Two-year outcomes of a randomized controlled trial of inhaled nitric oxide in premature infants.
OBJECTIVE
The European Union Nitric Oxide trial was designed to assess the potential benefits of inhaled nitric oxide (iNO) compared with placebo in infants with respiratory failure. This follow-up study evaluated respiratory, neurodevelopmental, and other outcomes for infants entered into the European Union Nitric Oxide trial to age 2 years.


METHODS
In a multicenter, randomized, double-blind study, preterm infants born at <29 weeks' gestation with moderate respiratory failure were allocated to receive iNO (5 ppm) or placebo for 7 to 21 days. Subjects underwent assessments at 1 and 2 years corrected for prematurity.


RESULTS
At 36 weeks' postmenstrual age, 696 of 792 infants were alive; 4 in the iNO arm subsequently died before age 2 years compared with 7 in the control arm. We evaluated 95% of the survivors at 12 months and 90% at 2 years. In the iNO arm, 244 of 363 (67.2%) infants had survived without disability at age 2 years compared with 270 of 374 (72.2%) who received placebo (P = .094). Mean (SD) cognitive composite scores (Bayley Scales of Infant and Toddler Development, third edition) were 94 (13) in the iNO group and 95 (14) in the placebo group; in the iNO group, 19% scored <85 and 9.5% developed cerebral palsy compared with 13.3% and 9%, respectively. There were no significant differences in hospitalizations overall or due to respiratory illness in use of home oxygen therapy or respiratory medications, in growth, or in other health outcomes.


CONCLUSIONS
At 2 years of age, low-dose (5 ppm) iNO started early (<24 hours after birth) for a median of 20 days did not affect neurodevelopmental or other health outcomes.
Department of Neonatology, CRC, Centre Hospitalier Intercommunal de Créteil, Créteil, France. xavier.durrmeyer@chicreteil.fr
Xavier
X
Durrmeyer
Helmut
H
Hummler
Manuel
M
Sanchez-Luna
Virgilio P
VP
Carnielli
David
D
Field
Anne
A
Greenough
Bart
B
Van Overmeire
Baldvin
B
Jonsson
Mikko
M
Hallman
Jean-Christophe
JC
Mercier
Neil
N
Marlow
Samantha
S
Johnson
James
J
Baldassarre
D000280:Administration, Inhalation; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D002675:Child, Preschool; D005062:European Union; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage*; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate
D001993:Bronchodilator Agents; D009569:Nitric Oxide
developmental outcomes; growth; inhaled nitric oxide; premature infants; randomized controlled trial