Drug Curbs Cerebral Palsy in Premature Babies, Study Says : Science: Medicine used to treat women in pre-term labor cuts risks for very low birth weight infants. But experts say further research is required.

In what may be the first major advance against cerebral palsy in the last 20 years, researchers report that a drug treatment commonly administered to women in pre-term labor might have the added benefit of reducing the risk of the disorder in prematurely born infants.

The finding, published today in Pediatrics, has generated excitement because infants born weighing less than 3.3 pounds--defined as very low birth weight--account for 25% of the estimated 7,000 cases of cerebral palsy diagnosed annually in the United States. The disorder, in which the brain does not properly control muscles and movement, is one of the most common childhood disabilities, usually requiring a lifetime of costly medical care and disability-related services.

Cerebral palsy cases have increased in recent years because more premature babies are surviving.

The study, co-authored by researchers at the California Birth Defects Monitoring Program and the National Institute of Neurological Disorders and Stroke, showed that very low birth weight infants had a much lower incidence of the disorder when their mothers were treated with magnesium sulfate shortly before giving birth.

“This intriguing finding means that use of a simple medication could significantly decrease the incidence of cerebral palsy and prevent lifelong disability and suffering,” said Zach W. Hall, director of the neurological institute.

In most cases, the disorder is present at birth and the cause is unknown. In some cases, it can be caused by an infection in the baby’s first month of life or by an injury in early childhood, such as a near-drowning or being severly shaken. The last major advance against cerebral palsy occurred about 20 years ago when researchers discovered a treatment for Rh disease, an incompatibility between the blood of a mother and her fetus that can cause the disorder.

Drawing from data in the California registry, the researchers compared 42 very low birth weight children with moderate to severe cerebral palsy to 75 very low birth weight children without the disorder. The two groups were similar for other variables, including gestational age, sex, race, mother’s age and type of medical insurance.

Of the children with cerebral palsy, only 7% of their mothers had received magnesium sulfate, while in unaffected children, 36% of the mothers had received the medication.

Magnesium sulfate is typically given intravenously to women with preeclampsia, which is associated with high blood pressure, to prevent convulsions, said Judith K. Grether, an epidemiologist with the California Birth Defects Monitoring Project and a co-author of the paper. It is prescribed somewhat less frequently to women in pre-term labor to slow or stop contractions. The drug is inexpensive and usually safe when given under close supervision.

Researchers at the California Birth Defects Monitoring Program were combing through data on mothers and their premature infants in 1993 when they became aware of a study suggesting that magnesium sulfate administered to women in pre-term labor appeared to protect infants from brain hemorrhages.

“We realized we had the data to look at that. And our knees started shaking with what we found,” Grether said. The state’s Birth Defects Monitoring Program collects and analyzes data in order to find causes and prevent birth defects.

Researchers spent months trying to find another reason for the difference in cerebral palsy rates, said Dr. Karin B. Nelson, a co-author of the paper at the National Institute of Neurological Disorders and Stroke.

“It’s our obligation to try to find another explanation, and we did try. But there aren’t that many things that act that powerfully,” she said.

Moreover, a similar retrospective study corroborating Nelson and Grether’s results was reported last month by Dr. John C. Hauth of the University of Alabama at Birmingham.

“I think the (Pediatrics journal) data is very, very exciting,” said Hauth, whose findings were published in the American Journal of Obstetrics and Gynecology. But he and others noted that although the new study reveals a strong association between magnesium sulfate and a lower incidence of cerebral palsy, it does not definitively establish a cause-and-effect relationship.

“It’s very suggestive, but it doesn’t prove anything,” he said. Future studies, he suggested, should follow women beginning in pre-term labor, rather than studying infants after the fact. One group of women would be given magnesium sulfate and a similar group of women a different treatment, then the very low birth weight babies would be compared for the incidence of cerebral palsy, he added.

Hauth and others say it’s too soon to ask obstetricians to use magnesium sulfate in preference to other treatments for preeclampsia and pre-term labor.

“We feel we have a firm conclusion, but we can’t conclude that the whole country should go to this,” Hauth said.

Nelson added: “It’s going to depend on the obstetrics community and their view of the evidence how this plays out. Those discussions are under way now.”

Many questions remain about the treatment, including whether it will work with all, or most, very low birth weight infants at risk and exactly how magnesium might prevent the disorder.

There is evidence that magnesium works as an antioxidant to reduce injury to tissues. It may also help stabilize circulation, Nelson said. “We do know magnesium operates in many ways in the cortex of the brain as well as in cardiac function,” Grether said.

Several other studies on the effects of magnesium are under way.

“We have all felt some urgency because if magnesium can help this much, we are eager to take that benefit to its full application,” Nelson said.