Association between immediate oxygenation response and survival in preterm infants receiving rescue inhaled nitric oxide therapy for hypoxemia from pulmonary hypertension: A systematic review and meta-analysis

Purpose: To investigate whether immediate response to inhaled nitric oxide (iNO) therapy is associated with reduced mortality in preterm infants with hypoxemic respiratory failure (HRF) and pulmonary hypertension (PH). Methods: A systematic review and meta-analysis of observational studies was conducted to examine the association between immediate response (improved oxygenation ≤6 h) compared to non-response, and all-cause mortality among preterm infants <34 weeks gestational age without congenital anomalies or genetic disorders who received iNO treatment. Adjusted and unadjusted odds ratio, were pooled using a random effects meta-analysis Hartung-Knapp-Sidik-Jonkman approach. Subgroup analyses were planned for infants with preterm premature rupture of membranes (PPROM) and those treated within 72 h after birth. Results: The primary analysis included 5 eligible studies, a total of 400 infants (196 responders; 204 non-responders). The studies were rated as low to moderate risk of bias based on the Quality in Prognostic Studies tool. Immediate iNO responsiveness was associated with reduced odds of mortality [odds ratio (OR) 0.22, 95 % confidence interval (95 % CI) (0.10–0.49)]. Although there was insufficient data for a subgroup analysis of infants with PPROM, infants treated with iNO within 72 h demonstrated consistent findings of reduced mortality [OR 0.21 95 % CI (0.13–0.36)]. Based on the GRADE approach, considering the risk of bias of included studies, the overall strength of evidence was rated as moderate. Conclusion: There is evidence to suggest that immediate improvement in oxygenation following iNO therapy is associated with reduced odds of mortality before discharge in preterm infants with HRF and clinically suspected or confirmed PH.