Cerebral injuries in neonatal encephalopathy treated with hypothermia: French LyTONEPAL cohort.
Journal
Pediatric research
ISSN: 1530-0447
Titre abrégé: Pediatr Res
Pays: United States
ID NLM: 0100714
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
received:
16
07
2021
accepted:
31
10
2021
revised:
04
10
2021
pubmed:
22
11
2021
medline:
15
10
2022
entrez:
21
11
2021
Statut:
ppublish
Résumé
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. Descriptive analysis of brain MRI and discharge neurological examination for infants included in the French national multicentric prospective observational cohort LyTONEPAL. 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. 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. The trial was registered at ClinicalTrials.gov (NCT02676063). In this multicentric cohort of infants with neonatal encephalopathy (LYTONEPAL) two-thirds survived with normal MRI and neurological examination at discharge. 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. 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. The neurological examination did not give evidence of brain injuries, thus questioning the reproducibility of the clinical exam or the neonatal brain functionality.
Sections du résumé
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
In this multicentric cohort of infants with neonatal encephalopathy (LYTONEPAL) two-thirds survived with normal MRI and neurological examination at discharge. 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. 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. The neurological examination did not give evidence of brain injuries, thus questioning the reproducibility of the clinical exam or the neonatal brain functionality.
Identifiants
pubmed: 34802036
doi: 10.1038/s41390-021-01846-3
pii: 10.1038/s41390-021-01846-3
doi:
Banques de données
ClinicalTrials.gov
['NCT02676063']
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
880-887Informations de copyright
© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.
Références
Pierrat, V. et al. Prevalence, causes, and outcome at 2 years of age of newborn encephalopathy: population based study. Arch. Dis. Child. Fetal Neonatal Ed. 90, F257–F261 (2005).
doi: 10.1136/adc.2003.047985
Kurinczuk, J. J., White-Koning, M. & Badawi, N. Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum. Dev. 86, 329–338 (2010).
doi: 10.1016/j.earlhumdev.2010.05.010
Weeke, L. C. et al. A novel magnetic resonance imaging score predicts neurodevelopmental outcome after perinatal asphyxia and therapeutic hypothermia. J. Pediatr. 192, 33–40.e2 (2018).
doi: 10.1016/j.jpeds.2017.09.043
Bednarek, N. et al. Impact of therapeutic hypothermia on MRI diffusion changes in neonatal encephalopathy. Neurology 78, 1420–1427 (2012).
doi: 10.1212/WNL.0b013e318253d589
Okereafor, A. et al. Patterns of brain injury in neonates exposed to perinatal sentinel events. Pediatrics 121, 906–914 (2008).
doi: 10.1542/peds.2007-0770
van Kooij, B. J. M. et al. Serial MRI and neurodevelopmental outcome in 9- to 10-year-old children with neonatal encephalopathy. J. Pediatr. 157, 221–227.e2 (2010).
doi: 10.1016/j.jpeds.2010.02.016
Martinez-Biarge, M. et al. White matter and cortical injury in hypoxic-ischemic encephalopathy: antecedent factors and 2-year outcome. J. Pediatr. 161, 799–807 (2012).
doi: 10.1016/j.jpeds.2012.04.054
Rutherford, M. et al. Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic–ischaemic encephalopathy: a nested substudy of a randomised controlled trial. Lancet Neurol. 9, 39–45 (2010).
doi: 10.1016/S1474-4422(09)70295-9
Inder, T. E. et al. Randomized trial of systemic hypothermia selectively protects the cortex on MRI in term hypoxic-ischemic encephalopathy. J. Pediatr. 145, 835–837 (2004).
doi: 10.1016/j.jpeds.2004.07.034
Miller, S. P. et al. Patterns of brain injury in term neonatal encephalopathy. J. Pediatr. 146, 453–460 (2005).
doi: 10.1016/j.jpeds.2004.12.026
Rao, S. et al. Long-term outcomes and risk factors associated with acute encephalitis in children. J. Pediatr. Infect. Dis. Soc. https://doi.org/10.1093/jpids/piv075 (2015).
