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Research Snapshot Theater: Veterinarian

Hypoxanthine: Early Outcome Biomarker for Hypoxic Ischemic Encephalopathy in an Ovine Model

Sunday, March 22, 2026
2:30 PM - 3:30 PM Central Time
Location: Connections Central - RST 12
  • EN

    Eesha Natarajan, MD

    University of California San Francisco Medical Center, California

    Disclosure(s): No relevant financial relationship(s) to disclose.

  • JM

    Jana Mike, MD, PhD

    Assistant Professor
    University of California San Francisco Medical Center

    Disclosure information not submitted.

  • YW

    Yasmine White, MD

    Neonatologist
    Kaiser Permanente Santa Clara

    Disclosure information not submitted.

  • EM

    Emin Maltepe, MD, PhD

    Professor
    University of California San Francisco Medical Center

    Disclosure information not submitted.

Introduction: Hypoxic-ischemic encephalopathy (HIE) is the leading cause of neonatal morbidity and mortality (~4 million neonates annually) globally. Roughly 96% of the disease burden lies in limited resources countries where therapeutic hypothermia, the standard of care, is often unavailable. The current need for HIE is to define an accessible tool usable in a narrow temporal window to diagnose and prognosticate disease. Metabolomics, which is the comprehensive analysis of metabolites in a biological specimen, is a promising modality.
The purpose of this study was to identify early plasma biomarkers for HIE and their association with neurologic outcome severity in the ovine model.


Methods: HIE was induced to near term lambs at 141-143 days gestation via umbilical cord occlusion (UCO). The lambs were divided into two cohorts. Cohort 1 had n=46 UCO lambs and n=19 controls. Validation cohort 2 had n=25 UCO lambs. Arterial blood samples were collected at multiple timepoints from birth to 6 days and analyzed by liquid chromatography-mass spectrometry. Neurologic impairment (staged based on motor function, activity at rest, and ability to feed) was assessed daily.


Results: We analyzed ~50,000 molecules. 1219 hypoxia biomarkers at end of asphyxia were identified in cohort 1 at p< 1e-6 using paired t-test. Most hypoxia biomarkers recovered after 48 hours. Hypoxia biomarkers identified in cohort 1 showed high significance in cohort 2. Twenty-two biomarkers were significantly associated with neurological outcome severity. Hypoxanthine, a purine metabolism derivative, was one of the most significantly changed biomarkers that strongly correlated with hypoxia and neurologic outcomes.


Conclusions: HIE triggers a specific biomarker response. Hypoxanthine significantly correlated with hypoxic injury and severity of neurological outcome. Further studies are needed to identify significant biomarkers, and define their role as diagnostic or prognostic markers, or therapeutic targets.