Pre-eclampsia, affecting two to three per cent of all pregnancies, occurs when a mother's blood pressure rises to the hypertensive range, and excretion of protein in the urine becomes too high. It is estimated to be responsible for about 60000 deaths worldwide.
It is not known why some expectant mothers develop pre-eclampsia, although oxidative stress has been proposed to play a part. The role of antioxidants to reduce oxidative stress had been supported by a small clinical trial that linked vitamin C and E intake to fewer biomarkers for pre-eclampsia for predominantly low-risk participants.
The new placebo-controlled, randomized clinical trial, published in on-line in The Lancet (DOI:10.1016/S0140-6736(06)68434-1), reports the effect of vitamin C (1000 mg) and vitamin E (RRR alpha-tocopherol, 400 IU), or placebo, for 2410 pregnant women at high-risk of pre-eclampsia at from 14 to 22 weeks of gestation.
The Vitamins in Pre-eclampsia (VIP) trial found that, although oxidative stress does seem to associated with pre-eclampsia, the use of supplements did not affect the incidence, which affect 15 per cent of the supplemented group and 16 per cent of the placebo group.
The VIP trial, led by Professor Lucilla Poston from King's College London, reported that the antioxidant group gave birth to lower birthweight babies (28 per cent versus 24 per cent for the supplement and placebo groups, respectively).
"We do not know why supplementation with vitamin C and vitamin E to above physiological doses does not reduce the risk of pre-eclampsia, but increases the rate of low birthweight babies," wrote Poston.
"A detrimental effect on placental function is possible, given the lower birthweight. Direct effects on fetal growth also cannot be excluded."
On the other hand, Poston and her colleagues noted that higher plasma levels of vitamin C at the start of the study was related to heavier babies, which agreed with observations from a Korean study.
"There was however no evidence that taking the small doses of vitamins in pregnancy specific multivitamin preparations gave any cause for concern," stressed Poston.
It should also be stressed that expectant mothers, as well as all women of child-bearing age, should continue to eat folic acid-rich or fortified foods and/or take folic acid supplements to reduce the risk of neural tube defects.
In an accompanying editorial, Marshall Lindheimer from the University of Chicago and Baha Sibai from the University of Cincinnati, added some perspective to the data, saying: "VIP focused on high-risk patients, a popular approach because these populations manifest a high incidence of pre-eclampsia, with, more often, sever diseases.
However, such study populations are also heterogeneous (here they included women with diabetes, chronic hypertension, renal disease, obesity, and multiple births). The preventive intervention might affect the disease subgroups differently.
Thus, in pre-eclampsia, studies of nulliparous women remain the gold standard even if the trials are larger and more costly."
Lindheimer and Sibai also pointed out that antioxidant supplements in areas of developing nations where nutrient deficiencies are rife, may produce different results.
Mike Rich, chief executive of UK maternity charity, Action on Pre-eclampsia, which has been championing the research, said he was disappointed with the results.
"There are no really effective drugs or treatments and we had held out a great deal of hope for the use of vitamins. Unfortunately they have not been shown to be effective.
The impact of pre-eclampsia around the world is massice, with one woman estimated to die from it every six minutes. We need more research into the disorder and we would call on government to make sure that trials such as the VIP Trial are funded in the future so that we can make sure that interventions become available," said Rich.