The Magpie trial: Magnesium lowers eclampsia risk [Classics Series]

1. Women with pre-eclampsia randomized to magnesium experienced a greater than 50% reduction in eclampsia compared to women on placebo.

Original Date of Publication: June 2002

Study Rundown: Pre-eclampsia is a multi-system hypertensive disorder of pregnancy associated with significant maternal morbidity and mortality. Worldwide, approximately 50 000-60 000 women die from manifestations of pre-eclampsia each year. Eclampsia, defined as convulsions or seizures superimposed on pre-eclampsia, affects 1 in 2000 deliveries and represents a leading cause of maternal mortality in countries where maternal mortality rates are high. One difficult decision for providers is how and when to administer medications to prevent the development of seizures in women with pre-eclampsia. In the 1990s, various anticonvulsants including benzodiazepines, phenytoin and barbiturates were used to prevent eclamptic seizures. Around this time, a systematic review of 4 trials comparing anticonvulsants to placebo for eclampsia prophylaxis identified magnesium as the drug with the most potential to reduce the risk of eclampsia. Theories for how magnesium sulfate might reduce the risk of eclampsia include relaxation of vascular smooth muscle, improvement in endothelial function and blocking of N-methyl-D-aspartate receptors in the brain to decrease neuronal excitability. Remaining questions included the magnitude of risk reduction attributable to magnesium as well as its tolerability and impact on the fetus. In the Magnesium sulphate for Prevention of Eclampsia (Magpie) trial, researchers randomized women with pre-eclampsia in labor to receive magnesium sulfate or placebo and assessed rates of eclampsia.

Findings demonstrate that magnesium sulfate meaningfully reduces the risk of eclamptic seizures among women with pre-eclampsia. This international investigation was 12 times larger than the previous largest trial on the topic and took over 3.5 years to complete. Strengths included an elegant blinded study design with central randomization as well as subgroup and sensitivity analyses. Drawbacks included variability by site in terms of route of administration (intramuscular or intravenous) as well as variability in loading dose (4mg or 5mg). Future investigations might assess whether tolerability of magnesium and efficacy varies by route of administration and loading dose.

Click to study in The Lancet

Dr. Alan Peaceman, MD, talks to 2 Minute Medicine: Northwestern University School of Medicine; Chief, Division of Obstetrics and Gynecology-Maternal Fetal Medicine.

“This trial was the first to demonstrate that magnesium sulphate meaningfully reduces the risk of eclampsia among women with pre-eclampsia. Findings provide reliable evidence that intrapartum magnesium is an intervention that reduces maternal morbidity and mortality associated with pre-eclampsia.”

In-Depth [randomized controlled trial]: A total of 10 141 pregnant women with pre-eclampsia, defined as persistently elevated blood pressures greater than 140/90 and proteinuria, were enrolled in this blinded, placebo-controlled international trial across 33 countries. Women were randomized on the basis of gestational age, severity of pre-eclampsia and proximity to delivery. Primary outcomes included eclampsia and fetal or infant death and analysis was performed via intention-to-treat.

Women randomized to magnesium experienced a 58% lower risk of eclampsia (CI 40-71% reduced risk) compared to women allocated to placebo (RR 0.32, p<0.0001). The overall number needed to treat (NNT) to prevent one seizure was 91; among severe pre-eclamptics the NNT was 63 and among mild pre-eclamptics the NNT was 109. Women on magnesium were more likely to report side effects, most commonly flushing, compared to women on placebo (24% vs. 5%). There were no differences in risk of fetal or neonatal death between groups.

Image: PD

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