Fellow Physician Loma Linda University Children's Hospital Loma Linda, California, United States
Background: Hypoxic-ischemic encephalopathy (HIE) is one of the leading etiologies for morbidity and mortality in term infants. There is a small treatment window of 6 hrs for moderate-severe HIE. In this time period, infants need to be assessed for treatment eligibility but the current methods to diagnose HIE can be inaccurate, and protracted. Hence, there is an urgent need for reliable and rapidly quantifiable biomarkers to assess the severity of HIE. MicroRNAs (miRNAs) are a class of noncoding nucleotide RNAs in hypoxic stress, regulating cell proliferation, invasion, and repairing damage. Recent studies show that miRNAs play a critical role in ischemic brain injury in human studies including cerebral ischemic stroke and neonatal HIE. Therefore, miRNAs might be potential therapeutic targets in the treatment of infants with hypoxic-ischemic brain injury. Objective: To measure miRNA profiles with miRNA sequencing in HIE infants and identify differentially expressed miRNAs. To correlate differentially expressed miRNAs with known predictors of HIE like SARNAT scoring and non-contrast MRI/MRS findings. Design/Methods: The participants (
Case: HIE, Control: Non HIE and non-cardiac patients) are consented based on the institutional HIE inclusion criteria from July 1st 2023-July 1st 2024. We will perform a brief chart review to confirm the patient’s perinatal history, birth weight, gestational age, gender, SARNAT scoring, non-contrast brain MRI, and MRS report details. After consenting, discarded plasma/serum samples will be collected at different time points. The total RNA will be extracted using a QIAGEN miRNeasy Serum/Plasma kit, and shipped to a commercial health technology company for miRNA sequencing, profiling, and data interpretation. Currently, 10 patients have been enrolled in the study. We are in the process of obtaining pilot study data where we will compare 5 HIE patients with 5 control patients. The study obtained IRB approval on June 24th, 2023. This project is supported by Pediatric Research Initiative grant approval from the institution, NIH NS112404 and NS126583-01A1.