The common practice of giving steroids to premature infants at 2 weeks of age to help wean them from ventilators is being called into question after a large federal study found that treatment so early in the child's development increases the risk of infection and slows growth.
About 7% of the infants born annually in the United States weigh less than 5.5 pounds at birth, according to the National Center for Health Statistics. About 1% weigh as little as 3.3 pounds when they arrive early, sometimes at just 25 weeks of gestation, or nearly four months short of full term.
Infants with very low birth weights are often treated with dexamethasone, a corticosteroid that has been shown to help them overcome underdeveloped lungs and immature gastrointestinal tracts. Since the mid-1980s, various studies have suggested that dexamethasone helps improve lung function and reduces the time that premature infants need to be on a ventilator.
Although the American Academy of Pediatrics has no written guidelines for using steroids, the practice has slowly become a common way of treating premature infants. Traditionally, the drug was given only to babies with very low birth weights who were at least 4 weeks old and on a ventilator. But in recent years, the trend has been to administer treatment much earlier.
"What this study says is that we should be very careful before thinking of steroids as the standard of care at 2 weeks," said Linda L. Wright, special assistant to the director of the Center for Research for Mothers and Children at the National Institute of Child Health and Human Development, which sponsored the study.
In full-term infants, the adrenal glands normally release a burst of corticosteroids during labor and delivery. Within hours, these substances bring about maturation of the heart, lungs and the nervous and gastrointestinal systems by stimulating production of essential proteins and enzymes throughout the body.
In premature infants, however, the underdeveloped adrenal glands are incapable of releasing enough corticosteroids. As a result, these infants, who weigh between 1 and 3 pounds, often battle serious respiratory disease and face a high incidence of brain hemorrhage and other debilitating complications. Medical costs run an estimated $2 billion a year to treat these high-risk babies, according to the National Institute of Child Health and Human Development.
But the early use of dexamethasone is far riskier and no more beneficial than waiting until infants reach 4 weeks of age, the researchers concluded. The study, published in the New England Journal of Medicine, involved 371 premature babies, born weighing between 1 and 3 pounds who were treated at 12 medical centers.
At 2 weeks of age, all the infants were still on ventilators and had low respiratory index scores, a measure of how much support they needed from ventilators and an indication of lung function. Half the infants were randomly assigned to receive dexamethasone intravenously for two weeks. The other half received a placebo. Researchers then switched treatment for the two groups for the next two weeks, giving dexamethasone to the babies who had received placebo and a placebo to those who had received dexamethasone.
The study found no significant differences in the time it took for babies to be weaned from their ventilators. Those who received the early dose of dexamethasone stayed on the ventilators for a median of 36 days, while those on placebo got off the ventilators in 37 days, a difference that is statistically insignificant. The rate of chronic lung disease was also not significantly different in the two groups, the study found.
But there were other important differences. Those babies who took dexamethasone at 2 weeks of age had a 50% increased risk of infection.
"Sepsis is a very serious consideration for these babies," Wright said. "You can give antibiotics, but it commonly causes them to be put back on the ventilator and often leads to a longer hospital stay."
Dexamethasone treatment had other troubling side effects as well. It increased blood pressure and glucose levels and slowed weight gain, overall growth and head circumference, an indicator of brain growth.
"When the drug was stopped, these babies grew again," Wright said. "But premature infants are already small, and we are very concerned that they exhibit catch-up growth. . . . The question is, do these kids ever catch up?"
What effect the findings will have on current practices is not yet clear.
"It's a really interesting study with a large population of patients and is very well-supported and done," said Dr. Khodayar Rais-Bahrami, a neonatologist at the Children's National Medical Center in Washington. "But I would like to point out that there is a body of scientific literature that shows that steroids are beneficial and that they do help premature babies' lungs to recover faster, in contrast with this, and to have less-chronic lung disease and earlier discharge from the hospital."
At Children's medical center, dexamethasone is used on a case-by-case basis.
"We don't have set criteria to give it on certain days," Rais-Bahrami said. "We have given it as early as 10 days of age and as late as 4 weeks of age."
The findings "will change things a little," he said. "But my own management style is . . . balancing the risks and benefits for each individual patient."
Experts also underscored that the latest study should in no way alter the use of dexamethasone in women experiencing premature labor. In 1994, an expert panel convened by the National Institutes of Health urged doctors to give injections of corticosteroids to women going through premature labor at 24 to 35 weeks of gestation. The panel found that the practice reduced the incidence of respiratory-distress syndrome by 50% and decreased infant mortality by about 40%.
There is no question that administering dexamethasone after birth can also help in weaning infants off of ventilators earlier, Wright said. But starting the drug at 2 weeks of age is what appears to be so risky.