Since free radicals may be responsible for hypoxic-ischemic brain damage in the fetus, we hypothesized that transplacental passage of antioxidants after the onset of fetal bradycardia would ameliorate hypoxic fetal brain injury. A fetal rabbit hypoxic model following repetitive uterine ischemia (5 episodes of 10 min uterine ischemia interspersed with 2 min reperfusion) was employed. 29 day old gestation pregnant rabbits were randomly administered ascorbic acid(A), Trolox (T), Trolox+ascorbic acid (T+A) and placebo, saline (C), in a masked manner. As fetal distress is usually diagnosed after onset of fetal bradycardia, these drugs or saline were administered following onset of uterine ischemia and subsequent fetal bradycardia. Ascorbic acid (1600 mg/kg bolus + 60 mg/kg/hr infusion) and/or Trolox (100 mg/kg bolus + 50mg/kg/hr) wereadministered in the same volume as saline to the dams. After hysterotomy, the placenta, brain and plasma of fetuses were collected. Cellular viability in the fetal cortex and hippocampus was significantly different between the groups (n=4-6/group, p<0.05, ANOVA; mean±SEM, see Fig). There was no difference in brain edema, as assessed by wet/dry ratio of brain. In groups, A and T+A, ascorbic acid levels significantly increased in the maternal plasma, placenta and fetal plasma, but not in the fetal brain, compared to controls. However, fetal brain total antioxidant levels significantly increased (to the same extent) in all drug groups, compared to controls. Maternal antioxidant treatment following the onset of fetal hypoxia resulted in the transplacental passage of the antioxidant and amelioration of brain injury. Non-toxic antioxidant therapies to the mother may be a viable clinical option after the onset of fetal bradycardia.

figure 1