Article Text

Download PDFPDF
Trends in the incidence and management of hypoxic-ischaemic encephalopathy in the therapeutic hypothermia era: a national population study
  1. Lara Shipley1,
  2. Chris Gale2,
  3. Don Sharkey3
  1. 1 Division of Child Health, Obstetrics and Gynaecology, School of Medicine, University of Nottingham, Nottingham, UK
  2. 2 Academic Neonatal Medicine, Imperial College London, London, UK
  3. 3 Academic Child Health, School of Medicine, University of Nottingham, Nottingham, UK
  1. Correspondence to Dr Don Sharkey, Academic Child Health, School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK; don.sharkey{at}


Objective Hypoxic-ischaemic encephalopathy (HIE) remains a leading cause of neonatal mortality and neurodisability. We aimed to determine the incidence of HIE and management patterns against national guidelines.

Design Retrospective cohort study using the National Neonatal Research Database.

Setting Neonatal units in England and Wales.

Patients Infants 34–42 weeks gestational age (GA) with a recorded diagnosis of HIE.

Main outcomes Incidence of HIE, mortality and treatment with therapeutic hypothermia (TH) were the main outcomes. Temporal changes were compared across two epochs (2011–2013 and 2014–2016).

Results Among 407 462 infants admitted for neonatal care, 12 195 were diagnosed with HIE. 8166 infants ≥36 weeks GA had moderate/severe HIE, 62.1% (n=5069) underwent TH and mortality was 9.3% (n=762). Of infants with mild HIE (n=3394), 30.3% (n=1027) underwent TH and 6 died. In late preterm infants (34–35 weeks GA) with HIE (n=635, 5.2%), 33.1% (n=210) received TH and 13.1% (n=83) died. Between epochs (2011–2013 vs 2014–2016), mortality decreased for infants ≥36 weeks GA with moderate/severe HIE (17.5% vs 12.3%; OR 0.69, 95% CI 0.59 to 0.81, p<0.001). Treatment with TH increased significantly between epochs in infants with mild HIE (24.9% vs 35.8%, p<0.001) and those born late preterm (34.3% vs 46.6%, p=0.002).

Conclusions Mortality of infants ≥36 weeks GA with moderate/severe HIE has reduced over time, although many infants diagnosed with moderate/severe HIE do not undergo TH. Increasingly, mild HIE and late preterm infants with HIE are undergoing TH, where the evidence base is lacking, highlighting the need for prospective studies to evaluate safety and efficacy in these populations.

  • neonatology
  • epidemiology
  • neurology

Statistics from


  • Twitter @DrCGale, @DrDonSharkey

  • Contributors LS and DS made substantial contributions to the concept, planning, design of the study and acquisition of data. LS and DS analysed and interpreted the data. All authors assisted in drafting and editing the manuscript. All authors approved the final version for publication. DS had full access to all the data in the study and takes full responsibility for the integrity of the data and accuracy of the data analysis.

  • Funding This study was partly supported by a University of Nottingham, School of Medicine Impact Funding award.

  • Competing interests CG has received support from Chiesi Pharmaceuticals to attend an educational conference; in the past 5 years he has been an investigator on received research grants from Medical Research Council, National Institute for Health Research, Canadian Institutes of Health Research, Department of Health in England, Mason Medical Research Foundation, Westminster Medical School Research Trust and Chiesi Pharmaceuticals, and has been an unremunerated member of the Neonatal Data Analysis Unit Board, which oversees the NNRD.

  • Patient consent for publication Not required.

  • Ethics approval Ethical approval was given by the London-City and East Research Ethics Committee (REC: 17/LO/1822).

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

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information. All data were extracted and supplied by the NDAU and are available from the corresponding author on reasonable request and with permission of the study team and NDAU.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.