Two-year neurodevelopmental outcomes of ventilated preterm infants treated with inhaled nitric oxide.
OBJECTIVE
In a randomized multi-center trial, we demonstrated that inhaled nitric oxide begun between 7 and 21 days and given for 24 days significantly increased survival without bronchopulmonary dysplasia (BPD) in ventilated premature infants weighing <1250 g. Because some preventative BPD treatments are associated with neurodevelopmental impairment, we designed a follow-up study to assess the safety of nitric oxide.


METHODS
Our hypothesis was that inhaled nitric oxide would not increase neurodevelopmental impairment compared with placebo. We prospectively evaluated neurodevelopmental and growth outcomes at 24 months postmenstrual age in 477 of 535 surviving infants (89%) enrolled in the trial.


RESULTS
In the treated group, 109 of 243 children (45%) had neurodevelopmental impairment (moderate or severe cerebral palsy, bilateral blindness, bilateral hearing loss, or score <70 on the Bayley Scales II), compared with 114 of 234 (49%) in the placebo group (relative risk, 0.92; 95% CI, 0.75-1.12; P = .39). No differences on any subcomponent of neurodevelopmental impairment or growth variables were found between inhaled nitric oxide or placebo.


CONCLUSIONS
Inhaled nitric oxide improved survival free of BPD, with no adverse neurodevelopmental effects at 2 years of age.
Walsh
Michele C
MC
Case Western Reserve University, Cleveland, OH, USA. mcw3@po.cwru.edu
Hibbs
Anna Maria
AM
Martin
Camilia R
CR
Cnaan
Avital
A
Keller
Roberta L
RL
Vittinghoff
Eric
E
Martin
Richard J
RJ
Truog
William E
WE
Ballard
Philip L
PL
Zadell
Arlene
A
Wadlinger
Sandra R
SR
Coburn
Christine E
CE
Ballard
Roberta A
RA
D000280:Administration, Inhalation; D001997:Bronchopulmonary Dysplasia / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D002658:Developmental Disabilities / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage*; D011446:Prospective Studies; D012127:Respiratory Distress Syndrome, Newborn / Q000150:complications / Q000188:drug therapy*; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
D016166:Free Radical Scavengers; D009569:Nitric Oxide