Vitamins C, E Fail to Prevent Preeclampsia


DALLAS — Supplementation with vitamins C and E did not prevent preeclampsia, reduce its severity, or lower adverse neonatal outcomes in a World Health Organization randomized trial of 1,365 high-risk women.

The observed negative results are consistent with those of most previous antioxidant trials, although none of the previously reported adverse effects, such as earlier and more severe preeclampsia or reduced birth weight, were observed in the current trial, Dr. Mario Merialdi said at the annual meeting of the Society for Maternal-Fetal Medicine.

“We found no evidence of harm to either mother or fetus attributable to supplementation with vitamin C and E,” he said.

Still, lead investigator Dr. Jose Villar, a senior fellow in perinatal medicine at the University of Oxford (England), advised caution. “It is always of concern to give ineffective drugs to pregnant women, even if one study does not demonstrate harm,” he said in an interview.

The recent VIP (Vitamins in Preeclampsia) trial showed that concomitant vitamin C and E supplementation did not reduce preeclampsia among 2,395 women at risk, but did increase the rate of babies born with a low birth weight (Lancet 2006;367:1145–54).

The WHO trial parallels the VIP trial, but specifically targeted high-risk women with nutritional deficiencies who lived in India, Vietnam, South Africa, and Peru. Because previous failed antioxidant trials were conducted in women with adequate nutritional status, the investigators theorized that supplementing potentially vitamin-deficient women might produce beneficial results, explained Dr. Merialdi, a reproductive health specialist with WHO in Geneva.

In all, 687 women were randomized to daily vitamin C (1 g) and vitamin E (400 IU), and 678 women were randomized to placebo before gestational week 20. Their mean age was 27 years. Risk factors were similar between the intervention and control groups, including history of previous preeclampsia (217 vs. 205), chronic hypertension (163 vs. 170), and multiple pregnancies (81 vs. 100). Compliance was similar in both groups at about 87%.

Supplementation did not reduce the risk of preeclampsia (relative risk 1.0), eclampsia (RR 1.5), or severe gestational hypertension (RR 0.8). Adjustment for maternal age did not modify these results, he said. The incidence of preeclampsia was not significantly different between the intervention and placebo groups (24.5% vs. 23.3%).

The secondary outcomes of low birth weight (defined as less than 2,500 g, and found in 33% of the intervention group vs. 36% in controls), small size for gestational age (defined as less than 10th percentile, in 23% vs. 26%), and preterm delivery (defined as delivery before 37 weeks, in 21% vs. 24%) tended to be lower with supplementation, but were not statistically different (RR 0.9 for all three).

Perinatal death also tended to be lower with supplementation, but did not reach statistically significant levels (RR 0.8), and the trial was underpowered to test this outcome.

A stratified analysis of those women with a history of preeclampsia demonstrated similar rates of preeclampsia in the supplement and control groups (26% vs. 28%), said Dr. Merialdi, who reported no financial conflicts of interest.

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