title: Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial): randomised placebo-controlled trial.
abstract: BACKGROUND
  Oxidative stress could play a part in pre-eclampsia, and there is some evidence to suggest that vitamin C and vitamin E supplements could reduce the risk of the disorder. Our aim was to investigate the potential benefit of these antioxidants in a cohort of women with a range of clinical risk factors.
  
  
  METHODS
  We did a randomised, placebo-controlled trial to which we enrolled 2410 women identified as at increased risk of pre-eclampsia from 25 hospitals. We assigned the women 1000 mg vitamin C and 400 IU vitamin E (RRR alpha tocopherol; n=1199) or matched placebo (n=1205) daily from the second trimester of pregnancy until delivery. Our primary endpoint was pre-eclampsia, and our main secondary endpoints were low birthweight (<2.5 kg) and small size for gestational age (<5th customised birthweight centile). Analyses were by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN 62368611 .
  
  
  RESULTS
  Of 2404 patients treated, we analysed 2395 (99.6%). The incidence of pre-eclampsia was similar in treatment placebo groups (15% [n=181] vs 16% [n=187], RR 0.97 [95% CI 0.80-1.17]). More low birthweight babies were born to women who took antioxidants than to controls (28% [n=387] vs 24% [n=335], 1.15 [1.02-1.30]), but small size for gestational age did not differ between groups (21% [n=294] vs 19% [n=259], 1.12 [0.96-1.31]).
  
  
  CONCLUSIONS
  Concomitant supplementation with vitamin C and vitamin E does not prevent pre-eclampsia in women at risk, but does increase the rate of babies born with a low birthweight. As such, use of these high-dose antioxidants is not justified in pregnancy.
authors.affiliation: Maternal and Fetal Research Unit, Division of Reproductive Health, Endocrinology and Development, King's College London, St Thomas' Hospital, London SE1 7EH, UK. lucilla.poston@kcl.ac.uk
authors.forename: L
authors.initials: L
authors.lastname: Poston
authors.forename: A L
authors.initials: AL
authors.lastname: Briley
authors.forename: P T
authors.initials: PT
authors.lastname: Seed
authors.forename: F J
authors.initials: FJ
authors.lastname: Kelly
authors.forename: A H
authors.initials: AH
authors.lastname: Shennan
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D011225:Pre-Eclampsia / Q000209:etiology / Q000517:prevention & control*; D011247:Pregnancy; D012307:Risk Factors; D016896:Treatment Outcome; D014810:Vitamin E / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D014810:Vitamin E; D001205:Ascorbic Acid