Intravenous magnesium sulfate supplementation before preterm delivery cuts the risk for handicapping cerebral palsy (CP) in half, according to research led by University of Alabama at Birmingham (UAB) obstetrician Dwight Rouse, MD, and published in the Aug 28 issue of The New England Journal of Medicine.
Magnesium sulfate is given routinely to prevent seizures in women with preeclampsia and to stop preterm labor, and previous research suggested that fetal exposure to magnesium sulfate before preterm birth might reduce the risk of CP.
“The association between magnesium sulfate and a lower incidence of cerebral palsy has biologic plausibility, because magnesium stabilizes blood vessels, protects against damage from oxygen depletion, and protects against injury from swelling and inflammation, all of which threaten the vulnerable preterm brain,” Rouse said. “Our study is the largest, most comprehensive effort to evaluate the effect of magnesium sulfate on the incidence of cerebral palsy in preterm infants.”
It is estimated that CP afflicts more than 200,000 Americans between the ages of 3 and 13, making it a leading cause of chronic childhood disability.
Early preterm birth is a risk factor for CP, and the magnitude of the risk rises the earlier a baby is born. During the past 20 to 30 years, the survival of infants born severely preterm has improved dramatically, and while some research suggests the rate of CP among the survivors of early preterm birth has decreased, other research suggests that it has not. Currently, approximately one of every three cases of CP is associated with early preterm birth.
The multicenter study, co-funded by the National Institute of Neurological Disorders and Stroke and conducted by the 20 participating research centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network, enrolled 2,241 women between Dec.1997 and March 2004. The women were randomly assigned to receive either placebo or magnesium sulfate. They all had similar characteristics, including gestational age (24 to 31 weeks) at randomization and risk factors for preterm birth. Some 87% of the women had experienced preterm membrane rupture.
Those in the treatment group were given six grams of magnesium sulfate intravenously over 20 to 30 minutes, followed by two grams of magnesium sulfate every hour after that—until either 12 hours had passed, labor subsided, or they had given birth. If the women in either group did not deliver within 12 hours, they were treated again if they went into labor by the 34th week of pregnancy.
On follow-up at 2 years of age, researchers found that babies born to women in the treatment group had a significantly lower rate of all forms of CP, 4.2% versus 7.3%, and of moderate or severe CP, 1.9% versus 3.5%. Children with moderate CP cannot walk unaided, and those with severe CP are profoundly disabled.
Rouse said the finding that magnesium sulfate protects against CP is consistent with two previous randomized trials, both of which were well done and which, in total, enrolled 1,600-plus women. "Our trial and the two others show that magnesium sulfate can reduce the risk of this devastating condition in preterm infants," he says. "Until we can prevent early preterm birth, the best that we obstetricians can do is to improve the prospects for infants who are born very early."