Abstracts

Pediatric Academic Societies 2025 Annual Meeting

Abstract

Background: Hypoxic ischemic encephalopathy (HIE) occurs when an infant’s brain is deprived of oxygenated blood flow during the perinatal period. This event triggers a cascade of ischemia-reperfusion injury, often resulting in brain injury, mortality, or lifelong disabilities. The mechanisms of HIE injury are both multiphasic and multifactorial, with initial ischemic cell death followed by secondary energy failure and a surge of inflammation. Preclinical data from animal models suggest that granulocyte-mediated pathways involving neutrophils and microglia contribute significantly to this inflammatory process. However, human data remains limited.

Objective: To assess plasma levels of granulocyte biomarkers in infants with moderate to severe HIE within the first 10 hours of life.

Methods: A phase-II randomized, placebo-controlled trial (NCT05778188) is currently enrolling infants with moderate to severe HIE across multiple NICUs in the USA. With written consent from participating families, plasma was collected within the first 10 hours of life, prior to the administration of any investigational product. Plasma was analyzed for levels of myeloperoxidase (MPO), cell-free DNA (as a marker for neutrophil extracellular trap formation), and neutrophil elastase (NE) via enzyme-linked immunosorbent assay (ELISA). Due to hemolysis or sample collection issues, not all samples were analyzable. Healthy adult plasma was used as negative controls.

Results: Pre-dose plasma from 19 infants (mean gestational age of 38 weeks; weight of 3133g) with moderate (n=15) or severe (n=4) HIE was analyzed. Moderate HIE infants had significantly elevated MPO levels compared to healthy adult controls (6.7-fold increase, P = 0.003). Severe HIE infants had MPO levels 3.8 times higher than moderate HIE infants. Similarly, cell-free DNA levels were 60% higher in moderate HIE infants compared to healthy adults, and severe HIE infants had levels 7.9 times higher than those with moderate HIE. NE levels followed a similar trend, with moderate HIE infants exhibiting a 6.5-fold increase compared to healthy adults (P = 0.003), and severe HIE infants showing levels 4.0 times higher than the moderate HIE group.

Conclusions: Our findings demonstrate that infants with moderate to severe HIE have elevated levels of MPO, cell-free DNA, and NE in the first 10 hours of life, suggesting significant granulocyte-mediated inflammation. These preliminary results highlight the potential role of granulocytes in the pathophysiology of ischemia-reperfusion injury in neonatal HIE, warranting further investigation.

A copy of the poster presentation is available for download from the Download PDF link on the right-hand panel.