Introduction: Increasing evidence suggests neuro-inflammation impacts the development of epilepsy after brain injury. We aimed to measure circulating biomarker concentrations among neonates undergoing therapeutic hypothermia (TH) for hypoxic-ischemic encephalopathy (HIE) and to evaluate their association with post-neonatal epilepsy (PNE) by 2-years of age.

Methods: This was an ancillary to the High-Dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial for neonates with HIE treated with TH and erythropoietin or placebo. Plasma was collected at three time points: 12-24, 36-48, and 74-86 hours after birth. Plasma concentrations of 28 biomarkers, including inflammatory-mediators and brain-injury markers, were measured. Longitudinal data was collected through parent survey and epilepsy outcomes adjudicated. Univariate statistics then multivariate regression models evaluated differences in biomarker measurements between neonates with and without PNE.

Results: Among 55 participants with biomarker measurements and longitudinal follow-up data, eight (15%) had a diagnosis of PNE by 2-years of age. There was no difference in maternal and infant characteristics between neonates with and without PNE (Table 1). 14 of 82 biomarker concentrations differed between neonates with and without PNE, with enrichment in the TNF-alpha pathway (p<0.05; Figure 1). Five of 14 biomarkers had ≥50% differences between groups (Figure 2). After multivariate regression, TNF-alpha, GFAP, and UCHL1 concentrations were associated with an increased risk of PNE (p<0.05, Figure 3).

Conclusion: In neonates with HIE undergoing TH, subsequent PNE was associated with differences in concentrations of pro-inflammatory and brain injury proteins, which upon validation may serve as prognostic biomarkers with implications on novel therapeutics to prevent epilepsy.

Adam Numis
University of California, San Francisco; UCSF Benioff Children's Hospital
United States

Sandra Juul
University of Washington School of Medicine, Seattle Children's Hospital
United States

Courtney Wusthoff
Stanford University
United States

Bryan Comstock
University of Washington
United States

Emily Voldal
Fred Hutch Cancer Center
United States

An Massaro
The George Washington University School of Medicine, Children's National Health Systems
United States

Theo Bammler
University of Washington
United States

Patrick Heagerty
University of Washington
United States

Yvonne Wu
University of California, San Francisco; UCSF Benioff Children's Hospital
United States

Hannah Glass
University of California, San Francisco; UCSF Benioff Children's Hospital
United States