One-year respiratory outcomes of preterm infants enrolled in the NO CLD trial

Many very low birth weight infants (VLBWI) with and without a history of bronchopulmonary dysplasia (BPD) continue to have symptomatic pulmonary disease in the first years after discharge, manifesting as wheezing, a dependence on pulmonary medications, and episodic re-hospitalization for respiratory disease. In the Nitric Oxide (to Prevent) Chronic Lung Disease (NO CLD) trial, inhaled nitric oxide (iNO) treatment increased survival without BPD at 36 weeks corrected gestational age in a group of VLBWI who presented a high risk for pulmonary morbidity. Moreover, iNO reduced the need of supplemental oxygen and assisted ventilation, as well as the number of infants discharged home on supplemental oxygen.
A follow-up analysis of the VLBWI enrolled in the NO CLD trial has been conducted in order to identify whether iNO treatment had a lasting impact on infants' pulmonary health beyond the initial neonatal hospitalization.
The NO CLD trial was a multicenter, randomized, double-blind, placebo-controlled study enrolling preterm infants (<1250 g) between 7 to 21 days of age at high risk for BPD. The follow-up analysis was performed at 12±3 months corrected age; long-term pulmonary morbidity and other outcomes were reported by parents during structured blinded interviews.
In total, 456 infants (85% of the infants enrolled in the NO CLD trial) were analyzed at 1 year. Compared with control infants, infants randomized to iNO received significantly less bronchodilators (odds ratio [OR] 0.53 [95% confidence interval 0.36-0.78]), inhaled steroids (OR 0.50 [0.32-0.77]), systemic steroids (OR 0.56 [0.32-0.97]), diuretics (OR 0.54 [0.34-0.85]), and supplemental oxygen (OR 0.65 [0.44-0.95]) after discharge from the neonatal intensive care unit. However, no significant differences in parental report of re-hospitalizations (OR 0.83 [0.57-1.21]) or wheezing or whistling in the chest (OR 0.70 [0.48-1.03]) were observed.
The odds ratios between VLBWI on iNO or on placebo were similar for all the respiratory medications studied; this is more consistent with a true effect of iNO than with a spurious finding. This effect could be dependent upon several mechanisms: (i) reduction in baseline airway resistance following the inhibition of abnormal elastin deposition or smooth muscle proliferation; (ii) increased alveolarization; (iii) stimulation of angiogenesis or inhibition of vascular smooth muscle proliferation; (iv) improved surfactant function; and (v) alterations in dynamic respiratory responses.
In conclusion, VLBWI treated with iNO were significantly less likely to use bronchodilators, steroids, diuretics, or oxygen after NICU discharge. Although the pulmonary benefit seems promising, any decision to institute routine use of this dosing regimen should also take into account the results of the ongoing 24-month neurodevelopmental assessment.

Top