A Randomized, Controlled Trial of Magnesium Sulfate for the Prevention of Cerebral Palsy

Abstract

Early preterm birth is associated with approximately one third of all cases of cerebral palsy and is a risk factor. A case–control study was the first to show a decrease in the incidence of cerebral palsy in the offspring of women who were given magnesium sulfate before preterm delivery. This randomized, placebo-controlled, double-blind trial tested the hypothesis that antenatal administration of magnesium sulfate would reduce the incidence of cerebral palsy in the children of women at high risk for early preterm delivery. At 20 sites across the United States from December 1997 through May 2004, 2241 women at high risk for spontaneous delivery at 24 through 31 weeks’ gestation were randomized to receive either intravenous magnesium sulfate (6 gm infusion for 20 to 30 minutes followed by a maintenance infusion of 2 gm per hour) or a placebo. The primary outcome was the composite of stillbirth or infant death by 1 year of age or moderate or severe cerebral palsy at or beyond 2 years of age. A trained psychologist or psychometrist administered and assessed scores on the Bayley Scales of Infant Development II. Baseline characteristics of the two groups were matched. Over 95% of the children were followed for 24 months. Corrections were made for prematurity. No significant differences were found for the primary composite outcome of moderate or severe cerebral palsy or death in the offspring of the magnesium sulfate group and the placebo group (11.3 versus 11.7%; relative risk, 0.97; 95% confidence interval [CI], 0.77 to 1.23; P = .80). However, women in the magnesium sulfate group had a significantly lower risk of giving birth to an infant who subsequently developed moderate or severe cerebral palsy than women in the placebo group (1.9% versus 3.5%, respectively; relative risk, 0.55; 95% CI, 0.32 to 0.95; P ≤ .03). There was no difference in scores on the Bayley scales of infant development between the two groups. No life threatening maternal events were noted in either group. This study is consistent with previous reports that antenatal magnesium sulfate does not reduce the combined risk of death or moderate or severe cerebral palsy, but may reduce the risk of cerebral palsy among survivors.