of the work. All authors were involved in editing of the manuscript for important intellectual content and approved the final version submitted for publication.

  • Funding The study was funded by the National Institute for Health Research and was supported by the NIHR Biomedical Research Centre based at Imperial College London, UK. PM is funded by a Medical Research Council doctoral fellowship. PJL is funded by a National Institute for Health Research clinical trials fellowship. VO is funded by the National Institute for Health Research doctoral fellowship.

  • Disclaimer The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health.

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval The North London Research Ethics Committee (11/H0717/6).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement This will be available from the corresponding author.

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