PEDIATRICS Vol. 100 No. 6 December 1997, pp. 1004-1114
SPECIAL ARTICLE:
Interventions for Perinatal Hypoxic-Ischemic Encephalopathy
From the * Department of Pediatrics, Pennsylvania State
University College of Medicine, Milton S. Hershey Medical Center,
Hershey, Pennsylvania; and the Department of Pediatrics, University
of Texas Southwestern Medical Center, Dallas, Texas.
| The first 300 words of the full text of this article appear below. |
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INTRODUCTION |
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Perinatal cerebral hypoxia-ischemia remains a frequent cause of the chronic handicapping conditions of cerebral palsy, mental retardation, learning disability, and epilepsy.1 Estimates suggest that between 2 and 4/1000 full-term newborn infants suffer asphyxia at or shortly before birth. Approximately 15% to 20% of such asphyxiated infants who exhibit hypoxic-ischemic encephalopathy actually die during the newborn period, and of the survivors, 25% will exhibit permanent neuropsychologic deficits. Given these incidence figures, physicians have searched for strategies to prevent or minimize the long-term consequences of perinatal cerebral hypoxia-ischemia.
In the past, therapeutic interventions for hypoxic-ischemic encephalopathy in full-term newborn infants consisted of those drugs that reduced the severity of cerebral edema arising from hypoxia-ischemia.2 Such agents included osmotic diuretics (mannitol, furosemide), glucocorticosteroids, and barbiturates. One by one, these drugs and other manipulations to treat brain swelling have been discarded, such that presently no agent has been proven useful to ameliorate perinatal hypoxic-ischemic brain damage in the clinical setting (but see below). Accordingly, there is no uniform standard of care in the brain-oriented therapy of full-term newborn infants sustaining cerebral hypoxia-ischemia, and it remains for future research to uncover new and effective strategies for the neurologically compromised infant.
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CHARACTERISTICS OF HYPOXIC-ISCHEMIC BRAIN DAMAGE |
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Hypoxic-ischemic brain damage is an evolving process, which begins during the insult and extends into the recovery period after resuscitation (reperfusion interval).3 Tissue injury takes the form of either selective neuronal necrosis or infarction, the latter with destruction of all cellular elements including neurons, glia, and blood vessels. When infarction occurs, the immediate area surrounding the infarct (penumbra) consists of neurons undergoing either necrosis or apoptosis (programmed cell death).4-7 It is the penumbral area that appears most amenable to reversal of cellular injury through therapeutic intervention.
At the cellular level, cerebral hypoxia-ischemia sets in motion a
cascade of biochemical events commencing with a shift from oxidative
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