This document discusses hypoxic ischemic encephalopathy (HIE), which is brain damage caused by a lack of oxygen and blood flow around the time of birth. It defines related terms like anoxia and hypoxia. It describes the effects of HIE on different body systems. It outlines the stages of HIE based on clinical signs. It discusses causes of fetal and newborn hypoxia, pathophysiology, treatment involving supportive care and seizure management, and prognosis which depends on factors like gestational age and severity of encephalopathy. Between 15-30% of infants with HIE die or are left with permanent neurological impairments.

1. Hypoxic Ischemic
Encephalopathy
Prof. Saad S Al-Ani
Senior Pediatric Consultant
Head of Pediatric Department
Khorfakkan Hospital . Sharjah
saadsalani@yahoo.com

2. Definitions
Anoxia
is a term used to indicate the consequences of complete lack of oxygen as a
result of a number of primary causes
Hypoxia
refers to an arterial concentration of oxygen that is less than normal
Ischemia
refers to blood flow to cells or organs that is insufficient to
maintain their normal function
Biagioni E, Mercuri E, Rutherford M, et al: Combined use of electroencephalogram and magnetic resonance
imaging in full-term neonates with acute encephalopathy. Pediatrics 2001;107:461
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3. Hypoxic-ischemic encephalopathy
Is an important cause of permanent
damage to CNS cells that may result in
neonatal death or be manifested later
as cerebral palsy or mental deficiency
Nelson Textbook of Pediatrics 19th ed.2010 . pages 566 - 568
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4. Fifteen to 20% of infants with hypoxic-
ischemic encephalopathy die in the neonatal
period
25-30% of survivors are left with permanent
neurodevelopmental abnormalities (cerebral
palsy, mental retardation).
Dixon G, Badawi N, Kurinczuk JJ, et al: Early developmental outcomes after
newborn encephalopathy. Pediatrics 2002;109:26-33
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5. Effects of Asphyxia
System
Effect
I. Central nervous system II.Cardiovascular
1.Hypoxic-ischemic encephalopathy 1.Myocardial ischemia
2.Infarction 2. Poor contractility
3. Intracranial hemorrhage 3. Cardiac stun
4.Seizures 4. Tricuspid insufficiency
5. Cerebral edema 5. Hypotension
6. Hypotonia
7. Hypertonia
Cowan F, Rutherford M, Groenendaal F, et al: Origin and timing of brain
lesions in term infants with neonatal encephalopathy. Lancet 2003;361:736-
42.
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6. Effects of Asphyxia
System Effect
(cont.)
III. Pulmonary V. Adrenal
1. Pulmonary hypertension Adrenal hemorrhage
2. Pulmonary hemorrhage
3. Respiratory distress syndrome
VI. Gastrointestinal
1. Perforation
IV. Renal
2. Ulceration with hemorrhage
Acute tubular or cortical
necrosis 3. Necrosis
Cowan F, Rutherford M, Groenendaal F, et al: Origin and timing of brain
lesions in term infants with neonatal encephalopathy. Lancet 2003;361:736-
42.
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7. Effects of Asphyxia
System Effect
(cont.)
VII. Metabolic
1. Inappropriate secretion of antidiuretic hormone
2. Hyponatremia
3. Hypoglycemia
VIII. Integument
4. Hypocalcemia
Subcutaneous fat necrosis
5. Myoglobinuria
IX. Hematology
Disseminated intravascular coagulation
Cowan F, Rutherford M, Groenendaal F, et al: Origin and timing of brain
lesions in term infants with neonatal encephalopathy. Lancet 2003;361:736-
42.
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8. Asphyxia
is considered in infants with:
1. Fetal acidosis (pH <7.0)
2. A 5-min Apgar score of 0-3
3. Hypoxic-ischemic encephalopathy:
i. Altered tone
ii. Depressed level of consciousness
iii. Seizures
And
4. Other multiorgan system signs
Battin MR, Dezoete A, Gunn TR, et al: Neurodevelopmental outcome of
infants treated with head cooling and mild hypothermia after perinatal
asphyxia. Pediatrics 2001;107:480
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9. Causes Of Fetal Hypoxia
(1) Inadequate oxygenation of maternal
blood
as a result of:
I. Hypoventilation during anesthesia
II. Cyanotic heart disease
III. Respiratory failure
IV. Carbon monoxide poisoning
(2) low maternal blood pressure
as a result of the hypotension that may:
I. Complicate spinal anesthesia
II. Result from compression of the vena cava and aorta by the gravid
uterus
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10. Causes Of Fetal Hypoxia
(cont.)
(3) Inadequate relaxation of the uterus
to permit placental filling as a result of uterine tetany caused by the
administration of excessive oxytocin
(4) Premature separation of the placenta
Johnson MV: MRI for neonatal encephalopathy in full-term
