Neurodevelopmental Outcomes of Premature Infants with Severe Respiratory Failure Enrolled in a Randomized Controlled Trial of Inhaled Nitric Oxide

Objectives

We hypothesized that inhaled nitric oxide (iNO) would not decrease death or neurodevelopmental impairment (NDI) in infants enrolled in the National Institute of Child Health and Human Development Preemie iNO Trial (PiNO) trial, nor improve neurodevelopmental outcomes in the follow-up group.

Study design

Infants <34 weeks of age, weighing <1500 g, with severe respiratory failure were enrolled in the multicenter, randomized, controlled trial. NDI at 18 to 22 months corrected age was defined as: moderate to severe cerebral palsy (CP; Mental Developmental Index or Psychomotor score Developmental Index <70), blindness, or deafness.

Results

Of 420 patients enrolled, 109 who received iNO (52%) and 98 who received placebo (47%) died. The follow-up rate in survivors was 90%. iNO did not reduce death or NDI (78% versus 73%; relative risk [RR], 1.07; 95% CI, 0.95-1.19), or NDI or Mental Developmental Index <70 in the follow-up group. Moderate-severe CP was slightly higher with iNO (RR, 2.41; 95% CI, 1.01-5.75), as was death or CP in infants weighing <1000 g (RR, 1.22; 95% CI, 1.05-1.43).

Conclusions

In this extremely ill cohort, iNO did not reduce death or NDI or improve neurodevelopmental outcomes. Routine iNO use in premature infants should be limited to research settings until further data are available.

Abbreviations: BPD, Bronchopulmonary dysplasia, BSID, Bayley Scales of Infant Development, CP, Cerebral palsy, ELBW, Extremely low birth weight, iNO, Inhaled nitric oxide, IVH, Intraventricular hemorrhage, MDI, Mental Developmental Index, NDI, Neurodevelopmental impairment, NICHD, National Institute of Child Health and Human Development, OI, Oxygenation index, PiNO, Preemie Inhaled Nitric Oxide trial, PDI, Psychomotor Developmental Index, PVL, Periventricular leukomalacia, RR, Relative risk