Preeclampsia is a major cause of maternal death and complicates 2 to 3 percent of pregnancies. Although speculative, preeclampsia likely involves a maternal inflammatory response that originates in the placenta. Because patients with preeclampsia have maternal and placental circulations with high levels of oxidative stress, antioxidants have been suggested as preventive therapy. Poston and colleagues conducted a randomized controlled trial of vitamins C and E in pregnant women who were at risk of preeclampsia.
They recruited 2,404 pregnant women at 14 to 21 weeks of gestation who had at least one risk factor, such as a history of preeclampsia; diagnosis of HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome; treatment for essential hypertension; gestational hypertension; treatment for diabetes type 1 or 2; antiphospholipid syndrome; chronic renal disease; multiple pregnancies; or abnormal uterine artery Doppler waveform. Women already receiving more than 200 mg of vitamin C or 40 IU of vitamin E were excluded. Patients were randomly assigned to receive 1,000 mg of vitamin C plus 400 IU of natural source vitamin E daily or identical placebos. Serum levels of cholesterol and vitamins C and E were measured before the study, and participants at two centers provided blood samples on at least one other occasion during gestational weeks 20 to 22, 30 to 32, and 34 to 36. Research midwives also provided reminders and collected unused medication to assess participant compliance.
The primary outcome was clinical diagnosis of preeclampsia, which was defined as gestational hypertension (diastolic readings of 90 mm Hg or more) and proteinuria (excretion of at least 300 mg protein over 24 hours). Secondary outcomes included birth weight less than 5 lbs 8 oz (2.5 kg); size below the fifth percentile for gestational age; birth before 37 weeks of gestation; and hospitalization for pregnancy-related conditions.
The 1,199 randomized women who received vitamin supplementation were comparable to the 1,205 women randomized to placebo. According to reports and pill counts, 80 percent of women in each group took at least one half of the medication. Overall, 15 percent of the women in the study developed preeclampsia. Risk factors caused a varied rate, however, with only 11 percent of obese primiparous women and women with a multiple pregnancy developing preeclampsia, compared with 32 percent of women with chronic renal disease. However, the 15 percent of women in the treatment groups who developed preeclampsia was not significantly different from the 16 percent of women in the control group who developed preeclampsia.
The secondary outcomes showed poorer results for mothers who received vitamin supplements. The researchers documented low birth weight in 28 percent of women in the intervention group compared with 24 percent in the control population. Small size for gestational age did not differ statistically between the two groups. Delivery before 37 weeks of completed gestation occurred in 29 percent of treated women compared with 27 percent in the control group.
The authors conclude that vitamin supplements during the second trimester are not associated with any change in the development of preeclampsia in women with risk factors. The poor outcomes in the intervention group, particularly low birth weight and small size for gestational age, raise concerns that vitamins C and E supplementation could potentially be harmful. The researchers also stress that the effects of vitamin supplements in pregnancy most likely depend on the normal intake of the mothers. Studies in developing countries could show benefit; however, based on the outcomes of this study, vitamin C and E supplements are only recommended for vitamin-deficient mothers.