Neonatal Encephalopathy



Neurologic dysfunction in infants >35 weeks of gestation notable for depressed level of consciousness, altered muscle tone and reflexes (with or without seizures) along with difficulty in initiation or maintenance of breathing and low Apgar scores. This nonspecific condition has many etiologies, most commonly hypoxic ischemic encephalopathy (HIE).


  • Represents approximately 20% of all neonatal death worldwide
  • Incidence in developed countries 2 to 9 per 1,000 live births
  • >50% of cases secondary to HIE

Risk Factors

  • Maternal risk factors:
    • Advanced age
    • Obesity
    • Diabetes
    • Severe preeclampsia
    • Infertility treatments
    • Thyroid disease
    • Seizures or neurologic disorder
    • Placental abnormalities
  • Fetal factors: intrauterine growth restriction
  • Intrapartum factors:
    • Sentinel event (placental abruption, uterine rupture, cord accident, among others)
    • Shoulder dystocia
    • Emergency cesarean delivery


  • Hypoxic ischemic event leading to brain injury with energy failure and ongoing secondary injury leading to encephalopathy and possibly seizures
  • Ongoing injury involves excitotoxic glutamate accumulation in synaptic space, alterations in cellular calcium management, free radical production and nitrosative/oxidative damage, mitochondrial failure, activation of proteases, and other cell death cascades with both acute and delayed cytokine production and neuroinflammation.
  • Other etiologies include various metabolic disorders, hypoglycemia, kernicterus, nonketotic hyperglycinemia, intracranial infection, perinatal arterial ischemic stroke (PAIS), and sinovenous thrombosis.

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