Collaborative Eclampsia Trial: Magnesium Sulfate for Eclampsia

When a woman with pre-eclampsia seized in a delivery suite in the early 1990s, the attending physician's choice of anticonvulsant depended largely on local tradition. In North America, magnesium sulfate had been used since the early twentieth century, championed by obstetricians in the United States who favored it over other agents. In Britain and much of Europe, diazepam or phenytoin was preferred. There was little properly controlled evidence to settle the choice.

The Collaborative Eclampsia Trial addressed that gap directly. It recruited 1,687 women with eclampsia into two randomized comparisons of standard regimens: magnesium sulfate against diazepam (453 and 452 women) and magnesium sulfate against phenytoin (388 and 387). The multicountry design was necessary because eclampsia was common enough in low-income settings to make recruitment feasible and because the question had global stakes.

The results published in The Lancet in 1995 were unambiguous on the primary outcome. Recurrent convulsions occurred in 13.2 percent of women given magnesium sulfate against 27.9 percent given diazepam, a 52 percent lower risk, and in 5.7 against 17.1 percent in the phenytoin comparison, 67 percent lower. Compared with phenytoin, women given magnesium were also less likely to need ventilation, develop pneumonia or go to intensive care, and their babies were less often intubated or sent to special care. Maternal mortality was lower with magnesium, but not significantly.

Questions persisted about magnesium dosing and monitoring in settings without reliable blood tests. The Magpie Trial, published in 2002, randomized 10,141 women with pre-eclampsia in 33 countries and found that magnesium sulfate halved the risk of eclampsia and probably reduced maternal deaths.

Today magnesium sulfate appears on the WHO Essential Medicines List specifically for eclampsia and severe pre-eclampsia. The 1995 trial's authors concluded that the evidence now favored magnesium sulfate over diazepam or phenytoin for eclampsia.