Anemia of Prematurity - Portal Neonatal

At the cellular level, neuronal injury in HIE is an evolving process. The magnitude of final neuronal
damage depends, first, on the extent of the initial insult. The nature, severity, and duration of the
primary injury are extremely critical in determining the extent of ultimate residual damage.
Following the initial phase of energy failure from the asphyxial injury, cerebral metabolism may
recover, only to deteriorate in the second phase.
Reperfusion injury is a second determinant of the extent of brain damage. By 6-24 hours after the
initial injury, a new phase of neuronal destruction sets in, characterized by apoptosis (ie,
programmed cell death). Also known as "delayed injury," this phase may continue for days to
weeks. The severity of brain injury in this phase correlates well with the severity of long-term
adverse neurodevelopmental outcome in infants. Modern treatment interventions are geared to
reducing the neuronal destruction that occurs during this phase of HIE. Local and systemic factors
such as intrauterine growth retardation (IUGR), preexisting brain pathology, or developmental
defects noted below (ie, low Apgar scores, frank neurologic deficits) increase the magnitude of
neuronal damage.
A large cascade of biochemical events follow HIE injury. Both hypoxia and ischemia increase the
release of excitatory amino acids (EAAs [glutamate and aspartate]) in the cerebral cortex and
basal ganglia. EAAs begin causing neuronal death immediately through the activation of receptor
subtypes such as kainate, N-methyl-D-aspartate (NMDA), and amino-3-hydroxy-5-methyl-4
isoxazole propionate (AMPA). Activation of receptors with associated ion channels (eg, NMDA)
leads to cell death due to increased intracellular concentration of calcium. A second important
mechanism for the destruction of ion pumps is the lipid peroxidation of cell membranes, in which
enzyme systems, such as the Na + /K + -ATPase, reside. This leads to influx into the cell water, cell
swelling, and death. EAAs also increase the local release of nitric oxide (NO), which may
exacerbate neuronal damage, although its mechanisms are unclear.
It is quite possible that EAAs disrupt factors that normally control apoptosis, increasing the pace
and extent of programmed cell death. The regional differences in severity of injury may be
explained by the fact that EAAs particularly affect the CA1 regions of the hippocampus, the
developing oligodendroglia, and the subplate neurons along the borders of the periventricular
region in the developing brain. This may be the basis for the disruption of long-term learning and
memory faculties in infants with HIE.
Frequency:
• In the US: Severe (stage 3-4) HIE is rare; 2-4 cases per 1000 births are reported.
• Internationally: Incidence in most technologically advanced nations of the world is the
same as that in the United States. However, in developing nations the incidence of HIE is
likely to be higher. Accurate statistics are not available.
Mortality/Morbidity: In severe HIE, the mortality rate is as high as 50%. Half of the deaths occur
in the first month of life. Some infants with severe neurologic disabilities die in infancy from
aspiration pneumonia and other infections.
Among infants who survive severe HIE, the most frequent sequelae are mental retardation,
epilepsy, and cerebral palsy. Careful arrangements must be made to have such infants treated in
special clinics capable of providing coordinated care, which addresses the multisystem problems of
this population.
The incidence of long-term complications depends on the severity of HIE. Up to 80% of infants
surviving severe HIE are known to develop serious complications, 10-20% develop moderately
serious disabilities, and up to 10% are normal. Among the infants who survive moderately severe
HIE, about 30-50% have serious long-term complications, and 10-20% have minor complications.
Infants with mild HIE tend to be free from serious CNS complications. Even in the absence of
obvious neurologic deficits in the newborn period, there may be long-term functional impairments.
Of school-aged children with a history of moderately severe HIE, 15-20% had significant learning