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Magnesium Sulfate Reduces Risk of Cerebral Palsy

ARTICLE IN BRIEF

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Expectant mothers at risk for delivering pre-term babies — who were given magnesium sulfate — had children with a significantly lower rate of cerebral palsy than those given placebo.

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There are 200,000 children diagnosed every year with cerebral palsy.Weber J, Kelley J. Health Assessment in Nursing, 2nd edition. Philadelphia: Lippincott Williams & Wilkins 2003.

A team of NIH investigators has discovered a simple way to reduce the risk of cerebral palsy (CP) in pre-term babies: magnesium sulfate (commonly known as Epsom salts).

In an extensive study of 2,241 women at risk for delivering pre-term infants, those who were given magnesium sulfate right before birth — 942 expectant mothers — had children with a significantly lower rate of cerebral palsy than 1,002 given placebo. The study was published Aug. 28 in The New England Journal of Medicine.

STUDY PROTOCOLS, RESULTS

The effort took years to enroll women at risk of delivering babies between 24 and 31 weeks; pregnant women were recruited from 20 centers that are part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network across the US.

The women were randomized to receive magnesium sulfate — an intravenous dose of 6 g bolus followed by an infusion of 2 g per hour until the child was delivered or for up to 12 hours — or an IV solution that contained a placebo. Those who survived were followed for two years, and the investigators were able to assess 95 percent of the babies.

At the end of two years, those who had been exposed to magnesium sulfate before pre-term birth were less likely to have signs of moderate or severe CP.

Deborah Hirtz, MD, a pediatric neurologist who followed the children throughout the study, said that 41 children in the magnesium sulfate group had CP — defined by involuntary movements or limb weakness that limited physical activity — compared to 74 children who had not been exposed to magnesium sulfate via their mothers during pre-term labor.

Of the babies in the magnesium sulfate group, 2.2 percent were classified as having mild CP, 1.5 percent as moderate, and 0.5 percent as severe. In the placebo group, 3.7 percent were classified as having mild CP, 2.0 percent moderate, and 1.6 percent severe.

Dr. Hirtz noted that children born prematurely have other problems in addition to the risk for CP, and this study did not show any overt differences in cognitive ability between those who had received magnesium sulfate and those who did not. But it is often difficult to test cognition in toddlers. The best the investigators could hope for during the first two years of life is to measure motor development.

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DR. DEBORAH HIRTZ said that 41 children in the magnesium sulfate group had cerebral palsy compared to 74 children who had not been exposed to magnesium sulfate via their mothers during pre-term labor.

AN OLD IDEA GAINS CREDIBILITY

The idea that magnesium sulfate could alter the course of the developing brain is not new. There were hints from observational studies. And more than a decade ago, Karin Nelson, MD, a child neurologist at the NINDS, collaborated with epidemiologist Judith Grether of the California state health department to follow all children born over a three-year period in three counties in northern California.

“We had a human laboratory to see what was related to cerebral palsy,” said Dr. Nelson. “We observed a powerful effect on the children whose mothers had received Epson salts right before birth. Epson salts are used to reduce pregnancy-induced high blood pressure and to help hold off pre-term delivery.”

They believed that their finding was real, but it was impossible to make such a bold claim with an observational study, Dr. Nelson said. “But it was an opportunity to pose the question and for others to carry out a double-blind, randomized study.”

She said that the current study results are “solid…it is a really convincing trial. It is a true benefit.”

Obstetricians have experience using magnesium sulfate in patients with pre-eclampsia (high blood pressure and protein in the urine) but it may take time to convince the field to administer magnesium sulfate during pre-term labor to reduce the risk for cerebral palsy, Dr. Nelson said.

Full term babies who develop CP rarely have warning signs of risk so it is not likely to be useful in these babies. Dr. Hirtz said that laboratory and clinical studies have offered a glimpse into why magnesium sulfate may work. It seems to stabilize blood vessels, protects against damage from oxygen depletion, and protects against injury from swelling and inflammation, and all of these events could work against the developing brain.

EXPERTS COMMENT

In an accompanying editorial, Australian physicians Fiona J. Stanley, MD, and Caroline Crowther, MD, said that “although promising, we would advise caution because of the differences between the populations that were eligible for entry into the individual studies and the different protocols used…Better understanding is needed of factors that might influence the likelihood that offspring will benefit from maternal magnesium sulfate treatment, such as the reason for imminent pre-term birth, the dose of magnesium sulfate, and the timing of administration relative to birth and gestational age.”

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DR. KARIN NELSON said that the current study results are “solid…it is a really convincing trial. It is a true benefit.”

Dr. Crowthers and her colleagues led the early clinical studies on magnesium sulfate after Dr. Nelson and her colleagues published their epidemiological findings in 1995. They also found a benefit.

“This is an extremely impressive piece of research,” said Laura Ment, MD, a professor of pediatrics and neurology at Yale University School of Medicine. Dr. Ment was on the data safety monitoring committee for the study and was following it with great interest for years. “It's a big deal not to walk, and this study showed that magnesium sulfate reduced the risk of cerebral palsy by almost 50 percent.”

While more pre-term babies are surviving, many are left with a number of problems, including developmental delays. No interventions have made a dent in the incidence of cerebral palsy, which has remained steady despite the best efforts in neonatal medicine. The causes of cerebral palsy are not well understood.

Major funding for the latest multi-center study was provided by NINDS, whose investigators worked closely with colleagues at the National Institute of Child and Human Development.

REFERENCE

• Rouse DJ, Hirtz DG, Roberts JM, et al., for the Eunice Kennedy Shriver NICHD Maternal–Fetal Medicine Units Network. A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy. N Engl J Med 2008;359:895–905.