Background Chronic lung disease and severe intraventricularhemorrhage or periventricular leukomalacia in premature infantsare associated with abnormal neurodevelopmental outcomes. Ina previous randomized, controlled, single-center trial of prematureinfants with the respiratory distress syndrome, inhaled nitricoxide decreased the risk of death or chronic lung disease aswell as severe intraventricular hemorrhage and periventricularleukomalacia. We hypothesized that infants treated with inhalednitric oxide would also have improved neurodevelopmental outcomes.
Methods We conducted a prospective, longitudinal follow-up studyof premature infants who had received inhaled nitric oxide orplacebo to investigate neurodevelopmental outcomes at two yearsof corrected age. Neurologic examination, neurodevelopmentalassessment, and anthropometric measurements were made by examinerswho were unaware of the children's original treatment assignment.
Results A total of 138 children (82 percent of survivors) wereevaluated. In the group given inhaled nitric oxide, 17 of 70children (24 percent) had abnormal neurodevelopmental outcomes,defined as either disability (cerebral palsy, bilateral blindness,or bilateral hearing loss) or delay (no disability, but onescore of less than 70 on the Bayley Scales of Infant DevelopmentII), as compared with 31 of 68 children (46 percent) in theplacebo group (relative risk, 0.53; 95 percent confidence interval,0.33 to 0.87; P=0.01). This effect persisted after adjustmentfor birth weight and sex, as well as for the presence or absenceof chronic lung disease and severe intraventricular hemorrhageor periventricular leukomalacia. The improvement in neurodevelopmentaloutcome in the group given inhaled nitric oxide was primarilydue to a 47 percent decrease in the risk of cognitive impairment(defined by a score of less than 70 on the Bayley Mental DevelopmentalIndex) (P=0.03).
Conclusions Premature infants treated with inhaled nitric oxidehave improved neurodevelopmental outcomes at two years of age.
Source Information
From the Departments of Pediatrics (K.K.L.M., J.D.M., K.H., M.D.S.) and Health Studies (D.H.), University of Chicago, Chicago.
Address reprint requests to Dr. Schreiber at the University of Chicago, MC 6060, 5841 S. Maryland Ave., Chicago, IL 60637, or at mschreiber{at}peds.bsd.uchicago.edu.
Inhaled Nitric Oxide
Dani C., Bertini G., Rubaltelli F. F., Hasan S. U., Lasser E. C., Van Meurs K., Stevenson D., Schreiber M. D., Marks J. D., Mestan K. K.L., Martin R. J., Walsh M. C.
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N Engl J Med 2005;
353:1626-1628, Oct 13, 2005.
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