A clinical trial led by John Kinsella, MD, a neonatologist with the Pediatric Heart Lung Center at The Children's Hospital in Denver and a professor of pediatrics at the University of Colorado at Denver and Health Sciences Center's School of Medicine, concluded that the use of inhaled nitric oxide shortly after birth appears to protect some premature newborns from brain injury. His trial and another, independent study led by a Philadelphia researcher also concluded that the treatment helps prevent chronic lung disease in some premature, low birth weight babies when given within the first two weeks of life. In the end, the treatment may lessen the need for oxygen therapy.
"Low-dose, inhaled nitric oxide reduced the risk of brain injury in premature newborns who required mechanical ventilation after birth, when given in the first 48 hours after birth," Kinsella said. "We are optimistic this therapy could prevent long-term developmental and neurological problems in many of these children. The remarkable effects of protecting against brain injury in these very young and very small babies provide insight into the interrelationship between the lungs and brain development."
Kinsella cautions, however, that children need to be studied for longer periods to understand better the long-term effects of treatment and to confirm the protective effects on brain development. Previous studies indicated the treatment can help full-term newborns with severe respiratory failure, but risks and benefits for lower birth weight babies has been more uncertain until now.
In 2004, more than a half-million premature babies (about 12.5 percent) were born in the United States, the highest number reported since comparable national data have been available, according to the national Centers for Disease Control and Prevention (CDC).
Premature infants, or those born at fewer than 37 weeks of pregnancy, have under-developed lungs and are more likely to succumb to respiratory failure. Oxygen and a ventilator can help them breathe and protect their brains, hearts, livers and other organs as their lungs develop. However, high oxygen levels or the prolonged use of ventilators can damage babies' lungs, impeding normal development and causing a chronic lung disease called bronchopulmonary dysplasia (BPD).
In the United States, more than 10,000 babies a year develop BPD at an estimated $2.4 billion a year in associated health care costs. Premature babies with very low birth weights (under 3 pounds) are at high risk of developing BPD and other breathing problems even if they do not require a ventilator. Ongoing lung problems associated with the condition include pulmonary hypertension, asthma, increased sensitivity to secondhand smoke, and respiratory infections. BPD can also lead to learning disabilities, impaired growth, and cardiovascular problems. In addition, it can affect neurodevelopment, causing conditions such as .
The two most recent studies were conducted independently at 37 medical centers and involved nearly 1,400 premature infants weighing between 1 to 3 pounds and who needed a ventilator to help them breathe. The studies were supported by the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH).
NHLBI Director Elizabeth G. Nabel, MD, said the current findings should help doctors better identify which babies might benefit from inhaled nitric oxide. "Successful and early treatment of breathing problems in these babies would represent a significant advance in improving the health and quality of life of a growing number of premature babies," Nabel said.
During the study led by Kinsella, nearly 800 babies were given either low-dose inhaled nitric oxide or a placebo within the first 48 hours of life, continuing over a period of 21 days or until the infants no longer needed breathing assistance. The treatment did not lower the overall incidence of BPD at 36 weeks of life but cut in half the risk for the condition among babies who weighed about 2 1/2 pounds at birth, or 1,000 to 1,250 grams. In addition, significantly fewer babies treated with inhaled nitric oxide developed brain damage, as indicated by head ultrasound.
Treated infants who weighed about 2 pounds at birth, or between 750 and 1,000 grams, had half the risk of brain damage compared to babies of similar size who did not receive treatment. Follow-up for these infants (continuing until 4 1/2 years of age) will help clarify the long term effects of this promising therapy on development.
The other study was led by Roberta A. Ballard, MD, a neonatologist at The Children's Hospital of Philadelphia and the University of Pennsylvania, and involved 582 premature, low birth weight babies at very high risk of developing BPD.
The infants in the Philadelphia-led study were randomly selected to receive inhaled nitric oxide treatment or a placebo seven to 21 days after birth. Overall, more of the treated babies survived without BPD at 36 weeks than the untreated babies (44 percent versus 37 percent). Even more encouraging, infants treated between seven and 14 days after birth had twice the rate of survival without BPD compared to untreated babies.