Perinatal asphyxia continues to be a major cause of neonatal morbidity, mortality and neurodevelopmental disability. In spite of major advance in monitoring technology and knowledge of fetal and neonatal pathologies, perinatal asphyxia or, more appropriately hypoxic-ischemic encephalopathy (HIE), remains a serious condition, causing significant mortality and long-term morbidity. Understanding the timing of the insult and contributing factors may be improved by adequate documentation of general medical and obstetric factors, determination of pH and blood gases in the cord blood and neonatal Neuro- imaging. Other diagnostic tools of crucial importance to predict the neurologic outcome after cerebral injury are measurements of markers of perinatal brain injury in biological fluids with the aim of improving the ability to detect fetuses and newborns at risk of brain injury at an earlier stage, when the window for therapeutic actions is still open.The aim of the work is to provide insight into the role of different biochemical markers and their reliability as indicators of hypoxic ischemic encephalopathy and to show whether detection of elevated serum concentrations of these proteins reflects long term neurodevelopmental impairment or not.