Inhaled nitric oxide (iNO) for preventing prematurity-related bronchopulmonary dysplasia (BPD): 7-year follow-up of the European Union Nitric Oxide (EUNO) trial

Abstract

ObjectivesMost studies of inhaled nitric oxide (iNO) for prevention of bronchopulmonary dysplasia (BPD) in premature infants have focused on short-term mortality and morbidity. Our aim was to determine the long-term effects of iNO.MethodsA 7-year follow-up was undertaken of infants entered into a multicenter, double-blind, randomized, placebo-controlled trial of iNO for prevention of BPD in premature infants born between 24 and 28 weeks plus six days of gestation. At 7 years, survival and hospital admissions since the 2-year follow-up, home oxygen therapy in the past year, therapies used in the previous month and growth assessments were determined. Questionnaires were used to compare general health, well-being, and quality of life.ResultsA total of 305 children were assessed. No deaths were reported. Rates of hospitalization for respiratory problems (6.6 vs. 10.5%, iNO and placebo group, respectively) and use of respiratory medications (6.6 vs. 9.2%) were similar. Two patients who received iNO and one who received placebo had received home oxygen therapy. There were no significant differences in any questionnaire-documented health outcomes.ConclusionsiNO for prevention of BPD in very premature infants with respiratory distress did not result in long-term benefits or adverse long-term sequelae. In the light of current evidence, routine use of iNO cannot be recommended for prevention of BPD in preterm infants.

Pharmacotherapy in Bronchopulmonary Dysplasia: What Is the Evidence?

“…Interestingly, follow-up at age one year of 456 infants enrolled in the NOCLD study showed a significantly lower use of bronchodilators, ICS, systemic PNS, diuretics, and supplemental oxygen post-NICU discharge in infants who received iNO ( 199 ). Follow-up at seven years of infants enrolled in the EUNO trial did not demonstrate a significant difference in the hospitalization rates or the use of respiratory medications between the two groups ( 200 ).…”

Bronchopulmonary dysplasia

“…In patients with pulmonary hypertension phosphodiesterase inhibitors, endothelin receptor antagonists and prostacyclin analogs are medications with the goal to decrease pulmonary vascular resistance and improve the degree of pulmonary hypertension. However, routine and preventive use of inhaled nitric oxide (iNO) is not recommended, and it does not improve outcomes of preterm infants with BPD 25,26 …”

“…However, routine and preventive use of inhaled nitric oxide (iNO) is not recommended, and it does not improve outcomes of preterm infants with BPD. 25,26 The presence of a patent ductus arteriosus (PDA) requires additional attention. After birth, the PDA normally closes.…”

Metabolic dysregulation in bronchopulmonary dysplasia: Implications for identification of biomarkers and therapeutic approaches

“…Increased citrulline could be a compensatory response to generate more nitrite oxide to prevent BPD-associated pulmonary hypertension, although this is highly speculative. In fact, inhaled nitric oxide was shown to prevent experimental BPD, but was not effective in preventing BPD in premature infants [ [87] , [88] , [89] , [90] , [91] ]. The effects of nitric oxide are often mediated via S-nitrosothiol formation.…”