Effect of Antioxidants on the Occurrence of Pre-Eclampsia in Women at Increased Risk: A Randomised Trial

Studies have implicated free radicals as promoters of maternal vascular disorders. If this is the case, timely supplementation with antioxidants could limit oxidative stress and enhance vascular endothelial function, thereby relieving or even preventing preeclampsia. This study enrolled 283 women at increased risk because of either abnormal results on a two-stage uterine artery Doppler waveform at 18 to 22 weeks’ gestation, preeclampsia, or hemolysis, elevated liver function tests, low platelets syndrome in the preceding pregnancy. They were randomly assigned to receive, starting before 22 weeks’ gestation, either vitamin C and vitamin E in daily doses of 1000 mg and 400 IU, respectively, or placebos. At monthly intervals, enzyme-linked immunosorbent assays were used to quantify plasminogen-activator inhibitor 1 (PAI-1), a marker of endothelial-cell activation, and PAI-2, which is synthesized by the placenta. Normally, the PAI-I/PAI-2 ratio declines as placental mass increases, but high ratios are found in patients with preeclampsia because of endothelial-cell activation and placental insufficiency.Vitamin supplementation correlated with a 21 percent reduction in the PAI-I/PAI-2 ratio during gestation. Plasma ascorbic acid increased 32 percent on average, and the α-tocopherol level increased by 54 percent. Intention-to-treat analysis showed that preeclampsia developed in 17 percent of placebo recipients but in only 8 percent of women given vitamins, for an adjusted odds ratio of 0.39. In patients completing the study, the odds ratio was 0.24. Small-for-gestational-age infants were less frequent in the vitamin-supplemented group, although not significantly so. If these results are confirmed in a large-scale multicenter trial, supplying extra vitamins C and E may help prevent preeclampsia in women at increased risk. Whether women at low risk are helped remains to be seen.Lancet 1999;354:810–816