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  • Clinical Research Article
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Risk factors for unfavorable outcome at discharge of newborns with hypoxic-ischemic encephalopathy in the era of hypothermia

Pediatric Research volume 93, pages 1975–1982 (2023)Cite this article

Abstract

Objective

To re-visit short-term outcomes and associated risk factors of newborns with hypoxic-ischemic encephalopathy (HIE) in an era where hypothermia treatment (HT) is widespread.

Methods

This is a prospective population-based cohort in French neonatal intensive care units (NICU). Neonates born at or after 34 weeks of gestational age with HIE were included; main outcomes were in-hospital death and discharge with abnormal or normal MRI. Associations of early perinatal risk factors, present at birth or at admission to NICU, with these outcomes were studied.

Results

A total of 794 newborns were included and HT was administered to 670 (84.4%); 18.3% died and 28.5% and 53.2% survived with abnormal and normal MRI, respectively. Severe neurological status, Apgar score at 5 mn ≤5, lactate at birth ≥11 mMoles/l, and glycemia ≥100 mg/dL at admission were associated with an increased risk of death (relative risk ratios (aRRR) (95% CI) 19.93 (10.00–39.70), 2.89 (1.22–1.62), 3.06 (1.60–5.83), and 2.55 (1.38–4.71), respectively). Neurological status only was associated with survival with abnormal MRI (aRRR (95% CI) 1.76 (1.15–2.68)).

Conclusion

Despite high use of HT in this cohort, 46.8% died or presented brain lesions. Early neurological and biological examinations were associated with unfavorable outcomes and these criteria could be used to target children who warrant further neuroprotective treatment.

Trial registration

Clinical trial registry, NCT02676063, ClinicalTrials.gov.

Impact

  • In this population-based cohort of newborns with HIE where 84% received hypothermia, 46.8% still had an unfavorable evolution (death or survival with abnormal MRI). Risk factors for death were high lactate, low Apgar score, severe early neurological examination, and high glycaemia.

  • While studies have established risk factors for HIE, few have focused on early perinatal factors associated with short-term prognosis. This French population-based cohort updates knowledge about early risk factors for adverse outcomes in the era of widespread cooling.

  • In the future, criteria associated with an unfavorable evolution could be used to target children who would benefit from another neuroprotective strategy with hypothermia.

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Fig. 1: Flowchart of the LyTONEPAL cohort.

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Data availability

Data cannot be shared publicly but will be available from the Grenoble University Hospital on request for researchers who meet the criteria for access to confidential data.

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Acknowledgements

We thank Alison Foote (Grenoble Alpes University Hospital, France) for critically editing the manuscript and Catherine de Launay du Couedic for the overall coordination of the data collection. We thank The LyTONEPAL Study Group Collaborators: Auvergne Rhône-Alpes: N. Bouchon-Guedj (Chambéry), G. Remerand (Clermont-Ferrand), M. Chevallier (Grenoble), O. Claris (Lyon, HFME), C.M. Loys (Lyon, Croix Rousse), H. Patural (Saint-Etienne); Bourgogne Franche-Comté: T. Dabudyk (Besançon), C. Chantegret (Dijon); Bretagne: J.M. Roué (Brest), M. Gromand (Rennes), A. Busnel (St-Brieuc), A. Sevestre (Vannes); Centre Val-de-Loire: J. Guerreiro (Orléans), G. Favrais (Tours); Grand Est: J. Nakhleh (Mulhouse), N. Bednarek (Reims), D. Astruc, (Strasbourg), B. Kassis-Makhoul (Troyes); Hauts de France: G. Ghostine (Amiens), J. Ghesquiere (Arras), L. Egreteau (Calais), S.M. Dhahbi (Creil), S. Klosowski (Lens), F. Flamein (Lille), J. Balitalike (Valenciennes); Ile-de-France: D. Brau (Argenteuil), V. Zupan-Simunek (Clamart), C. Huon (Colombes), M. Tauzin (Créteil), M. Merhi (Evry), N. Le Sache (Le Kremlin-Bicêtre), B. Heller Roussin (Montreuil), D. Mellah (Meaux), A. Lapillonne, E. Leroy Terquem (Paris, Necker), J. Patkai (Paris, Port Royal), V. Biran (Paris, Robert Debré), I. Guellec (Paris, Trousseau), A. Durandy (Poissy), P. Boize (Pontoise), F. Goudjil (St Denis); Nouvelle Aquitaine: P. Jouvencel (Bayonne), O. Brissaud (Bordeaux), F. Mons (Limoges), K. Norbert (Pau), A. Parizel (Poitiers); Occitanie: G. Cambonie (Montpellier), M. Di Maio (Nîmes), R. Salloum (Perpignan), M.O. Marcoux (Toulouse); Pays de Loire: S. Le Bouedec (Angers), C. Flamant (Nantes), Y. Montcho (Le Mans); Provence Alpes Côte d’Azur: C. Desrobert (Marseille La Conception), V. Brevaut-Malaty (Marseille, Nord), F. Casagrande (Nice), R. Salloum (Perpignan); Martinique: S. Ketterer Martinon (Fort de France); Normandie: A. Cénéric (Caen), J. Mourdie (Le Havre), A. Chadie (Rouen); La Réunion: M. Carbonnier (Saint-Pierre), D. Ramful (Saint-Denis).

