title: Inhaled nitric oxide in preterm infants: a systematic review.
abstract: BACKGROUND
  Studies of the efficacy of inhaled nitric oxide (iNO) to prevent or treat respiratory failure in preterm infants have had variable and contradictory findings.
  
  
  OBJECTIVE
  To systematically review the evidence on the use of iNO in infants born at ≤ 34 weeks' gestation who receive respiratory support.
  
  
  METHODS
  Medline, Embase, the Cochrane Central Register of Controlled Studies, PsycInfo, ClinicalTrials.gov, and proceedings of the 2009 and 2010 Pediatric Academic Societies meetings were searched in June 2010. Additional studies from reference lists of eligible articles, relevant reviews, and technical experts were considered. Two investigators independently screened search results and abstracted data from eligible articles. We focus here on mortality, bronchopulmonary dysplasia (BPD), the composite outcome of death or BPD, and neurodevelopmental impairment.
  
  
  RESULTS
  Fourteen randomized controlled trials, 7 follow-up studies, and 1 observational study were eligible for inclusion. Mortality rates in the NICU did not differ for infants treated with iNO compared with controls (risk ratio [RR]: 0.97 [95% confidence interval (CI): 0.82-1.15]). BPD at 36 weeks for iNO and control groups also did not differ for survivors (RR: 0.93 [95% CI: 0.86-1.003]). A small difference was found in favor of iNO in the composite outcome of death or BPD (RR: 0.93 [95% CI: 0.87-0.99]). There was no evidence to suggest a difference in the incidence of cerebral palsy (RR: 1.36 [95% CI: 0.88-2.10]), neurodevelopmental impairment (RR: 0.91 [95% CI: 0.77-1.12]), or cognitive impairment (RR: 0.72 [95% CI: 0.35-1.45]).
  
  
  CONCLUSIONS
  There was a 7% reduction in the risk of the composite outcome of death or BPD at 36 weeks for infants treated with iNO compared with controls but no reduction in death alone or BPD. 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.affiliation: Department of Pediatrics, Johns Hopkins School of Medicine, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA. pdonohue@jhmi.edu
authors.forename: Pamela K
authors.initials: PK
authors.lastname: Donohue
authors.forename: Maureen M
authors.initials: MM
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: Brandyn D
authors.initials: BD
authors.lastname: Lau
authors.forename: Karen A
authors.initials: KA
authors.lastname: Robinson
authors.forename: Marilee C
authors.initials: MC
authors.lastname: Allen
mesh_terms: D000280:Administration, Inhalation; D001997:Bronchopulmonary Dysplasia / Q000453:epidemiology* / Q000517:prevention & control*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000453:epidemiology / Q000517:prevention & control; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D012127:Respiratory Distress Syndrome, Newborn / Q000453:epidemiology / Q000517:prevention & control
chemical_list: D009569:Nitric Oxide