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

Lancet. 1999 Sep 4;354(9181):810-6. doi: 10.1016/S0140-6736(99)80010-5.


Background: Oxidative stress has been implicated in the pathophysiology of pre-eclampsia. This randomised controlled trial investigated the effect of supplementation with vitamins C 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 pre-eclampsia by abnormal two-stage uterine-artery 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. Pre-eclampsia 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, pre-eclampsia 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 pre-eclampsia was 0.24 (0.08-0.70, p=0.002).

Interpretation: Supplementation with vitamins C and E may be beneficial in the prevention of pre-eclampsia in women at increased risk of the disease. Multicentre trials are needed to show whether vitamin supplementation affects the occurrence of pre-eclampsia in low-risk women and to confirm our results in larger groups of high-risk women from different populations.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antioxidants / therapeutic use*
  • Ascorbic Acid / therapeutic use*
  • Cohort Studies
  • Female
  • Humans
  • Oxidative Stress
  • Plasminogen Activator Inhibitor 1 / blood
  • Plasminogen Activator Inhibitor 2 / blood
  • Pre-Eclampsia / diagnostic imaging
  • Pre-Eclampsia / etiology
  • Pre-Eclampsia / prevention & control*
  • Pregnancy
  • Risk Factors
  • Ultrasonography, Doppler
  • Ultrasonography, Prenatal
  • Vitamin E / therapeutic use*


  • Antioxidants
  • Plasminogen Activator Inhibitor 1
  • Plasminogen Activator Inhibitor 2
  • Vitamin E
  • Ascorbic Acid