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Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale
Published on: August 25, 2014
Neurodevelopmental outcomes of premature infants treated with inhaled nitric oxide
Karen K L Mestan1, Jeremy D Marks, Kurt Hecox
1Department of Pediatrics, University of Chicago, Chicago, IL 60637, USA.
Insights
Inhaled nitric oxide treatment in premature infants significantly improved neurodevelopmental outcomes at two years, reducing the risk of abnormal development and cognitive impairment.
Area of Science:
- Neonatal Medicine
- Developmental Pediatrics
- Respiratory Medicine
Background:
- Premature infants with chronic lung disease, intraventricular hemorrhage, or periventricular leukomalacia face abnormal neurodevelopmental outcomes.
- Previous research indicated inhaled nitric oxide (iNO) reduced mortality and severe lung/brain injury in premature infants.
- This study hypothesized iNO would also enhance neurodevelopmental outcomes.
Purpose of the Study:
- To investigate the effect of inhaled nitric oxide on neurodevelopmental outcomes in premature infants.
- To assess long-term neurodevelopmental status at two years of corrected age.
Main Methods:
- A prospective, longitudinal follow-up study was conducted on premature infants who received either inhaled nitric oxide or placebo.
- Neurodevelopmental assessments, neurologic examinations, and anthropometric measurements were performed by blinded examiners.
- Outcomes were evaluated at two years of corrected age.
Main Results:
- 138 children were evaluated; 24% in the iNO group had abnormal neurodevelopmental outcomes versus 46% in the placebo group (RR 0.53, P=0.01).
- The benefit persisted after adjusting for covariates like birth weight, sex, and presence of lung or brain injury.
- A primary driver was a 47% reduction in cognitive impairment risk (Bayley Mental Developmental Index < 70) in the iNO group (P=0.03).
Conclusions:
- Inhaled nitric oxide treatment in premature infants is associated with improved neurodevelopmental outcomes at two years of age.
- iNO therapy may be a beneficial intervention for mitigating long-term neurodevelopmental deficits in this vulnerable population.
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.
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