Nitric oxide does not benefit early preterm infants

Although inhaled nitric oxide (iNO) has proved effective in improving oxygenation in late preterm infants, studies of its efficacy in infants born at or before 34 weeks have produced variable and contradictory findings. Now a systematic review of findings from 22 trials of iNO use in 3,461 early preterm infants concludes that the evidence does not support routine use of iNO to treat these infants. The review, which appears in Pediatrics, examined 14 randomized, controlled trials (RCTs), 7 follow-up studies, and 1 observation study.

First and foremost, the analysis showed that mortality rates in the neonatal intensive care unit did not differ between infants who were treated with iNO and those who were not. The iNO dose or birth weight did not affect this finding. Nor did investigators find any statistically significant differences in rates of bronchopulmonary dysplasia (BPD) at 36 weeks’ postmenstrual age (PMA) between the iNO group and controls in any of the RCTs. The risk of BPD was mixed when iNO was given at a maximum dose of 10 ppm in 4 RCTs; meta-analysis revealed a 25% reduction in risk of BPD for treated infants at 36 weeks compared with controls. Investigators did find a small (7%) but statistically significant reduction in the risk of the composite outcome of death or BPD at 36 weeks’ PMA in favor of iNO therapy.

Neither the RCTs themselves or investigators’ meta-analyses of findings provided any evidence that treatment of preterm infants with iNO has any effect on rates of other complications of prematurity, such as patent ductus arteriosus, sepsis, necrotizing enterocolitis, severe retinopathy of prematurity, pulmonary hemorrhage, or air leaks. The analysis also revealed no evidence to suggest a difference in the incidence of cerebral palsy or neurodevelopmental or cognitive impairment. Investigators also found no evidence for an optimal iNO dose or duration of therapy.

Donohue PK, Gilmore MM, Cristofalo E, et al. Inhaled nitric oxide in preterm infants: a systematic review. Pediatrics. 2011;127(2):e413-e421.