Response to Inhaled Nitric Oxide and Mortality Among Very Preterm Neonates With Pulmonary Hypertension

Area of Science:

• Neonatal Medicine
• Pediatric Cardiology
• Respiratory Physiology

Background:

• Inhaled nitric oxide (iNO) is used for acute pulmonary hypertension in very preterm neonates, based on observed FiO2 improvements.
• The clinical effectiveness and prognostic value of iNO responsiveness in this population remain understudied.

Purpose of the Study:

• To identify factors predicting predischarge mortality in very preterm neonates receiving iNO for acute pulmonary hypertension.
• To specifically evaluate the role of iNO responsiveness as a predictor of mortality.

Main Methods:

• Prospective observational cohort study across 12 Canadian tertiary NICUs (2018-2022).
• Included very preterm neonates (<32 weeks GA) with acute pulmonary hypertension requiring iNO and FiO2 ≥ 0.50.
• Analyzed early (≤72h) and late (>72h) onset pulmonary hypertension cohorts separately; defined iNO response as FiO2 reduction ≥ 0.20.

Main Results:

• Early onset group (n=262) had higher iNO response (71%) and lower mortality (34%) vs. late onset group (n=109; 41% response, 49% mortality).
• In early onset, greater FiO2 reduction with iNO correlated with lower mortality (aOR 0.74 per 0.10 FiO2 decrease).
• In late onset, only illness severity (lower pre-iNO FiO2, higher pH) predicted mortality, not iNO response (aOR 0.47).

Conclusions:

• iNO responsiveness is linked to better outcomes in very preterm neonates with early acute pulmonary hypertension.
• The prognostic significance of iNO response for late-onset pulmonary hypertension in this population is uncertain.
• Further research into the distinct pathophysiology of late-onset pulmonary hypertension is warranted.