Inhaled Nitric Oxide in Extremely Premature Neonates With Respiratory Distress Syndrome

Inhaled nitric oxide (iNO) is increasingly prescribed to extremely premature neonates with respiratory distress syndrome (RDS). Most of this off-label use occurs during the first week of life. We studied this practice, hypothesizing that it would not be associated with improved survival.

We queried the Pediatrix Medical Group Clinical Data Warehouse to identify all neonates born at 22 to 29 weeks' gestation from 2004 to 2014. In our study sample, we included singletons who required mechanical ventilation for treatment of RDS and excluded those with anomalies. The primary outcome was death before discharge. Through a sequential risk set approach, each patient who received iNO during the first 7 days of life ("case patient") was matched by using propensity scores to a patient who had not received iNO at a chronological age before the case patient's iNO initiation age (defined as the index age for the matched pair). The association between iNO status and in-hospital mortality was evaluated in a Cox proportional hazards regression model by using age as the time scale with patients entering the risk set at their respective index age.

Among 37 909 neonates in our study sample, we identified 993 (2.6%) who received iNO. The 2 matched cohorts each contained 971 patients. We did not observe a significant association between iNO exposure and mortality (hazard ratio, 1.08; 95% confidence interval, 0.94-1.25; P = .29).

Off-label prescription of iNO is not associated with reduced in-hospital mortality among extremely premature neonates with RDS.