Antioxidant therapy to prevent preeclampsia: a randomized controlled trial.
OBJECTIVE
To study whether antioxidant supplementation will reduce the incidence of preeclampsia among patients at increased risk.


METHODS
A randomized, placebo-controlled, double-blind clinical trial was conducted at four Brazilian sites. Women between 12 0/7 weeks and 19 6/7 weeks of gestation and diagnosed to have chronic hypertension or a prior history of preeclampsia were randomly assigned to daily treatment with both vitamin C (1,000 mg) and vitamin E (400 International Units) or placebo. Analyses were adjusted for clinical site and risk group (prior preeclampsia, chronic hypertension, or both). A sample size of 734 would provide 80% power to detect a 40% reduction in the risk of preeclampsia, assuming a placebo group rate of 21% and alpha=.05. The alpha level for the final analysis, adjusted for interim looks, was 0.0458.


RESULTS
Outcome data for 707 of 739 randomly assigned patients revealed no significant reduction in the rate of preeclampsia (study drug, 13.8% [49 of 355] compared with placebo, 15.6% [55 of 352], adjusted risk ratio 0.87 [95.42% confidence interval 0.61-1.25]). There were no differences in mean gestational age at delivery or rates of perinatal mortality, abruptio placentae, preterm delivery, and small for gestational age or low birth weight infants. Among patients without chronic hypertension, there was a slightly higher rate of severe preeclampsia in the study group (study drug, 6.5% [11 of 170] compared with placebo, 2.4% [4 of 168], exact P=.11, odds ratio 2.78, 95% confidence interval 0.79-12.62).


CONCLUSIONS
This trial failed to demonstrate a benefit of antioxidant supplementation in reducing the rate of preeclampsia among patients with chronic hypertension and/or prior preeclampsia.


BACKGROUND
ClinicalTrials.gov, www.ClinicalTrials.gov, NCT00097110


METHODS
I.
Spinnato
Joseph A
JA
Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, Cincinnati, Ohio 40267-0526, USA. spinnaja@ucmail.uc.edu
Freire
Salvio
S
Pinto E Silva
Joao Luiz
JL
Cunha Rudge
Marilza Vieira
MV
Martins-Costa
Sérgio
S
Koch
Matthew A
MA
Goco
Norman
N
Santos
Cleide de Barros
Cde B
Cecatti
Jose Guilherme
JG
Costa
Roberto
R
Ramos
José Geraldo
JG
Moss
Nancy
N
Sibai
Baha M
BM
D000328:Adult; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D011225:Pre-Eclampsia / Q000517:prevention & control*; D011247:Pregnancy; D011256:Pregnancy Outcome; D014810:Vitamin E / Q000627:therapeutic use*
D000975:Antioxidants; D014810:Vitamin E; D001205:Ascorbic Acid