While INO has been shown to improve oxygenation in critically ill term and premature infants with severe hypoxemia, the neurodevelopmental outcome of those premature infants treated with INO remains unknown.

We report the prospective neurodevelopmental assessment in early childhood of a group of 24 extremely ill prematures ≤1500 g with oxygenation indices(OI) of 39 (± 19 SD) treated with INO at 20 ppm as a rescue therapy. Despite a significant improvement in oxygenation within 1 hour after initiating INO, mortality was high at 58%. Thirteen neonates died during hospitalization and one infant died at 5.5 months of adjusted age after discharge from the hospital.

At 22 (± 10 SD) months of adjusted age, 10 long-term survivors had Bayley mental and psychomotor developmental indices of 81 (± 21 SD) and 64 (± 22 SD) respectively. Of the 10 children, 5 (50%) were disabled, 2(20%) were developmentally delayed, and 3 (30%) had a normal development. Three of the disabled children had a ventriculoperitoneal shunt for posthemorrhagic hydrocephalus.

In view of the poor outcome of this group of very low birth weight infants with 58% mortality and 70% neurodevelopmental disability/delay in survivors, properly randomized, controlled trials at a lower OI and with lower doses of INO are needed to examine the role of INO for the treatment of critically ill premature neonates with severe hypoxemic respiratory failure.