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

Dwight J. Rouse, M.D., Deborah G. Hirtz, M.D., Elizabeth Thom, Ph.D., Michael W. Varner, M.D., Catherine Y. Spong, M.D., Brian M. Mercer, M.D., Jay D. Iams, M.D., Ronald J. Wapner, M.D., Yoram Sorokin, M.D., James M. Alexander, M.D., Margaret Harper, M.D., John M. Thorp, Jr., M.D., Susan M. Ramin, M.D., Fergal D. Malone, M.D., Marshall Carpenter, M.D., Menachem Miodovnik, M.D., Atef Moawad, M.D., Mary J. O'Sullivan, M.D., Alan M. Peaceman, M.D., Gary D.V. Hankins, M.D., Oded Langer, M.D., Steve N. Caritis, M.D., James M. Roberts, M.D., for the Eunice Kennedy Shriver NICHD Maternal–Fetal Medicine Units Network

ABSTRACT

Background Research suggests that fetal exposure to magnesium sulfate before preterm birth might reduce the risk of cerebral palsy.

Methods In this multicenter, placebo-controlled, double-blind trial, we randomly assigned women at imminent risk for delivery between 24 and 31 weeks of gestation to receive magnesium sulfate, administered intravenously as a 6-g bolus followed by a constant infusion of 2 g per hour, or matching placebo. The primary outcome was the composite of stillbirth or infant death by 1 year of corrected age or moderate or severe cerebral palsy at or beyond 2 years of corrected age.

Results A total of 2241 women underwent randomization. The baseline characteristics were similar in the two groups. Follow-up was achieved for 95.6% of the children. The rate of the primary outcome was not significantly different in the magnesium sulfate group and the placebo group (11.3% and 11.7%, respectively; relative risk, 0.97; 95% confidence interval [CI], 0.77 to 1.23). However, in a prespecified secondary analysis, moderate or severe cerebral palsy occurred significantly less frequently in the magnesium sulfate group (1.9% vs. 3.5%; relative risk, 0.55; 95% CI, 0.32 to 0.95). The risk of death did not differ significantly between the groups (9.5% vs. 8.5%; relative risk, 1.12; 95% CI, 0.85 to 1.47). No woman had a life-threatening event.

Conclusions Fetal exposure to magnesium sulfate before anticipated early preterm delivery did not reduce the combined risk of moderate or severe cerebral palsy or death, although the rate of cerebral palsy was reduced among survivors. (ClinicalTrials.gov number, NCT00014989 [ClinicalTrials.gov] .)