Vitamins C, E: No Effect on Preeclampsia


From the New England Journal of Medicine

Major Finding: The rates of preeclampsia were not significantly different between groups, occurring in 7.2% of the women receiving vitamin C and vitamin E and 6.7% of the placebo group.

Data Source: A large multicenter trial of 10,154 low-risk, nulliparous women from 16 clinical centers.

Disclosures: The study was supported by grants from the National Institute of Child Health and Human Development; the National Heart, Lung, and Blood Institute; and the National Center for Research Resources. Some of the investigators disclosed financial conflicts.

Daily supplementation with vitamins C and E starting between 9 and 16 weeks' gestation did not reduce the rate of pregnancy-associated hypertension, according to a large multicenter trial in low-risk, nulliparous women.

The findings “provide no support for the use of vitamin C and E supplementation in pregnancy to reduce the risk of preeclampsia or its complications,” wrote Dr. James M. Roberts of the University of Pittsburgh and his colleagues (N. Engl. J. Med. 2010;362:1282-91).

The study randomized 10,154 nulliparous women from 16 clinical centers. All women had singleton pregnancies, with gestational age at randomization ranging between 9 weeks, 0 days and 16 weeks, 6 days. The women were randomly assigned to take 1,000 mg of vitamin C and 400 IU of vitamin E daily, or matching placebo, until the end of their pregnancies. They returned any unused study drug each month and received a new batch, at which time they reported any side effects, and had their blood pressure and urine protein levels measured.

The primary outcome of the study was a composite of pregnancy-associated hypertension and serious adverse outcomes in the mother, fetus, or neonate, while the secondary outcomes included preeclampsia and other maternal and neonatal outcomes.

After some subjects were lost to follow-up or removed, a total of 4,993 women from the vitamin arm and 4,976 from the placebo arm were included in the final analysis.

Neither the primary or secondary outcomes of the study were significantly affected by vitamin treatment. A total of 6.1% of the vitamin group and 5.7% of the placebo group met criteria for the primary outcome. Similarly, the rates of the secondary outcome, preeclampsia, were not significantly different between groups—occurring in 7.2% of the vitamin group and 6.7% of the placebo group.

Several other studies have found a similar lack of benefit to antioxidant vitamins in terms of altering the risk of hypertension in pregnancy, and the authors suggested several possible explanations.

First, although there is evidence of oxidative stress in preeclampsia, it might not necessarily be important in the pathophysiology of the disease. Or, perhaps it is relevant, but only to a subset of preeclamptic women.

Yet another suggestion was that supplemental vitamin C and E may not be beneficial if women already have adequate concentrations at baseline. It has been suggested that the therapeutic antioxidant window might be between 8 and 10 weeks' gestation at the initiation of intervillous blood flow. However a post hoc subgroup analysis limited to women who were treated before 13 weeks' gestation showed no difference in outcome.

This and other studies have found no benefit of the antioxidant vitamins C and E in altering the risk of hypertension in pregnancy.

Source James E. Reinaker/Elsevier Global Medical News

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