Seizure Burden and Neurologic Outcomes After Neonatal Encephalopathy

Affiliations

¹ From the Department of Pediatrics (H.M.A.), King Abdullah bin Abdulaziz University Hospital, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia; Department of Pediatrics (E.F.P.), Centre Hospitalier Universitaire Sainte-Justine and the University of Montreal, Quebec; Neurosciences and Mental Health Program (M.-A.T., J.P.V., E.W., C.D.H., E.W.Y.T.), Hospital for Sick Children Research Institute; Department of Paediatrics (C.I.S.C., D.K., E.W., L.L., C.D.H., E.W.Y.T.), Department of Radiology (E.W.), and Department of Psychology (E.M.), The Hospital for Sick Children and the University of Toronto, Ontario, Canada; and Epilepsia Helsinki (P.N.), Department of Clinical Neurophysiology, HUS Diagnostic Center, University of Helsinki and Helsinki University Hospital, Finland.
² From the Department of Pediatrics (H.M.A.), King Abdullah bin Abdulaziz University Hospital, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia; Department of Pediatrics (E.F.P.), Centre Hospitalier Universitaire Sainte-Justine and the University of Montreal, Quebec; Neurosciences and Mental Health Program (M.-A.T., J.P.V., E.W., C.D.H., E.W.Y.T.), Hospital for Sick Children Research Institute; Department of Paediatrics (C.I.S.C., D.K., E.W., L.L., C.D.H., E.W.Y.T.), Department of Radiology (E.W.), and Department of Psychology (E.M.), The Hospital for Sick Children and the University of Toronto, Ontario, Canada; and Epilepsia Helsinki (P.N.), Department of Clinical Neurophysiology, HUS Diagnostic Center, University of Helsinki and Helsinki University Hospital, Finland. emily.tam@sickkids.ca.

PMID: 36990719
PMCID: PMC10186227
DOI: 10.1212/WNL.0000000000207202

Seizure Burden and Neurologic Outcomes After Neonatal Encephalopathy

Huda M Alharbi et al. Neurology. 2023.

. 2023 May 9;100(19):e1976-e1984.

doi: 10.1212/WNL.0000000000207202. Epub 2023 Mar 29.

Affiliations

¹ From the Department of Pediatrics (H.M.A.), King Abdullah bin Abdulaziz University Hospital, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia; Department of Pediatrics (E.F.P.), Centre Hospitalier Universitaire Sainte-Justine and the University of Montreal, Quebec; Neurosciences and Mental Health Program (M.-A.T., J.P.V., E.W., C.D.H., E.W.Y.T.), Hospital for Sick Children Research Institute; Department of Paediatrics (C.I.S.C., D.K., E.W., L.L., C.D.H., E.W.Y.T.), Department of Radiology (E.W.), and Department of Psychology (E.M.), The Hospital for Sick Children and the University of Toronto, Ontario, Canada; and Epilepsia Helsinki (P.N.), Department of Clinical Neurophysiology, HUS Diagnostic Center, University of Helsinki and Helsinki University Hospital, Finland.
² From the Department of Pediatrics (H.M.A.), King Abdullah bin Abdulaziz University Hospital, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia; Department of Pediatrics (E.F.P.), Centre Hospitalier Universitaire Sainte-Justine and the University of Montreal, Quebec; Neurosciences and Mental Health Program (M.-A.T., J.P.V., E.W., C.D.H., E.W.Y.T.), Hospital for Sick Children Research Institute; Department of Paediatrics (C.I.S.C., D.K., E.W., L.L., C.D.H., E.W.Y.T.), Department of Radiology (E.W.), and Department of Psychology (E.M.), The Hospital for Sick Children and the University of Toronto, Ontario, Canada; and Epilepsia Helsinki (P.N.), Department of Clinical Neurophysiology, HUS Diagnostic Center, University of Helsinki and Helsinki University Hospital, Finland. emily.tam@sickkids.ca.

PMID: 36990719
PMCID: PMC10186227
DOI: 10.1212/WNL.0000000000207202

Abstract

Background and objectives: Seizures are common during neonatal encephalopathy (NE), but the contribution of seizure burden (SB) to outcomes remains controversial. This study aims to examine the relationship between electrographic SB and neurologic outcomes after NE.

Methods: This prospective cohort study recruited newborns ≥36 weeks postmenstrual age around 6 hours of life between August 2014 and November 2019 from a neonatal intensive care unit (NICU). Participants underwent continuous electroencephalography for at least 48 hours, brain MRI within 3-5 days of life, and structured follow-up at 18 months. Electrographic seizures were identified by board-certified neurophysiologists and quantified as total SB and maximum hourly SB. A medication exposure score was calculated based on all antiseizure medications given during NICU admission. Brain MRI injury severity was classified based on basal ganglia and watershed scores. Developmental outcomes were measured using the Bayley Scales of Infant Development, Third Edition. Multivariable regression analyses were performed, adjusting for significant potential confounders.

Results: Of 108 enrolled infants, 98 had continuous EEG (cEEG) and MRI data collected, of which 5 were lost to follow-up, and 6 died before age 18 months. All infants with moderate-severe encephalopathy completed therapeutic hypothermia. cEEG-confirmed neonatal seizures occurred in 21 (24%) newborns, with a total SB mean of 12.5 ± 36.4 minutes and a maximum hourly SB mean of 4 ± 10 min/h. After adjusting for MRI brain injury severity and medication exposure, total SB was significantly associated with lower cognitive (-0.21, 95% CI -0.33 to -0.08, p = 0.002) and language (-0.25, 95% CI -0.39 to -0.11, p = 0.001) scores at 18 months. Total SB of 60 minutes was associated with 15-point decline in language scores and 70 minutes for cognitive scores. However, SB was not significantly associated with epilepsy, neuromotor score, or cerebral palsy (p > 0.1).

Discussion: Higher SB during NE was independently associated with worse cognitive and language scores at 18 months, even after adjusting for exposure to antiseizure medications and severity of brain injury. These observations support the hypothesis that neonatal seizures occurring during NE independently contribute to long-term outcomes.

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Conflict of interest statement

H.M. Alharbi, E.F. Pinchefsky, M.-Y. Tran, C.I. Salazar Cerda, J. Parokaran Varghese, D. Kamino, E. Widjaja, E. Mamak, L. Ly, and P. Nevalainen report no disclosures relevant to the manuscript. C.D. Hahn has served as a consultant on clinical trial design for Takeda Pharmaceuticals and UCB Pharma SRL. E.W.Y. Tam reports no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.

Figures

**Figure. Predicted Bayley-3 Composite Language and Cognitive Scores With Increasing Total Seizure Burden**
The dotted lines indicate duration of seizure burden associated with 15-point decline in the Bayley score.

See this image and copyright information in PMC

References

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Seizure Burden and Neurologic Outcomes After Neonatal Encephalopathy

Affiliations

Seizure Burden and Neurologic Outcomes After Neonatal Encephalopathy

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical