Research on baby pigs at the University of Wisconsin-Madison may soon help doctors improve the way they care for premature infants.

Nutritional scientists Barb Mickelson and Norlin J. Benevenga from the College of Agricultural and Life Sciences examined the growth-suppressing side effects of dexamethasone, a medication commonly used to help premature infants breathe.

After establishing that baby pigs and human babies respond similarly to the drug, the researchers investigated how dexamethasone changes protein metabolism. What they found out might lead to clues about how to counteract the side effects of the drug.

Frank Greer, a pediatrician at Meriter Hospital and a professor at UW-Madison”s Medical School, is working with Mickelson and Benevenga, and hopes to apply the results of their research to his own tiny patients at Meriter.

Pediatricians use dexamethasone as an effective and inexpensive treatment for respiratory distress syndrome, a potentially life-threatening condition for premature infants. However, the steroid-type drug is known to cause growth problems in human infants. Mickelson says the new research shows piglets build less muscle and lung tissue, and gain weight more slowly while on the drug.

Earlier work by other researchers found that weight gain and linear growth declined by 40 percent and 60 percent respectively after two weeks of dexamethasone treatment. Mickelson found that two-week old piglets treated with the drug for up to four days gained 15 percent to 30 percent less weight than untreated piglets, depending on how much of the drug they received.

As for the drug”s other side effects, Mickelson says, “We saw a 15-percent to 25-percent decrease in the rate of protein synthesis in skeletal muscle and lung. Dexamethasone interfered with the ability of certain tissues to synthesize protein and thus grow.”

Human infants commonly receive dexamethasone treatment lasting from three days to three weeks and suffer similar growth setbacks, according to medical experts.

According to Mickelson”s study, dexamethasone could compromise an infant”s health because it changes how the body uses amino acids, the building blocks of body proteins. During dexamethasone treatment, amino acids are not used to build protein. Instead the body uses them for energy or to make fat. These negative effects begin within 24 to 48 hours of the first dose, and subside within 24 to 48 hours after the last dose.

“We have a better idea of the mechanism thanks to Barb”s study,” says Greer. The study was partially funded by the Meriter Foundation.

Wisconsin has fewer premature infants born each year compared with other states — about five percent. Nevertheless, many of these babies require dexamethasone treatment to survive. Greer estimates that one to two percent of the premature infants at Meriter require dexamethasone treatment each year.

“At birth, a baby pig”s body composition is very similar to a preterm human”s in that energy reserves are very limited,” Mickelson said during a presentation of her study results. “Preterm infants often get poor nutritional support in the first weeks of life, which together with dexamethasone treatment could result in even poorer growth and potentially have long lasting negative effects on development.”

Although Mickelson says most infants will grow at an appropriate rate after dexamethasone treatment ends, she believes clinicians need to know more about how much drug to give and for how long. “We hope to minimize the growth suppression seen during dexamethasone treatment,” Mickelson says.

Mickelson suggests future research should look at the effects of boosting nutritional intake, particularly protein, to preserve body protein during treatment, and to perhaps help the animal, or infant, catch-up on growth after treatment. She also suggests studying how growth factors, such as growth hormone and insulin-like growth factor, combined with an enhanced diet, might help offset the side effects of the drug.

Dexamethasone appears to interfere with the way growth hormone works, says Greer. Thus, premature babies on dexamethasone may need extra growth hormone along with extra protein to counteract the negative side effects.