Current insights in brain protection for the sick newborn infant

This paper presents an overview of the modern antenatal and postnatal strategies in brain protection for both preterm and term born infants. It is known, that the two most common causes of neonatal brain injury are prematurity and hypoxic-ischemic encephalopathy (HIE) in the term born infant. Approximately one in nine babies is born before term. Nowadays these preterm born infants more often survive the neonatal period due to developments in treatment options in the last decades. They are however at a high risk for developing brain damage and neurodevelopmental impairment later in life. Approximately 40 % of survivors develop long-term intellectual or physical impairment, including cerebral palsy (CP). Term born infants born after perinatal asphyxia may also survive with a variety of neurocognitive disorders due to brain damage as a result from the hypoxic ischemic encephalopathy (HIE). Untreated, the sequelae of moderate to severe HIE includes a 60 to 65 % risk of mental retardation, CP, hydrocephalus, seizures, or death. The main goal in neonatal care for these surviving but vulnerable infants is to preserve brain function and prevent further brain damage, in order to improve neurocognitive outcome and the subsequent quality of life. In preterm brain protection antenatal strategies besides educating and supporting pregnant women regarding life style and healthy food intake, centralization of care for extreme preterm born infants, fetal monitoring in high risk pregnancies, administration of antenatal steroids for lung maturity, the use of intravenous magnesium sulfate administration to mothers just before preterm delivery are of great importance. In the postnatal strategies setting optimal oxygen saturation, the avoidance of prolonged artificial mechanical ventilation, hypoglycemia, hypocapnia electrolytic imbalances, hyperbilirubinemia, blood pressure shifts, stress and pain, inflammation, necrotizing enterocolitis as well as adequate feeding strongly predict neurocognitive outcome. In the term asphyxiated infants the brain experiences a cascade of problems occurring after energy failure which in fact are the basis of neuroprotective strategies. These strategies consist of anti-oxidative, anti-inflammatory, anti-excitatoxic and anti-apoptotic agents, and in the future possibly neurogenetic approaches, including stem cell therapy. In antenatal strategies prevention of asphyxia starts at promoting a healthy pregnancy and of an early recognition of fetal, placental or perinatal risk factors for hypoxia. Recent experimental trials have shown a possible beneficial effect of antenatal administration of the anti-oxidative agent allopurinol in a HIE. In postnatal strategies two methods to achieve therapeutic hypothermia were evaluated in newborn infants with HIE: whole body cooling and selective head cooling with mild systemic hypothermia with the conclusion: hypothermia should be instituted in term infants with moderate-to-severe hypoxic ischemic encephalopathy if identified before six hours of age. Monitoring of brain activity by means of amplitude integrated electroencephalography to identify infants with HIE is promising. Potential agents with either anti-oxidative, anti-inflammatory, anti-excitatoxic or anti-apoptotic capacities are currently being investigated in various phases of research.