Hypoxic Ischemic Encephalopathy (HIE) occurs when a term infant experiences intrapartum asphyxia and lack of oxygen. It can cause death or disabilities like cerebral palsy. Diagnosis involves assessing the infant at birth using the APGAR score and neurological staging. Imaging tools like MRI are useful to detect brain injury patterns. HIE management aims to prevent further brain damage through temperature control, seizure treatment, and potentially neuroprotective drugs. The condition remains a major cause of newborn mortality and morbidity.

1. Hypoxic Ischemic Encephalopathy
 Dr Raghavendra .
Fellow in neonatology

2. 6/22/2015
Definitions
 Hypoxia/anoxia : denotes a partial or complete lack of
oxygen, respectively, in one or more tissues of the body,
including the blood stream.
 Asphyxia : is the state in which pulmonary or placental
gas exchange is affected leading to progressive
hypoxemia, which is severe enough to be associated with
acidosis.
 Ischemia : is a reduction in or cessation of blood flow
that arises from either systemic hypotension, cardiac
arrest, or occlusive vascular disease.

3. APGAR Score

4. Apgar Score
 Total Score = 10
score 7-10 normal
score 5-6 mild birth asphyxia
score 3-4 moderate birth asphyxia
score 0-2 severe birth asphyxia

5. Hypoxic-Ischemic Encephalopathy
 Definition :
It is the term used to designate the clinical and
neuropathological findings of an encephalopathy that
occurs in a full term infant who has experienced a
significant episode of intrapartum asphyxia.

6. Incidence of HIE
 Occurs in 1-6 per 1000 live term births in
developed countries
 25% die or have multiple disabilities.
 4% have mild to moderate forms of cerebral palsy.
 10% have developmental delay .

7. Etiology of HIE
 Maternal:
 Cardiac arrest
 Asphyxiation
 Severe anaphylaxis
 Status epilepticus
 Hypovolemic shock
 Uteroplacental:
 Placental abruption
 Cord prolapse
 Uterine rupture
 Hyper stimulation with
oxytocic agents
 Fetal:
 Fetomaternal hemorrhage
 Twin to twin transfusion
 Severe isoimmune hemolytic
disease
 Cardiac arrhythmia

8. Path physiology
 Immature brain is more resistant to hypoxic-ischemic
events compared to older children & adults
 This may be due to:
 Lower cerebral metabolic rate
 Immaturity in the development of the balance of
neurotransmitters & Plasticity of the immature CNS.
 Gestational age plays an important role in the
susceptibility of CNS structures
 < 20 weeks: Insult leads to neuronal heterotopia or
polymicrogyria
 26-36 weeks: Insult affects white matter, leading to
periventricular leukomalacia
 Term: Insult affects primarily gray matter

9.  Other factors that influence the distribution of
CNS injury:
 Cellular susceptibility (neuron most susceptible)
 Vascular territories (watershed areas)
 Regional susceptibility (areas of higher metabolic
rates, ie. Thalamus)
 Degree of asphyxia

10. PATHOPHYSIOLOGY OF BRAIN INJURY
 Mainly associated with two phases
 1. Primary energy failure .
 2. secondary energy failure.

11. Primary Energy Failure
• The impairment of cerebral blood flow leads to decreases in oxygen and
glucose, which leads to less energy (ATP)) and increased lactate production.
• low ATP levels cause failure of many of the mechanisms that maintain cell
integrity, particularly the sodium/potassium (Na/K) pumps and mechanisms
to maintain low intracellular calcium.
• This leads to the release of glutamate, a prominent excitatory
neurotransmitter. The glutamate binds to glutamate receptors allowing
additional influx of intracellular calcium and sodium.
• Increased intracellular calcium has detrimental effects leading to cerebral
edema, ischemia, micro vascular damage with resultant necrosis and/or
apoptosis
•
• Excitotoxic –oxidative cascade get activated.
• necrosis cell death.

12. Potential pathways for brain injury after hypoxia-ischemia.
Perlman J M Pediatrics 2006;117:S28-S33
©2006 by American Academy of Pediatrics

13. Secondary Energy Failure
 Continuation of excitotoxic –oxidative cascade .
 Activation of microglia –inflammatory response .
 Activation of caspase proteins.
 Reduction in levels of growth factors , protein synthesis.
 Apoptosis cell death.

