Inhaled nitric oxide in term and near-term infants: Neurodevelopmental follow-up of The Neonatal Inhaled Nitric Oxide Study Group (NINOS)

Background: Inhaled nitric oxide (INO) improved oxygenation and reduced the occurrence of death or extracorporeal membrane oxygenation in term and nea r-term hypoxic neonates. We report the results of neurodevelopmental follow -up of infants enrolled in the NINOS trial. Methods: Hypoxic infants greater than or equal to 34 weeks' gestation and < 14 days of age were randomized to 20 ppm INO or 100% oxygen as control. Com prehensive neurodevelopmental assessment of survivors occurred at 18 to 24 months of age. Results: A total of 235 infants were enrolled in the original trial. There were 36 deaths, 20 of 121 infants in the control group and 16 of 114 infant s in the INO-treated group. Of the 199 surviving infants, 173 (86.9%) were seen for follow-up (88 members of the control group and 85 members of the I NO-treated group), and 135 infants were normal (69 [79.3%] members of the c ontrol group and 66 [77.6%] members of the INO-treated group). Twenty-two i nfants had sensorineural hearing loss (12 members of the control group and 10 members of the INO-treated group). Moderate to severe cerebral palsy occ urred in 13 infants (7 infants in the control group and 6 infants in the IN O-treated group). Mental developmental index scores (87 +/- 18.7 in the con trol group vs 85 +/- 21.7 in the INO-treated group) and psychomotor develop mental index scores (93.6 +/- 17.5 in the control group vs 85.7 +/- 21.2 in the INO-treated group) were not different. A total of 29.6% of the control group compared with 34.5% of the INO-treated group had at least one disabi lity. Infants with congenital diaphragmatic hernia, enrolled in a separate but parallel trial, had similar outcomes with a higher incidence of sensori neural hearing loss. Conclusion: Inhaled nitric oxide is not associated with an increase in neur odevelopmental, behavioral, or medical abnormalities at 2 years of age.