Oxidative stress occurs when the production of damaging free radicals and other oxidative molecules exceeds the capacity of the body's antioxidant defenses. Oxidative stress is implicated in diseases that are associated with prematurity (such as retinopathy, cerebral palsy, intraventricular hemorrhage, and necrotizing enterocolitis). Nonenzymatic antioxidant reserve is the first line of defense against free radicals. We hypothesized that an in utero redox imbalance because of stress would diminish the fetal antioxidant reserve. We tested aspects of this hypothesis by investigating whether the presence of labor or gestational age at delivery (term vs preterm) alters the maternal/fetal nonenzymatic antioxidant reserve peripartum.
Fetal redox consumption was calculated from the difference in the nonenzymatic antioxidant reserve that was measured in umbilical venous and arterial blood that was collected prospectively at delivery from 39 newborn infants. Eight women were delivered at term by elective cesarean delivery in the absence of labor; 31 women labored either at term (n = 20) or preterm (<37 weeks, n = 11). Maternal venous blood was collected on admission and within 1 hour of delivery. Nonenzymatic antioxidant reserve was measured in the plasma and red blood cells of each specimen by the quantitation of glutathione content (glutathione in red blood cell lysate) and the plasma total free radical-trapping antioxidant potential. Glutathione was measured with the use of a colorimetric assay and expressed in nanomoles per milligram of hemoglobin. The plasma total radical-trapping antioxidant potential was estimated with the use of a controlled, kinetic assay based on the time that was required to inhibit peroxyl-free radical generated under controlled conditions. The differences between both umbilical venous and umbilical arterial total radical-trapping antioxidant potential and glutathione were computed to estimate fetal nonenzymatic antioxidant reserve consumption. The differences between maternal total radical-trapping antioxidant potential and glutathione before and after delivery were computed to estimate maternal peripartal nonenzymatic antioxidant reserve consumption.
Fetal red blood cell glutathione content was significantly greater than maternal red blood cell glutathione content, independent of delivery route. The calculation of the fetal nonenzymatic antioxidant reserve consumption and maternal peripartal nonenzymatic antioxidant reserve consumption revealed that women who labored at term experienced an up-regulation in red blood cell glutathione content, while their fetuses had significantly lower red blood cell glutathione consumption. In contrast, there was consumption of plasma antioxidants in preterm fetuses, as illustrated by a doubling of the fetal nonenzymatic antioxidant reserve consumption (elective cesarean delivery in the absence of labor, 0.9 +/- 0.5 min/microL; term labor, 1.0 +/- 0.1 min/microL; preterm labor, 2.0 +/- 0.4 min/microL; one-way analysis of variance; P =.04). This was mostly due to a lower umbilical arterial total radical-trapping antioxidant potential in preterm versus term fetuses (umbilical arterial, 3.3 min/microL versus umbilical venous 5.4 min/microL; paired t test; P =.001; power, 0.98). Generally, maternal total radical-trapping antioxidant potential remained unchanged peripartum.
Term labor triggers a compensatory up-regulation of nonenzymatic antioxidant reserve in the fetal red blood cell compartment that may act to protect against the relative hyperoxia that is experienced by the newborn infant at birth. In contrast, the decreased nonenzymatic antioxidant reserve in the fetal red blood cell and plasma compartments after preterm labor and delivery would enhance the vulnerability to free radical damage of the preterm neonate. These findings suggest that the two compartments of nonenzymatic antioxidant reserve have distinct physiologic roles in the peripartal defense against free radicals and that their development is, in some fashion, ontogenes, in some fashion, ontogenetically regulated.