Evidence map›Paper›PMID 40101305›Full record

ArticlePediatric neurology2025

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

Khyzer B Aziz, Jordan Kuiper, Alison Kilborn, Hrishikesh Kambli, Srishti Jayakumar, Gwendolyn J Gerner, Aylin Tekes, Charlamaine Parkinson, Ernest M Graham, Carl E Stafstrom and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pediatric neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Khyzer B AzizDivision 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 KuiperDepartment of Environmental and Occupational Health, The George Washington University Milken Institute School of Public Health, Washington, District of Columbia.
Alison KilbornDivision of Neonatology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland.
Hrishikesh KambliDivision of Neonatology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland.
Srishti JayakumarDivision 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 GernerNeuroscience 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 TekesNeuroscience 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 ParkinsonDivision 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 GrahamNeuroscience 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 StafstromNeuroscience 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 CampbellMeso Scale Diagnostics, LLC., Rockville, Maryland.
Catherine DemosMeso Scale Diagnostics, LLC., Rockville, Maryland.
Martin StengelinMeso Scale Diagnostics, LLC., Rockville, Maryland.
George SigalMeso Scale Diagnostics, LLC., Rockville, Maryland.
Jacob WohlstadterMeso Scale Diagnostics, LLC., Rockville, Maryland.
Allen D EverettDivision of Pediatric Cardiology, Departmentof Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland.
Frances J NorthingtonDivision 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-ValdezDivision 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.

Funding

Elucidating factors affecting blood levels of tau and GFAP in adults at risk for neurodegenerationU01NS114144 · NINDS · MESO SCALE DIAGNOSTICS, LLC · PI STENGELIN, MARTIN · 2020 to 2024
$3.3M
Advanced therapeutic hypothermia efficacy network modeling in neonatal HIER01HD110091 · NICHD · JOHNS HOPKINS UNIVERSITY · PI EVERETT, ALLEN D, NORTHINGTON, FRANCES J · 2022 to 2025
$2.7M
Precision Medicine for Neonatal Hypoxic-Ischemic Encephalopathy: Combined Neuroimaging Clinical Approach to Link Phenotypes to PrognosisR01NS126549 · NINDS · JOHNS HOPKINS UNIVERSITY · PI Kenichi Oishi · 2022 to 2026
$2.0M
NICHD NIH HHS R01 HD110091NINDS NIH HHS R01 NS126549NINDS NIH HHS U01 NS114144
6 · The paper itself

Abstract

backgroundUnderstanding 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.

methodsThis 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.

resultsIn 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.

conclusionsTau 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.

Indexed as

Glial Fibrillary Acidic ProteinHypoxia-Ischemia, BrainNeurofilament ProteinsSeizurestau ProteinsBiomarkersFemaleHumansInfant, NewbornLongitudinal StudiesMagnetic Resonance ImagingMaleRetrospective StudiesBiomarkersGFAP protein, humanGlial Fibrillary Acidic ProteinMAPT protein, humanneurofilament protein LNeurofilament Proteinstau ProteinsBrain MRIGlial fibrillary acidic proteinNeurofilament-light chainTau

Identifiers

PMID40101305
PMCPMC11981826

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.