title: Neurodevelopmental outcomes of premature infants with severe respiratory failure enrolled in a randomized controlled trial of inhaled nitric oxide.
abstract: OBJECTIVE
  We hypothesized that inhaled nitric oxide (iNO) would not decrease death or neurodevelopmental impairment (NDI) in infants enrolled in the National Institute of Child Health and Human Development Preemie iNO Trial (PiNO) trial, nor improve neurodevelopmental outcomes in the follow-up group.
  
  
  METHODS
  Infants <34 weeks of age, weighing <1500 g, with severe respiratory failure were enrolled in the multicenter, randomized, controlled trial. NDI at 18 to 22 months corrected age was defined as: moderate to severe cerebral palsy (CP; Mental Developmental Index or Psychomotor score Developmental Index <70), blindness, or deafness.
  
  
  RESULTS
  Of 420 patients enrolled, 109 who received iNO (52%) and 98 who received placebo (47%) died. The follow-up rate in survivors was 90%. iNO did not reduce death or NDI (78% versus 73%; relative risk [RR], 1.07; 95% CI, 0.95-1.19), or NDI or Mental Developmental Index <70 in the follow-up group. Moderate-severe CP was slightly higher with iNO (RR, 2.41; 95% CI, 1.01-5.75), as was death or CP in infants weighing <1000 g (RR, 1.22; 95% CI, 1.05-1.43).
  
  
  CONCLUSIONS
  In this extremely ill cohort, iNO did not reduce death or NDI or improve neurodevelopmental outcomes. Routine iNO use in premature infants should be limited to research settings until further data are available.
authors.affiliation: NICHD Neonatal Research Network. srhintz@stanford.edu
authors.forename: Susan R
authors.initials: SR
authors.lastname: Hintz
authors.forename: Krisa P
authors.initials: KP
authors.lastname: Van Meurs
authors.forename: R
authors.initials: R
authors.lastname: Perritt
authors.forename: W Kenneth
authors.initials: WK
authors.lastname: Poole
authors.forename: Abhik
authors.initials: A
authors.lastname: Das
authors.forename: David K
authors.initials: DK
authors.lastname: Stevenson
authors.forename: Richard A
authors.initials: RA
authors.lastname: Ehrenkranz
authors.forename: James A
authors.initials: JA
authors.lastname: Lemons
authors.forename: Betty R
authors.initials: BR
authors.lastname: Vohr
authors.forename: Roy
authors.initials: R
authors.lastname: Heyne
authors.forename: David O
authors.initials: DO
authors.lastname: Childers
authors.forename: Myriam
authors.initials: M
authors.lastname: Peralta-Carcelen
authors.forename: Anna
authors.initials: A
authors.lastname: Dusick
authors.forename: Yvette R
authors.initials: YR
authors.lastname: Johnson
authors.forename: Brenda
authors.initials: B
authors.lastname: Morris
authors.forename: Robert
authors.initials: R
authors.lastname: Dillard
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Vaucher
authors.forename: Jean
authors.initials: J
authors.lastname: Steichen
authors.forename: Ira
authors.initials: I
authors.lastname: Adams-Chapman
authors.forename: Ganesh
authors.initials: G
authors.lastname: Konduri
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Myers
authors.forename: Marissa
authors.initials: M
authors.lastname: de Ungria
authors.forename: Jon E
authors.initials: JE
authors.lastname: Tyson
authors.forename: Rosemary D
authors.initials: RD
authors.lastname: Higgins
mesh_terms: D000280:Administration, Inhalation; D016009:Chi-Square Distribution; D002657:Child Development / Q000187:drug effects; D002658:Developmental Disabilities / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D009420:Nervous System / Q000187:drug effects / Q000254:growth & development*; D009569:Nitric Oxide / Q000008:administration & dosage*; D016012:Poisson Distribution; D012127:Respiratory Distress Syndrome, Newborn / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D018570:Risk Assessment; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D009569:Nitric Oxide