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Therapeutic hypothermia for mild neonatal encephalopathy: a systematic review and meta-analysis
  1. Ujwal Kariholu1,2,
  2. Paolo Montaldo1,
  3. Theodora Markati1,2,
  4. Peter J Lally1,
  5. Russell Pryce1,3,
  6. Justinas Teiserskas2,
  7. Natasha Liow2,
  8. Vânia Oliveira1,
  9. Aung Soe3,
  10. Seetha Shankaran4,
  11. Sudhin Thayyil1
  1. 1Centre for Perinatal Neuroscience, Imperial College London, London, UK
  2. 2Neonatal Unit, Imperial College Healthcare NHS Trust, London, UK
  3. 3Neonatal Unit, Medway Hospital NHS Trust, Gillingham, UK
  4. 4Neonatal Perinatal Medicine, Wayne State University, Detroit, Michigan, USA
  1. Correspondence to Dr Sudhin Thayyil, Centre for Perinatal Neuroscience, Imperial College London, London W12 0HS, UK; s.thayyil{at}


Objectives To examine if therapeutic hypothermia reduces the composite outcome of death, moderate or severe disability at 18 months or more after mild neonatal encephalopathy (NE).

Data source MEDLINE, Cochrane database, Scopus and ISI Web of Knowledge databases, using ‘hypoxic ischaemic encephalopathy’, ‘newborn’ and ‘hypothermia’, and ‘clinical trials’ as medical subject headings and terms. Manual search of the reference lists of all eligible articles and major review articles and additional data from the corresponding authors of selected articles.

Study selection Randomised and quasirandomised controlled trials comparing therapeutic hypothermia with usual care.

Data extraction Safety and efficacy data extracted independently by two reviewers and analysed.

Results We included the data on 117 babies with mild NE inadvertently recruited to five cooling trials (two whole-body cooling and three selective head cooling) of moderate and severe NE, in the meta-analysis. Adverse outcomes occurred in 11/56 (19.6%) of the cooled babies and 12/61 (19.7%) of the usual care babies (risk ratio 1.11 (95% CIs 0.55 to 2.25)).

Conclusions Current evidence is insufficient to recommend routine therapeutic hypothermia for babies with mild encephalopathy and significant benefits or harm cannot be excluded.

  • hypoxic ischaemic encephalopathy
  • therapeutic hypothermia
  • meta-analysis
  • newborn

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  • Patient consent for publication Not required.

  • Contributors UK searched the literature, extracted the data and drafted the manuscript along with PM and PJL. RP and TM extracted the data and examined the study quality with NL. JT searched the literature. VO, AS and SS interpreted the data and assisted in developing the manuscript. ST conceived the idea, performed the meta-analysis and supervised the entire work.

  • Funding PM is funded by an MRC doctoral fellowship, VO by an NIHR doctoral fellowship and PJL by an NIHR clinical trials fellowship. This research was supported by the NIHR Biomedical Research Centre based at Imperial College London.

  • 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.

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

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