Reproductive Health · 1995
Collaborative Eclampsia Trial: Magnesium Sulfate for Eclampsia
The Eclampsia Trial Collaborative Group: Which anticonvulsant for women with 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. Three drugs, three camps, and no rigorous head-to-head data to settle the argument.
The Collaborative Eclampsia Trial addressed that gap directly. Investigators across hospitals in Africa, the Americas, Asia, and Europe randomized 1,687 women who had already had at least one eclamptic convulsion to one of three regimens: magnesium sulfate, diazepam, or phenytoin. 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. Women assigned to magnesium sulfate had a 52 percent lower rate of recurrent seizure than those given diazepam, and a 67 percent lower rate than those given phenytoin. No secondary endpoint favored either comparator. Maternal deaths were too few for a statistically powered comparison, but the seizure data left no reasonable clinical equipoise.
Reception was not uniformly immediate. Some European units were slow to abandon phenytoin, and questions persisted about magnesium dosing protocols and monitoring requirements in settings without reliable serum assay capability. The Magpie Trial, published in 2002, extended the evidence to prophylaxis, showing magnesium sulfate also cut seizure risk in women with severe pre-eclampsia who had not yet convulsed, and that result accelerated adoption more broadly.
Today magnesium sulfate appears on the WHO Essential Medicines List specifically for eclampsia and severe pre-eclampsia. The drug is cheap, the evidence is strong, and access in low-income countries remains the principal barrier to consistent implementation. The 1995 trial's contribution was to remove any scientific uncertainty about which drug to give; what remains is a logistics and health-systems problem.
Key People
- The Collaborative Eclampsia Trial Group — Multinational investigators who conducted the three-arm randomized trial
- Lelia Duley — Oxford perinatal epidemiologist, key contributor to the eclampsia trial program
- A. Metin Gulmezoglu — WHO reproductive health researcher involved in translating trial results to policy
Lancet, 1995
Related landmarks
- 1997 · Dolly the Cloned Sheep (Reproductive Health)
- 1992 · Czeizel & Dudas: Folic Acid Prevents First-Occurrence Neural Tube Defects (Reproductive Health)
- 1991 · MRC Vitamin Study: Folic Acid Prevents Neural Tube Defect Recurrence (Reproductive Health)
- 2002 · Magpie Trial: Magnesium Sulfate for Pre-eclampsia (Reproductive Health)