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Inhaled nitric oxide fails to improve survival in high-risk preterm infants

Use of inhaled nitric oxide in high-risk preterm infants between 5 and 24 days of birth was safe but did not improve survival without broncopulmonary dysplasia under certain circumstances, according to findings recently published in JAMA Pediatrics.

“With modern neonatal care, approximately 40% of survivors with gestational age younger than 30 weeks develop bronchopulmonary dysplasia,” Shabih U. Hasan, MD, DCH, FRCPC, of the department of pediatrics at the Cumming School of Medicine, University of Calgary, Alberta, Canada, and colleagues wrote. “Prevention and treatment of evolving [broncopulmonary dysplasia] is an important clinical concern because it is associated with long-term pulmonary disease and neurodevelopmental impairment.”

Researchers hypothesized that administering inhaled nitric oxide to infants younger than 30 weeks’ gestation with birth weight less than 1,250 g who received mechanical ventilation or positive pressure respiratory support on postnatal days 5 to 14 would decrease the incidence of broncopulmonary dysplasia at 36 weeks’ postmenstrual age.

The study included 451 neonates treated with either inhaled nitric oxide (n = 229) or a nitrogen placebo (n = 222). Gestation age and mean birth weights were similar between both groups.

Dosages started at 20 parts per million, were lowered to 10 parts per million between 72 and 96 hours after starting treatment and then lowered again to 5 parts per million on day 10 or 11. Infants remained on the latter dose until the completion of therapy at 24 days.

According to results, survival without broncopulmonary dysplasia at 36 weeks’ postmenstrual age was comparable between groups (placebo, 31.5% vs. nitric oxide, 34.9%).

Hasan and colleagues also found that between the two groups, rates for severe broncopulmonary dysplasia (26.6% vs. 20.5%), postnatal corticosteroid use for broncopulmonary dysplasia (41% vs. 41.5%), and mean days of positive pressure respiratory support (55 vs. 54), oxygen therapy (88 vs. 91) and hospitalization (105 vs. 108) were similar.

Respiratory outcomes were also similar between groups at the following time points: discharge to home, 1 year, age 18 to 24 months’ postmenstrual age, and at neurodevelopmental assessments at 18 and 24 months’ postmenstrual age. No differences in the occurrence of common morbidities were reported.

“Within our study, we identified clinically relevant imbalances between treatment groups for maternal race and presence of prolonged rupture of membranes,” Hasan and colleagues wrote. “Ruptured membrane data were not reported in the NO CLD trial. However, the overall percentage of such cases in our study (7.3%) is unlikely to have a major effect on the primary outcome.”

“The discrepancy in maternal race is important to consider,” the researchers added. “We report a small (10%) but nonsignificant increase in survival without [broncopulmonary dysplasia] among infants of black race treated with inhaled nitric oxide.” – by Janel Miller

Disclosures: Hasan reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.