Oxidative Stress and Preeclampsia: Rationale for Antioxidant Clinical Trials

Preeclampsia remains a frequent and potentially dangerous complication of pregnancy. The cause remains largely unknown, but oxidative stress and a generalized inflammatory state are features of the maternal syndrome. The placenta appears to be the principal source of free radical synthesis but maternal leukocytes and the maternal endothelium are also likely contributors. Recent reports have suggested an important role for placental trophoblast NAD(P)H oxidase in free radical generation in preeclampsia. The antioxidant vitamin E is now known to have multiple actions in addition to prevention of lipid peroxidation (ie, inhibition of NAD(P)H oxidase activation and the inflammatory response). In view of the abnormally low plasma vitamin C concentrations in preeclampsia, a combination of vitamins C and E is a promising prophylactic strategy for prevention of preeclampsia. Several multicenter randomized clinical trials are now underway. The potential use of antioxidants and the recognized, albeit modest, benefit of low-dose aspirin prophylaxis have heightened the need for a reliable predictive test for preeclampsia. A combination test involving several relevant biomarkers is likely to provide the best predictive potential.