Inhaled nitric oxide in premature infants for preventing bronchopulmonary dysplasia: a meta-analysis

Abstract Background The effectiveness of NO in the treatment of BPD is debatable. To conduct a meta-analysis to guide clinical decision making regarding the efficacy and safety of inhaled nitric oxide in the treatment of bronchopulmonary dysplasia (BPD) in premature infants. Methods Data from clinical randomized controlled trials (RCTS) published in PubMed, Embase, Cochrane Library, Wanfang, CNKI, and VIP databases for premature infants were searched from the database's inception to March 2022. Review Manager 5.3 statistical software was used for heterogeneity analysis. Results There were 905 references in total, with 11 RCTS that met the screening criteria being meta-analyzed. The incidence of BPD was recorded in both the iNO and control groups, with the iNO group having a lower incidence (RR = 0.91, 95%CI 0.85–0.97, P = 0.006). At the initial dose of 5ppm, subgroup analysis revealed no significant difference in the incidence of BPD between two groups (P = 0.09). The group treated with 10 ppm iNO had a lower incidence of BPD (RR = 0.90, 95%CI 0.81–0.99, P = 0.03). The iNO group increased the incidence of necrotizing enterocolitis (NEC) (RR = 1.33, 95%CI 1.04–1.71, P = 0.03). At the initial dose of 10 ppm, subgroup analysis revealed no significant difference in the incidence of NEC between the two groups (P = 0.41). NEC was more pervasive in the 5 ppm iNO initial dosage group than in the control group (RR = 1.41, 95%CI 1.03–1.91, P = 0.03). There were no statistically significant differences in the incidences of in-hospital mortality, intracranial hemorrhage (all grades) or leukomalacia, and pulmonary hemorrhage (PH). Conclusions INO can reduce the risk of BPD in preterm infants with a gestational age of ≤ 34 weeks who require respiratory support, but it has no statistically significant impact on BPD mortality and no serious adverse responses, although it may raise the risk of NEC. Simultaneously, when the initial dose of iNO ≥ 10ppm, the effect of lowering the incidence of BPD while lowering the incidence of NEC can be realized. However, scarcity of multi-center large-sample clinical research is still needed.