World Health Organisation multicentre randomised trial of supplementation with vitamins C and E among pregnant women at high risk for pre-eclampsia in populations of low nutritional status from developing countries.
Villar J., Purwar M., Merialdi M., Zavaleta N., Thi Nhu Ngoc N., Anthony J., De Greeff A., Poston L., Shennan A., WHO Vitamin C and Vitamin E trial group None.
OBJECTIVE: To determine if vitamin C and E supplementation in high-risk pregnant women with low nutritional status reduces pre-eclampsia. DESIGN: Multicentred, randomised, controlled, double-blinded trial. SETTING: Antenatal care clinics and Hospitals in four countries. POPULATION: Pregnant women between 14 and 22 weeks' gestation. METHOD: Randomised women received 1000 mg vitamin C and 400 iu of vitamin E or placebo daily until delivery. MAIN OUTCOME MEASURES: Pre-eclampsia, low birthweight, small for gestational age and perinatal death. RESULTS: Six hundred and eighty-seven women were randomised to the vitamin group and 678 to the placebo group. Groups had similar gestational ages (18.1; SD 2.4 weeks), socio-economic, clinical and demographical characteristics and blood pressure at trial entry. Risk factors for eligibility were similar, except for multiple pregnancies: placebo group (14.7%), vitamins group (11.8%). Previous pre-eclampsia, or its complications, was the most common risk factor at entry (vitamins 41.6%, placebo 41.3%). Treatment compliance was 87% in the two groups and loss to follow-up was low (vitamins 2.0%, placebo 1.3%). Supplementation was not associated with a reduction of pre-eclampsia (RR: 1.0; 95% CI: 0.9-1.3), eclampsia (RR: 1.5; 95% CI: 0.3-8.9), gestational hypertension (RR: 1.2; 95% CI: 0.9-1.7), nor any other maternal outcome. Low birthweight (RR: 0.9; 95% CI: 0.8-1.1), small for gestational age (RR: 0.9; 95% CI: 0.8-1.1) and perinatal deaths (RR: 0.8; 95% CI: 0.6-1.2) were also unaffected. CONCLUSION: Vitamins C and E at the doses used did not prevent pre-eclampsia in these high-risk women.