Inhaled Nitric Oxide for Pulmonary Hypertension and Bronchopulmonary Dysplasia in Extreme Prematurity; Benefits with Targeted Use

Background: Preterm infants are at risk for early pulmonary hypertension (PH) that is associated with high risk of bronchopulmonary dysplasia (BPD) or death. While inhaled nitric oxide (iNO), is an effective treatment for PH in term infants, there is insufficient evidence for BPD prevention; however, the preterm infants were not screened for early PH and iNO was not targeted for PH in these studies. We hypothesized that early detection of PH and targeted iNO therapy will improve respiratory outcomes in extreme prematurity.

Aim/ methods: 164 infants less than 30 weeks gestation who needed ventilation during the 18 month study period were enrolled. On echocardiographic (ECHO) diagnosis by peaditaric cardiologist, 46 infants were detected to have PH at 72 - 96 hours of age. They were randomized to receive iNO at 5ppm (study group, n=23) or placebo (control group, n=23) till 14 days of age or resolution of PH, whichever was earlier. ECHO was done every 48 hours in both groups. The demographic profile, ventilator and surfactant use, PDA closure, nutrition and inotrope use were similar in the 2 groups. The 2 groups were analyzed for oxygenation index (OI) at 7 days, incidence of BPD and death.

Results: The mean OI on day 7 in the study and control groups were 9.7 and 14.1 respectively (p<0.05). Duration of ventilation in the study and control groups were 13.6 days and 19.6 days respectively (p<0.05). 4 infants in the study group, and 8 in the control group had BPD (p<0.05). There was 1 death in each group.

Conclusion: Early detection of PH and targeted iNO therapy improves oxygenation and reduces BPD in extreme prematurity.