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Changing clinical characteristics of infants treated for hypoxic-ischaemic encephalopathy in England, Wales and Scotland: a population-based study using the National Neonatal Research Database
  1. Lory Hage1,
  2. Dusha Jeyakumaran2,
  3. Jon Dorling3,
  4. Shalini Ojha4,
  5. Don Sharkey4,
  6. Nicholas Longford2,
  7. Neena Modi2,
  8. Cheryl Battersby2,
  9. Chris Gale2
  1. 1 Department of Medicine, Imperial College London, London, UK
  2. 2 Neonatal Medicine, School of Public Health, Faculty of Medicine, Imperial College London Faculty of Medicine, London, UK
  3. 3 Division of Neonatal-Perinatal Medicine, Dalhousie University Faculty of Medicine, Halifax, Nova Scotia, Canada
  4. 4 Division of Academic Child Health, University of Nottingham, Nottingham, UK
  1. Correspondence to Dr Chris Gale, Academic Neonatal Medicine, Imperial College London, London SW10 9NH, UK; christopher.gale{at}


Background Therapeutic hypothermia is standard of care for babies with moderate/severe hypoxic-ischaemic encephalopathy and is increasingly used for mild encephalopathy.

Objective Describe temporal trends in the clinical condition of babies diagnosed with hypoxic-ischaemic encephalopathy who received therapeutic hypothermia.

Design Retrospective cohort study using data held in the National Neonatal Research Database.

Setting National Health Service neonatal units in England, Wales and Scotland.

Patients Infants born from 1 January 2010 to 31 December 2017 with a recorded diagnosis of hypoxic-ischaemic encephalopathy who received therapeutic hypothermia for at least 3 days or died in this period.

Main outcomes Primary outcomes: recorded clinical characteristics including umbilical cord pH; Apgar score; newborn resuscitation; seizures and treatment on day 1. Secondary outcomes: recorded hypoxic-ischaemic encephalopathy grade.

Results 5201 babies with a diagnosis of hypoxic-ischaemic encephalopathy received therapeutic hypothermia or died; annual numbers increased over the study period. A decreasing proportion had clinical characteristics of severe hypoxia ischaemia or a diagnosis of moderate or severe hypoxic-ischaemic encephalopathy, trends were statistically significant and consistent across multiple clinical characteristics used as markers of severity.

Conclusions Treatment with therapeutic hypothermia for hypoxic-ischaemic encephalopathy has increased in England, Scotland and Wales. An increasing proportion of treated infants have a diagnosis of mild hypoxic-ischaemic encephalopathy or have less severe clinical markers of hypoxia. This highlights the importance of determining the role of hypothermia in mild hypoxic-ischaemic encephalopathy. Receipt of therapeutic hypothermia is unlikely to be a useful marker for assessing changes in the incidence of brain injury over time.

  • neonatology
  • neurology

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  • Twitter @lorysophie, @shaliniojha7, @DrDonSharkey, @NeenaModi1, @DrCBattersby, @DrCGale

  • Contributors The research question for this study was conceived by CG and developed by CG, JD, SO, CB and LSH. LSH, DJ and CB undertook the data extraction. LSH, DJ and NL undertook data analysis. NM leads the National Neonatal Research Database. LSH, DJ and CG drafted the first draft of the manuscript. All authors were involved in interpretation, review and revision of the draft manuscript and approval of the final version. LSH had full access to all the data in the study and take full responsibility for the integrity of the data and accuracy of the data analysis. CG is the guarantor and affirms that the manuscript is an honest, accurate and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

  • Competing interests JD reports grants from NIHR, during the conduct of the study, and grants from NIHR, outside the submitted work. JD was a member of the NIHR HTA General Board (from 2017 to 2018) and the NIHR HTA Maternity, Newborn and Child Health Panel (from 2013 to 2018). JD was also funded by Nutrinia in 2017 and 2018 for part of his salary to work as an expert advisor on a trial of enteral insulin. SO reports grants from the National Institute of Health Research, Medical Research Council, and the Derby Hospitals Charity. DS reports grants from the National Institute for Health Research, Medical Research Council, Engineering and Physical Sciences Research Council, outside the submitted work. He is also a committee member of the NIHR Research for Patient Benefit East Midlands Regional Assessment Panel and a non-executive director of SurePulse Medical. NM reports grants from the Medical Research Council, National Institute of Health Research, March of Dimes, British Heart Foundation, HCA International, Health Data Research UK, Shire Pharmaceuticals, Chiesi Pharmaceuticals, Prolacta Life Sciences and Westminster Children’s Research Fund, outside the submitted work. She is a member of the scientific advisory board of Nestle International. NM led the development of and directs the National Neonatal Research Database. CG reports grants from Medical Research Council, the National Institute for Health Research, the Mason Medical Research Foundation, Rosetrees Foundation and Canadian Institute for Health Research, outside the submitted work; and grants and personal fees to attend an educational conference from Chiesi Pharmaceuticals, outside the submitted work; he is a voluntary, unremunerated member of the Neonatal Data Analysis Unit Steering Board, which oversees the National Neonatal Research Database (NNRD), and is vice-chair of the NIHR Research for Patient Benefit London Regional Assessment Panel.

  • Patient consent for publication Not required.

  • Ethics approval Research ethics committee approval for the study was obtained from East Midlands-Leicester Central Research Ethics Committee (17/EM/0307) as an amendment to, and using data extracted for, the Optimising newborn nutrition during therapeutic hypothermia: an observational study using routinely collected data (NIHR16/79/03). Approval for inclusion of their data in this study was obtained from all English, Scottish and Welsh neonatal units. The National Research Ethics Service has approved the National Neonatal Research Database as a research database (16/LO/1093).

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

  • Data availability statement Data are available in a public, open access repository. Data can be extracted from the NNRD.

    Details of how to access the National Neonatal Research Database may be found at:

  • 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.

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