Barnett, A. et al. Neurological and perceptual-motor outcome at 5 - 6 years of age in children with neonatal encephalopathy: relationship with neonatal brain MRI. Neuropediatrics 33, 242–248 (2002).
doi: 10.1055/s-2002-36737
Kasdorf, E., Engel, M., Heier, L. & Perlman, J. M. Therapeutic hypothermia in neonates and selective hippocampal injury on diffusion-weighted magnetic resonance imaging. Pediatr. Neurol. 51, 104–108 (2014).
doi: 10.1016/j.pediatrneurol.2014.03.002
Kuenzle, C. et al. Prognostic value of early MR imaging in term infants with severe perinatal asphyxia. Neuropediatrics 25, 191–200 (1994).
doi: 10.1055/s-2008-1073021
Walsh, B. H. et al. The frequency and severity of magnetic resonance imaging abnormalities in infants with mild neonatal encephalopathy. J. Pediatr. 187, 26–33.e1 (2017).
doi: 10.1016/j.jpeds.2017.03.065
Jacobs, S. E. et al. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst. Rev. CD003311. https://doi.org/10.1002/14651858.CD003311.pub3 (2013).
Saliba, E. & Debillon, T. Hypothermia for hypoxic-ischemic encephalopathy in fullterm newborns. Arch. Pediatr. Organe . Soc. Francaise Pediatr. 17(Suppl 3), S67–S77 (2010).
Debillon, T., Bednarek, N. & Ego, A. LyTONEPAL: long term outcome of neonatal hypoxic encephalopathy in the era of neuroprotective treatment with hypothermia: a French population-based cohort. BMC Pediatr. 18, 255 (2018).
Sarnat, H. B. & Sarnat, M. S. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch. Neurol. 33, 696–705 (1976).
doi: 10.1001/archneur.1976.00500100030012
Mercuri, E. et al. Head growth in infants with hypoxic-ischemic encephalopathy: correlation with neonatal magnetic resonance imaging. Pediatrics 106, 235–243 (2000).
doi: 10.1542/peds.106.2.235
D’Alton, M. E. et al. 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).
doi: 10.1097/01.AOG.0000445580.65983.d2
Agut, T. et al. Early identification of brain injury in infants with hypoxic ischemic encephalopathy at high risk for severe impairments: accuracy of MRI performed in the first days of life. BMC Pediatr. 14, 177 (2014).
doi: 10.1186/1471-2431-14-177
Charon, V. et al. Comparison of early and late MRI in neonatal hypoxic-ischemic encephalopathy using three assessment methods. Pediatr. Radiol. 45, 1988–2000 (2015).
doi: 10.1007/s00247-015-3419-4
Charon, V. et al. Early MRI in neonatal hypoxic-ischaemic encephalopathy treated with hypothermia: prognostic role at 2-year follow-up. Eur. J. Radiol. 85, 1366–1374 (2016).
doi: 10.1016/j.ejrad.2016.05.005
Barkovich, A. J. et al. Prediction of neuromotor outcome in perinatal asphyxia: evaluation of MR scoring systems. AJNR 19, 143–149 (1998).
pubmed: 9432172
pmcid: 8337350
Azzopardi, D. et al. The TOBY Study. Whole body hypothermia for the treatment of perinatal asphyxial encephalopathy: a randomised controlled trial. BMC Pediatr. 8, 17 (2008).
doi: 10.1186/1471-2431-8-17
Shankaran, S. et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N. Engl. J. Med 353, 1574–1584 (2005).
doi: 10.1056/NEJMcps050929
Shankaran, S. et al. Neonatal magnetic resonance imaging pattern of brain injury as a biomarker of childhood outcomes following a trial of hypothermia for neonatal hypoxic-ischemic encephalopathy. J. Pediatr. 167, 987–993.e3 (2015).
