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


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  • Trial registration number: ISRCTN86677348
    Link to trial:

Dr J Villar, Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK. Email


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.