Reproductive Health · 2002
Magpie Trial: Magnesium Sulfate for Pre-eclampsia
Magnesium Sulphate for Prevention of Eclampsia
For decades, the treatment of pre-eclampsia in wealthy countries diverged sharply from practice in low-income settings. North American obstetric units favored intravenous magnesium sulfate to prevent eclamptic seizures, a practice rooted in empirical experience rather than trial evidence. Much of Europe and the developing world used phenytoin or diazepam instead, and the absence of a large comparative trial meant neither camp could claim definitive proof. By the late 1990s, pre-eclampsia was killing an estimated 50,000 women a year globally, making the evidence gap a practical crisis.
The Magpie Trial, coordinated from the University of Leeds 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 and extended across hospitals in sub-Saharan Africa, South Asia, Latin America, and higher-income countries, a geographic spread deliberately designed to make findings transferable to the settings where the disease caused the most deaths. Douglas Altman at the Centre for Statistics in Medicine, Oxford, provided statistical oversight for a trial unusually complex in its multinational structure.
The primary result was unambiguous. Eclampsia occurred in 0.8% of women given magnesium sulfate versus 1.9% of controls, a relative reduction of roughly 58%. Maternal mortality was lower in the treatment arm, though the trial was not large enough to achieve statistical significance for that endpoint. The side-effect profile, flushing and injection-site discomfort being the most common, was judged manageable in both well-equipped and resource-limited hospitals.
Publication in the Lancet in 2002 ended the debate that had persisted since early-twentieth-century reports first described magnesium sulfate for eclampsia. Professional bodies including WHO revised their obstetric care guidelines to designate magnesium sulfate as the preferred agent for eclampsia prophylaxis and treatment. Phenytoin, which had never produced comparable trial evidence, was largely displaced from labor ward protocols within a few years.
The reach of Magpie's evidence mattered as much as the result itself. 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. Countries that adopted the protocol after 2002 documented falls in eclampsia rates in routine practice, and the treatment is now on the WHO List of Essential Medicines.
Key People
- Lelia Duley — Chief investigator; perinatal medicine, Leeds
- Douglas Altman — Statistical oversight; Centre for Statistics in Medicine, Oxford
- A. Metin Gulmezoglu — WHO contributor; reproductive health research coordination
Lancet, 2002
Related landmarks
- 2002 · Women's Health Initiative: Estrogen plus Progestin Hormone Therapy (Reproductive Health)
- 2004 · Women's Health Initiative: Estrogen-Alone Hormone Therapy (Reproductive Health)
- 1997 · Dolly the Cloned Sheep (Reproductive Health)
- 1995 · Collaborative Eclampsia Trial: Magnesium Sulfate for Eclampsia (Reproductive Health)