Vitamins C and E and the risks of preeclampsia and perinatal complications

N Engl J Med. 2006 Apr 27;354(17):1796-806. doi: 10.1056/NEJMoa054186.


Background: Supplementation with antioxidant vitamins has been proposed to reduce the risk of preeclampsia and perinatal complications, but the effects of this intervention are uncertain.

Methods: We conducted a multicenter, randomized trial of nulliparous women between 14 and 22 weeks of gestation. Women were assigned to daily supplementation with 1000 mg of vitamin C and 400 IU of vitamin E or placebo (microcrystalline cellulose) until delivery. Primary outcomes were the risks of maternal preeclampsia, death or serious outcomes in the infants (on the basis of definitions used by the Australian and New Zealand Neonatal Network), and delivering an infant whose birth weight was below the 10th percentile for gestational age.

Results: Of the 1877 women enrolled in the study, 935 were randomly assigned to the vitamin group and 942 to the placebo group. Baseline characteristics of the two groups were similar. There were no significant differences between the vitamin and placebo groups in the risk of preeclampsia (6.0 percent and 5.0 percent, respectively; relative risk, 1.20; 95 percent confidence interval, 0.82 to 1.75), death or serious outcomes in the infant (9.5 percent and 12.1 percent; relative risk, 0.79; 95 percent confidence interval, 0.61 to 1.02), or having an infant with a birth weight below the 10th percentile for gestational age (8.7 percent and 9.9 percent; relative risk, 0.87; 95 percent confidence interval, 0.66 to 1.16).

Conclusions: Supplementation with vitamins C and E during pregnancy does not reduce the risk of preeclampsia in nulliparous women, the risk of intrauterine growth restriction, or the risk of death or other serious outcomes in their infants. ( number, ISRCTN00416244.).

Publication types

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

MeSH terms

  • Adult
  • Antioxidants / therapeutic use*
  • Ascorbic Acid / therapeutic use*
  • Dietary Supplements*
  • Female
  • Fetal Death / prevention & control
  • Fetal Growth Retardation / prevention & control*
  • Humans
  • Hypertension
  • Infant Mortality
  • Infant, Newborn
  • Infant, Small for Gestational Age
  • Parity
  • Pre-Eclampsia / prevention & control*
  • Pregnancy
  • Pregnancy Complications
  • Pregnancy Outcome*
  • Respiratory Distress Syndrome, Newborn / prevention & control
  • Risk
  • Vitamin E / therapeutic use*


  • Antioxidants
  • Vitamin E
  • Ascorbic Acid

Associated data

  • ISRCTN/ISRCTN00416244