Inhaled nitric oxide usage in preterm infants in the NICHD neonatal research network: Inter-site variation and propensity evaluation

Objective:The use of inhaled nitric oxide (iNO) in preterm infants remains controversial. In October 2010, a National Institutes of Health consensus development conference cautioned against use of iNO in preterm infants. This study aims (1) to determine the prevalence and variability in use of iNO in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NICHD NRN) before and after the consensus conference and (2) separately, to examine associations between iNO use and severe bronchopulmonary dysplasia (BPD) or death.

Study design:The NICHD NRN Generic Database collects data including iNO use on very preterm infants. A total of 13 centers contributed data across the time period 2008 to 2011. Infants exposed or not to iNO were compared using logistic regression, which included factors related to risk as well as their likelihood of being exposed to iNO.

Result:A total of 4885 infants were assessed between 2008 and 2011; 128 (2.6%) received iNO before day 7, 140 (2.9%) between day 7 and 28, and 47 (1.0%) at >28 days. Center-specific iNO use during 2008 to 2010 ranged from 21.9 to 0.4%; 12 of 13 sites reduced usage and overall NRN iNO usage decreased from 4.6 to 1.6% (P<0.001) in 2011. The use of iNO started between day 7 and day 14 was more prevalent among younger infants with more severe courses in week 1 and associated with increased risk of severe BPD or death (odds ratio 2.24; 95% confidence interval 1.23 to 4.07).

Conclusion:The variability and total use of iNO decreased in 2011 compared with 2008 to 2010. iNO administration started at ≥day 7 was associated with more severe outcomes compared with infants without iNO exposure.