Nitric Oxide Therapy Helps Some Premature Infants

Reduces breathing problems and brain injury, though not for all babies, studies find

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By Serena Gordon
HealthDay Reporter

WEDNESDAY, July 26, 2006 (HealthDay News) -- One of the biggest problems in treating premature infants is that their tiny lungs simply aren't developed enough to nourish their bodies and brains with the oxygen they need.

Because of this, many premature infants end up on mechanical ventilation to assist their breathing. And two new studies suggest that adding nitric oxide to that ventilator therapy may reduce the risk of serious breathing problems and prevent brain injury in at least some premature infants.

"This is a very simple intervention -- blending a gas with the breathing machine -- that can have long-term benefits," said one of the studies' authors, Dr. Steven Abman. He is a professor of pulmonary medicine at the University of Colorado School of Medicine's Pediatric Heart Lung Center, and The Children's Hospital, in Denver.

Those benefits include reducing the risk of a common complication called bronchopulmonary dysplasia (BPD). This lung disease occurs when babies are on mechanical ventilators for long periods or are given high levels of extra oxygen. About 10,000 babies in the United States develop BPD each year. BPD increases the risk of long-term lung problems, high blood pressure in the lungs and neurodevelopmental disorders, such as cerebral palsy and learning problems, according to the National Institutes of Health.

Unfortunately, nitric oxide therapy doesn't appear to benefit all premature babies. That's why Dr. Ann Stark, chief of neonatology at Texas Children's Hospital, said more studies needed to be done before widespread use of nitric oxide in preemies begins. She said there are just too many unanswered questions regarding this therapy right now.

"We don't know which patients to use this in; we don't know when to start therapy; we don't know how long to continue therapy; we don't know what the most effective dose is. And, this drug is really expensive. That cost is justified if you know there's a benefit, but we need to prove the benefit to justify that cost," Stark said.

The two new studies -- both of which are published in the July 27 issue of the New England Journal of Medicine, along with an editorial from Stark -- attempted to answer some of the questions regarding nitric oxide therapy in premature infants.

In the first study, Abman, his colleague Dr. John Kinsella and other doctors from across the country conducted a randomized trial that included nearly 800 premature infants. Within the first two days of life, these babies were given either nitric oxide at a dose of five parts per million (ppm) or a placebo gas. The therapy continued for three weeks or until the babies didn't need assistance breathing, whichever came first.

Only babies who weighed between 1,000 grams and 1,250 grams at birth (about 2.5 pounds) had a reduction in BPD from the nitric oxide therapy -- 30 percent of the treated babies had BPD compared to 60 percent of the placebo group. Using ultrasound to scan the babies' brains, the researchers found a reduction in the risk of brain injury for all of the babies, regardless of their weight.

"There was an overall reduction in brain injury," said Kinsella, a professor in the section of neonatology at the medical school's Pediatric Heart Lung Center. But, he added, the researchers still needed to learn if "these early markers [indicating no brain injury] translate into a lack of long-term cognitive effects."

That's a concern shared by Stark, who explained that babies' brains can look fine on ultrasound but still have damage.

"Ultrasound is a very imprecise test of what the brain is doing. You can have a normal ultrasound and still have neurodevelopmental outcomes," she said.

Kinsella said the researchers will be following up with the babies in this study until at least four-and-a-half years of age to see if the benefits are long-lasting.

The second study included nearly 600 premature infants from all over the United States. All weighed less than 1,250 grams at birth. Nitric oxide or placebo treatment began between seven and 21 days after birth. The babies received at least 24 days of treatment, beginning at 20 ppm nitric oxide for the first two to four days, then decreasing to 10, five and two ppm weekly.

The researchers found that the rate of BPD was reduced in the treatment group: 56 percent of the treated group had BPD compared to 63 percent of the placebo group. The treated babies also needed less supplemental oxygen therapy and were discharged sooner from the hospital.

"In addition to improving the rate of survival without BPD in these premature infants, we found that inhaled nitric oxide was associated with less severe lung disease among the treated infants who did develop BPD," study author Dr. Roberta A. Ballard, a professor of pediatrics and obstetrics and gynecology and formerly chief of the neonatology division at The Children's Hospital of Philadelphia and the University of Pennsylvania, said in a prepared statement.

While the results from these studies were encouraging, Stark still advocated a cautious approach regarding nitric oxide therapy, and suggested that its use still be limited to clinical trials.

"There's still a lot we don't know," she said, adding that in the past, there have been therapies that looked promising in premature infants that didn't prevent long-term complications.

More information

To learn what you can do to help prevent premature birth, visit the March of Dimes.

SOURCES: Steven Abman, M.D., professor, section of pulmonary medicine, and John Kinsella, M.D., professor, section of neonatology, Pediatric Heart Lung Center, University of Colorado School of Medicine and The Children's Hospital, Denver; Ann Stark, M.D., professor of pediatrics, Baylor College of Medicine, and chief of neonatology, Texas Children's Hospital, Houston; July 27, 2006, New England Journal of Medicine

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