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Healthcare organizational factors associated with delayed therapeutic hypothermia in neonatal hypoxic-ischemic encephalopathy: the LyTONEPAL cohort

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Abstract

Initiation of therapeutic hypothermia (TH) within 6 h of life is a major concern for treating neonatal hypoxic ischemic encephalopathy (HIE). We aimed to determine clinical and healthcare organizational factors associated with delayed TH in a French population-based cohort of neonates with moderate/severe HIE. Time to reach a rectal temperature of 34 °C defines optimal and delayed (within and over 6 h, respectively) TH. Clinical and healthcare organizational factors associated with delayed TH were analysed among neonates born in cooling centres (CCs) and non-cooling centres (non-CCs). Among 629 neonates eligible for TH, 574 received treatment (91.3%). TH was delayed in 29.8% neonates and in 20.3% and 36.2% of those born in CCs and non-CCs, respectively. Neonates with moderate HIE were more exposed to delayed TH in both CCs and non-CCs. After adjustment for HIE severity, maternal and neonatal characteristics and circumstances of birth were not associated with increased risk of delayed TH. However, this risk was 2 to 5 times higher in maternities with < 1999 annual births, when the delay between birth and call for transfer (adjusted odds ratio [aOR] 2.47, 95% confidence interval [CI] [1.03 to 5.96]) or between call for transfer and admission (aOR 6.06, 95%CI [2.60 to 14.12]) was > 3 h and when an undesirable event occurred during transfer (aOR 2.66, 95%CI [1.11 to 6.37].

  Conclusion: Increasing early identification of neonates who could benefit from TH and access to TH in non-CCs before transfer are modifiable factors that could improve care of neonates with HIE.

  Trial registration: The trial was registered at ClinicalTrials.gov (NCT02676063).

What is Known:

• International recommendations are to initiate therapeutic hypothermia before 6 h of life in neonates with moderate or severe hypoxic ischemic encephalopathy.

What is New:

•In this French population-based cohort of infants with hypoxic ischemic encephalopathy, nearly one-third of neonates eligible for treatment did not have access to hypothermia in the therapeutic window of 6 h of life.

.

• Among infants born in non-cooling centres, healthcare organizational factors involved in delayed care were the small size of maternities (1999 annual births), a time interval of more than 3 h between birth and call for transfer and between call for transfer and admission in neonatology, and the occurrence of an undesirable event during transfer.

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Abbreviations

HIE:

Hypoxic ischemic encephalopathy

TH:

Therapeutic hypothermia

CC:

Cooling centre

Non-CC:

Non-cooling centre

WG:

Weeks’ gestation

aOR:

Adjusted odds ratio

CI:

Confidence interval

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Acknowledgements

We thank members of the LyTONEPAL Study Group, all the regional teams participating in the study, and all French maternity and neonatal units for their substantial contribution to acquisition of data; and Laura Smales for her helpful contribution for proofreading. We are grateful for the participation of all families of infants in the LyTONEPAL cohort study.

Funding

National Program for Clinical Research (PHRC-N-13–0327).

J.B has received support from The American Memorial Committee.

Author information

Author notes

  1. Véronique Pierrat and Anne Ego are both last co-authors.

Authors and Affiliations

  1. Université Paris Cité, CRESS, Obstetrical Perinatal and Pediatric Epidemiology Research Team, EPOPé, INSERM, INRAE, 75004, Paris, France

    Jonathan Beck, Isabelle Guellec, Pierre-Yves Ancel & Véronique Pierrat

  2. Department of Neonatology, Reims University Hospital Alix de Champagne, Reims, France

    Jonathan Beck, Gauthier Loron & Nathalie Bednarek

  3. Univ. Grenoble Alpes, CNRS, Neonatal Intensive Care Unit Grenoble Alpes University Hospital, Grenoble INP Institute of Engineering Univ. Grenoble Alpes, TIMC-IMAG, 38000, Grenoble, France

    Thierry Debillon

  4. Neonatal Intensive Care Unit, Nice University Hospital, Côte d’Azur University, Nice, France

    Isabelle Guellec

  5. Center for Clinical Investigation U1406, Grenoble Alpes University Hospital, Grenoble, France

    Antoine Vilotitch & Anne Ego

  6. Université de Reims Champagne Ardenne, 3804, 51097, Reims, CReSTIC EA, France

    Gauthier Loron & Nathalie Bednarek

  7. Center for Clinical Investigation P1419, APHP, APHP Centre-Université Paris Cité, 75014, Paris, France

    Pierre-Yves Ancel

  8. Department of Neonatology, CHI Créteil, Créteil, France

    Véronique Pierrat

  9. Public Health Department, Univ. Grenoble Alpes, CNRS, Grenoble Alpes University Hospital, Grenoble INP Institute of Engineering Univ. Grenoble Alpes, TIMC-IMAG, 38000, Grenoble, France

    Anne Ego

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Contributions

JB, AV, TD, AE and PYA had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. JB, TD, VP, AE and PYA conceptualized the study and wrote the manuscript. JB and AV performed the statistical analysis. TD obtained funding and supervised the study. IG, GL and NB contributed to interpretation of the results and reviewed and approved the final manuscript.

Corresponding author

Correspondence to Jonathan Beck.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

Informed consent was obtained from both parents. The study protocol was approved by the Advisory National Committee on the treatment of personal health data for research purposes (Comité Consultatif sur le Traitement de l’Information en matière de Recherche sur la Santé, reference no. 14.724). Authorizations were obtained from the National French data protection authority (Commission Nationale Informatique et Libertés, DR-2015–136) and the Regional Ethics committee CPP (Comité de Protection des Personnes Sud Est; Institutional Review Board no. 5891).

Conflict of interest

The authors declare no competing interests.

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Communicated by Daniele De Luca

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Beck, J., Debillon, T., Guellec, I. et al. Healthcare organizational factors associated with delayed therapeutic hypothermia in neonatal hypoxic-ischemic encephalopathy: the LyTONEPAL cohort. Eur J Pediatr 182, 181–190 (2023). https://doi.org/10.1007/s00431-022-04666-7

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