Consensus definition and diagnostic criteria for neonatal encephalopathy-study protocol for a real-time modified delphi study

Aoife Branagan^{1

2

3

4}, Tim Hurley^{1

2

4}, Fiona Quirke^{4

5}, Declan Devane^{5

6

7

8}, Petek E Taneri^{5

6}, Nadia Badawi^{9

10}, Bharati Sinha¹¹, Cynthia Bearer^{12

13}, Frank H Bloomfield¹⁴, Sonia L Bonifacio¹⁵, Geraldine Boylan^{16

17}, Suzann K Campbell¹⁸, Lina Chalak¹⁹, Mary D'Alton²⁰, Linda S deVries²¹, Mohamed El Dib²², Donna M Ferriero²³, Chris Gale²⁴, Pierre Gressens²⁵, Alistair J Gunn²⁶, Sarah Kay²⁷, Beccy Maeso²⁸, Sarah B Mulkey^{29

30}, Deirdre M Murray^{16

17}, Karin B Nelson³¹, Tetyana H Nesterenko³², Betsy Pilon³³, Nicola J Robertson^{34

35}, Karen Walker^{36

37}, Courtney J Wusthoff³⁸, Eleanor J Molloy^{39

40

41

42

43

44}; Steering Group for DEFiNE (Definition of Neonatal Encephalopathy)

Affiliations

¹ Discipline of Paediatrics, Trinity College Dublin, the University of Dublin, Dublin, Ireland.
² Trinity Translational Medicine Institute (TTMI), St James Hospital & Trinity Research in Childhood Centre (TRiCC), Dublin, Ireland.
³ Neonatology, The Coombe Hospital, Dublin, Ireland.
⁴ Health Research Board Neonatal Encephalopathy PhD Training Network (NEPTuNE), Dublin, Ireland.
⁵ Health Research Board-Trials Methodology, Research Network (HRB-TMRN), University of Galway, Galway, Ireland.
⁶ School of Nursing and Midwifery, University of Galway, Galway, Ireland.
⁷ Evidence Synthesis Ireland, University of Galway, Galway, Ireland.
⁸ Cochrane Ireland, University of Galway, Galway, Ireland.
⁹ Cerebral Palsy Alliance Research Institute, Specialty of Child & Adolescent Health, Sydney Medical School, Faculty of Medicine & Health, The University of Sydney, Sydney, NSW, Australia.
¹⁰ Grace Centre for Newborn Intensive Care, Sydney Children's Hospital Network, The University of Sydney, Westmead, NSW, Australia.
¹¹ Department of Pediatrics, Boston Medical Center, Boston, MA, USA.
¹² Division of Neonatology, Department of Pediatrics, Rainbow Babies & Children's Hospital, Cleveland, OH, USA.
¹³ Case Western Reserve University School of Medicine, Cleveland, OH, USA.
¹⁴ Liggins Institute, University of Auckland, Auckland, New Zealand.
¹⁵ Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA.
¹⁶ INFANT Research Centre, Cork, Ireland.
¹⁷ Department of Pediatrics and Child Health, University College Cork, Cork, Ireland.
¹⁸ Department of Physical Therapy, College of Applied Health Sciences, University of Illinois at Chicago, Chicago, IL, USA.
¹⁹ Division of Neonatal-Perinatal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
²⁰ Department of Obstetrics and Gynecology, Columbia University, New York, NY, USA.
²¹ Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands.
²² Division of Newborn Medicine, Department of Pediatrics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
²³ Departments of Neurology and Pediatrics, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
²⁴ Neonatal Medicine, School of Public Health, Faculty of Medicine, Chelsea and Westminster Campus, Imperial College London, London, UK.
²⁵ Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France.
²⁶ Departments of Physiology and Paediatrics, School of Medical Sciences, University of Auckland, Auckland, New Zealand.
²⁷ PEEPS-HIE, Manchester, UK.
²⁸ James Lind Alliance, School of Healthcare Enterprise and Innovation, University of Southampton, Southampton, UK.
²⁹ Children's National Hospital, Washington, DC, USA.
³⁰ Departments of Neurology and Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
³¹ National Institutes of Health, National Institute of Neurological Diseases and Stroke, Bethesda, MD, USA.
³² Department of Neonatology, Cleveland Clinic Children's Hospital, Cleveland, OH, USA.
³³ Hope for HIE, West Bloomfield, MI, USA.
³⁴ Institute for Women's Health, University College London, London, UK.
³⁵ Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
³⁶ Department of Newborn Care, Royal Prince Alfred Hospital, Sydney, Local Health District, Sydney, Australia.
³⁷ Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
³⁸ Division of Child Neurology, Stanford University, Palo Alto, CA, USA.
³⁹ Discipline of Paediatrics, Trinity College Dublin, the University of Dublin, Dublin, Ireland. Eleanor.molloy@tcd.ie.
⁴⁰ Trinity Translational Medicine Institute (TTMI), St James Hospital & Trinity Research in Childhood Centre (TRiCC), Dublin, Ireland. Eleanor.molloy@tcd.ie.
⁴¹ Neonatology, The Coombe Hospital, Dublin, Ireland. Eleanor.molloy@tcd.ie.
⁴² Health Research Board Neonatal Encephalopathy PhD Training Network (NEPTuNE), Dublin, Ireland. Eleanor.molloy@tcd.ie.
⁴³ Neonatology, Children's Health Ireland, Dublin, Ireland. Eleanor.molloy@tcd.ie.
⁴⁴ Neurodisability, Children's Hospital Ireland (CHI) at Tallaght, Dublin, Ireland. Eleanor.molloy@tcd.ie.

