Nitric Oxide Is Found to Benefit Premature Infants
Inhaled nitric oxide can significantly reduce lung and brain damage in many premature infants, allowing them to be taken off respirators sooner and sent home earlier, two studies report today in the New England Journal of Medicine.
The treatment may not help the most premature and sickest babies, but it can provide long-lasting benefits for many others, according to the clinical trials involving more than 1,400 premature infants.
Physicians are not yet ready, however, to recommend widespread use of the technique until the infants have been studied at least until the age of 2.
“This is a very promising therapy, and we suspect that the benefits will continue as the babies get older,” said Dr. John P. Kinsella of the University of Colorado School of Medicine in Denver, who led one study. “We have limited tools to improve lung outcomes in these infants and even fewer to reduce brain injury. That’s the source of the excitement about these findings.”
But neonatologists have strong memories of earlier studies in which steroids were successfully used to boost lung function in premature infants, only to have the children later develop severe mental impairments.
Smaller nitric oxide studies that followed children for several years show no obvious adverse effects, but “we tend to be very, very cautious,” said Mary Anne Berberich of the National Heart, Lung and Blood Institute, which sponsored the trials.
An estimated half a million U.S. children each year are born prematurely -- before the 37th week of gestation. That is the largest number since statistics have been collected, according to a federal report issued this month.
At least 10,000 of those babies develop a chronic lung disease called bronchopulmonary dysplasia, caused by the use of ventilators to help them breathe, excessive oxygenation of the lungs and other factors not yet understood. Medical care for these children costs more than $2.4 billion a year, and many of them develop mental impairment and long-term breathing difficulties.
Nitric oxide is naturally present in a newborn’s lungs to help the lung transition from breathing in amniotic fluid to breathing in air, but premature infants have unusually low levels of it, Berberich said.
Some small, early studies of the gas suggested it had little or no value. But researchers now recognize that some of the studies were conducted on extremely sick infants who were probably going to die despite the best efforts of physicians, said Dr. Roberta A. Ballard of the Children’s Hospital of Philadelphia, who led the second study.
Ballard’s team studied premature infants who had survived for at least a week. Nitric oxide was given to 294 infants beginning between seven and 21 days after birth for at least 24 days. Another 288 received a placebo.
Overall, the team observed a modest increase in the infants’ survival without developing lung disease. About 43.9% of those receiving the gas had no lung disease at the 36th week after conception, compared with 36.8% of those receiving a placebo.
The effect was much more pronounced among those who received the gas in the second week of life. About 49.1% of those receiving nitric oxide beginning between seven and 14 days did not develop chronic lung disease, compared with 27.8% of those receiving placebo.
Even among those who did develop lung disease, the symptoms were milder in those who received the gas, Ballard said.
In contrast, Kinsella’s team began administering the gas or a placebo to 793 premature newborns within 48 hours of birth and continued it until the infants were removed from a respirator.
Overall, the treatment did not reduce the incidence of lung disease. But in a subgroup of infants weighing about 2 1/2 pounds, the incidence was reduced by half. In addition, among those weighing at least 2 pounds, the gas reduced the incidence of brain damage by half.
