Birth Size and Gestational Age Specific Outcomes of Inhaled Nitric Oxide Therapy in Preterm Neonates with Clinically Diagnosed Pulmonary Hypertension

Abstract

Objective Among neonates of 22 to 29 weeks' gestational age (GA) who required mechanical ventilation for the treatment of respiratory distress syndrome (RDS) and clinically diagnosed pulmonary hypertension (PH), we tested our hypothesis that the association between early treatment with inhaled nitric oxide (iNO) and survival would vary according to birth size and GA. Study Design Because iNO was not randomly prescribed to patients in this cohort, we used propensity score matching to pair a neonate who received iNO at a chronological age of ≤7 days with an unexposed neonate with similar baseline characteristics. The primary outcome was inhospital mortality, which we evaluated based on size for GA and GA strata using the Cox proportional hazards regression model. Results Among 1,531 neonates who met study criteria, we created a propensity score matched cohort of 615 pairs of neonates (iNO-exposed and unexposed). The risk of inhospital mortality for iNO-exposed neonates was observed only in the minority (<10%) who were large for GA, though this finding did not persist when matching for illness severity. Conclusion Early treatment with iNO is not associated with survival in most extremely premature neonates with RDS and clinically diagnosed PH when stratified for birth size or GA.

Controversies in neonatology: The efficacy of inhaled nitric oxide in preterm infants with persistent pulmonary hypertension

“…In our study, the median maximum dose for iNO was observed to be 20 (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) among positive responders, compared to 40 in negative responders. Inhaled nitric oxide has a good safety profile used at 20ppm, while lower doses may be equally as effective as higher doses.…”

“…As literature on PHT primarily centres on preterm infants with moderate or severe BPD, data on EOPAH and HRF is scarce. Despite significant evidence demonstrating that iNO has no effect on reducing the morbidity or mortality of extremely premature neonates, the offlabel prescription of iNO is increasing (30,31). On the other hand, evidence suggests that iNO can be beneficial for a selected subpopulation of extremely premature neonates (32,33).…”

Epidemiologic evaluation of inhaled nitric oxide use among neonates with gestational age less than 35 weeks

“…Pulmonary hypertension exists in the preterm neonate and can be responsive to iNO. However, in preterm neonates, the evidence has not shown significant improvements in mortality, 7–23 chronic lung disease, 8,15,17–19,22–25 retinopathy of prematurity, 19,26 reduction in cerebral palsy, 8,12,15,24 reduction in neurodevelopmental delays, 8–10,12,15,18,24,27 or long term pulmonary function 28 . In 2010, the National Institutes of Health (NIH) 29 published an expert consensus statement regarding the use of iNO in preterm neonates which recommended cautious use.…”