PMID: 38902453
PMCID: PMC11798824
DOI: 10.1038/s41390-024-03303-3

Consensus definition and diagnostic criteria for neonatal encephalopathy-study protocol for a real-time modified delphi study

Aoife Branagan et al. Pediatr Res. 2025 Jan.

. 2025 Jan;97(1):430-436.

doi: 10.1038/s41390-024-03303-3. Epub 2024 Jun 20.

Authors

Affiliations

¹ Discipline of Paediatrics, Trinity College Dublin, the University of Dublin, Dublin, Ireland.
² Trinity Translational Medicine Institute (TTMI), St James Hospital & Trinity Research in Childhood Centre (TRiCC), Dublin, Ireland.
³ Neonatology, The Coombe Hospital, Dublin, Ireland.
⁴ Health Research Board Neonatal Encephalopathy PhD Training Network (NEPTuNE), Dublin, Ireland.
⁵ Health Research Board-Trials Methodology, Research Network (HRB-TMRN), University of Galway, Galway, Ireland.
⁶ School of Nursing and Midwifery, University of Galway, Galway, Ireland.
⁷ Evidence Synthesis Ireland, University of Galway, Galway, Ireland.
⁸ Cochrane Ireland, University of Galway, Galway, Ireland.
⁹ Cerebral Palsy Alliance Research Institute, Specialty of Child & Adolescent Health, Sydney Medical School, Faculty of Medicine & Health, The University of Sydney, Sydney, NSW, Australia.
¹⁰ Grace Centre for Newborn Intensive Care, Sydney Children's Hospital Network, The University of Sydney, Westmead, NSW, Australia.
¹¹ Department of Pediatrics, Boston Medical Center, Boston, MA, USA.
¹² Division of Neonatology, Department of Pediatrics, Rainbow Babies & Children's Hospital, Cleveland, OH, USA.
¹³ Case Western Reserve University School of Medicine, Cleveland, OH, USA.
¹⁴ Liggins Institute, University of Auckland, Auckland, New Zealand.
¹⁵ Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA.
¹⁶ INFANT Research Centre, Cork, Ireland.
¹⁷ Department of Pediatrics and Child Health, University College Cork, Cork, Ireland.
¹⁸ Department of Physical Therapy, College of Applied Health Sciences, University of Illinois at Chicago, Chicago, IL, USA.
¹⁹ Division of Neonatal-Perinatal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
²⁰ Department of Obstetrics and Gynecology, Columbia University, New York, NY, USA.
²¹ Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands.
²² Division of Newborn Medicine, Department of Pediatrics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
²³ Departments of Neurology and Pediatrics, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
²⁴ Neonatal Medicine, School of Public Health, Faculty of Medicine, Chelsea and Westminster Campus, Imperial College London, London, UK.
²⁵ Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France.
²⁶ Departments of Physiology and Paediatrics, School of Medical Sciences, University of Auckland, Auckland, New Zealand.
²⁷ PEEPS-HIE, Manchester, UK.
²⁸ James Lind Alliance, School of Healthcare Enterprise and Innovation, University of Southampton, Southampton, UK.
²⁹ Children's National Hospital, Washington, DC, USA.
³⁰ Departments of Neurology and Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
³¹ National Institutes of Health, National Institute of Neurological Diseases and Stroke, Bethesda, MD, USA.
³² Department of Neonatology, Cleveland Clinic Children's Hospital, Cleveland, OH, USA.
³³ Hope for HIE, West Bloomfield, MI, USA.
³⁴ Institute for Women's Health, University College London, London, UK.
³⁵ Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
³⁶ Department of Newborn Care, Royal Prince Alfred Hospital, Sydney, Local Health District, Sydney, Australia.
³⁷ Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
³⁸ Division of Child Neurology, Stanford University, Palo Alto, CA, USA.
³⁹ Discipline of Paediatrics, Trinity College Dublin, the University of Dublin, Dublin, Ireland. Eleanor.molloy@tcd.ie.
⁴⁰ Trinity Translational Medicine Institute (TTMI), St James Hospital & Trinity Research in Childhood Centre (TRiCC), Dublin, Ireland. Eleanor.molloy@tcd.ie.
⁴¹ Neonatology, The Coombe Hospital, Dublin, Ireland. Eleanor.molloy@tcd.ie.
⁴² Health Research Board Neonatal Encephalopathy PhD Training Network (NEPTuNE), Dublin, Ireland. Eleanor.molloy@tcd.ie.
⁴³ Neonatology, Children's Health Ireland, Dublin, Ireland. Eleanor.molloy@tcd.ie.
⁴⁴ Neurodisability, Children's Hospital Ireland (CHI) at Tallaght, Dublin, Ireland. Eleanor.molloy@tcd.ie.

