Neurodevelopmental outcomes of premature infants with severe respiratory failure enrolled in a randomized controlled trial of inhaled nitric oxide.
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.
Hintz
Susan R
SR
NICHD Neonatal Research Network. srhintz@stanford.edu
Van Meurs
Krisa P
KP
Perritt
R
R
Poole
W Kenneth
WK
Das
Abhik
A
Stevenson
David K
DK
Ehrenkranz
Richard A
RA
Lemons
James A
JA
Vohr
Betty R
BR
Heyne
Roy
R
Childers
David O
DO
Peralta-Carcelen
Myriam
M
Dusick
Anna
A
Johnson
Yvette R
YR
Morris
Brenda
B
Dillard
Robert
R
Vaucher
Yvonne
Y
Steichen
Jean
J
Adams-Chapman
Ira
I
Konduri
Ganesh
G
Myers
Gary J
GJ
de Ungria
Marissa
M
Tyson
Jon E
JE
Higgins
Rosemary D
RD
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
D009569:Nitric Oxide