Neonatal encephalopathy is a clinically defined syndrome of disturbed neurological function in the early postnatal days of life in the term infant. It is manifested by a combination of signs, including altered consciousness, abnormal muscle tone or reflexes, altered autonomic function, or seizures. Etiologies of neonatal encephalopathy include the following: (1) a combination of intrapartum or antepartum hypoxia and ischemia (hypoxic-ischemic encephalopathy [HIE]), which may be accompanied by prenatal signs of fetal distress, and vascular pathologies, including intracranial bleeding and stroke; (2) injuries secondary to birth trauma; (3) infections; (4) genetic disorders; (5) metabolic disorders; and (6) congenital brain abnormalities. This chapter focuses on neonatal encephalopathy in term newborn infants, with particular emphasis on infants who present with biochemical and clinical evidence of HIE, and the current diagnostic and treatment approaches to such injury. Other etiologies associated with central nervous system damage including vascular malformations and birth trauma are briefly discussed as well.
EPIDEMIOLOGY OF ENCEPHALOPATHY
Neonatal encephalopathy occurs in 1 to 6 per 1000 live full-term births, with a recent population-based estimate of 1.9 to 3.8 per 1000 live births. Mortality ranges from 7% to 26%, and an additional 25% of infants will have long-term disabilities. In a few recent studies, neonates with mild encephalopathy have been noted to have an increased risk of motor, cognitive, or behavioral deficits on long term follow-up. Neonates with severe encephalopathy have an increased risk (> 60%) of death or of cerebral palsy and mental retardation. Infants with severe HIE related to an intrapartum event develop either spastic quadriplegia or a dyskinetic type of cerebral palsy. Neonates with moderate encephalopathy also are at risk of death or deficits, such as cognitive impairment, visual motor or visual perceptive dysfunction, hyperactivity, and delayed school readiness, although the risk is approximately half that of those with severe encephalopathy.
The cause and timing of such injuries leading to encephalopathy is usually unknown. Since neonatal encephalopathy has multiple causes, the American College of Obstetrics and Gynecology–American Academy of Pediatrics Executive Summary delineates certain criteria that may suggest a hypoxic-ischemic insult secondary to an acute intrapartum event. These include metabolic acidosis with a cord pH below 7 or a base deficit of 12 mmol/L or greater, Apgar scores less than 5 at 5 and 10 minutes, multisystem organ involvement apparent within 72 hours of birth and neuroimaging consistent with hypoxia-ischemia, along with early-onset of encephalopathy, and exclusion of other etiologies such as trauma, coagulation disorders, and genetic and metabolic causes. Signs consistent with an acute peripartum or intrapartum event are a sentinel event occurring immediately before or during labor; a sudden sustained fetal bradycardia; or absence of fetal heart rate variability in the presence of persistent, late, or variable decelerations, usually after a sentinel event before which the fetal heart rate pattern was normal.
The vast majority of infants with encephalopathy do not have an identifiable intrapartum ...