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Brain Injury in the Small Premature Infant: Magnitude of the Problem

Brain injury in the small premature infant is a problem of major importance. In the U.S., approximately 55,000 infants are born each year with a birth weight of less than 1500 g. Because of major advances in neonatal intensive care, nearly 85 percent to 90 percent of these infants now survive. Approximately 10 percent of the survivors later exhibit cerebral palsy, especially spastic diplegia, and an additional 25 percent to 50 percent exhibit cognitive, attentional, and/or behavioral deficits that result in failure to succeed in school. Two recent reports focus on outcome in the smallest of these infants.

Infants born at 25 or fewer weeks of gestation were assessed formally for neurologic and developmental outcomes at a mean of 30 months of postnatal age in a prospective study by Wood and colleagues. The 308 surviving children represented only 39 percent of the starting cohort of all such infants born in the U.K. and Ireland during a 10-month period. Only 49 percent of the surviving infants escaped without disability. The neurologic sequelae observed included severe "neuromotor" deficits (i.e., cerebral palsy) in 10 percent and cognitive deficits (as measured on the imperfect Bayley Scales of Infant Development) in 30 percent (severe, in 19 percent).

Hack and colleagues studied 333 infants with a birth weight of less than 1000 g (mean gestational age, 26.4 weeks) treated during a 3-year period at a single neonatal intensive care unit in a large medical center in the U.S. Seventy-two percent of the infants survived, and 92 percent of the survivors were followed to 20 months of age. Approximately 50 percent of the infants had no disability. Fifteen percent had cerebral palsy, and impaired cognition was observed in 42 percent. Thus, in both studies, cognitive disturbance was more prevalent than motor disturbance, although both types of disability were common.

Comment: The observed neurologic disability relates in considerable part to cerebral white matter injury. Preventing this injury will require an understanding of its pathogenesis. Currently, a combination of hypoxia-ischemia and maternal-fetal infection-inflammation appears to play an important role. Hypoxia-ischemia is particularly common in small premature infants because of the high frequency of labile blood pressure coupled with a maturation-dependent impairment in cerebrovascular autoregulation. Maternal-fetal infection-inflammation with cytokine attack on cerebral white matter is particularly common because maternal vaginal infection frequently precedes premature labor. The most promising preventive interventions appear to be (1) early detection of the impairment of cerebrovascular autoregulation by noninvasive techniques such as near-infrared spectroscopy and correction of the disturbed autoregulation, and (2) therapies for hypoxic-ischemic injury (such as free-radical scavengers) and for maternal-fetal infection (such as maternal antibiotics or anticytokine agents). Wood and colleagues emphasize the urgency of bringing these interventions to the clinical-trial stage.

— JJ Volpe

Joseph J. Volpe, MD, is Neurologist-in-Chief, Children's Hospital, and Bronson Crothers Professor of Neurology, Harvard Medical School, Boston, MA.

Published in Journal Watch Neurology September 20, 2000

Citation(s):

Wood NS et al. Neurologic and developmental disability after extremely preterm birth. N Engl J Med 2000 Aug 10 343 378-384.

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Hack M et al. Neurodevelopment and predictors of outcomes of children with birth weights of less than 1000 g. Arch Pediatr Adolesc Med 2000 Jul 154 725-731.

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