Antioxidant therapy to prevent preeclampsia.

Preeclampsia is a 2-stage disorder. Stage 1 is decreased placental perfusion and generates stage 2 of the disorder, the maternal syndrome characteristic of preeclampsia. How the 2 stages are linked has been a topic of intense investigation for many years. One candidate phenomenon, which includes many other suggested linkages, is oxidative stress. This hypothesis predicts that the administration of antioxidants would decrease oxidative stress and modify stage 2. Experience with the treatment of preeclampsia including a small trial of antioxidants in women with manifest preeclampsia makes it clear that the use of any therapy once preeclampsia is evident will not be successful. Trials evaluating prophylactic aspirin and supplemental calcium from early pregnancy suggest that therapy before evident preeclampsia may be successful in selected populations. Guided by these concepts and by experience with antioxidant therapy in other settings, 1 small study (<80 women in the treatment arm) was very encouraging with an almost two-thirds reduction of the frequency of preeclampsia in high-risk women. Antioxidants currently are being evaluated in several larger trials in the United States, Canada, Mexico, England, and in several developing nations. These studies should definitively establish the efficacy and safety of this therapy for the mother and fetus.