title: Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial.
abstract: 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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynaecology, Guy's, King's, and St Thomas' School of Medicine, St Thomas' Hospital, London, UK.
authors.forename: L C
authors.initials: LC
authors.lastname: Chappell
authors.forename: P T
authors.initials: PT
authors.lastname: Seed
authors.forename: A L
authors.initials: AL
authors.lastname: Briley
authors.forename: F J
authors.initials: FJ
authors.lastname: Kelly
authors.forename: R
authors.initials: R
authors.lastname: Lee
authors.forename: B J
authors.initials: BJ
authors.lastname: Hunt
authors.forename: K
authors.initials: K
authors.lastname: Parmar
authors.forename: S J
authors.initials: SJ
authors.lastname: Bewley
authors.forename: A H
authors.initials: AH
authors.lastname: Shennan
authors.forename: P J
authors.initials: PJ
authors.lastname: Steer
authors.forename: L
authors.initials: L
authors.lastname: Poston
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D018384:Oxidative Stress; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D017396:Plasminogen Activator Inhibitor 2 / Q000097:blood; D011225:Pre-Eclampsia / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control*; D011247:Pregnancy; D012307:Risk Factors; D018608:Ultrasonography, Doppler; D016216:Ultrasonography, Prenatal; D014810:Vitamin E / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D017395:Plasminogen Activator Inhibitor 1; D017396:Plasminogen Activator Inhibitor 2; D014810:Vitamin E; D001205:Ascorbic Acid