infants. Lancet 2003;361:713-4
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11. Causes Of Fetal Hypoxia
(cont.)
(5) Impedance to the circulation of blood
through the umbilical cord as a result of compression or knotting of
the cord
(6) Uterine vessel vasoconstriction by cocaine
(7) placental insufficiency from numerous causes
including toxemia and postmaturity.
Johnson MV: MRI for neonatal encephalopathy in full-term
infants. Lancet 2003;361:713-4
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12. Fetal hypoxia
Abnormal Doppler velocimetry .
On an umbilical artery Doppler flow velocity waveform
The umbilical placental impedance is so high that the diastolic component
shows flow in a reverse direction. This finding is an indication of severe
intrauterine hypoxia and intrauterine growth restriction .
Nelson Textbook of Pediatrics (on 20 November 2003) 2003 Elsevier
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13. Causes of after birth hypoxia
(1)Anemia severe enough to lower the oxygen content of the blood to
a critical level, as after severe hemorrhage or hemolytic disease
(2) Shock severe enough to interfere with the transport of oxygen to vital
organs as a result of
i. Overwhelming infection
ii. Massive blood loss
iii. Intracranial or adrenal hemorrhage
Crowley P: Prophylactic corticosteroids for preterm birth. Cochrane
Database Syst Rev 2002;Issue 1. De Felice C, Toti P, Laurini RN, et
al: Early neonatal brain injury in histologic chorioamnionitis. J Pediatr
05/26/2010 Khorfakkan Hospital Pediatric Department2001;138:101
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14. Causes of after birth hypoxia (cont.)
(3) Deficit in arterial oxygen saturation
from failure to breathe adequately postnatally because of
i. Cerebral defect
ii. Narcosis
iii. Injury
(4) Failure of oxygenation of an adequate amount
of blood as a result of severe forms of cyanotic congenital heart disease or
pulmonary disease
Crowley P: Prophylactic corticosteroids for preterm birth. Cochrane
Database Syst Rev 2002;Issue 1. De Felice C, Toti P, Laurini RN, et
al: Early neonatal brain injury in histologic chorioamnionitis. J Pediatr
2001;138:101
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15. Pathophysiology
Within minutes of the onset of total fetal hypoxia :
1.Bradycardia
2. Hypotension
3. decreased cardiac output
4. severe metabolic as well as respiratory acidosis occur
The initial circulatory response of the fetus
* is increased shunting through the ductus venosus, ductus
arteriosus, and foramen ovale
* with transient maintenance of perfusion of the brain, heart, and
adrenals in preference to the lungs (because of pulmonary
vasoconstriction), liver, kidneys, and intestine.
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16. Patterns of periodic fetal heart rate (FHR)
deceleration
A shows early deceleration occurring during the peak of uterine
contractions as a result of pressure on the fetal head
. Hon EH: An Atlas of Fetal Heart Rate Patterns . New Haven,
CT, Harty Press, 1968.)
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17. Patterns of periodic fetal heart rate
(FHR) deceleration (cont . )
B, Late deceleration caused by uteroplacental
insufficiency
. Hon EH: An Atlas of Fetal Heart Rate Patterns . New Haven,
CT, Harty Press, 1968.)
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18. Patterns of periodic fetal heart rate
(FHR) deceleration (cont.)
C, Variable deceleration as a result of umbilical cord compression
. Hon EH: An Atlas of Fetal Heart Rate Patterns . New Haven,
CT, Harty Press, 1968.)
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19. Clinical Manifestations
Hypoxic-Ischemic Encephalopathy in Term
Infants
Signs: Stage 1 Stage 2
Stage 3
I. Level of consciousness
Hyperalert , Lethargic Stuporous coma
II. Muscle tone
Normal Hypotonic Flaccid
III. Posture
Normal Flexion Decerebrate
Biagioni E, Mercuri E, Rutherford M, et al: Combined use of
electroencephalogram and magnetic resonance imaging in full-term
neonates with acute encephalopathy. Pediatrics 2001;107:461
05/26/2010 Khorfakkan Hospital Pediatric Department
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20. Clinical Manifestations
Hypoxic-Ischemic Encephalopathy in Term
Infants (cont.)
Signs: Stage 1 Stage 2
Stage 3
IV. Tendon reflexes
Clonus ,Hyperactive Hyperactive Absent
V. Myoclonus
Present Present Absent
VI. Moro reflex
Strong Weak Absent
Biagioni E, Mercuri E, Rutherford M, et al: Combined use of
electroencephalogram and magnetic resonance imaging in full-term
neonates with acute encephalopathy. Pediatrics 2001;107:461
05/26/2010 Khorfakkan Hospital Pediatric Department
20

