MicroRNA Expression Profiles as Diagnostic and Prognostic Biomarkers of Perinatal Asphyxia and Hypoxic-Ischaemic Encephalopathy

Abstract

Introduction: Perinatal asphyxia is a leading cause of neonatal death. Up to one-third of asphyxiated neonates suffer from hypoxic-ischaemic encephalopathy (HIE) with substantial long-term morbidity. Currently available diagnostic and prognostic tools bear limitations, and additional reliable biomarkers are needed for all stages of clinical management. A novel tool in neuroscientific research is micro-ribonucleic acid (miRNA) profiling. The aim of the present study was to determine miRNA expression profiles of healthy and asphyxiated neonates with and without HIE and to assess their potential as diagnostic and prognostic biomarkers. Methods: We prospectively enrolled 49 neonates with a gestational age of ≥36 weeks, 15 of which fulfilled the diagnostic criteria of perinatal asphyxia and 34 served as healthy controls. Dried blood spots were collected from umbilical cord blood (UCB) and from venous blood upon admission to neonatal intensive care unit (NICU) and at 48 h of life. Samples were analysed by means of FirePlex™ technology (Abcam, Cambridge, MA, USA). Results: In the UCB, miRNA expression levels of hsa-mir-124-3p, hsa-mir-1285-5p, and hsa-mir-331-5p were significantly lower in asphyxiated neonates compared to healthy controls. Asphyxiated neonates requiring therapeutic hypothermia had significantly increased expression of hsa-miR-30e-5p and significantly decreased expression of hsa-miR-142-3p, hsa-miR-338-3p, hsa-miR-34b-3p, hsa-miR-497-5p, and hsa-miR-98-5p at the time of admission to the NICU. At 48 h, infants suffering from moderate/severe HIE with a poor long-term neurodevelopmental outcome showed a significant increase in hsa-mir-145-5p. Discussion/Conclusion: MiRNA profiling shows promise as a biomarker for perinatal asphyxia, hypothermia-requiring HIE, and poor neurodevelopmental outcome. Confirmatory studies are called for.