Hypoxic-Ischemic

Encephalopathy (birth
asphyxia )

Neonatal hypoxic ischemic encephalopathy

Neonatal hypoxic ischemic encephalopathy (HIE) is a type of brain
dysfunction that occurs when the brain doesn’t receive enough
oxygen or blood flow for a period of time. HIE may develop during
pregnancy, labor and delivery or in the postnatal period.

This may lead to multi-organ failure with the brain being the
most affected . HIE may cause serious impairments later in
life, such as cerebral palsy, breathing problems, and severe
physical and intellectual disabilities.
Hypoxic = not enough oxygen
Ischemic = not enough blood flow
Encephalopathy = brain disorder
 Etiology
• Prenatal events are those which cause fetal hypoxia/ischemia e.g.
maternal hypoxia/hypotension, uterine tetany, premature separation
of placenta, impedance of blood through umbilical cord, or placental
insufficiency due to toxemia or postmaturity.

• Perinatal events of newborn are the most common (80%), it

include:-
✓ Hypoxia e.g. severe cardiac or pulmonary disease.
✓ Anemia e.g. severe hemorrhage or hemolytic disease.
✓ Shock e.g. overwhelming sepsis, massive blood loss, and
intracranial or adrenal hemorrhages.
Infants at risk: Preterm infants, infants with CHD.
Pathology

The pathophysiology and pathology of HIE are quite unique. The mode
of cell death includes necrosis and apoptosis. Necrosis occurs in
conditions of primary energy failure following the initial injury. On the
other hand, apoptosis occurs days after the initial injury. The damaged
area in the brain depends on the mode of injury. Severe and prolonged
insults result in diffuse and marked neuronal necrosis. The cerebral
cortex-deep nuclear pattern of neuronal injury appears to be related to
insults that are less severe and due to partial asphyxia. The deep nuclear-
brainstem pattern of injury to the basal ganglia-thalamus-brainstem
occurs in infants with total asphyxia.
The response to HIE is different between full-term
versus premature infant in that:
in term infant it usually → focal or multifocal cortical
infarcts & necrosis, whereas
in premature infant → PVL (periventriculer
leukomalacia), IVH, or status marmoratus of basal
ganglia.

Apoptosis is the process of programmed cell death.

Status marmoratus is a congenital condition due to
maldevelopment of the corpus striatum associated with
choreoathetosis, in which the striate nuclei have a marble-like
appearance caused by altered myelination in the putamen, caudate,
and thalamus (there are bilateral hyperdensities restricted to the
thalamus). It is associated with athetoid cerebral palsy and spastic
quadriplegia
Apoptosis
Multi-organ systemic effects of asphyxia

• CNS; hypoxic-ischemic encephalopathy, infarction, intracranial

hemorrhage, seizures, cerebral edema, hypotonia, hypertonia.
• CVS; myocardial ischemia, poor contractility, tricuspid insufficiency,
hypotension.
• Pulmonary; pulmonary hypertension, pulmonary hemorrhage, RDS.
• Renal; acute tubular or cortical necrosis, myoglobinuria.
• Adrenal; adrenal hemorrhage.
• GIT; stress ulcer, necrosis, perforation.
• Metabolic; hypoglycemia, hypocalcemia, hyponatremia.
• Hematology; DIC.
• Integument; subcutaneous fat necrosis.
Clinical Manifestations
At birth, affected infants may have neurologic impairment

and may fail to breathe spontaneously. Pallor, cyanosis, apnea, a

slow heart rate, and unresponsiveness to stimulation are also
nonspecific initial signs of potential HIE.

During the next hours, infants may be hypotonic, may change from a
hypotonic to a hypertonic state, or their tone may appear normal.

Cerebral edema may develop during the next 24 hr and result in

profound brainstem depression.
 Cont …

During this time, seizure activity may occur; it may be severe

and refractory to typical doses of anticonvulsants.

Although most often a result of the HIE, seizures in asphyxiated

newborns may also be caused by vascular events
(hemorrhage, arterial ischemic stroke, or sinus
venous thrombosis), metabolic derangements (hypocalcemia,
hypoglycemia), CNS infection, and cerebral dysgenesis or genetic
disorders

.
 Cont…

In addition to CNS dysfunction, systemic organ

dysfunction is noted in up to 80% of affected neonates.
Myocardial dysfunction and cardiogenic shock,
persistent pulmonary hypertension, RDS, gastrointestinal
perforation, and acute kidney and liver injury are
associated with perinatal asphyxia secondary to
inadequate perfusion.
Hypoxic Ischemic Encephalopathy Symptoms

