Treating premature babies with nitric oxide gas improved their cognitive function at age 2 and lowered their risk of developing neurological complications such as cerebral palsy, according to a study published today in the New England Journal of Medicine.
But a separate study concurrently published in the journal reported that the therapy did not help survival in a group of smaller and sicker premature babies and may have even worsened it in the sickest infants.
Experts said nitric oxide therapy, while promising for some premature infants, cannot be generally recommended until further research identifies which babies would benefit.
Each year, an estimated 60,000 U.S. babies are born so prematurely that they need assistance with breathing. Their lungs lack a critical substance known as a surfactant, which eases inflation of the lungs.
Although survival of babies as young as 24 weeks is now possible because of treatment with oxygen, mechanical ventilators and animal surfactants, many premature babies still die. Others develop chronic lung disease and later complications such as blindness, deafness, cerebral palsy and cognitive delays.
Neonatologists became interested in the possible use of nitric oxide to help prevent lung damage in premature babies after they found that it helped full-term babies surmount chronic lung disease.
In one of the studies, researchers led by Dr. Michael D. Schreiber, professor of pediatrics at the University of Chicago, gave either nitric oxide or a placebo to 207 premature infants born at less than 34 weeks' gestation. All of the infants were experiencing respiratory distress.
The scientists had reported in 2003 that the nitric oxide treatment increased the infants' survival rate and reduced rates of chronic lung disease and serious brain bleeding.
In their follow-up study published today, Schreiber's group assessed 138 of those children at age 2.
The scientists found that 16% of the 68 who had received nitric oxide had a significant delay in mental development, compared with 34% of the 70 babies in the placebo group.
Developmental delay was measured by a standard battery of tests that assess language, thinking and motor skills.
When the scientists pooled cognitive problems with other complications of prematurity, such as cerebral palsy, blindness and hearing loss, they found that 24% of the nitric oxide group experienced such problems, compared with 46% of the placebo group.
In the second study, scientists led by Dr. Krisa Van Meurs, professor of pediatrics-neonatology at Stanford University's School of Medicine, tracked 420 premature infants with respiratory failure treated at 14 academic medical centers and 26 hospitals. Half of the babies received nitric oxide.
The overall figures in the study showed no significant improvement in death or lung disease rates in babies given nitric oxide versus a placebo. In both cases, about half of the infants died, and two-thirds developed chronic lung disease.
But further analysis showed that larger babies in the study -- those more than 2.2 pounds at birth -- did have a higher survival rate and less chronic lung disease with nitric oxide treatments.
Those improvements, however, appeared to be offset by the effect of nitric oxide on babies born weighing less than 2.2 pounds.
Those babies suffered higher rates of death and severe brain bleeding.
The most fragile babies, Van Meurs said, may not be able to tolerate nitric oxide because it interferes with blood clotting and thus increases the risk of brain bleeding.