title: Inhaled nitric oxide in preterm infants.
abstract: OBJECTIVE
  To systematically review the evidence on the use of inhaled nitric oxide (iNO) in preterm infants born at or before 34 weeks gestation age who receive respiratory support.
  
  
  METHODS
  We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Studies (CENTRAL) and PsycInfo in June 2010. We also searched the proceedings of the 2009 and 2010 Pediatric Academic Societies Meeting and ClinicalTrials.gov. We identified additional studies from reference lists of eligible articles and relevant reviews, as well as from technical experts.
  
  
  METHODS
  Questions were developed in collaboration with technical experts, including the chair of the upcoming National Institutes of Health Office of Medical Applications of Research Consensus Development Conference. We limited our review to randomized controlled trials (RCTs) for the question of survival or occurrence of bronchopulmonary dysplasia (BPD) and for the question on short-term risks. All study designs were considered for long-term pulmonary or neurodevelopmental outcomes, and for questions about whether outcomes varied by subpopulation or by intervention characteristics. Two investigators independently screened search results, and abstracted data from eligible articles.
  
  
  RESULTS
  We identified a total of 14 RCTs, reported in 23 articles, and eight observational studies. Mortality rates in the NICU did not differ for infants treated with iNO versus those not treated with iNO (RR 0.97 (95% CI 0.82, 1.15)). BPD at 36 weeks for iNO and control groups also did not differ (RR 0.93 (0.86, 1.003) for survivors). A small difference was found between iNO and control infants in the composite outcome of death or BPD (RR 0.93 (0.87, 0.99)). There was inconsistent evidence about the risk of brain injury from individual RCTs, but meta-analyses showed no difference between iNO and control groups. We found no evidence of differences in other short term risks. There was no evidence to suggest a difference in the incidence of cerebral palsy (RR 1.36 (0.88, 2.10)), neurodevelopmental impairment (RR 0.91 (0.77, 1.12)), or cognitive impairment (RR 0.72 (0.35, 1.45)). Evidence was limited on whether the effect of iNO varies by subpopulation or by characteristics of the therapy (timing, dose and duration, mode of delivery, or concurrent therapies).
  
  
  CONCLUSIONS
  There was a seven percent reduction in the risk of the composite outcome of death or BPD at 36 weeks PMA for infants treated with iNO compared to controls, but no reduction in death or BPD alone. Further studies are needed to explore particular subgroups of infants and to assess long term outcomes including function in childhood. There is currently no evidence to support the use of iNO in preterm infants with respiratory failure outside the context of rigorously conducted randomized clinical trials.
authors.forename: Marilee C
authors.initials: MC
authors.lastname: Allen
authors.forename: Pamela
authors.initials: P
authors.lastname: Donohue
authors.forename: Maureen
authors.initials: M
authors.lastname: Gilmore
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Cristofalo
authors.forename: Renee F
authors.initials: RF
authors.lastname: Wilson
authors.forename: Jonathan Z
authors.initials: JZ
authors.lastname: Weiner
authors.forename: Karen
authors.initials: K
authors.lastname: Robinson
mesh_terms: D001930:Brain Injuries / Q000139:chemically induced / Q000188:drug therapy / Q000453:epidemiology; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D001997:Bronchopulmonary Dysplasia / Q000188:drug therapy / Q000401:mortality; D002547:Cerebral Palsy / Q000139:chemically induced / Q000188:drug therapy / Q000453:epidemiology; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D007234:Infant, Premature; D007363:Intensive Care Units, Neonatal / Q000706:statistics & numerical data; D015201:Meta-Analysis as Topic; D009569:Nitric Oxide / Q000008:administration & dosage / Q000627:therapeutic use*; D011247:Pregnancy; D047928:Premature Birth; D016032:Randomized Controlled Trials as Topic; D012138:Respiratory Therapy; D012306:Risk; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D009569:Nitric Oxide