Magpie Trial: Magnesium Sulfate for Pre-eclampsia

For decades, obstetricians disagreed about which drug should be used against eclamptic seizures. North American units favored magnesium sulfate on the strength of clinical experience, with little trial evidence behind it, while much of Europe and the developing world used phenytoin or diazepam. In 1995 the Collaborative Eclampsia Trial of 1,687 women showed that, once a woman had fitted, magnesium sulfate cut recurrent convulsions by 52% compared with diazepam and by 67% compared with phenytoin. Whether it should be given to women with pre-eclampsia, before any seizure, had not been tested against placebo on a large scale. Pre-eclampsia complicates 2 to 8% of pregnancies and accounts for about a tenth of maternal deaths.

The Magpie Trial, coordinated from Oxford under Lelia Duley, randomized 10,141 women with pre-eclampsia at 175 hospitals across 33 countries to intravenous magnesium sulfate or placebo. Recruitment ran from 1998 to 2001 at hospitals in sub-Saharan Africa, South Asia, Latin America and higher-income countries. Douglas Altman of the Centre for Statistics in Medicine in Oxford was on the writing committee.

Eclampsia occurred in 0.8% of women given magnesium sulfate and 1.9% of those given placebo, a relative reduction of 58%, or 11 fewer women with eclampsia per 1,000 treated. Maternal mortality was lower in the treatment arm, though the trial was not large enough to achieve statistical significance for that endpoint. There was no clear difference in the risk of the baby dying, and side effects were reported by 24% of women given magnesium sulfate and 5% of those given placebo.

The results appeared in the Lancet in June 2002. WHO guidance came to recommend magnesium sulfate over other anticonvulsants, and its fact sheet on pre-eclampsia now calls it the primary treatment for preventing seizures. In the United Kingdom, a national survey in 2005 and 2006 found that 99% of women with eclampsia were treated with magnesium sulfate.

Because the trial had been conducted in low-resource facilities alongside tertiary centers, it answered the practical objection that magnesium sulfate required intensive monitoring beyond what rural hospitals could provide. The same UK survey found eclampsia had fallen to 2.7 cases per 10,000 births, significantly fewer than in 1992. Magnesium sulfate has been on the WHO Model List of Essential Medicines for eclampsia and severe pre-eclampsia since 1995, but WHO reports that its use is still limited in many low-resource settings.