Hypoxic-ischemic cerebral injury that occurs during the perinatal period is one of the most commonly recognized causes of severe, long-term neurologic deficits in children; it is often referred to as cerebral palsy. Despite improvements in perinatal practice during the past several decades, the incidence of cerebral palsy attributed to intrapartum asphyxia has remained essentially unchanged, primarily because management strategies were supportive and not targeted toward the processes of ongoing injury. Two processes of neuronal injury can be demonstrated after hypoxia-ischemia: neuronal necrosis and apoptosis. Because the mechanisms of these processes likely differ, strategies to minimize brain damage in an affected infant after hypoxia-ischemia likely will have to include interventions that target both processes. The goals of management of a newborn infant who has sustained a hypoxic-ischemic insult and is at risk for evolving injury should include (1) early identification of the infant at highest risk for evolving to the syndrome of hypoxic-ischemic encephalopathy, (2) supportive care to facilitate adequate perfusion and nutrients to the brain, and (3) consideration of interventions to ameliorate the processes of ongoing brain injury. Although the neurology group was unable to develop a definitive framework for the study of neuroprotective strategies for neonatal encephalopathy, it (1) listed key questions to be addressed before exploring possible study designs for managing hypoxic-ischemic encephalopathy in neonates, (2) identified important study-design issues, (3) determined general principles and key elements for neuroprotective-treatment strategies, (4) identified potential treatment strategies, (5) proposed a clinical-trial framework, and (6) identified key elements for a potential clinical-trial framework comparing hypothermia with hypothermia “plus” for moderate-to-severe encephalopathy.

Birth asphyxia (BA), assumed to be related to intrapartum related hypoxia-ischemia, accounts for one million neonatal deaths annually. In the low resource setting BA is usually defined as a failure to initiate or sustain spontaneous breathing at birth. In the resource replete setting BA is a biochemical definition related to impaired gas exchange, due to interruption of placental blood flow (PBF). An umbilical arterial pH <7.00 referred to as severe fetal acidemia, reflects a degree of acidosis, where potential risk of adverse neurologic sequelae is increased. However, even with this degree of acidemia, the likelihood of mortality or adverse neurologic sequelae remains low. The aim is to focus on the definition of BA in the low resource setting, and compare it to the diagnosis in the resource replete setting, highlighting the importance of interruption of placental blood flow as it relates to morbidity and mortality. With asphyxia, the fetus aims to redistribute cardiac output to protect more vital organs e.g., brain, myocardium, and adrenal gland at the expense of decreased flow to organs such as kidney or intestine. In an experimental newborn model, animals subjected to asphyxia immediately develop primary apnea with bradycardia sustained blood pressure and normal pH. Recovery of respirations follows basic interventions, i.e. stimulation coupled with reversal of asphyxia. However, if asphyxia is sustained, secondary apnea manifests with bradycardia, hypotension, and pH <7.00. More intensive resuscitation including bag mask ventilation ± intubation ± cardio-pulmonary resuscitation may be necessary for correction upon reversal of asphyxia. Identification of a severely acidemic state (cord arterial pH < 7.00) in the newborn, may help to differentiate the truly asphyxiated intrapartum related cases that result in mortality, from those cases where mortality is related to delay in or ineffective basic resuscitation.