Repeat courses of corticosteroids in mothers linked to increased rate of cerebral palsy among children

When pregnant women are at high risk for preterm birth, giving them a single injection of corticosteroids has been shown to reduce the baby's chances of having serious lung problems after birth.

But some women receive multiple injections of corticosteroids, and a new study shows that repeat courses of corticosteroids are linked to an increased rate of cerebral palsy among children of these mothers.

“Our study shows that you get almost all of the benefit from a single round of therapy and that multiple rounds raise the risk of cerebral palsy, which is a severely disabling condition,” said John M. Thorp, M.D., a study co-author and McAllister distinguished professor of obstetrics and gynecology at the University of North Carolina at Chapel Hill School of Medicine.

“That's why we concluded that exposure to repeat courses should be limited,” Thorp said.

The study results are published in the Sept. 20, 2007, issue of the New England Journal of Medicine . The lead author is Ronald J. Wapner, M.D., of Drexel University in Philadelphia. The study was conducted for the Maternal-Fetal Medicine Units Network of the National Institute of Child Health and Human Development, which provided grant funding. Research took place at 14 sites across the United States, including UNC-Chapel Hill.

The researchers followed women between 23 weeks and 32 weeks pregnant who remained pregnant after an initial dose of corticosteroids. They were randomly assigned to receive weekly courses of the corticosteriod betamethasone or placebo injections.

Children born to women enrolled in the study were given physical and neurological examinations at ages 2 to 3 years old. A total of 556 children were examined. Of these, 486 (87.4 percent) had physical exams and 465 (83.6 percent) were evaluated for brain function using a measurement tool called the Bayley Scales of Infant Development.

The researchers found that there were no meaningful differences in weight, head circumference or Bayley scores between children whose mothers received a single dose of corticosteroids. However, six children in the group whose mothers received multiple injections had cerebral palsy, compared to only one child in the placebo group.

“Although not statistically significant, the rate of cerebral palsy in infants exposed to multiple courses is of concern and suggests that exposure to repeat courses of antenatal corticosteroids should be limited,” the researchers concluded.

The Sept. 20 issue also includes a separate study that examined the same question and an editorial that discusses both studies. The editorial was written by Alan D. Stiles, M.D., Brewer distinguished professor and chairman of pediatrics in the UNC School of Medicine.

The other study reached similar results, with one key difference: the researchers found smaller head sizes among the infants exposed to repeat courses of corticosteroids. But the study authors reached a different conclusion from Thorp and his co-authors, in favor of using repeat courses.

In the editorial, Stiles noted that both studies found that repeat courses produced better results than single courses in terms of reducing lung problems in the infants. However, both studies also found lower birth weights in the infants exposed to repeat courses.

“More information is needed before it is clear which strategy is optimal,” Stiles wrote. “Further study is warranted of school-age neurodevelopmental performance, including the possible increased risk of cerebral palsy among these children, as well as among offspring of women in other trials of weekly corticosteroid therapy, with attention to the doses used.”