Funding

The study was funded by 2013 French Program for Hospital Clinical Research (PHRC-N-13-0327). The funder had no role in the design and conduct of the study.

Author information

Authors and Affiliations

  1. Neonatal Intensive Care Unit, Grenoble Alpes University Hospital, 38000, Grenoble, France

    Thierry Debillon & Marie Chevallier

  2. Université Grenoble Alpes, CNRS, Public Health Department, Grenoble Alpes, Grenoble Institute of Engineering Université Grenoble Alpes, TIMC-IMAG, 38000, Grenoble, France

    Thierry Debillon, Marie Chevallier & Anne Ego

  3. Department of Obstetrics and Gynecology, Bordeaux University Hospital, Bordeaux, France

    Loïc Sentilhes

  4. Department of Obstetrics and Gynecology, Trousseau Hospital, Assistance Publique-Hôpitaux de Paris, Sorbonne Paris City University, Paris, France

    Gilles Kayem

  5. Université de Paris, CRESS, Obstetrical Perinatal and Pediatric Epidemiology Research Team, EPOPé, INSERM, INRAE, F-75004, Paris, France

    Gilles Kayem, Jennifer Zeitlin, Véronique Pierrat, Isabelle Guellec & Pierre Yves Ancel

  6. Division of Neonatology, Department of Pediatrics, Gynecology and Obstetrics, School of Medicine, University of Geneva, Geneva, Switzerland

    Olivier Baud

  7. Inserm U1141, Sorbonne Paris City University, Paris, France

    Olivier Baud

  8. Data Engineering Unit, Public Health Department Grenoble Alpes University Hospital, 38000, Grenoble, France

    Antoine Vilotitch

  9. Department of Neonatal Medicine, Lille University Hospital, Jeanne de Flandre Hospital, Lille, France

    Véronique Pierrat

  10. Clinical Research Unit, Center for Clinical Investigation P1419, Assistance Publique Hôpitaux de Paris, F-75014, Paris, France

    Pierre Yves Ancel

  11. Neonatal and Pediatric Intensive Care Unit, Reims University Hospital Alix de Champagne, Reims, France

    Nathalie Bednarek

  12. Inserm CIC U1406, 38000, Grenoble, France

    Anne Ego

Authors
  1. Thierry Debillon
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Contributions

T.D., N.B., and A.E. conceptualized and designed the study, wrote the grant proposal, supervised data collection, drafted the manuscript and reviewed and revised it. L.S., G.K., O.B., P.Y.A., and I.G. helped design the study and critically reviewed and revised the manuscript. J.Z., M.C., and V.P. critically reviewed the manuscript for important intellectual content. A.V. carried out the statistical analysis and reviewed the manuscript.

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Correspondence to Thierry Debillon.

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Debillon, T., Sentilhes, L., Kayem, G. et al. Risk factors for unfavorable outcome at discharge of newborns with hypoxic-ischemic encephalopathy in the era of hypothermia. Pediatr Res 93, 1975–1982 (2023). https://doi.org/10.1038/s41390-022-02352-w

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