Hypoxic Ischemic Encephalopathy

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Introduction

Hypoxic Ischemic Encephalopathy (HIE) is an injury to the brain, occurring in the neonatal period (under 28 days old) in which there is a deprivation of oxygen supply to the brain, also termed an anoxic brain injury. It is a common cause of neonate mortality and developmental psychomotor disorders in the pediatric population worldwide. HIE is one of the major causes of cerebral palsy.

Attributing neonatal encephalopathy to perinatal hypoxic–ischemic injury requires combinations of parameters indicative of metabolic acidosis in the first postnatal hours with low cord pH (<7.0), base deficit of over 12, and evidence of a need for respiratory support also starting in the first minutes, with low Apgar scores at and beyond 5 min.

Epidemiology

• The incidence of HIE is ~1–8 per 1,000 live births in technically advanced countries and is up to 10-20 per 1,000 live births in less developed countries.

Etiology

Maternal factor

Fetal factor

Delivery condition

Mechanism of Injury / Pathological Process

Various conditions, both prenatally and postnatally can cause an hypoxic-ischemic (HI) event. This includes pre-eclampsia, umbilical cord knotting, shoulder dystocia and placental abruption. In these events, there is an impairment in oxygenated blood flow to the fetus, leading to both systemic and cellular responses. This then leads to a depletion of energy for the cells involved. This energy crisis or primary energy failure starts an 'ischemic cascade' - which then goes on to cause a simultaneous disruption in the blood-brain barrier, neuronal cell loss and inflammatory response. These in turn, then feed into five events of an HI injury, which are influenced by each other and by the preceding events. They are described by Greco et al (2020) as:

• Oxidative stress
• Intracellular calcium accumulation
• Mitochondrial dysfunction
• Excitotoxicity
• Inflammation

Greco et al.also describes an HI injury occuring in 3 phases:

1. First immediate phase = Primary neuronal death.
2. Second phase = Latent phase
3. Third phase = Secondary energy failure/ delayed neuronal death.

The first phase occurs during the initial insult, with primary energy failure, which results in oxidative metabolism failure, cytotoxic oedema and the accumulation of cerebral circulation.

The second phase lasts about six hours to fifteen hours and occurs with the restoration of cerebral blood flow.

The third phase can occur days after the initial HI insult. It is associated with encephalopathy and increased seizure activity. In this phase excitotoxicity, apoptosis and microglial activation are described. It is generally far more extensive in damage.

Clinical Presentation/manifestation

Fetal asphysia:

Meconium stained liquor:

APGAR score

Seizure

tone

Classification of HIE

There are three classification system of HIE

Sarnat and Sarnat staging

Harvey B. Sarnat and Margaret S. Sarnat first published a study related to the Sarnat staging system with 21 neonates with encephalopathy attributed to a “well-defined episode of fetal distress or an Apgar score of ≤5 at 1 or 5 min after delivery.”. Their staging system for the sequential evolution of clinical signs and electroencephalogram (EEG) changes was intended to facilitate formulation of prognosis for neurologic outcome.

Later, modifications of the Sarnat Scoring System have been employed in the major trials of therapeutic hypothermia for neonatal hypoxic–ischemic encephalopathy (HIE) to identify neonates at highest risk for abnormal neurodevelopmental outcome.

Thompson scoring

In 1997, Thompson et al. tested a numeric scoring system with fewer clinical assessment-based items in 45 neonates with HIE. In contrast to the Sarnat scale, the Thompson score did not require categorization of severity of encephalopathy but rather relied on a simple numeric score to describe the peak severity of encephalopathy.

By design, the Thomspon score did not require specific training or depend on the availability of advanced technologies (e.g., magnetic resonance imaging, computed tomography, cerebral function monitoring).

The score consisted of clinical assessment of nine signs: tone, level of consciousness, seizures, posture, Moro, grasp, suck, respiratory pattern, and fontanelle findings. Each sign was scored from 0 to 3, making highest score of 27 and lowest score of 0.

It has performed daily until a score of 0 was achieved or the infant was discharged from the hospital.

Limitations:

• unclear inclusion criteria for infants (“if clinical signs of hypoxic–ischemic encephalopathy developed after birth”)
• a small sample size.

Investigations

• EEG
• Cranial ultrasound
• CT scan
• MRI

Management / Interventions

Medical Management

• Therapeutic hypothermia
  • Hypothermia is the current standard of care for infants with HIE. Recommendations stipulated are cooling the whole body to a core temperature of 33.5°C for 72 hours starting 6 hours after birth. This method of treatment, however, is not completely effective and there is often a high prevalence of complications and even mortality.

• Various neuroprotective treatments are being studied which are targeted at the ischemic cascade. These include Magnesium Sulphate, Argon, Xenon, Melatonin Erythropoietin (EPO), Allopurinol, and even stem cells and cord blood mononuclear cells.

Prognosis

Depending upon the severity of brain damage and medical treatment, usally:

Mild or moderate cases could be cured completely, but severe cases represent poor prognosis with high mortality or cerebral complications such as mental retardation and cerebral palsy.

Overall mortality: 20%

Overall incidence of sequel: 30%

Mild: 100% good prognosis

Moderate: 80% normal

Severe: 50 5 death , 50% sequel

Presence of seizure increases chance of cerebral palsy by 50-70 times

Prevention

• Better obstetric care
• Skilled resuscitation teams and neonatal facilities

Resources

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