Biomarkers in neonatal hypoxic–ischemic encephalopathy—Review of the literature to date and future directions for research

The widespread introduction of therapeutic hypothermia as a standard of care in hypoxic–ischemic encephalopathy (HIE) has brought increasing pressure on clinicians to make an early and accurate assessment of the degree of hypoxic injury (HI) that has occurred and the severity of the encephalopathy that will ensue. No single blood-based marker is currently robust enough to detect significant HI or predict outcome. However, research in the field has been active in the last 10 years and we know that HIE is associated with predictable alterations in the expression of a number of inflammatory proteins, neuron-specific proteins, metabolite pathways, and microRNA. These alterations evolve quickly over the first hours and days of life. Predictive power varies depending on the timing of measurement of the biomarker, the sample type, and the case mix of the cohort examined. Combining clinical data with biochemical measurements is currently the most likely path toward improved detection and prediction of outcome in neonatal HIE.