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

J Perinat Med. 2020 Sep 7;49(1):104-110. doi: 10.1515/jpm-2020-0164.

Abstract

Objectives: Most 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.

Methods: A 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.

Results: A 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.

Conclusions: iNO 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.

Keywords: bronchopulmonary dysplasia (BPD); inhaled nitric oxide; long-term outcomes.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Inhalation
  • Bronchodilator Agents / pharmacology
  • Bronchodilator Agents / therapeutic use*
  • Bronchopulmonary Dysplasia / mortality
  • Bronchopulmonary Dysplasia / prevention & control*
  • Child
  • Child Development / drug effects*
  • Europe / epidemiology
  • Female
  • Follow-Up Studies
  • Health Status
  • Hospitalization / statistics & numerical data*
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Male
  • Nitric Oxide / pharmacology
  • Nitric Oxide / therapeutic use*

Substances

  • Bronchodilator Agents
  • Nitric Oxide