The composite endpoint of stillbirth, infant death within one year, or cerebral palsy at two years or later did not differ between randomized groups, Dwight J. Rouse, M.D., of the University of Alabama here, and colleagues reported in the Aug. 28 issue of the New England Journal of Medicine.
However, a prespecified secondary analysis showed that moderate or severe cerebral palsy occurred almost 50% less often in the offspring of women who received magnesium sulfate.
"Consistent with the results of previous trials, our findings suggest that magnesium sulfate may reduce the chance that cerebral palsy will subsequently be diagnosed in a child who was at high risk for preterm birth," the authors concluded.
The results confirm those reported earlier this year at the Society of Maternal-Fetal Medicine meeting (See: Magnesium Sulfate for Preterm Birth Prevents Cerebral Palsy But Not Death).
Preterm birth carries an increased risk of cerebral palsy, and the magnitude of the risk correlates inversely with gestational age at birth. About a third of cerebral palsy cases involve preterm birth.
Evidence dating to the mid-1990s has indicated that administration of intravenous magnesium sulfate to delay labor may protect infants from cerebral palsy during the first year of life, the authors said.
The association has biologic plausibility in data suggesting that magnesium may reduce vascular instability, prevent hypoxic damage, and prevent cytokine or excitatory amino acid damage, they noted.
"We performed this study to test the hypothesis that the administration of magnesium sulfate to women at high risk for early preterm delivery would reduce the risk of cerebral palsy in their children," the authors said.
The study involved 2,241 women at "imminent risk" of preterm birth. The women were at 24 through 31 weeks gestation and had ruptured membranes, intact membranes but in active labor and dilated 4 to 8 cm, or if a preterm delivery was anticipated within two to 24 hours, because of fetal growth restriction, for example.
The women were randomized to intravenous magnesium sulfate or placebo. If delivery had not occurred within 12 hours and was no longer considered imminent, the infusion was stopped and resumed when delivery once again appeared imminent.
When the study ended, the rate of the composite endpoint was 11.3% in the magnesium sulfate group and 11.7% in the placebo group.
However, moderate or severe cerebral palsy occurred in just 1.9% of the magnesium sulfate group compared with 3.5% of the placebo group (RR 0.55, 95% CI 0.32 to 0.95).
The overall incidence of cerebral palsy also was lower in the magnesium sulfate group (4.2% versus 7.3%).
The risk of death did not differ significantly between groups (9.5% with magnesium sulfate and 8.5% with placebo), and no woman had a life-threatening event.
The findings "provide additional reassurance that magnesium sulfate, when used for neuroproection, does not significantly increase neonatal or infant mortality," Fiona J. Stanley, M.D., of the University of Western Australia in Perth, and Caroline Crowther, M.D., of the University of Adelaide in Australia, said in an editorial.
"The reduction in the rates of cerebral palsy with use of magnesium sulfate does not seem to be attributable to higher mortality rates among infants with brain damage," they added.
However, the editorialists urged caution about using magnesium sulfate to prevent cerebral palsy until more is known about factors that might explain the benefits.
"Information from long-term follow-up of children whose mothers received antenatal magnesium sulfate also is needed to clarify the neuroprotective role of this therapy before preterm birth," Drs. Stanley and Crowther concluded.
|The study was supported by the National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke.
- Reviewed by Dori F. Zaleznik, MD Associate Clinical Professor of Medicine, Harvard Medical School, Boston
New England Journal of MedicineSource Reference: Rouse DJ, et al "A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy" N Engl J Med 2008; 359: 895-905.
New England Journal of MedicineSource Reference: Stanley FJ, Crowther C "Antenatal magnesium sulfate for neuroprotection before preterm birth?" N Engl J Med 2008; 59: 962-964.