Dexamethasone may pose a risk of intestinal perforation in preemies

April 2001

BETHESDA, Md. — A treatment commonly used to reduce the risk of chronic lung disease in extremely premature infants does not reduce the risk of death or chronic lung disease in these infants and may increase the risk for perforation of the intestines, according to a new study.

In the largest, most comprehensive study of its kind, the researchers concluded that early postnatal doses of dexamethasone are not indicated to prevent lung disease in extremely low birth weight infants. The study by the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network appeared recently in the New England Journal of Medicine.

Survival rate

“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, MD.

Approximately 70% of extremely low birth weight infants (weighing <1 kg) survive to hospital discharge. Of these, about 30% develop chronic lung disease requiring supplemental oxygen. The incompletely developed lungs of these infants, most of whom are extremely premature, are 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.

Attempt to reduce chronic lung disease

Some studies have suggested that dexamethasone given from 24 to 48 hours after birth may reduce the risk for chronic lung disease. The anti-inflammatory drug, dexamethasone is chemically resembles cortisol and is often prescribed to dampen the inflammatory response that causes lung damage in young preemies.

However, infants in these studies were typically given large doses of the drug, which interfered with the infants’ growth and increased their blood sugar and blood pressure.

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 this advantaged disappeared by 36 weeks of age. However, significantly more infants in the dexamethasone group than the control group (13% vs. 4%) 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.”

For more information:

• Stark AR, Carlo WA, Tyson JE, et al. Adverse effects of early dexamethasone treatment in extremely-low-birth-weight infants. N Engl J Med. 2001;344:95-101.