In the largest, most comprehensive study of its kind, the study authors concluded in the January 11, New England Journal of Medicine, that early postnatal doses of the drug, dexamethasone, are not indicated to prevent lung disease in extremely low birth weight infants.
"This study shows that early moderate doses of dexamethasone do not increase the survival of preterm infants or prevent chronic lung disease and may actually endanger their health," said NICHD Director, Duane Alexander, M.D.
Approximately 70 percent of extremely low birth weight infants (weighing less than 1 kg or 2.2 pounds) survive to hospital discharge; of these, about 30 percent develop chronic lung disease requiring supplemental oxygen to breathe. The lungs of these infants most of whom are extremely premature are incompletely developed at birth and easily injured by mechanical ventilators, oxygen, and infection. In addition, there is preliminary evidence that these infants have inadequate levels of the stress hormone cortisol, which may make them susceptible to an exaggerated response to injury and infection. (Cortisol plays a role in "switching off" an immune response after an infection or other threat has subsided.) Dexamethasone is an anti-inflammatory drug chemically resembling cortisol that may be prescribed to dampen the inflammatory response.
Some studies have suggested that dexamethasone given from 24 to 48 hours after birth may reduce the risk for chronic lung disease. However, infants in these studies were typically given large doses of the drug, which interfered with infants' growth and increased their blood sugar and blood pressure.
"We began the trial with the hope that we could lower the dose of dexamethasone, and reduce the risk of these side effects," said study co-author Linda Wright, NICHD program official for the Network.
In all, the researchers enrolled 220 infants from the 13 centers taking part in the trial. Roughly half were treated with dexamethasone and half with a placebo. Fewer infants in the dexamethasone group needed oxygen therapy after 28 days but by 36 weeks corrected age this advantage had disappeared. Also, significantly more infants in the dexamethasone group than the control group (13 percent versus 4 percent) developed spontaneous perforation of the intestines. After review of the data by the trial's Data and Safety Monitoring Committee, the researchers terminated the trial early.
"Given these serious complications and the lack of discernible benefit," the researchers wrote, "we think that early dexamethasone treatment to prevent chronic lung disease in extremely low birth weight infants is not indicated."