DESCRIPTION

Neurologic dysfunction more often identified in infants >35 weeks of gestation notable for depressed consciousness, altered muscle tone, and reflexes (with or without seizures) along with low Apgar scores. This nonspecific condition has many etiologies, most commonly hypoxic ischemic encephalopathy (HIE). Encephalopathy of prematurity is a separate entity associated with preventricular leukomalacia and axonal injury, among other findings.

EPIDEMIOLOGY

• Represents approximately 20% of all neonatal deaths worldwide.
• Incidence in developed countries is 2 to 8 per 1,000 live births.
• ~50% of cases are 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
  • Genetic/metabolic disorders
  • Cerebrovascular pathology
• Intrapartum factors:
  • Sentinel event (placental abruption, uterine rupture, cord accident, among others)
  • Shoulder dystocia
  • Emergency cesarean delivery
  • Chorioamnionitis/infection

PATHOPHYSIOLOGY

• Hypoxic ischemic event leading to brain injury with energy failure and ongoing secondary injury, leading to encephalopathy and possibly seizures.
• Injury involves excitotoxic glutamate accumulation in synaptic space, intracellular calcium influx, 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.