Abstract
Background
Hypothermia is widely used for infants with hypoxic–ischemic neonatal encephalopathy but its impact remains poorly described at a population level. We aimed to describe brain imaging in infants born at ≥36 weeks’ gestation, with moderate/severe encephalopathy treated with hypothermia.
Methods
Descriptive analysis of brain MRI and discharge neurological examination for infants included in the French national multicentric prospective observational cohort LyTONEPAL.
Results
Among 575 eligible infants, 479 (83.3%) with MRI before 12 days of life were included. MRI was normal for 48.2% (95% CI 43.7–52.8). Among infants with brain injuries, 62.5% (95% CI 56.2–68.5) had damage to more than one structure, 19.8% (95% CI 15.0–25.3) showed a pattern-associating injuries of basal ganglia/thalami (BGT), white matter (WM) and cortex. Overall, 68.4% (95% CI 62.0–74.3) of infants with normal MRI survived with a normal neurological examination. The rate of death was 15.4% (95% CI 12.3–19.0), predominantly for infants with the combined BGT, cortex, and/or WM injuries.
Conclusions
Among infants with neonatal encephalopathy treated with hypothermia, two-thirds of those with normal MRI survived with a normal neurological examination at discharge. When present, brain injuries often involved more than one structure.
Trial registration
The trial was registered at ClinicalTrials.gov (NCT02676063).
Impact
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In this multicentric cohort of infants with neonatal encephalopathy (LYTONEPAL) two-thirds survived with normal MRI and neurological examination at discharge.
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In total, 10% of newborns showed a pattern associating injuries of the basal ganglia—thalami, white matter, and cortex, which was correlated with a high risk of death at discharge.
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The evolution of MRI techniques and sequences in the era of hypothermia calls for a revisiting of imaging protocol in neonatal encephalopathy, especially for the timing.
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The neurological examination did not give evidence of brain injuries, thus questioning the reproducibility of the clinical exam or the neonatal brain functionality.
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Acknowledgements
We thank members of the LyTONEPAL Study Group and all the regional teams participating in the study and all French maternity and neonatal units for their substantial contribution to the acquisition of data; Laura Smales and Grace Stockton for their helpful contribution to proofreading. We are grateful for the participation of all families of infants in the LyTONEPAL cohort study. We thank the American Memorial Committee for their considerable support. This study was funded by the National Program for Clinical Research (PHRC-N-13-0327).
The LyTONEPAL Study Group Collaborators
Auvergne Rhone 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).
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J.B., T.D., A.V., C.L., A.E., and P.-Y.A. 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. J.B., T.D., N.B., V.P., A.E., and P.-Y.A. conceptualized the study and wrote the manuscript. J.B. and A.V. performed the statistical analysis. C.L., A.V., M.A., and L.-H.P. coordinated data collection and had responsibility for technical support. T.D. obtained funding and supervised the study. All authors contributed to the data analysis and interpretation of the results and reviewed and approved the final manuscript.
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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 (Comité de Protection des Personnes Sud Est; Institutional Review Board no. 5891).
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Beck, J., Bednarek, N., Pierrat, V. et al. Cerebral injuries in neonatal encephalopathy treated with hypothermia: French LyTONEPAL cohort. Pediatr Res 92, 880–887 (2022). https://doi.org/10.1038/s41390-021-01846-3
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DOI: https://doi.org/10.1038/s41390-021-01846-3
