Vitamin C and Vitamin E in Pregnant Women at Risk for Pre-eclampsia (VIP Trial): Randomized Placebo-Controlled Trial

Abstract

Although at least one small-scale study has suggested that supplemental vitamins C and E may lower the risk of preeclampsia, others have yielded negative results. The present randomized, placebo-controlled trial evaluated these antioxidants in 2410 women, seen at 25 centers, who were viewed as being at increased risk of preeclampsia because of such factors as preeclampsia in the preceding pregnancy, HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), eclampsia in any past pregnancy at any gestational stage, essential hypertension requiring medication, and type 1 or type 2 diabetes. Participants were assigned to receive either 1000 mg vitamin C plus 400 IU vitamin E or a matched placebo each day from the second trimester of pregnancy to delivery. Preeclampsia developed in 15% of study participants. Vitamin supplementation did not lower the risk regardless of the level of risk at entry to the trial. Risk rates ranged from 11% in primiparous obese women and those with multiple pregnancies to 32% in women having chronic renal disease. The risk for women with multiple risk factors was 26%. There were no group differences in either severe preeclampsia (with marked hypertension) or early-onset preeclampsia (delivery for preeclampsia before 34 weeks gestation). More women in the supplemented group were treated for gestational hypertension. Infants whose mothers received vitamin supplements were significantly likelier to have low birth weight, but there was no difference in small-for-gestational-age infants. Preterm births were comparably frequent in the supplemented and control groups, but infants of supplemented mothers more often had a cord arterial blood pH less than 7. The risk of perinatal death was similar in the 2 groups. These findings fail to support routine supplementation with vitamins C and E for pregnant women at increased risk of developing preeclampsia. Supplementation may have adverse effects such as low birth weight and low arterial cord blood pH and, for this reason, cannot be recommended, at least in the doses used in this trial.