August 4, 2006

Nitric Oxide Treatment May Help Premature Babies

premature baby

Very small premature babies, those under three pounds, are at high risk for delayed growth and lasting developmental problems. Two new studies show that treating premature babies with nitric oxide gas can help prevent chronic lung disease, and may also protect against brain injury.

In 2004, more than a half million babies in the U.S. (about 12.5%) were born prematurely, before completing 37 weeks of pregnancy. Because their lungs are not fully developed, premature infants have trouble breathing on their own. Oxygen and, in many cases, a mechanical breathing machine, or ventilator, can help premature infants breathe until the lungs have a chance to mature. However, this treatment can damage the lungs and interfere with normal development, leading to a chronic lung disease known as bronchopulmonary dysplasia (BPD). BPD brings a higher risk of ongoing lung problems such as pulmonary hypertension (high blood pressure in the arteries that supply blood to the lungs); neurodevelopmental problems such as cerebral palsy; learning disabilities; hearing and vision problems; heart problems and impaired growth. Very small babies are at high risk for BPD even if they only require ventilator care for short periods

Previous studies have shown that inhaled nitric oxide (iNO) can help full-term newborns with severe respiratory failure. Two research teams set out to study iNO treatment in premature and very low birthweight babies. The studies, which were supported by NIH's National Heart, Lung, and Blood Institute, involved infants born at less than 34 weeks of pregnancy who weighed between about one and three pounds at birth and needed a ventilator to help them breathe. INO Therapeutics of Clinton, NJ, supplied nitric oxide and gas delivery equipment for the two studies. The results were published in the July 27, 2006, issue of the New England Journal of Medicine.

In the first study, a team led by Dr. John P. Kinsella of the Pediatric Heart Lung Center at Children's Hospital in Denver gave nearly 800 babies either iNO or a harmless placebo gas for comparison starting within the first 48 hours of life and continuing through 21 days or until they no longer needed breathing assistance. Treatment did not lower the overall incidence of BPD at 36 weeks, but it did appear to cut the risk of BPD in half among the larger babies who weighed around two and a half pounds at birth. In addition, significantly fewer babies treated with iNO had evidence of brain damage in ultrasound scans prior to hospital discharge.

In the second study, a team led by Dr. Roberta A. Ballard, professor of pediatrics and obstetrics and gynecology at The Children's Hospital of Philadelphia and the University of Pennsylvania, randomly selected nearly 600 very low birthweight premature babies at high risk of developing BPD to begin iNO treatment or a placebo at between seven and 21 days of age. Treatment continued for at least 24 days. More babies treated with iNO survived without BPD by 36 weeks than those who didn't receive treatment (44% versus 37%). The benefits were even more apparent among the infants who began treatment between seven and 14 days after birth — those babies had twice the rate of survival without BPD as those who did not receive treatment. In addition, iNO was associated with less severe lung disease among the treated infants who did develop BPD.

Previous studies using iNO have had mixed results, but the results of these current studies are promising. The researchers are cautiously optimistic that this therapy may prove to be beneficial. However, the children in these studies need to be followed for longer periods to better understand the long-term effects of iNO treatment on their development. Both teams will continue to follow their participants — the first team for another four and a half years, the second for another two.

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