Seizures May Worsen Outcomes of Neonatal Hypoxic-Ischemic Encephalopathy: A Longitudinal Serum Biomarkers Study

Khyzer B. Aziz, Division of Neonatology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland; Neuroscience Intensive Care Nursery Program, Johns Hopkins School of Medicine, Baltimore, Maryland; Division of General Internal Medicine, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland.
Jordan Kuiper, Department of Environmental and Occupational Health, The George Washington University Milken Institute School of Public Health, Washington, District of Columbia.
Alison Kilborn, Division of Neonatology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland.
Hrishikesh Kambli, Division of Neonatology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland.
Srishti Jayakumar, Division of Neonatology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland; Neuroscience Intensive Care Nursery Program, Johns Hopkins School of Medicine, Baltimore, Maryland.
Gwendolyn J. Gerner, Neuroscience Intensive Care Nursery Program, Johns Hopkins School of Medicine, Baltimore, Maryland; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland.
Aylin Tekes, Neuroscience Intensive Care Nursery Program, Johns Hopkins School of Medicine, Baltimore, Maryland; Division of Pediatric Radiology and Pediatric Neuroradiology, Department of Radiology, Johns Hopkins Hospital, Baltimore, Maryland.
Charlamaine Parkinson, Division of Neonatology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland; Neuroscience Intensive Care Nursery Program, Johns Hopkins School of Medicine, Baltimore, Maryland.
Ernest M. Graham, Neuroscience Intensive Care Nursery Program, Johns Hopkins School of Medicine, Baltimore, Maryland; Department of Obstetrics and Gynecology, Johns Hopkins School of Medicine, Baltimore, Maryland.
Carl E. Stafstrom, Neuroscience Intensive Care Nursery Program, Johns Hopkins School of Medicine, Baltimore, Maryland; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland.
Christopher Campbell, Meso Scale Diagnostics, LLC., Rockville, Maryland.
Catherine Demos, Meso Scale Diagnostics, LLC., Rockville, Maryland.
Martin Stengelin, Meso Scale Diagnostics, LLC., Rockville, Maryland.
George Sigal, Meso Scale Diagnostics, LLC., Rockville, Maryland.
Jacob Wohlstadter, Meso Scale Diagnostics, LLC., Rockville, Maryland.
Allen D. Everett, Division of Pediatric Cardiology, Departmentof Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland.
Frances J. Northington, Division of Neonatology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland; Neuroscience Intensive Care Nursery Program, Johns Hopkins School of Medicine, Baltimore, Maryland.
Raul Chavez-Valdez, Division of Neonatology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland; Neuroscience Intensive Care Nursery Program, Johns Hopkins School of Medicine, Baltimore, Maryland. Electronic address: rchavez2@jhmi.edu.

Document Type

Journal Article

Publication Date

5-1-2025

Journal

Pediatric neurology

Volume

166

DOI

10.1016/j.pediatrneurol.2025.02.008

Keywords

Brain MRI; Glial fibrillary acidic protein; Neurofilament-light chain; Tau

Abstract

BACKGROUND: Understanding if neonatal seizures (Sz) worsen brain injury and outcomes would optimize treatment decisions. We hypothesized that serum central nervous system-specific biomarkers would discriminate neonates with Sz and relate to outcomes. METHODS: This is a retrospective cohort study (April 2009 to November 2019), including neonates in three groups: (1) only Sz without HIE (Sz-no HIE), (2) HIE with Sz (Sz-HIE), and (3) HIE without Sz (no Sz-HIE). Levels of glial fibrillary acidic protein (GFAP, astrocytic reactivity), Tau (neuronal injury), and neurofilament light chain (NF-L, axonal degeneration) were studied at admission/<6 h, <72 h, and 72-144 h of life against time to achieve full oral feeds and NICHD-NRN MRI score. RESULTS: In 145 neonates included (61% male; 33% black), admission GFAP levels were higher in Sz-HIE than in no Sz-HIE. During the first 72 hours of life, GFAP, Tau, and NF-L levels were similar between Sz-no HIE and Sz-HIE but higher than in no Sz-HIE. After 72 hours, NF-L and Tau remained higher in both Sz groups (versus no Sz-HIE). In adjusted regression models, higher Tau and NF-L percentiles related to longer time to reach full oral feeding and higher odds of more than minimal brain injury in MRI in Sz-HIE. CONCLUSIONS: Tau and NF-L levels are higher in those neonates developing Sz. Although relationships with worse brain injury may be driven by the HIE severity itself, modeling shows Sz as the most important feature, providing support to the notion that Sz may worsen brain injury in neonates with HIE even after TH.

Department

Environmental and Occupational Health

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