Preventive, rescue and reparative neuroprotective strategies for the fetus and neonate

Neonatal encephalopathy remains a major contributor to death and disability around the world. Acute hypoxia-ischaemia before, during or after birth creates a series of events that can lead to neonatal brain injury. Understanding the evolution of injury underpinned the development of therapeutic hypothermia. This review discusses the determinants of injury, including maturity, the pattern of exposure to HI, impaired placental function, often associated with fetal growth restriction and in the long-term, socio-economic deprivation. Chorioamnionitis has been associated with the presence of NE, but it is important to note that experimentally, inflammation can either sensitize to greater neural injury after HI or alleviate injury, depending on its precise timing. As fetal surveillance tools improve it is likely that improved detection of specific pathways will offer future opportunities for preventive and reparative interventions in utero and after birth.