Prevention of Preeclampsia through Administration of Antioxidants

Abstract & Commentary

By John C. Hobbins, MD, Professor and Chief of Obstetrics, University of Colorado Health Sciences Center, Denver, is Associate Editor for OB/GYN Clinical Alert.

Dr. Hobbins reports no financial relationship to this field of study.

Synopsis: Use of calcium, vitamin E, and vitamin C show no significant reduction in the rate of preeclampsia.

Source: Spinnato JA, et al. Antioxidant therapy to prevent preeclampsia. Obstet Gynecol. 2007;110:1311-1318.

Among various agents that have been used to prevent preeclampsia, the ones that have attracted the greatest attention have been low-dose aspirin, calcium, and vitamins C and E. In December, a study emerged in Obstetrics and Gynecology that tested the latter two antioxidants' abilities to decrease the incidence of preeclampsia in at-risk patients.

Spinnato et al initiated a randomized trial in 4 Brazilian centers in which patients who had preeclampsia in a previous pregnancy or who had the diagnosis of chronic hypertension were given either vitamin E and C (combined) in standard dosage or a placebo. Of the 753 fulfilling the admission criteria the authors had follow-up on 705 patients (355 in the treatment arm and 352 in the placebo arm). The average time of entry and initiation of treatment was 15 weeks.

The rate of preeclampsia in the treatment group was 13.8% vs 15.6% in the control group (OR=0.87; 95% CI 0.61-1.25). Interestingly, although the above figures showed no difference in preeclampsia in the vitamin group, there was a concerning, but statistically insignificant, trend towards a higher rate of severe preeclampsia in chronic hypertensives on the study medication (6.5% vs 2.8%). The authors concluded simply that antioxidants did not seem to work to prevent preeclampsia in those predisposed to this condition.


The authors indicated that they were stimulated by a paper by Chappell et al in 1999 that showed a decrease in preeclampsia by giving vitamin E and C to patients with abnormal uterine artery waveforms. However, more recent studies using criteria other than uterine artery findings have failed to show a difference in the incidence of preeclampsia when using these agents. It seems that the ideal study would be to combine a history of preeclampsia, chronic hypertension, and uterine artery waveform analysis in the same time type of randomized trial. Unfortunately, the latter test has not caught on in the United States, as it has in Europe. Although the numbers were insufficient in the chronic hypertensive group in the above study to tell a difference in outcome, the trend towards a higher rate of severe preeclampsia in the treated group should get our attention and needs to be further explored.

It is intriguing that the trials using uterine artery waveform to predict preeclampsia demonstrate that this method seems to work best in identifying those at greatest risk for severe preeclampsia. Also, as indicated in a meta-analysis by Coomarasamy assessing the prowess of low-dose aspirin in the prevention of preeclampsia, this agent seemed to perform quite well in those with abnormal uterine artery waveform, halving the rate of severe preeclampsia.

The point here is that, so far, calcium, vitamin E, and vitamin C do not seem to represent the great hope for prevention of preeclampsia, but low-dose aspirin may provide some benefit, especially in those at greatest risk.

Although this may seem an "apples and oranges" issue, our colleagues in other specialties may now be moving to a higher dose of aspirin to prevent strokes (168 mg vs the commonly used baby aspirin dose of 84 mg). Since the aim is the same—eg, to prevent micro clotting in the peripheral circulation (as well as macro clotting), this may represent a better approach to preeclampsia prevention with, expectedly, the same low risk to mother and fetus.

The old adage that prevention of stroke would require one simply to "lick an aspirin once a day" now needs to be amended. The same may be true for preeclampsia.