Evidence map›Paper›PMID 41912893›Full record

ArticlePediatric research2026

Hypoxanthine-early biomarker of outcomes in an ovine model of neonatal hypoxic ischemic encephalopathy.

Jana K Mike, Eesha Natarajan, Janica Ha, Yasmine White, Ariana Iranmahboub, Rachel S Hutchings, Christian Vento, Hadiya Manzoor, Aijun Wang, Brian D Goudy and 6 more

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Article in Pediatric research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

16 authors.

Jana K Mike *Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
Eesha Natarajan *Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA. Eesha.Natarajan@ucsf.edu.
Janica HaDepartment of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
Yasmine WhiteDepartment of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
Ariana IranmahboubDepartment of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
Rachel S HutchingsDepartment of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
Christian VentoDepartment of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
Hadiya ManzoorDepartment of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
Aijun WangDepartment of Biomedical Engineering, University of California Davis, Davis, CA, USA.
Brian D GoudyDepartment of Pediatrics, University of California Davis, Davis, CA, USA.
Satyan LakshminrusimhaDepartment of Pediatrics, University of California Davis, Davis, CA, USA.
Michael A SmithDepartment of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
Martina A SteurerDepartment of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
Jeffrey R FinemanDepartment of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
Donna M FerrieroDepartment of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
Emin MaltepeDepartment of Pediatrics, University of California San Francisco, San Francisco, CA, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHypoxic-ischemic encephalopathy (HIE) is the leading cause of neonatal morbidity and mortality globally. An early tool to diagnose and prognosticate disease could aid in timely intervention and reduction in disease burden. We aimed to identify biomarkers for HIE and define whether these biomarkers are associated with neurologic outcome severity in our ovine model.

methodsStudy Cohort 1 (n = 46) included lambs with HIE induced via umbilical cord occlusion (UCO) and healthy controls (n = 19). Cohort 2 (n = 25 UCO lambs) served as a validation cohort for identified biomarkers. Blood samples collected at multiple early time points were analyzed using untargeted liquid chromatography-mass spectrometry. Biomarkers were considered significant at p < 1e-6. Neurological outcome biomarkers were identified using ordinal logistic regression.

resultsA total of 145 hypoxia biomarkers were identified, exhibiting a consistent and reproducible temporal pattern across both cohorts. Hypoxanthine level at 20 min of life showed a strong correlation with the severity of neurologic outcomes.

conclusionsHypoxanthine emerged as a significant neurologic outcome biomarker in our study. Our findings support the potential utility of metabolomics for early diagnosis and prognostication in HIE. Further clinical validation is warranted to translate these biomarkers into accessible diagnostic and predictive tools, particularly for resource-limited settings. IMPACT: Our study identified plasma hypoxanthine as an early biomarker for hypoxic-ischemic encephalopathy (HIE) in an ovine model and uncovered a novel correlation between hypoxanthine levels and the severity of neurologic impairment in asphyxiated lambs. These findings highlight the potential of metabolomics in the early detection of HIE, paving the way for improved diagnostic and prognostic strategies. Translating these insights into clinical practice could enable the development of predictive tools for outcome assessment and resource allocation, ultimately enhancing early intervention and optimizing care for neonates at risk of HIE.

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PMID41912893

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