An accurate diagnosis of HIE requires evidence for both hypoxia and ischemia , in the form of history and laboratory findings, as well as encephalopathy, based on clinical signs. The specific etiology can be made only after careful review of the pregnancy, delivery, and neurological examination of the affected infant. In order for an acute neurological injury to be designated as HIE the American Academy of Pediatrics and the American College of Obstetrics and Gynecology put forth specific criteria for HIE in its 1996 guidelines. These include following conditions:

Among these criteria, one of the most powerful predictor of the extent of brain injury is the amount of dysfunction in other organs susceptible to hypoxia and ischemia , including the kidneys, liver, and heart. These organs have the advantage of being able to assay function and dysfunction directly, including blood biomarkers of cell injury. Biomarkers of brain injury have not yet been validated for HIE.

Clinical experience suggests that type of hypoxic-ischemic injury and its duration can be highly predictive of the pattern of injury to the brain. Acute and total injury for just 10–11 min can result in irreversible brain injuries. These injuries tend to be predominantly localized into the deep gray matter structures of the brain such as basal ganglia and thalamus while leaving much of the cerebral cortex intact. On the other hand, partial and prolonged events (over an hour or longer) results in injury to the cerebral cortex and subcortical white matter but tends to spare deep gray matter structures. In addition, advances in neuroimaging allow clinicians to better define the brain structures that are affected. Some of the most frequently used imaging modalities are ultrasonography, CT, and MRI. EEG, when applied broadly over the scalp can also help localize damage, at least within cortical structures. Of these imaging techniques, MRI gives the greatest amount of information about area of brain affected, ischemic components, and evidence of blood in the tissue. The utility of various imaging modalities is summarized in Table 5.2. The advantages of different imaging techniques must be balanced with practical considerations of the time, expense, and availability of the various imaging modalities as well as how medically stable the patient is to travel to an imaging facility, in the case of CT or MRI as opposed to being able to do ultrasound in the neonatal unit.

The mainstay of management for HIE is to ensure adequate substrate delivery in order to match brain metabolic demands. This includes adequate ventilation and perfusion, as well as correction of acidosis or other metabolic derangements caused by the original hypoxia or ischemia . Correction of metabolic disturbances addresses brain metabolic needs directly. It also helps to restore proper cerebral autoregulation of blood flow. Proper care for any infant suffering from HIE requires attention to disturbance to other systems besides neurological functions. From the perspective of brain health, addressing other end organ dysfunction helps to support uninjured brain tissue as well as repair of damaged areas.

Two aspects of management help to lower the metabolic demands of the brain. First is the treatment of seizures. Seizures are common after HIE , and they place an extra metabolic demand on the brain. Barbiturates, particularly phenobarbital, as well as benzodiazepines for acute management, have been the mainstays of drug therapy. Ongoing studies of newer antiepileptics are ongoing and may expand treatment options, particularly in refractory seizures that often accompany severe HIE. However, given the potential side effects of antiepileptic drugs, treatment options must take into consideration minimizing the number and duration of pharmacological therapy.

The second intervention that helps lower brain metabolic demands is hypothermia . Several multicenter clinical trials have demonstrated a beneficial role of either selectively cooling the head or whole body cooling. Benefits have been reported when cooling was maintained for 72 h. This method of neuroprotection appears to provide beneficial effects through mechanisms such as decrease in energy consumption, reducing accumulation of extracellular glutamate and reactive oxygen species as well as inhibition of deleterious inflammatory events and apoptotic cell death pathways. Such neuroprotection strategy that impacts multiple mechanisms not only directly improves odds of positive outcome in long term but it might widen the window for opportunities to make other therapeutic options to be effective for a longer period of time as well. Other interventions aimed at protecting the brain during this time are also under active investigation, including preventing excitotoxicity and oxidative damage.

Like prognostication for many injuries or illnesses, making a definitive prognosis for any individual is difficult. However, large groups of data have been collected on children with HIE that allow guidance of clinical decisions and prognosis for patients and their families. The most helpful clinical markers are: Apgar scores , and particularly the ‘extended’ Apgar scores that are recorded after 5 min of birth. Research suggests that infants with depressed Apgar scores of 3 or less (out of 10) after 15 min or longer have mortality rate as high as 60 % within a year and a similar rate of Cerebral Palsy (CP) in the survivors. Also, certain specific aspects of neurological syndrome such as severity of the neonatal encephalopathy, presence of seizures and the duration of hypotonia are all negative prognostic signs. In case of injury severity, it has been reported that when infants are diagnosed with the most severe form of HIE, their mortality rate is as high as 80 % but when they are diagnosed with less severe forms of the disease, the likelihood decrease precipitously. On the other hand, presence of seizures can increase the risk of neurological sequelae by as much as 40-fold. While seizures themselves can harm the brain, their negative prognostic significance is more likely related to them being a marker of a very substantial initial injury .

Neuroimaging tools such as ultrasound and magnetic resonance imaging (MRI) are also routinely used to predict long-term outlooks. Ultrasound images are most useful in predicting outcomes from injury to deeper cortical structures such as basal ganglia and thalamus in term infants. However, MRI scans have been the most valuable imaging modality for outcome prediction. Using MRI it has been shown that term infants with injury to the basal ganglia and thalamus associated with severe HIE have the worst neurological outcomes compared to injury to watershed areas of brain associated with longer and less severe HIE.

Another common form of neonatal brain injury is stroke. In newborn infants, incidence of neonatal stroke is 1 in 4000 live births. While stroke can refer to both ischemia and hemorrhage of either arterial or venous origin, for the majority of neonates, stroke is arterial ischemic event, as determined by the pattern of injury. While the cause for arterial ischemic stroke in newborns is most often unknown, the presumed mechanism is thromboembolic, as opposed to local clots associated with atherosclerotic disease, for example. There is a male predominance in neonatal strokes and also a tendency of left-sided MCA occlusion. The predilection for the left side is likely due to hemodynamics that favors passage of emboli to this side. Why boys have more strokes than girls is unknown.