Symptoms of HIE depend on the severity and extent of the brain

injury. They also depend on which areas of the brain were
affected. Babies born with HIE may:
Be floppy and unreactive to sights or sounds.
Be very tense and react more to stimulation than a healthy newborn.
Have abnormal (not typical) movements or seizures.
Have feeding problems due to weak muscles in their mouth and throat.
Have a weak cry.
Problems with the heart, lungs, kidneys and liver.
Have low or high muscle tone.
Have breathing problems.
HIE is always diagnosed within the first few hours of
delivery. Problems during pregnancy or after birth may
also cause brain injury or dysfunction. However, because
they do not occur around the time of delivery, those
cases aren't classified as HIE
Hypoxic Ischemic Encephalopathy
Diagnosis.
HIE may be suspected if a significant risk factor occurred during labor
and delivery. HIE is diagnosed within the first six hours of life.
If your doctor suspects HIE, they will perform physical exams to monitor
brain function. Diagnosis is based on physical exams, blood work, and
details of labor and delivery. Once a baby has been diagnosed with HIE, a
neurologist (brain specialist) will perform a second exam to confirm the
diagnosis. A video electroencephalogram (EEG) is used to monitor for
seizures and signs of brain dysfunction.
A series of neuroimaging tests, including a head ultrasound and magnetic
resonance imaging (MRI), may also be done to create pictures of the
brain. These pictures are used to detect brain injury, which can lead to
developmental problems.
 Investigations
• US of brain is of limited value except in premature infant.

• CT scan has limited ability to identify cortical injury in the 1st few

days of life.

• MRI (diffusion-weighed) is the preferred imaging because it has

increased sensitivity and specificity to brain injury.

• Amplitude integrated EEG (aEEG) can detect seizure activity &

also can determine which infants are at highest risk for significant
brain injury (in order to plan early intervention).
Mild hypoxic-ischemic encephalo
neonate; HIE stage II-severe hypoxic
 Treatment
It should be started before, during, & immediately after
delivery.

Before delivery; Fetal hypoxia can be detected by IUGR & ↑

vascular
resistance which should alert the obstetrician about the treatable
causes of fetal distress.

✓ During delivery; Fetal distress is indicated by: bradycardia, ↓ beat-

to beat variability, late (type II) deceleration, & acidosis (pH <7.20)
detected by fetal scalp blood analysis.
These signs necessitate administration of high concentrations of
oxygen to the mother and immediate delivery (probably by C/S).
 Cont..

✓ After delivery; Asphyxiated infant is indicated by ↓ Apgar scores

e.g. pallor, cyanosis, apnea, bradycardia, unresponsive to stimuli and
may has meconium-stained amniotic fluid. Thus he need vigorous
resuscitation (see above) with the following measures:-

• Systemic (or selective) cerebral hypothermia should be done

within the 1st 6 hr after birth to core temp of 33.50C.
It cans ↓ mortality & neurodevelopmental impairment in term or
near-term infants with HIE because it may ↓ the rate of apoptosis
and suppresses production of neurotoxic mediators.
Cooling therapy has not been proven to be safe for babies born
prematurely.
Cooling therapy uses a cooling blanket and machine to
lower your baby’s body temperature. Lowering body
temperature helps prevent further brain injury from
occurring.
SE of cerebral hypothermia includes: thrombocytopenia (usually
without bleeding), reduced heart rate, subcutaneous fat necrosis, and
the potential for overcooling and the cold injury syndrome.
…………………………………………………………………………
………………
• Seizures due to HIE is usually severe & refractory to the usual doses
of anticonvulsants, thus Phenobarbital loading dose may be given
initially as 20 mg/kg, but can be given up to 40-50 mg/kg to control
the seizure. Phenytoin 20 mg/kg, Lorazepam 0.1 mg/kg, or
levetiracetam can also be used.

Note: Remember & treat other causes of convulsion in asphyxiated

infant e.g. hypoglycemia, metabolic disturbances, infection...etc
.
 Cont….

High-dose erythropoietin given as an adjunct to therapeutic

hypothermia shows some promise in decreasing MRI indicators of
brain injury and short-term motor outcomes.

• Supportive Care directed at management of other organ system

dysfunction. Hyperthermia has been found to be associated with
impaired neurodevelopment, so it is important to prevent
hyperthermia before initiation of hypothermia. Careful attention to
ventilatory status and adequate oxygenation, BP, hemodynamic
status, acid–base balance, and possible infection is important
 Prognosis
The outcome of HIE, which correlates with the timing and severity of the insult,
ranges from complete recovery to death.
The area of injury can also determine short & long term sequelae as follows:-

✓ Cortical necrosis → stupor, coma, seizures, or hypotonia; later on →

CP, cognitive delay, epilepsy, & ataxia.

✓ Periventricular injury (injury to motor tracts, especially of lower

limbs) e.g. PVL → bilateral and symmetric weakness in lower limbs;
later on → spastic diplegia.

✓ Parasagittal injury (cortex and subcortical white matter) → proximal

limb weakness (especially upper); later on → spastic quadriparesis.

✓ Basal ganglia & white matter injury → microcephaly and poor head
growth during the 1st year of life.
Factors associated with poor prognosis include:-
• Low (0–3) 10 min Apgar score
• Need for CPR in the delivery room
• Delayed onset (≥ 20 min) of spontaneous breathing
• Severe neurologic signs (coma, hypotonia, hypertonia)
• Seizures onset ≤ 12 hr or difficult to treat
• Severe, prolonged (~7 days) EEG findings including burst
suppression pattern
• Prominent MRI basal ganglia/thalamic lesions
• Oliguria/anuria >24 hr
• Abnormal neurologic exam ≥ 14 days
END