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Association Between Seizures and Neurodevelopmental Outcome at Two and Five Years in Asphyxiated Newborns With Therapeutic Hypothermia - 08/03/24

Doi : 10.1016/j.pediatrneurol.2024.01.023 
Juliette F. Langeslag, MD a, b, Wes Onland, MD, PhD a, b, Floris Groenendaal, MD, PhD c, Linda S. de Vries, MD, PhD c : Prof., Anton H. van Kaam, MD, PhD a, b : Prof., Timo R. de Haan, MD, PhD a, b,

The PharmaCool Study Group

Chris H.P. van den Akker, Willem P. de Boode, Filip Cools, Henk J. ter Horst, Koen P. Dijkman, Floris Groenendaal, Timo R. de Haan, Sinno H.P. Simons, Sylke J. Steggerda, Suzanne Mulder-Tollenaer, Alexandra Zecic

a Department of Neonatology, Amsterdam UMC Location University of Amsterdam, Emma Children's Hospital, Amsterdam, the Netherlands 
b Amsterdam Reproduction & Development Research Institute, Amsterdam, the Netherlands 
c Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, and Brain Center, Utrecht, the Netherlands 

Communications should be addressed to: Dr. de Haan; Department of Neonatology (Room H4-134); Emma Children's Hospital Amsterdam UMC; Meibergdreef 9, PO box 22700; Amsterdam 1100 DD, The Netherlands.Department of Neonatology (Room H4-134)Emma Children's Hospital Amsterdam UMCMeibergdreef 9PO box 22700Amsterdam1100 DDThe Netherlands

Abstract

Objective

To investigate the association between the presence and severity of seizures in asphyxiated newborns and their neurodevelopmental outcome at ages two and five years.

Methods

Retrospective data analysis from a prospectively collected multicenter cohort of 186 term-born asphyxiated newborns undergoing therapeutic hypothermia (TH) in 11 centers in the Netherlands and Belgium. Seizures were diagnosed by amplitude-integrated electroencephalography (EEG) and raw EEG signal reading up to 48 hours after rewarming. Neurodevelopmental outcome was assessed by standardized testing at age two and five years. Primary outcome was death or long-term neurodevelopmental impairment (NDI) including cerebral palsy. Associations were calculated using univariate and multivariate logistic regression analyses adjusting for Thompson score and a validated brain magnetic resonance imaging (MRI) score.

Results

Seventy infants (38%) had seizures during TH or rewarming, and 44 (63%) of these needed two or more antiseizure medications (ASMs). Overall mortality was 21%. Follow-up data from 147 survivors were available for 137 infants (93%) at two and for 94 of 116 infants (81%) at five years. NDI was present in 26% at two and five years. Univariate analyses showed a significant association between seizures and death or NDI, but this was no longer significant after adjusting for Thompson and MRI score in the multivariate analysis; this was also true for severe seizures (need for two or more ASMs) or seizures starting during rewarming.

Conclusion

The presence or severity of seizures in newborns undergoing TH for hypoxic-ischemic encephalopathy was not independently associated with death or NDI up to age five years after adjusting for several confounders.

Il testo completo di questo articolo è disponibile in PDF.

Keywords : Hypothermia, Asphyxia, Seizures, Antiepileptic drugs, Outcome, Association


Mappa


 Collaborators: PharmaCool Study Group: Chris H.P. van den Akkera, Willem P. de Booded, Filip Coolse, Henk J. ter Horstf, Koen P. Dijkmang, Floris Groenendaalc, Timo R. de Haana, Sinno H. P. Simonsh, Sylke J. Steggerdai, Suzanne Mulder-Tollenaerj, Alexandra Zecick. Affiliations aAmsterdam UMC Location University of Amsterdam, Department of Neonatology, Emma Children's Hospital, Amsterdam, the Netherlands; cDepartment of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, and Brain Center, Utrecht, the Netherlands; dDepartment of Neonatology, Radboud University Medical Center-Amalia Children's Hospital; eDepartment of Neonatology, Universitair Ziekenhuis Brussel, Belgium; fDepartment of Neonatology, University Medical Center Groningen, Beatrix Children's Hospital, University of Groningen; gDepartment of Neonatology, Maxima Medical Center Veldhoven; hDepartment of Neonatology, Sophia Children's Hospital, Erasmus MC; iDepartment of Neonatology, Leiden University Medical Center; jDepartment of Neonatology, Isala Medical Center; kDepartment of Neonatology, University Hospital, Gent, Belgium.
 Funding sources: This study was funded by a Project Grant from The Netherlands Organization for Health Research and Development ZonMW Priority Medicines for Children Grant Number: 40-41500-98-9002.
 Role of funder/sponsor: The funding agency had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit it for publication.


© 2024  The Author(s). Pubblicato da Elsevier Masson SAS. Tutti i diritti riservati.
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