It is now clear that oxygen-derived free radicals play an important part in several models of experimentally induced reperfusion injury. Although there are certainly multiple components to clinical ischemic and reperfusion injury, it appears likely that free-radical production may make a major contribution at certain stages in the progression of the injury. The primary source of superoxide in reperfused reoxygenated tissues appears to be the enzyme xanthine oxidase, released during ischemia by a calcium-triggered proteolytic attack on xanthine dehydrogenase. Reperfused tissues are protected in a variety of laboratory models by scavengers of superoxide radicals or hydroxyl radicals or by allopurinol or other inhibitors of xanthine oxidase. Dysfunction induced by free radicals may thus be a major component of ischemic diseases of the heart, bowel, liver, kidney, and brain.

The low-birth-weight infant remains at much higher risk of mortality than the infant with normal weight at birth. In the neonatal period, when most infant deaths occur, the proportion of low-birth-weight infants, especially those with very low weight, is the major determinant of the magnitude of the mortality rates. Furthermore, differences in low-birth-weight rates account for the higher neonatal mortality rates observed in some groups, particularly those characterized by socioeconomic disadvantages. Much of the recent decline in neonatal mortality can be attributed to increased survival among low-birth-weight infants, apparently as a result of hospital-based services. The application of these services is currently considered cost-effective, although whether this will continue to be true in the future is unclear because of the increased survival of very tiny infants. Although low-birth-weight infants remain at increased risk of both postneonatal mortality and morbidity in infancy and early childhood, the risk is substantially smaller than that of neonatal death. In addition, these adverse later outcomes have not offset the gains achieved in the neonatal period. Nonetheless, the increased survival of high-risk infants raises concern about their future requirements for special medical and educational services and about the stress on their families. Despite increased access to antenatal services, only moderate declines in the proportion of low-birth-weight infants has been observed, and almost no change has occurred in the proportion of those with very low weight at birth. In addition, in many areas of the country the birth-weight-specific neonatal mortality rates are similar for groups at high and low risk of neonatal death. In view of these findings, continuation of the current decline in neonatal mortality and reduction of the mortality differentials between high- and low-risk groups require the identification and more effective implementation of strategies for the prevention of low-weight births.