HIE Birth Injuries and Cerebral Palsy

Hypoxic Ischemic Encephalopathy is essentially damage to cells in the central nervous system (the brain and spinal cord) due to a lack of blood flow often caused by a difficult childbirth.

Hypoxic-ischemic encephalopathy (HIE) can result in what is later recognized as developmental delay, intellectual disability, or in some circumstances, the development of a neurological condition called cerebral palsy. In spite of major advances in monitoring technology and knowledge of fetal / neonatal pathologies, hypoxic-ischemic encephalopathy remains a serious condition still today, causing significant mortality and long-term disability.

HIE is characterized by clinical and laboratory evidence of acute or subacute brain injury due to asphyxia (ie, hypoxia, acidosis). Most often, the underlying cause remains unknown. The exact time of brain injury often remains uncertain, and an abnormal brain (e.g., growth failure, impaired development) may be an underlying risk factor.

Hypoxic Birth Injuries and Cerebral Palsy

Hypoxia & Cerebral Palsy

Hypoxic Ischemic Encephalopathy is also commonly referred to as:

  • HIE
  • Cerebral hypoxia
  • Perinatal asphyxia
  • Birth asphyxia
  • Neonatal asphyxia
  • Hypoxia
  • Ischemia

Diagnosing Hypoxic Ischemic Encephalopathy

The American Academy of Pediatrics (AAP) and American College of Obstetrics and Gynecology (ACOG) have published guidelines to assist in the diagnosis of severe HIE.

Brain hypoxia and ischemia due to systemic hypoxemia, reduced cerebral blood flow (CBF), or both, are the primary physiological processes that trigger HIE. The initial compensatory adjustment to an asphyxial event is an increase in the CBF due to hypoxia and hypercapnia. This is accompanied by a redistribution of cardiac output such that the brain receives an increased proportion of the cardiac output. A borderline increase in the systemic blood pressure (BP) further enhances the compensatory response. The BP increase is due to increased release of epinephrine; these are classic early cardiovascular compensatory responses to asphyxia.

In adults, CBF is maintained at a constant level despite a wide range in systemic BP. This phenomenon is known as the cerebral autoregulation, which helps to maintain the cerebral perfusion. The physiological aspects of CBF autoregulation has been well studied in perinatal and adult experimental animals. In human adults, the BP range at which CBF is maintained has been shown to be 60-100 mm Hg. However, such a range of BP in the human fetus and the newborn infant has not been studied with much rigor due to limitations of human experimentation in the fetus and newborn.

Limited data on the preterm infant suggests that a range of blood pressures exist over which cerebral blood flow is stable. Based on this human data, along with other animal data, some experts have postulated that in the healthy term newborn the BP range at which the CBF autoregulation is maintained is quite narrow (perhaps between 10-20 mm Hg, compared to the 40 mm Hg range in adults noted above). The autoregulatory zone may also be set at a lower level, about the mid point of the normal BP range for the fetus and newborn. However, the precise upper and lower limits of the BP values above and below which (respectively) the CBF autoregulation is lost remains unknown for the human newborn.

In the fetus and newborn suffering from acute asphyxia, after the early compensatory adjustments fail, the CBF can become pressure-passive, at which time brain perfusion is dependent on systemic BP. As BP falls, CBF falls below critical levels, and the brain continues to suffer from diminished blood supply and a lack of sufficient oxygen to meet its needs. This leads to intracellular energy failure. During the early phases of brain injury, brain temperature drops, and local release of the neurotransmitter, such as g-aminobutyric acid transaminase (GABA), increase. These changes reduce cerebral oxygen demand, transiently minimizing the impact of asphyxia.

At the cellular level, neuronal injury in HIE is an evolving process. The magnitude of the final neuronal damage depends on both the severity of the initial insult and the damage due to reperfusion injury and apoptosis. The extent, nature, severity, and the duration of the primary injury are all important in affecting the magnitude of the residual neurological damage.

Following the initial phase of energy failure from the asphyxial injury, cerebral metabolism may recover, only to deteriorate in the secondary phase, or reperfusion. This new phase of neuronal damage, starting at about 6-24 hours after the initial injury, is characterized by cerebral edema and apoptosis. This phase has been called the “delayed phase of neuronal injury.” The duration of the delayed phase is not known precisely in the human fetus and newborn but appears to increase over the first 24-48 hours and then start to resolve thereafter.

Additional factors that influence outcome include the nutritional status of the brain, severe intrauterine growth restriction, preexisting brain pathology or developmental defects of the brain, and the frequency and severity of seizure disorders that manifest at an early postnatal age (within hours of birth).

At the biochemical level, a large cascade of events follow HIE injury. Both hypoxia and ischemia increase the release of excitatory amino acids (EAAs), such as glutamate and aspartate, in the cerebral cortex and basal ganglia. EAAs cause neuronal death 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 opening of ion channels (eg, NMDA) lead to increased intracellular and subcellular calcium concentration and cell death. 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 can cause cerebral edema and neuronal death. EAAs also increase the local release of nitric oxide (NO), which may exacerbate neuronal damage, although its mechanisms are unclear.

The EAAs may also disrupt the factors that control apoptosis, increasing the pace and extent of programmed cell death. One mechanism for apoptosis or programmed cell death is thought to be related to calcium influx into the cell and nucleus of the cell after activation of the EAAs. 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 of Hypoxic Ischemic Encephalopathy

In the United States and in most technologically advanced countries, the incidence of severe (stage 3) HIE is between 2-4 cases per 1000 births.

Internationally, HIE is reported to be high in countries with limited resources; however, precise figures are not available. The World Health Organization reports that approximately 1 million children worldwide die from a diagnosis of birth asphyxia, and about the same number may survive with significant long-term neurological disability.

In severe HIE, the mortality rate has been reported to be 50-75% Most deaths (55%) occur in the first month, due to multiple organ failure or termination of care. Some infants with severe neurologic disabilities die in their infancy from aspiration pneumonia or systemic infections.

Among the infants who survive severe HIE, the sequelae include intellectual disability, epilepsy, and cerebral palsy of varying degrees. The latter can be in the form of hemiplegia, paraplegia, or quadriplegia. Such infants need careful evaluation and support. They may need to be referred to specialized clinics capable of providing coordinated comprehensive follow-up care.

The incidence of long-term complications depends on the severity of HIE. Up to 80% of infants who survive severe HIE develop serious complications, 10-20% develop moderately serious disabilities, and up to 10% are normal. Among the infants who survive moderately severe HIE, 30-50% may suffer from serious long-term complications, and 10-20% with minor neurological morbidities. Infants with mild HIE tend to be free from serious CNS complications.

Even in the absence of obvious neurologic deficits in the newborn period, long-term functional impairments may be present. In a cohort of school-aged children with a history of moderately severe HIE, 15-20% had significant learning difficulties, even in the absence of obvious signs of brain injury. Thus, all children who have moderate or severe HIE should be monitored well into their school ages.

Preterm infants can also suffer from HIE, but the pathology and manifestations are slightly different. Most often, the condition is noted in infants who are term at birth. The symptoms of moderate-to-severe HIE are almost always manifested at birth or within a few hours after birth.

If you have questions regarding hypoxic ischemic encephalopathy, or would like to discuss your situation with a cerebral palsy lawyer, call 1-855-833-3707.