8: A randomized controlled trial of antioxidant vitamins to prevent serious complications associated with pregnancy related hypertension in low risk, nulliparous women

Abstract

Oxidative stress is proposed as a central pathophysiological factor in preeclampsia. Although in a small randomized controlled trial in 1999, antioxidant Vitamins C and E reduced the incidence of preeclampsia by 60%, recent larger trials of low risk and high risk women showed no benefit and suggested fetal risk. This trial evaluated the effectiveness of antioxidant therapy to prevent serious morbidity associated with pregnancy related hypertension. In this randomized, placebo controlled, doubly masked trial of low risk nulliparous women, daily treatment with Vitamins C (1000 mg) and E (400 IU) (vitamins) or placebo began at 9 - 16 weeks gestation. The primary outcome was severe pregnancy related hypertension or pregnancy related hypertension with at least one of the following: renal or hepatic dysfunction, thrombocytopenia, eclampsia, indicated preterm delivery < 32 weeks gestation, small for gestational age infant (< 3rd centile), stillbirth or neonatal death up to discharge. Secondary outcomes included preeclampsia diagnosis and measures of maternal and fetal/neonatal safety. From 2003 - 2008 10,154 women enrolled. Loss to follow up was 1.8% resulting in 4993 recieiving vitamins and 4976 placebo. Recruitment was at an average of 13.4 weeks with 44% enrolled before 13 weeks. Demographic findings did not differ by treatment. The racial mix was diverse with 31% Hispanic and 26% African American. The mean prepregnancy BMI was 25.4 ± 6.0, 16% were smokers, and 77% entered the trial taking multivitamins. Vitamin therapy did not reduce the primary outcome (vitamins = 6.1% placebo = 5.8%) or the incidence of preeclampsia (vitamins = 7.2% placebo = 6.7%). Therapy initiated with the antioxidant Vitamins C and E prior to 17 weeks gestation in nulliparous low risk women does not reduce the frequency of serious complications associated with pregnancy related hypertension, nor does this treatment reduce the diagnosis of preeclampsia.