Fast track — ArticlesVitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial): randomised placebo-controlled trial
Introduction
Pre-eclampsia affects 2–3% of all pregnancies, and every year is responsible for about 60 000 deaths worldwide.1 In the UK, hypertensive disease in pregnancy is a major cause of maternal death.2 Pre-eclampsia is a syndrome in which the placenta is implicated in the evolution of a generalised maternal inflammatory response, characterised by activation of maternal vascular endothelial cells and leucocytes.3, 4 Markers of oxidative stress are present in the placenta and maternal circulation of affected women, suggesting it as a cause of the disorder. As such, antioxidants might help to prevent pre-eclampsia, though this notion has yet to be tested in large randomised trials.4, 5
In 1999, we published the results of a small, randomised controlled trial6 in which we assigned women at risk of pre-eclampsia daily vitamin C (1000 mg) and vitamin E (400 IU) from 16–22 weeks' gestation. The primary outcome was a reduction in maternal concentrations of biomarkers of pre-eclampsia; the disorder itself was a secondary outcome. The trial was stopped early after an interim analysis showed a significant improvement in the primary outcome (plasminogen-activator inhibitor [PAI]1-to-PAI-2 ratio); rate of pre-eclampsia was also reduced. Women entered the trial mainly on the basis of an abnormal uterine artery doppler waveform (a recognised risk factor for pre-eclampsia). The findings of another, smaller study7 of women judged at risk of pre-eclampsia on the basis of their clinical history indicated no evidence of benefit with the same antioxidants.
Neither of these previous trials was powered to assess clinical outcomes. Our aim, therefore, was to assess whether supplementation with vitamin C and vitamin E prevents pre-eclampsia in women at increased risk. We also looked at rate of low birthweight and babies born small for gestational age, since maternal and fetal disease can be affected independently.
Section snippets
Participants
Between Aug 6, 2003, and June 27, 2005, we did a randomised controlled trial (the Vitamins in Pre-eclampsia [VIP] trial) to which we enrolled women with clinical risk factors for pre-eclampsia from 25 UK hospitals in ten geographical areas. The last baby was delivered on Dec 3, 2005. Eligible women could be referred to trial centres from any location in the UK. 13 women were recruited in Amsterdam, Holland.
Our inclusion criteria were gestational age 14+0−21+6 weeks plus one or more of the
Results
Figure 1 shows the trial profile. Of 2404 women enrolled and treated, we analysed 2395 (99·6%). Based on counts of returned pills from 2070 women, 80% (n=1653) of women took at least 50% of their tablets, 65% (n=1345) took 80% or more, and 32% (n=661) took all of their tablets; 6% (n=125) did not take any tablets. Neither compliance nor baseline characteristics differed greatly between groups (table 1) or subgroups. More than a quarter of women were taking multivitamin supplements at enrolment.
Discussion
Our findings do not lend support to the hypothesis that vitamin C (1000 mg) and vitamin E (400 IU) supplements given prophylactically from the second trimester of pregnancy lead to a reduction in the rate of pre-eclampsia in women at risk for the condition. Instead, they indicate an association between supplementation with antioxidants and low birthweight, and an umbilical artery cord pH of less than 7·0, which could be attributable to the earlier onset of pre-eclampsia in this group than in
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2022, Molecular Aspects of MedicineCitation Excerpt :There is some evidence that in women with low antioxidant status, such as in developing countries and low socioeconomic status, early administration of enriched milk containing several minerals and vitamins starting in first trimester, including 200 mg vitamin C and 400 mg vitamin E, reduced the incidence of preeclampsia (Wibowo et al., 2012). The effects on birthweights are even more diverse, with some studies finding lower birth weights in the groups receiving antioxidants or high dose vitamin E (Boskovic et al., 2005; Poston et al., 2006). Furthermore, it might also well be that too high concentrations of antioxidants may affect the normal physiology of reactive species.
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