The use of inhaled nitric oxide in critically ill preterm infants smaller than 1500 g with acute respiratory failure didn't show significant benefits in reducing their mortality rates or bronchopulmonary dysplasia. This finding contradicts the findings of a smaller study that suggested it may protect the respiratory and central nervous systems during a critical phase of neonatal development. Among the investigators who participated in the National Institute of Child Health and Human Development Neonatal Research Network's multi-center study, "Inhaled nitric oxide for preterm infants with severe respiratory failure," was Emory University's Pediatrics Chair Barbara J. Stoll, MD. The study results will be published in the July 7 issue of the "New England Journal of Medicine."
"Inhaled nitric oxide has been shown to improve outcomes and the need for extra corporeal membrane oxygenation in term infants with hypoxic respiratory failure," says Dr. Stoll, professor, Department of Pediatrics, Emory School of Medicine. "However previous small randomized control trials of inhaled nitric oxide in preterm infants have been inconclusive."
During the blinded and controlled study, 420 premature infants were randomly assigned to receive either placebo (simulated flow) or inhaled nitric oxide. The infants were born at less than 34 weeks gestation, weighing between 401 and 1500 g, and with respiratory failure more than four hours after treatment with surfactant. Surfactant is normally secreted by cells lining the alveoli of the lungs and prevents the alveolar walls from sticking together. The absence of surfactant in the immature lungs of premature babies can cause lungs to collapse.
There was no significant difference between the incidence of bronchopulmonary dysplasia or death between the group given inhaled nitric oxide and the placebo group (80 percent vs. 82 percent). The rate of bronchopulmonary dysplasia alone was 60 percent in the group given inhaled nitric oxide and 68 percent in the placebo group. The rate of death was 52 percent in the group given in nitric oxide and 44 percent in the placebo group.
While there was no significant benefit of inhaled nitric oxide in the entire study group, a post hoc analysis of the study demonstrated a significantly lower rate of death or bronchopulmonary dysplasia in those infants with a birth weight above 1000 g who were treated using inhaled nitric oxide (50 percent) compared to infants in the placebo group (69 percent).
Unfortunately, Dr. Stoll notes, when comparing the inhaled nitric oxide group with the placebo group for infants specifically weighing less than 1000 g, there was also increased mortality (62 percent vs. 48 percent) and severe intracranial hemorrhage (43 percent vs. 33 percent).
The investigators who participated in the study are part of the National Institute of Child Health and Human Development Neonatal Research Network. Emory University's Division of Neonatology-Perinatal Medicine in the Department of Pediatrics has been a member of the multi-center network of academic neonatal centers since 1991.