Neurodevelopmental outcomes of premature infants treated with inhaled nitric oxide.
BACKGROUND
Chronic lung disease and severe intraventricular hemorrhage or periventricular leukomalacia in premature infants are associated with abnormal neurodevelopmental outcomes. In a previous randomized, controlled, single-center trial of premature infants with the respiratory distress syndrome, inhaled nitric oxide decreased the risk of death or chronic lung disease as well as severe intraventricular hemorrhage and periventricular leukomalacia. We hypothesized that infants treated with inhaled nitric oxide would also have improved neurodevelopmental outcomes.


METHODS
We conducted a prospective, longitudinal follow-up study of premature infants who had received inhaled nitric oxide or placebo to investigate neurodevelopmental outcomes at two years of corrected age. Neurologic examination, neurodevelopmental assessment, and anthropometric measurements were made by examiners who were unaware of the children's original treatment assignment.


RESULTS
A total of 138 children (82 percent of survivors) were evaluated. In the group given inhaled nitric oxide, 17 of 70 children (24 percent) had abnormal neurodevelopmental outcomes, defined as either disability (cerebral palsy, bilateral blindness, or bilateral hearing loss) or delay (no disability, but one score of less than 70 on the Bayley Scales of Infant Development II), as compared with 31 of 68 children (46 percent) in the placebo group (relative risk, 0.53; 95 percent confidence interval, 0.33 to 0.87; P=0.01). This effect persisted after adjustment for birth weight and sex, as well as for the presence or absence of chronic lung disease and severe intraventricular hemorrhage or periventricular leukomalacia. The improvement in neurodevelopmental outcome in the group given inhaled nitric oxide was primarily due to a 47 percent decrease in the risk of cognitive impairment (defined by a score of less than 70 on the Bayley Mental Developmental Index) (P=0.03).


CONCLUSIONS
Premature infants treated with inhaled nitric oxide have improved neurodevelopmental outcomes at two years of age.
Department of Pediatrics, University of Chicago, Chicago, IL 60637, USA.
Karen K L
KK
Mestan
Jeremy D
JD
Marks
Kurt
K
Hecox
Dezheng
D
Huo
Michael D
MD
Schreiber
D000280:Administration, Inhalation; D001766:Blindness / Q000453:epidemiology / Q000517:prevention & control; D001997:Bronchopulmonary Dysplasia / Q000453:epidemiology / Q000517:prevention & control*; D002543:Cerebral Hemorrhage / Q000517:prevention & control; D002547:Cerebral Palsy / Q000453:epidemiology / Q000517:prevention & control; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000453:epidemiology* / Q000517:prevention & control*; D004522:Educational Status; D005260:Female; D005500:Follow-Up Studies; D006312:Hearing Loss, Bilateral / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D007234:Infant, Premature; D008607:Intellectual Disability / Q000453:epidemiology / Q000517:prevention & control; D007969:Leukomalacia, Periventricular / Q000517:prevention & control; D016014:Linear Models; D008297:Male; D009483:Neuropsychological Tests; D009569:Nitric Oxide / Q000627:therapeutic use*; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy* / Q000401:mortality; D012307:Risk Factors; D016896:Treatment Outcome
D009569:Nitric Oxide