Magnesium sulfate for the prevention of cerebral palsy: a randomized, controlled trial

Cerebral palsy (CP) is characterized by abnormal control of movement and posture, resulting in limitation of activity and is caused by non-progressive damage or dysfunction of the developing brain. Preterm birth is a risk factor for CP, with the magnitude of the risk being inversely correlated with gestational age (GA). The administration of magnesium sulfate to mothers delivering prematurely might prevent CP in their infants, as preliminarily suggested in a case-control study. This protective association has biologic plausibility, because magnesium may protect the preterm brain by reducing vascular instability, and preventing hypoxic or cytokine damage.
The American Eunice Kennedy Shriver NICHD Maternal-Fetal Medicine Units Network conducted a multicenter, placebo-controlled, double-blind study to assess if the administration of magnesium sulfate to women at high risk for early preterm delivery would reduce the risk of CP in their children. Results have been published in the New England Journal of Medicine.
Women at imminent risk for delivery between 24 and 31 weeks of gestation were randomized to receive magnesium sulfate (bolus of 6 g i.v., followed by a constant infusion of 2 g per hour), or placebo. The primary outcome was the composite of stillbirth or infant death by 1 year of corrected age or moderate or severe CP at 2 years of corrected age or beyond.
The rate of the primary outcome was not significantly different in the magnesium sulfate group vs placebo (11.3% and 11.7%, respectively; relative risk [RR]=0.97; 95% Confidence interval: 0.77 to 1.23). However, moderate or severe CP alone occurred significantly less frequently in the magnesium sulfate group (1.9% vs 3.5%; relative risk [RR]=0.55; 95% Confidence Interval: 0.32 to 0.95). The risk of death did not differ significantly between the groups. No woman had a life-threatening event.
Neither the present trial nor the trials of Crowther et al (JAMA 2003) and Marret et al (Gynecol Obstet Fertil 2008) demonstrated a statistically significant effect of magnesium sulfate on the composite outcome of death or cerebral palsy.
Noteworthy, in the present trial death was three to four times more common than moderate or severe CP. Therefore, when the rate of death does not differ between groups, the potential for a difference in the rates of CP to result in a significant difference in the rate of the composite outcome is small. When considering death and CP as separate outcomes, magnesium sulfate had no significant effect on the risk of fetal or infant death, but significantly reduced the risk of moderate or severe CP among surviving children.

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