21. Clinical Manifestations
Hypoxic-Ischemic Encephalopathy in Term
Infants (cont.)
Signs: Stage 1 Stage 2
Stage 3
VII. Pupils
Mydriasis Miosis Unequal Poor light reflex
VIII. Seizures
None Common Decerebration
IX. Electroencephalographic
Normal Low voltage changing Burst
suppression
to seizure activity Rutherford M, etto isoelectric of
Biagioni E, Mercuri E, al: Combined use
electroencephalogram and magnetic resonance imaging in full-term
neonates with acute encephalopathy. Pediatrics 2001;107:461
05/26/2010 Khorfakkan Hospital Pediatric Department
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22. Clinical Manifestations
Hypoxic-Ischemic Encephalopathy in Term
Infants (cont.)
Signs: Stage 1 Stage 2
Stage 3
X. Duration
<24 hr if progresses; otherwise, Days to weeks
may remain normal24 hr to 14 days
XI. Outcome
Good Variable Death, severe deficits
Biagioni E, Mercuri E, Rutherford M, et al: Combined use of
electroencephalogram and magnetic resonance imaging in full-term
neonates with acute encephalopathy. Pediatrics 2001;107:461
05/26/2010 Khorfakkan Hospital Pediatric Department
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23. Treatment
Therapy is supportive and directed at the organ system
manifestations
Careful attention to :
• Ventilatory status and adequate oxygenation
• Blood volume,
• Hemodynamic status
• Acid-base balance
• Possible infection
is important
Dixon G, Badawi N, Kurinczuk JJ, et al: Early
developmental outcomes after newborn encephalopathy.
Pediatrics 2002;109:26-33.
05/26/2010 Khorfakkan Hospital Pediatric Department
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24. Treatment (cont.)
No established effective treatment is available for the brain tissue injury,
although many drugs (phenobarbital, allopurinol, calcium channel blockers)
and procedures (total body or local cranial hypothermia) are under study
Aggressive treatment of seizures is critical and may necessitate
continuous electroencephalographic monitoring.
Dixon G, Badawi N, Kurinczuk JJ, et al: Early
developmental outcomes after newborn encephalopathy.
Pediatrics 2002;109:26-33.
05/26/2010 Khorfakkan Hospital Pediatric Department
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25. Treatment (cont.)
Seizure activity may be severe and refractory to the usual
doses of anticonvulsants
Phenobarbital, the drug of choice, is given with an intravenous loading
dose (20 mg/kg); additional doses of 10 mg/kg (up to 40-50 mg/kg total) may
be needed.
Phenobarbital levels should be monitored 24 hr after the loading dose
and maintenance therapy (5 mg/kg/24 hr) are begun
Phenytoin (20 mg/kg loading dose) or lorazepam (0.1 mg/kg) may
be needed for refractory seizures.
Dixon G, Badawi N, Kurinczuk JJ, et al: Early
developmental outcomes after newborn encephalopathy.
Pediatrics 2002;109:26-33.
05/26/2010 Khorfakkan Hospital Pediatric Department
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26. Prognosis
The outcome of hypoxic-ischemic encephalopathy ranges from
complete recovery to death
The prognosis depending on :
1.Whether the metabolic and cardiopulmonary complications
(hypoxia, hypoglycemia, shock) can be treated
2. Infant's gestational age
(outcome is poorest if the infant is preterm)
3. Severity of the encephalopathy
Battin MR, Dezoete A, Gunn TR, et al: Neurodevelopmental outcome of infants
treated with head cooling and mild hypothermia after perinatal asphyxia.
Pediatrics 2001;107:480.
05/26/2010 Khorfakkan Hospital Pediatric Department
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27. Prognosis (Cont.)
Severe encephalopathy characterized by :
1.Flaccid coma
2.Apnea
3.Absence oculocephalic reflexes
4. Refractory seizures
Is associated with a poor prognosis
Battin MR, Dezoete A, Gunn TR, et al: Neurodevelopmental outcome of infants
treated with head cooling and mild hypothermia after perinatal asphyxia.
Pediatrics 2001;107:480.
05/26/2010 Khorfakkan Hospital Pediatric Department
27

28. Prognosis (Cont.)
1. A low Apgar score at 20 min
2. Absence of spontaneous respirations at 20 min of age
3. Persistence of abnormal neurologic signs at 2 wk of age
predict death or severe cognitive and motor deficits
Battin MR, Dezoete A, Gunn TR, et al: Neurodevelopmental outcome of infants
treated with head cooling and mild hypothermia after perinatal asphyxia.
Pediatrics 2001;107:480.
05/26/2010 Khorfakkan Hospital Pediatric Department
28

29. Prognosis (Cont.)
Brain death
after neonatal hypoxic-ischemic encephalopathy is diagnosed by:
1. Clinical findings of coma unresponsive to pain, auditory, or visual stimulation
2. Apnea with Pco2 rising from 40 to over 60 mm Hg
3. Absent brainstem reflexes
(pupil, oculocephalic, oculovestibular, corneal, gag, sucking)
Battin MR, Dezoete A, Gunn TR, et al: Neurodevelopmental outcome of infants
treated with head cooling and mild hypothermia after perinatal asphyxia.
Pediatrics 2001;107:480.
05/26/2010 Khorfakkan Hospital Pediatric Department
29

30. Thank you
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