Effects of fetal asphyxia on brain cell structure and function: limits of tolerance

The objective of this paper is to review the published information available on the effect of hypoxia on fetal cerebral integrity, and to attempt to define limits of fetal tolerance to asphyxia Data were obtained in experimental animals following imposed hypoxia or asphyxia. Studies were carried out in the fetus by physiologic, biochemical, histologic, and behavioral techniques. Human data were collected from newborns at birth and during subsequent development. It has been established that acute asphyxia of the fetus in utero may result in a spectrum of effects on the fetus, including death, or survival with permanent neurologic damage, or apparent complete recovery. The severity of damage depends on the degree and duration of asphyxia and a number of sensitizing factors, including prior metabolic and cardiovascular status of the fetus, differential sensitivity of the heart and brain to asphyxia, gestational age, plasticity, intermittency of asphyxial insults, and the pattern of intermittency. The fetus has a number of compensatory mechanisms that allow it to survive periods of oxygen limitation without permanent damage to the brain. The fetus can increase cerebral blood flow to increase oxygen delivery to the brain, and can decrease its metabolism by electrophysiological and behavioral state changes. Cerebral ischemia and reduced metabolism to < 50% of control is probably necessary for permanent brain damage to occur. In human pregnancy, factors consistent with intrapartum asphyxia lasting until delivery as a cause of fetal neurologic damage include absent fetal heart rate variability, umbilical cord arterial pH < 6.8, base access < -20 mEql-1, severe and prolonged newborn depression with Apgar score of < or = 3 at 10 min, seizure activity in the first day of life, and damage to the noncerebral organs and regions. However, these factors are neither independently nor collectively predictive of asphyxial brain damage. It is concluded that permanent neurologic damage or death can occur in the fetus due to single or repetitive episodes of hypoxia or asphyxia, but it is not yet possible to predict the occurrence or extent of such damage in an individual fetus.