Steroids Given to premature babies May Harm Brain Growth

Giving premature babies even low doses of steroids after birth interferes with development of the brain's cerebellum, which is important to motor skills, learning and behavior, new research finds.

For the study, researchers analyzed MRIs of 172 babies born very early (under 32 weeks' gestation) at two medical centers, the University of British Columbia and the University of California, San Francisco. Full term is considered 40 weeks' gestation.

Preemies are sometimes given steroids known as glucocorticoids after birth to improve lung function and to stabilize low blood pressure, both of which are common problems.

The study found that preemies given the steroids hydrocortisone or dexamethasone had on average a 10 percent smaller cerebellum than premature babies not given the drug. Most of the infants had their brains scanned shortly after birth and again at around what would have been full term.

"Their cerebellums were growing slower," said lead study author Dr. Emily Tam, an assistant professor of neurology and pediatrics at University of California, San Francisco. "And we know from other studies that a smaller cerebellum in preemies is associated with poorer outcomes."

Mothers-to-be who are at risk of preterm labor are also often given steroids (usually betamethasone) before the baby is born to speed up maturation of the lungs. Researchers did not see any connection between prebirth steroids and smaller cerebellums. More controversy surrounds their use in babies after birth.

The study is published in the Oct. 19 issue of Science Translational Medicine.

About 13 percent of babies are born prematurely each year in the United States, according to the study. Premature babies can have all sorts of difficulties. Some 5 to 10 percent of very preterm infants have cerebral palsy, and up to half have behavioral disorders or learning disabilities.

Prior research has found that high-dose steroids may interfere with cerebellum growth, Tam said. Previous research has also found that children given steroids right after birth are more prone to learning and behavioral problems, said Dr. Pierre Gressens, a professor of pediatric neurology at the Centre for the Developing Brain at Imperial College in London and a lab chief at INSERM in Paris.

The American Academy of Pediatrics recommends avoiding high-dose dexamethasone in babies after birth, according to background information in the study.

In practice, some hospitals never use steroids in premature babies, while others routinely give steroids, Gressens said. In the study, about 20 percent of the 172 babies had been given steroids post-birth, Tam said.

The new research suggests that steroids should be given after birth only with the utmost caution, carefully balancing potential risks and benefits, Gressens said.

"There are situations where steroids are useful for a short time for the lungs, but doctors have to remember there is a particular toxicity of this steroid," Gressens said.

Tam agreed that doctors should be very cautious in giving steroids to premature babies.

"Even a low dose of dexamethasone or hydrocortisone are associated with decreased brain development, which would make us need to be careful when using these drugs," she said.

"They are very effective drugs," she continued. "We wouldn't want to say don't use them entirely, because we don't have very good alternatives. But when you think about options, don't jump straight to the steroid. You always have to think about the risk and benefit balance. Now there's more risk they have to consider when they think about using this drug."

Tam and her colleagues plan to follow the children as they get older to see if the smaller cerebellums result in motor, learning or behavioral issues.

In a second study, also led by UCSF researchers and published in the same journal issue, researchers showed that a small molecule drug blocked the negative effects of steroids on the cerebellum in mice.

The drug worked by stimulating a pathway that's involved with growth of neurons, which is what steroids appear to hamper, Gressens said.

"If you give a small molecule which stimulates the pathway, in a way you reverse the toxicity of the steroid, and if you reverse the effect on growth, the cerebellum goes back to normal size," he said. "There is potential for application in humans, but it's still a long time from clinical applications, maybe 5 to 10 years."