Common treatment to delay labour decreases preterm infants’ risk for cerebral palsy

Preterm infants born to mothers receiving intravenous magnesium sulphate — a common treatment to delay labour — are less likely to develop cerebral palsy than are preterm infants whose mothers do not receive it, report researchers in a large National Institutes of Health research network.

The study results appear in the August 28, 2008 New England Journal of Medicine.

"A third of all cases of cerebral palsy are associated with preterm birth," said NIH Director Elias A. Zerhouni, M.D. "This study shows a significant reduction in cerebral palsy among preterm infants whose mothers were given magnesium sulphate."

The researchers theorised that magnesium sulphate protects against cerebral palsy because it can stabilise blood vessels, protect against damage from oxygen depletion, and protects against injury from swelling and inflammation.

Cerebral palsy refers to a group of neurological disorders affecting control of movement and posture and which limit activity. The brain may be injured or develop abnormally during pregnancy, birth or in early childhood. The causes of cerebral palsy are not well understood.

The research was conducted by investigators in 20 participating research centres of the Maternal Foetal Medicine Units Network of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The study’s first author was Dwight J. Rouse, M.D., of the University of Alabama at Birmingham. Major funding was provided by NIH’s National Institute of Neurological Disorders and Stroke (NINDS).

A 1995 study by NINDS researcher Karin Nelson, M.D., and a researcher at the California Department of Health Services found that mothers of preterm infants who did not have cerebral palsy were more likely to have received magnesium sulphate than were mothers of infants who had cerebral palsy. Two larger randomised studies that subsequently were undertaken suggested that magnesium sulphate given to pregnant women delivering prematurely might protect their infants against cerebral palsy, but their results were inconclusive.

"Our study is the largest, most comprehensive effort to date that looked at using this inexpensive and commonly used treatment to reduce the occurrence of cerebral palsy after preterm birth," said Deborah Hirtz, M.D., paediatric neurologist at NINDS, and an author of the study. "Cerebral palsy can’t always be prevented, but the data from our study and its predecessors will help obstetricians make informed treatment decisions for the women under their care."

Women at the 20 participating NICHD Maternal Foetal Medicine Unit Network sites were eligible to participate. The women were from 24 to 31 weeks pregnant and at risk for preterm delivery. When the women went into labour, they were assigned at random to receive intravenously a solution of either magnesium sulphate or a placebo. The women in the treatment group were given 6 grams of magnesium sulphate intravenously over 20 to 30 minutes, followed by 2 grams of magnesium sulphate every hour after that until either 12 hours had passed, labour had 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 labour by the 34th week of pregnancy.

For purposes of their statistical analysis, the researchers calculated the rates of moderate cerebral palsy, severe cerebral palsy, and death among the infants in the study. The study authors did not include mild cerebral palsy in this calculation, as mild cerebral palsy will often disappear with time.

When the researchers considered only moderate and severe cerebral palsy together, cerebral palsy occurred less frequently in the magnesium sulphate group (1.9 percent) as compared to the placebo group (3.5 percent).

For their primary calculation, the researchers grouped the proportions of infants with moderate and severe cerebral palsy together with the proportion of infants who died. The researchers included the death rate in this primary calculation, because mortality among preterm infants is very high. The researchers found that a total of 11.3 percent of infants in the magnesium sulphate group had either moderate or severe cerebral palsy, or had died at birth or were stillborn. In contrast, a total of 11.7 percent of the infants in the placebo group had moderate to severe cerebral palsy or had died.

The proportion of deaths occurring in the magnesium sulphate group (9.5 percent) did not differ significantly from those in the placebo group (8.5 percent).

There was no difference in the average gestational age between the two groups of infants.

Cerebral palsy was diagnosed in 41 children from 942 magnesium sulphate-treated pregnancies, as compared to 74 children from 1,002 placebo-treated pregnancies. Of the children in the magnesium sulphate group, 2.2 percent had cerebral palsy classified as mild, 1.5 percent as moderate, and 0.5 percent as severe. A higher proportion of children in the placebo group than in the magnesium sulphate group had cerebral palsy. Of the children in the placebo group, 3.7 percent had mild cases of cerebral palsy, 2.0 percent had moderate cases, and 1.6 percent had severe cases.

"This is a major advance," said Catherine Y. Spong, M.D., Chief of NICHD’s Pregnancy and Perinatology Branch and an author of the study. "Our results show that obstetricians can use magnesium sulphate, which they have experience prescribing, to reduce the risk of a devastating condition, cerebral palsy, in preterm infants."

(Source: New England Journal of Medicine: National Institutes of Health: August 2008)