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Am Fam Physician. 2008;78(11):online

Background: Oxidative stress has been associated with the endothelial changes that are central to the pathophysiology of preeclampsia. Because of this association, several studies have treated women at risk of preeclampsia with antioxidants during pregnancy. Although an early study using vitamins C and E reported significant reductions in the intervention groups, subsequent studies have failed to prove a benefit. Spinnato and colleagues conducted a large placebo-controlled, double-blind clinical trial of vitamins C and E in women at high risk of preeclampsia.

The Study: Participants were enrolled at one of four large urban centers in Brazil. Women presenting for prenatal care between 12 and 19 weeks' gestation were eligible for the study if they had a history of preeclampsia or non-proteinuric chronic hypertension. Women were excluded from the study if they had a multiple pregnancy, fetal anomaly, diabetes mellitus, proteinuria, or if they used aspirin or anticoagulants, or had a contraindication to the study agents. After screening, participants were randomly assigned to receive vitamin C (1,000 mg) plus vitamin E (400 IU) daily or identical placebos. Participants were discouraged from using antioxidant vitamins, calcium, or aspirin during the study. Follow-up was typically every four weeks until 26 to 28 weeks' gestation, every two to three weeks until 36 weeks' gestation, and then weekly until delivery. Weight, blood pressure, urinary protein, and compliance with study medications were assessed at each follow-up visit.

The primary outcome was the development of preeclampsia, defined as hypertension of 140/90 mm Hg or greater, plus proteinuria of 300 mg per 24 hours, or 2+ or greater by dipstick on two or more occasions four hours apart. A blinded external reviewer verified each identified case of preeclampsia. Secondary outcomes included the severity of preeclampsia, abruptio placentae, premature rupture of membranes, preterm birth, low birth weight, and infants considered small for gestational age.

Results: The 355 mothers assigned to intervention were comparable with the 352 assigned to placebo in all significant variables. The incidence of preeclampsia was not significantly different between intervention and placebo groups when all patients were considered or when only compliant patients were studied. The differences between the groups remained nonsignificant when adjusted for smoking, prepregnancy body mass, and mean arterial pressure at enrollment or analyzed by risk for preeclampsia.

The two groups did not differ in the incidence of gestational diabetes, abruptio placentae, cesarean delivery, or induction of labor. The groups also showed no differences in perinatal outcomes, including fetal or neonatal death, preterm delivery, low birth weight, small for gestational age, and Apgar scores. Premature rupture of membranes was observed more frequently in the intervention group. The study medicines were well tolerated by the participants. A small number of patients (seven intervention and six placebo) discontinued treatment because of perceived side effects.

Conclusion: The authors conclude that anti-oxidant supplementation with vitamins C and E was not associated with reduced incidence of preeclampsia in women with chronic hypertension or previous preeclampsia.

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