PMID: 38902453
PMCID: PMC11798824
DOI: 10.1038/s41390-024-03303-3

Abstract

Background: 'Neonatal encephalopathy' (NE) describes a group of conditions in term infants presenting in the earliest days after birth with disturbed neurological function of cerebral origin. NE is aetiologically heterogenous; one cause is peripartum hypoxic ischaemia. Lack of uniformity in the terminology used to describe NE and its diagnostic criteria creates difficulty in the design and interpretation of research and complicates communication with families. The DEFINE study aims to use a modified Delphi approach to form a consensus definition for NE, and diagnostic criteria.

Methods: Directed by an international steering group, we will conduct a systematic review of the literature to assess the terminology used in trials of NE, and with their guidance perform an online Real-time Delphi survey to develop a consensus diagnosis and criteria for NE. A consensus meeting will be held to agree on the final terminology and criteria, and the outcome disseminated widely.

Discussion: A clear and consistent consensus-based definition of NE and criteria for its diagnosis, achieved by use of a modified Delphi technique, will enable more comparability of research results and improved communication among professionals and with families.

Impact: The terms Neonatal Encephalopathy and Hypoxic Ischaemic Encephalopathy tend to be used interchangeably in the literature to describe a term newborn with signs of encephalopathy at birth. This creates difficulty in communication with families and carers, and between medical professionals and researchers, as well as creating difficulty with performance of research. The DEFINE project will use a Real-time Delphi approach to create a consensus definition for the term 'Neonatal Encephalopathy'. A definition formed by this consensus approach will be accepted and utilised by the neonatal community to improve research, outcomes, and parental experience.

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Conflict of interest statement

Competing interests: The authors declare no competing interests. Ethical approval: Ethical approval has been obtained for the project from the ethics committee of the Coombe Woman and Infants University Hospital, Dublin (REC number 13-2022). Consent to participate: Informed consent will be obtained from each participant via the online software platform prior to beginning participation in the study.

Figures

**Fig. 1. Neonatal Encephalopathy as an umbrella diagnosis.**
A scheme representing movement from the initial umbrella diagnosis of ‘Neonatal Encephalopathy’ to a final aetiological diagnosis after appropriate investigation and analysis is carried out.

**Fig. 2. The DEFiNE project outline.**
An outline of the five stage process this project will proceed through to develop a consensus definition for Neonatal Encephalopathy.

See this image and copyright information in PMC

References

1. Aslam, S., Strickland, T. & Molloy, E. J. Neonatal encephalopathy: Need for recognition of multiple etiologies for optimal management. Front Pediatr.7, 142 (2019). - PMC - PubMed
1. Executive Summary: Neonatal Encephalopathy and Neurologic Outcome, Second Edition. Report of the american college of obstetricians and gynecologists’ task force on neonatal encephalopathy. Obstet. Gynecol.123, 896–901 (2014). - PubMed
1. Jacobs, S. E. et al. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst. Rev.2013, Cd003311 (2013). - PMC - PubMed
1. Shankaran, S. et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N. Engl. J. Med.353, 1574–1584 (2005). - PubMed
1. Gluckman, P. D. et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: Multicentre randomised trial. Lancet365, 663–670 (2005). - PubMed

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Consensus definition and diagnostic criteria for neonatal encephalopathy-study protocol for a real-time modified delphi study

Affiliations

Consensus definition and diagnostic criteria for neonatal encephalopathy-study protocol for a real-time modified delphi study

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical