Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial

Background Oxidative stress has been implicated in the pathophysiology of preeclampsia. This randomised controlled trial investigated the effect of supplementation with vitamins 0 and E in women at increased risk of the disorder on plasma markers of vascular endothelial activation and placental insufficiency and the occurrence of pre-eclampsia. Methods 283 women were identified as being at increased risk of preeclampsia by abnormal two-stage uterine-artety doppler analysis or a previous history of the disorder and were randomly assigned vitamin C (1000 mg/day) and vitamin E (400 IU/day) or placebo at 16-22 weeks' gestation. Plasma markers of endothelial activation (plasminogen-activator inhibitor 1 [PAI-1]) and placental dysfunction (PAI-2) were measured every month until delivery. Preeclampsia was assessed by the development of proteinuric hypertension. Analyses were done by intention to treat, and in the cohort who completed the study. Findings Supplementation with vitamins C and E was associated with a 21% decrease in the PAI-1/PAI-2 ratio during gestation (95% CI 4-35, p=0.015). In the intention-to-treat cohort, preeclampsia occurred in 24 (17%) of 142 women in the placebo group and 11 (8%) of 141 in the vitamin group (adjusted odds ratio 0.39 [0.17-0.90], p=0.02). In the cohort who completed the study (81 placebo group, 79 vitamin group), the odds ratio for preeclampsia was 0 24 (0.08-0.70, p=0.002). Interpretation Supplementation with vitamins C and E may be beneficial in the prevention of preeclampsia in women at increased risk of the disease. Multicentre trials are needed to show whether vitamin supplementation affects the occurrence of preeclampsia in low-risk women and to confirm our results in larger groups of high-risk women from different populations.