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Magnesium Sulphate Halves Eclampsia Risk In Pre-Eclampsia Women

A landmark study among 10,141 pregnant women with pre-eclampsia in 33 countries finds magnesium sulphate reduces by more than 50 percent their chances of developing eclampsia.

Clinicians said that the striking findings and low cost of magnesium sulphate ($5 per patient) could result in a significant change in the clinical management of pre-eclampsia worldwide.

Because of the conclusive evidence, the Magnesium Sulphate for Prevention of Eclampsia (MAGPIE) trial was stopped early. The intervention had an overall 58 percent reduction in risk compared with placebo.

The study, directed by Dr Lelia Duley, Resource Centre for Randomised Trials, Institute of Health Sciences, Oxford, England, is the largest trial ever conducted for the hypertensive disorders of pregnancy. It is 12 times larger than any previous trial of magnesium sulphate versus placebo, and took 3.5 years to complete recruitment.

An estimated 8 percent of pregnant women develop pre-eclampsia. Eclampsia is more common in less-developed countries, and causes some 50,000 maternal deaths a year worldwide.

Anticonvulsants are used for pre-eclampsia in the belief they prevent eclamptic convulsions. Research in the United States, where it was first used in obstetrics almost a century ago suggested that the anticonvulsant magnesium sulphate offers the best hope for reducing the development of eclampsia among women with pre-eclampsia. However, no adequate trials have been done prior to the MAGPIE trial.

Women taking part in the trial had not given birth or were 24 hours or less postpartum. Their blood pressure was 140/90 mm Hg or more, and proteinuria of 1+ (30 mg/dL) or more, and there was clinical uncertainty about using magnesium sulphate.

Each woman was assigned a uniquely numbered treatment pack, containing nine 10 mL ampoules labeled "MAGPIE Trial Treatment." Each 10 mL "active" ampoule contained 5 g magnesium sulphate heptahydrate (MgSO4 ·7H2 O) 50 percent solution, which is approximately 2 mmoL magnesium/mL. Each placebo ampoule contained 10 mL normal saline. Each pack also contained 10 mL calcium gluconate, for use in the event of toxicity, and an eclampsia rescue pack.

Clinicians found that magnesium sulphate not only more than halved the risk of eclampsia, it also reduced the relative risk of maternal death. Twenty-four percent of women given magnesium sulphate reported side effects compared with 5 percent of women given placebo.

For women randomised before delivery, there was no clear difference in the risk of infant mortality (around 12 percent in both arms).

Dr Duley and colleagues said their trial results should be made available to women with pre-eclampsia, and those responsible for their care. Duration of treatment should not normally exceed 24 hours, as the reassurance about safety applies only to the regimens used in the MAGPIE trial. Serum monitoring is not necessary.

Clinicians said a number of questions remain to be answered: What is the minimum effective dose? When is the optimal time to give it? Should it be used at the primary-care level for women being transferred for secondary of tertiary care? What are the long-term consequences of exposure for the mother and her child?

At the same time, additional research is continuing on the long-term follow-up of a proportion of the women and children in the MAGPIE Trial, and on the cost implications of the findings for a range of settings.

"Results from the Magpie Trial demonstrate clearly that magnesium sulphate is effective in considerably reducing the risk of eclampsia for women with pre-eclampsia," Dr Duley and colleague contend.
Lancet 2002; 359: 1877-90.

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