Hypoxic Ischaemic Encephalopathy

Abnormal neurological behaviour in the neonatal period arising as a result of a hypoxic-ischaemic event.

• This can present in a number of ways
  • need for resuscitation (i.e. not breathing or low respiratory rate post-delivery)
  • neurological depression (e.g. floppy)
  • seizures
• Occurs in 1-6/1000 live births (term) in developed countries
  • ~65% have mild disease and don’t have many complications
  • ~25% have serious disease that could result in severe handicap/death
  • 5% have moderate disease that can result in cerebral palsy
  • 10% will have developmental delay (this is close to the figure for the general population though)
• NOTE: HIE affects preterm and term infants differently
  • In preterm infants- insult affects white matter- periventricular leukomalacia
  • In term infants- insult affects mainly grey matter

Aetiology/Risk Factors

• Maternal
  • Cardiac arrhythmia/arrest
  • Asphyxiation
  • Anaphylaxis
  • Status epilepticus
  • Hypovolaemic shock
• Foetal
  • Fetomaternal haemorrhage (e.g. with invasive obstetric investigations)
  • Twin-twin transfusion
  • Severe haemolytic disease of the newborn
  • Cardiac arrhythmia
• Uteroplacental
  • Placental Abruption
  • Cord Prolapse
  • Uterine rupture
  • Hyperstimulation with oxytocic agents

Pathophysiology

(see also Excitotoxicity)

• Acute HIE leads to primary and secondary events:
  • Primary neuronal damage: cytotoxic changes due to failure of microcirculation → inhibition of energy-producing molecular processes → ATPase membrane pump failure → cytotoxic edema and free radical formation → compromised cellular integrity
  • Secondary neuronal damage: May extend up to 72 hours or more after the acute insult and results in an inflammatory response and cell necrosis or apoptosis (fueled by reperfusion)

Presentation

• No specific test.  HIE is a clinical diagnosis (supported by imaging)
• Abnormal neurological examination in the first few days of life (including reflexes and tone) may be the most useful tool
• Essential criteria include:
  • Metabolic acidosis (cord pH<7 or base deficit of >12)
  • Early onset encephalopathy
  • Multisystem organ dysfunction
    • Acute renal failure (20%)
    • Myocardial dysfunction and hypotension (28-50%)
    • Abnormal liver function tests (80-85%)
    • Coagulation impairment

 

Investigations

• Cerebral function monitoring (amplitude-EEG)
  • In infants who have moderate to severe HIE…
    • Marginally abnormal/normal aEEG may just reflect dysfunction and is reassuring (upper margin >10μV and lower >5μV is normal; if lower margin falls <5μV- moderately abnormal)
    • Severely abnormal aEEG suggests permanent damage and has a poor prognosis (upper margin <10μV)
• MRI scan in the first 7-10 days should be done in Grade II-III HIE to evaluate any brain damage
  • Cranial USS can be used (hypoechoic regions) but is relatively nonspecific
• Make sure to investigate other problems associated with HIE, usually comprising
  • FBC, LFT, U&E, Glucose
  • Urine dipstick

Management

• Hypothermia
  • 
  • Start as early as possible (within several hours of birth)
  • Aim to cool to maintain rectal temperature at 33-34°C for 72 hours
    • NB the infants observations will be dramatically abnormal at this temperature.  They require close monitoring of blood gases, glucose and other investigations regularly to prevent further complications (of disease or treatment).
  • Re-warm slowly