Relationship of Neonatal Seizure Burden Before Treatment and Response to Initial Antiseizure Medication

Adam L Numis¹, Hannah C Glass², Bryan A Comstock³, Fernando Gonzalez⁴, Nathalie L Maitre⁵, Shavonne L Massey⁶, Dennis E Mayock⁷, Ulrike Mietzsch⁸, Niranjana Natarajan⁹, Gregory M Sokol¹⁰, Sonia Bonifacio¹¹, Krisa Van Meurs¹¹, Cameron Thomas¹², Kaashif Ahmad¹³, Patrick Heagerty³, Sandra E Juul⁷, Yvonne W Wu¹⁴, Courtney J Wusthoff¹⁵

Affiliations

¹ Department of Neurology and Weill Institute for Neuroscience, University of California San Francisco, San Francisco, CA; Department of Pediatrics UCSF Benioff Children's Hospital, University of California San Francisco, San Francisco, CA. Electronic address: Adam.numis@ucsf.edu.
² Department of Neurology and Weill Institute for Neuroscience, University of California San Francisco, San Francisco, CA; Department of Pediatrics UCSF Benioff Children's Hospital, University of California San Francisco, San Francisco, CA; Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, CA.
³ Department of Biostatistics, University of Washington, Seattle, WA.
⁴ Department of Pediatrics UCSF Benioff Children's Hospital, University of California San Francisco, San Francisco, CA.
⁵ Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA.
⁶ Departments of Neurology and Pediatrics, Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
⁷ Division of Neonatology, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA.
⁸ Division of Neonatology, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN.
⁹ Division of Pediatric Neurology, Department of Neurology, University of Washington School of Medicine, Seattle, WA.
¹⁰ Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN.
¹¹ Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA.
¹² Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH; Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
¹³ Pediatrix Medical Group of San Antonio, Children's Hospital of San Antonio, San Antonio, TX.
¹⁴ Department of Neurology and Weill Institute for Neuroscience, University of California San Francisco, San Francisco, CA; Department of Pediatrics UCSF Benioff Children's Hospital, University of California San Francisco, San Francisco, CA.
¹⁵ Departments of Neurology & Pediatrics, Stanford University, Stanford, CA.

PMID: 38360261
DOI: 10.1016/j.jpeds.2024.113957

Free article

Relationship of Neonatal Seizure Burden Before Treatment and Response to Initial Antiseizure Medication

Adam L Numis et al. J Pediatr. 2024 May.

Free article

. 2024 May:268:113957.

doi: 10.1016/j.jpeds.2024.113957. Epub 2024 Feb 13.

Authors

Affiliations

¹ Department of Neurology and Weill Institute for Neuroscience, University of California San Francisco, San Francisco, CA; Department of Pediatrics UCSF Benioff Children's Hospital, University of California San Francisco, San Francisco, CA. Electronic address: Adam.numis@ucsf.edu.
² Department of Neurology and Weill Institute for Neuroscience, University of California San Francisco, San Francisco, CA; Department of Pediatrics UCSF Benioff Children's Hospital, University of California San Francisco, San Francisco, CA; Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, CA.
³ Department of Biostatistics, University of Washington, Seattle, WA.
⁴ Department of Pediatrics UCSF Benioff Children's Hospital, University of California San Francisco, San Francisco, CA.
⁵ Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA.
⁶ Departments of Neurology and Pediatrics, Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
⁷ Division of Neonatology, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA.
⁸ Division of Neonatology, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN.
⁹ Division of Pediatric Neurology, Department of Neurology, University of Washington School of Medicine, Seattle, WA.
¹⁰ Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN.
¹¹ Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA.
¹² Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH; Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
¹³ Pediatrix Medical Group of San Antonio, Children's Hospital of San Antonio, San Antonio, TX.
¹⁴ Department of Neurology and Weill Institute for Neuroscience, University of California San Francisco, San Francisco, CA; Department of Pediatrics UCSF Benioff Children's Hospital, University of California San Francisco, San Francisco, CA.
¹⁵ Departments of Neurology & Pediatrics, Stanford University, Stanford, CA.

PMID: 38360261
DOI: 10.1016/j.jpeds.2024.113957

Abstract

Objective: To assess among a cohort of neonates with hypoxic-ischemic encephalopathy (HIE) the association of pretreatment maximal hourly seizure burden and total seizure duration with successful response to initial antiseizure medication (ASM).

Study design: This was a retrospective review of data collected from infants enrolled in the HEAL Trial (NCT02811263) between January 25, 2017, and October 9, 2019. We evaluated a cohort of neonates born at ≥36 weeks of gestation with moderate-to-severe HIE who underwent continuous electroencephalogram monitoring and had acute symptomatic seizures. Poisson regression analyzed associations between (1) pretreatment maximal hourly seizure burden, (2) pretreatment total seizure duration, (3) time from first seizure to initial ASM, and (4) successful response to initial ASM.

Results: Among 39 neonates meeting inclusion criteria, greater pretreatment maximal hourly seizure burden was associated with lower chance of successful response to initial ASM (adjusted relative risk for each 5-minute increase in seizure burden 0.83, 95% CI 0.69-0.99). There was no association between pretreatment total seizure duration and chance of successful response. Shorter time-to-treatment was paradoxically associated with lower chance of successful response to treatment, although this difference was small in magnitude (relative risk 1.007, 95% CI 1.003-1.010).

Conclusions: Maximal seizure burden may be more important than other, more commonly used measures in predicting response to acute seizure treatments.

Keywords: EEG; erythropoietin; hypoxic–ischemic encephalopathy; neonatal encephalopathy.

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Conflict of interest statement

Declaration of Competing Interest This study was supported by the National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS) R01NS104322, U01NS092764, and U01NS092553. A.N. received grant support during the study period from NINDSK23NS105918. C.W. received grant support during the study period from NINDSK02NS102598. The authors reported no conflicts of interest.

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Relationship of Neonatal Seizure Burden Before Treatment and Response to Initial Antiseizure Medication

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Relationship of Neonatal Seizure Burden Before Treatment and Response to Initial Antiseizure Medication

Authors

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Abstract

Conflict of interest statement

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