15.  The interval between primary and secondary energy
failure represents an latent phase.
 That corresponds to a therapeutic window. duration is
approximately 6 hrs.
 Cell death in the brain exposed to HI is delayed over
several days to weeks after an injury ,apoptosis and
necrosis continue depending on the region and
severity of the injury.

16. Status of infant at birth
 Depressed on initial assessment.
 Generalized hypotonia.
 Apgars 3 or less @ 1min and 6 or less @ 5min.
 Major resuscitation required.
 Large base deficit by blood gas.
 Poor feeding to deep coma (encephalopathic)

18. Prognosis based on apgars
 Score at 1, 5 minutes does not give prognosis indicator.
 The longer the score remains lower, the greater its
significance.
 0-3 @ 1min has mortality of 5-10%.
 may be increased to 53% if at 20min apgars score 0-3
 0-3 @ 5min , CP risk app. 1%.
 may be increased to 9% if for 15min.
 dramatic rise to 57% CP risk if for 20min

19. Newborn neurological assessment
 Staging system of Sarnat and Sarnat, levene score.
Thompson score
 Means of recording severity of insult to brain, to
initiate med management and to predict ultimate
prognosis.
 Infants occasionally sustain insult to brain arising from
complication of systemic disease, Seizures in 50-70%

22. Summary of staging
 Mild(stage1) : Hyper alertness, uninhibited reflexes,
sympathetic over activity , duration < 24 hrs
 Moderate(stage2) : Lethargy-stupor, hypotonia,
suppressed primitive reflexes, seizures
 Severe(stage3) : Coma, flaccid tone, suppressed
brainstem function, seizures, increased ICP

23. Assessment Tools in HIE
 Amplitude-integrated EEG (aEEG)
 When performed early, it may reflect dysfunction rather than
permanent injury
 Most useful in infants who have moderate to severe
encephalopathy.
 Evoked Potentials
 Brainstem auditory evoked potentials, visual evoked potentials
and somatosensory evoked potentials can be used in full-term
infants with HIE
 More sensitive and specific than aEEG alone
 However, not as available as aEEG and there is a lack of
experience among pediatric neurologists
 Therefore aEEG is preferred because of easy access, application,
and interpretation

24. Standard 16-channel electroencephalogram showing a typically abnormal burst
suppression background pattern.
(Courtesy AC van Huffelen, PhD, Department of Neurophysiology, University Medical Center, Utrecht, The
Netherlands.)

25.  Neuroimaging.
 Cranial ultrasound: Not the best in assessing
abnormalities in term infants. Echogenicity develops
gradually over days.
 CT: Less sensitive than MRI for detecting changes in the
central gray nuclei.
 MRI: Most appropriate technique and is able to show
different patterns of injury. Presence of signal
abnormality in the internal capsule later in the first
week has a very high predictive value for
neurodevelopmental outcome.

26. Fetal hypoxia
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 .
Abnormal Doppler velocimetry.
On an umbilical artery Doppler flow velocity waveform

27. Patterns of periodic fetal heart rate (FHR)
deceleration
 Variable deceleration as a result of umbilical cord
compression

28. CT BRAIN OF HIE CHILD

31. 6/22/2015
Management
 Prevention, prevention, prevention
 Insure physiological oxygen and acid-base balance
 Maintain environmental temp and humidity
 Correct caloric, fluid and electrolyte disturbances
 Maintain blood volume and hemostasis
 Treat infection
 Neuro-resus measures to reduce cerebral oedema ineffective
 Sz treated with PB, dilantin or lorazepam
 Newer modalities- excitatory amino antagonists, oxygen free
radical inhibitors/scavengers, ca channel blockers, nitric
oxide synthetase inhibitors
 Hypothermia

32. References
 Allan WC. The clinical spectrum and prediction of outcome in
hypoxic-ischemic encephalopathy. Neoreviews 2002; 3; e108-e115
 Delivoria-Papadopoulos M, et al. Biochemical basis of hypoxic-
ischemic encephalopathy. Neoreviews 2010; 11; e184-e193
 Fanaroff and Martin’s Neonatal-Perinatal Medicine: Diseases of
the Fetus and Infant, 9th edition. 2011, p 952-976
 Marro, PJ, et al. Pharmacology review: Neuroprotective treatments
for hypoxic-ischemic injury. Neoreviews 2010; 11; e311-e315.
 Newborn Infant Nurs Rev. Author manuscript; available in PMC
2012 September 1.