doi: 10.1016/j.jpeds.2015.08.013
Guillot, M. et al. Influence of timing of initiation of therapeutic hypothermia on brain MRI and neurodevelopment at 18 months in infants with HIE: a retrospective cohort study. BMJ Paediatr. Open 3, e000442 (2019).
doi: 10.1136/bmjpo-2019-000442
Shankaran, S. et al. Childhood outcomes after hypothermia for neonatal encephalopathy. N. Engl. J. Med. 366, 2085–2092 (2012).
doi: 10.1056/NEJMoa1112066
Shapiro, K. A. et al. Early changes in brain structure correlate with language outcomes in children with neonatal encephalopathy. NeuroImage Clin. 15, 572–580 (2017).
doi: 10.1016/j.nicl.2017.06.015
Tusor, N. et al. Prediction of neurodevelopmental outcome after hypoxic-ischemic encephalopathy treated with hypothermia by diffusion tensor imaging analyzed using tract-based spatial statistics. Pediatr. Res. 72, 63–69 (2012).
doi: 10.1038/pr.2012.40
Cheong, J. L. Y. et al. Prognostic utility of magnetic resonance imaging in neonatal hypoxic-ischemic encephalopathy: substudy of a randomized trial. Arch. Pediatr. Adolesc. Med. 166, 634–640 (2012).
doi: 10.1001/archpediatrics.2012.284
De Wispelaere, L. A. et al. Electroencephalography and brain magnetic resonance imaging in asphyxia comparing cooled and non-cooled infants. Eur. J. Paediatr. Neurol. 23, 181–190 (2019).
doi: 10.1016/j.ejpn.2018.09.001
Sargent, M. A., Poskitt, K. J., Roland, E. H., Hill, A. & Hendson, G. Cerebellar vermian atrophy after neonatal hypoxic-ischemic encephalopathy. AJNR 25, 1008–1015 (2004).
pubmed: 15205139
pmcid: 7975683
Le Strange, E., Saeed, N., Cowan, F. M., Edwards, A. D. & Rutherford, M. A. MR imaging quantification of cerebellar growth following hypoxic-ischemic injury to the neonatal brain. AJNR 25, 463–468 (2004).
pubmed: 15037473
pmcid: 8158542
Annink, K. V. et al. Cerebellar injury in term neonates with hypoxic-ischemic encephalopathy is underestimated. Pediatr. Res. https://doi.org/10.1038/s41390-020-01173-z (2020).
Murray, D. M. et al. The predictive value of early neurological examination in neonatal hypoxic-ischaemic encephalopathy and neurodevelopmental outcome at 24 months. Dev. Med. Child Neurol. 52, e55–e59 (2010).
doi: 10.1111/j.1469-8749.2009.03550.x
Grass, B. et al. Short-term neurological improvement in neonates with hypoxic-ischemic encephalopathy predicts neurodevelopmental outcome at 18–24 months. J. Perinat. Med. 48, 296–303 (2020).
doi: 10.1515/jpm-2019-0391
Brazelton, T. B. The Brazelton Neonatal Behavior Assessment Scale: introduction. Monogr. Soc. Res. Child Dev. 43, 1–13 (1978).
doi: 10.2307/1165847
Sánchez Fernández, I., Morales-Quezada, J. L., Law, S. & Kim, P. Prognostic value of brain magnetic resonance imaging in neonatal hypoxic-ischemic encephalopathy: a meta-analysis. J. Child Neurol. 32, 1065–1073 (2017).
doi: 10.1177/0883073817726681
Shankaran, S. et al. Brain injury following trial of hypothermia for neonatal hypoxic-ischaemic encephalopathy. Arch. Dis. Child. Fetal Neonatal Ed. 97, F398–F404 (2012).
pubmed: 23080477