CLEVELAND -- A study published in the July 27 New England Journal of Medicine states that delivering nitric oxide to the lungs of premature, very low birth-weight babies during their second week of life improves their chances of surviving without chronic lung disease. The study of nearly 600 babies was conducted by the multicenter nitric oxide Chronic Lung Disease Study Group (NOCLD) as a result of cutting-edge research conducted by Dr. Richard Martin and his team at Rainbow Babies & Children’s Hospital.
"We have been studying the effects of nitric oxide in our labs at Rainbow for many, many years. Our researchers played a major role in applying our lab work to these clinical trials," said Dr. Martin, chief of neonatology at Rainbow. "Nitric oxide is a substance naturally produced in the body and we already know the benefit to full-term infants with pulmonary hypertension, but the value for preterm infants was the focus of the study.
"Our laboratory research with young animals has indicated a key role for nitric oxide (made in the body) in ensuring normal growth and development of lungs and airways. The results of this clinical trial tell us that nitric oxide treatment can help these very tiny babies when administered over several weeks, beginning on or before the second week of life," said Dr. Martin.
Dr. Michele C. Walsh and Dr. Anna Maria Hibbs of Rainbow were also instrumentally involved in designing and enrolling infants in this new trial. Rainbow’s Level III Neonatal Intensive Care Unit (NICU) is an international leader in treating very low birth-weight infants, and
"Survival rates for premature infants have vastly improved in recent years, but many of them still suffer long-term complications," said Dr. Walsh, medical director for Rainbow’s NICU. "Chronic lung disease is a critical long-term complication for premature infants, so these new results are an encouraging step for further investigation. Successful and early treatment of breathing problems in these tiny babies could represent a significant advance in improving their health and quality of life in the future."
The NOCLD clinical trial included 21 NICU’s throughout the country, enrolling infants with birth weights between 500 and 1250 grams, or about one to three pounds. Their median gestational age was 26 weeks (full term babies are born at about 40 weeks gestational age). All the infants received oxygen through ventilators and were at risk for developing chronic lung disease, also known as bronchopulmonary dysplasia, because their lungs were immature and underdeveloped. In this condition, scarring and inflammation in the lung tissue make breathing difficult, and the infant will often require prolonged mechanical ventilation and hospitalization.
The trial was randomized and double-blinded, with 294 infants receiving inhaled nitric oxide and 288 receiving placebo. The rate of survival without chronic lung disease at 36 weeks after the mother’s last menstrual period was 43.9 percent in treated infants, compared to 36.8 percent in the control group.
The effect was more dramatic in the infants entered earlier (between seven and 14 days): 49.1 percent in treated infants vs. 27.8 in the control group. Chronic lung disease was also less severe in treated infants at 40 and 44 weeks, with treated infants having shorter hospitalizations and less need for mechanical ventilation or oxygen therapy than the control group.
The NOCLD team expects to provide definitive recommendations for clinical use of nitric oxide after it analyzes follow-up studies of the children’s neurodevelopmental status at two years of age. The follow-up studies are expected to be complete by the end of 2007.
The National Heart, Lung and Blood Institute of the National Institutes of Health funded this study. INO Therapeutics, of Clinton, N.J., supplied nitric oxide and gas delivery equipment. The Clinical Steering Committee for the study consisted of Dr. Roberta Ballard, William E. Troup, M.D., of the University of Missouri, Kansas City; Richard J. Martin, M.D., Anna Maria Hibbs, M.D., and Michele C. Walsh, M.D., of Rainbow Babies & Children’s Hospital, Cleveland; Philip L. Ballard, M.D., Ph.D., of the Children’s Hospital of Philadelphia; and Jeffrey D. Merrill, M.D., of the Hospital of the University of Pennsylvania.