A Meta-analysis Of The Prevention And Treatment Of Bronchopulmonary Dysplasia In Preterm Infants With Inhaled Nitric Oxide

Objective:The Meta-analysis was used to comprehensively evaluate the clinical effect of inhaled nitric oxide(i NO)in the prevention and treatment of bronchopulmonary dysplasia(BPD)in preterm infants,and to provide guidance for clinical application.Methods:By searching the Chinese Biomedical Literature Database(CBM),Chinese Journal Full-text Dataset(CNKI),Wanfang Database,Weipu Database,Pub Med,EMbase,The Cochrane Library,and using the Chinese search term "nitric oxide;premature infants;randomized controlled "Random or RCT",English search term"Nitric Oxide;Premature Infant;randomized controlled trial or randomized or placebo",searched to include all randomized controlled trials on nitric oxide inhalation in preterm infants to prevent bronchopulmonary dysplasia(randomized controlled trial),RCT)and semi-randomized controlled trials.Perform literature screening according to the inclusion and exclusion criteria,and collect the required data for inclusion studies that meet the criteria.The composite outcomes of mortality,BPD incidence,mortality,and BPD incidence in the i NO treatment group and control group of preterm infants were selected as the main outcome indicators,and were divided into gestational ages ≤ 34 weeks according to the different gestational age ranges in the literature inclusion criteria.Grouping and comparison of main outcome indicators with gestational age ≤ 32 weeks,re-integrating the research data of different weight stratifications and uniformly dividing them into birth weights<1000g and birth weights ≥ 1000 g.Grades 3 to 4 intraventricular hemorrhage,pulmonary hemorrhage,neonatal necrotizing enterocolitis,arterial duct occlusion,retinopathy of prematurity,neurodevelopmental disability,and oxygenation time,mechanical ventilation time,and hospitalization time were selected as the secondary outcomes.index.The quality evaluation method provided by the Cochrane Collaboration was used to evaluate the quality of the literature.Analysis was performed using Revman5.3 software.Results: A total of 19 RCTs including 4117 children met the criteria,15 were in English and 4 were in Chinese.Nine of these RCTs were assessed as having a low risk of bias,four were of moderate risk,and the remaining six were of high risk of bias.Meta analysis results show:(1)Main outcome indicators: There was no significant difference in mortality between the i NO treatment group and the control group in preterm infants(P> 0.05),and the incidence of BPD in the i NO treatment group was reduced [RR = 0.91,95% CI(0.85,0.97),P <0.05],the combined results of mortality and BPD incidence were reduced [RR = 0.93,95% CI(0.89,0.98),P<0.05].Subgroup analysis: When the gestational age was ≤34 weeks,there was no significant difference in mortality and BPD incidence between the i NO treatment group and the control group(P> 0.05),and the combined results of mortality and BPD incidence in the i NO treatment group were reduced [RR = 0.93,95% CI(0.88,0.99),P <0.0.05];when the gestational age was ≤ 32 weeks,there was no significant difference in the overall results of mortality,mortality,and BPD incidence in the i NO treatment group compared with the control group(P> 0.05),the incidence of BPD in the i NO treatment group decreased [RR = 0.89,95% CI(0.81,0.98),P<0.05].When the birth weight was less than 1000 g,compared with the control group,the combined results of mortality,BPD incidence,mortality,and BPD incidence were not significantly different(P> 0.05);when the birth weight was greater than 1000 g,the i NO treatment group Compared with the control group,there was no significant difference in mortality(P> 0.05).The incidence of BPD in the i NO treatment group was reduced [RR = 0.67,95% CI(0.51,0.89),P <0.05],mortality and BPD incidence The overall result of the reduction was [RR = 0.80,95% CI(0.66,0.98),P <0.05].(2)Secondary outcome indicators: Compared with the control group,there was no statistical difference in the incidence of grade 3 to 4 intraventricular hemorrhage and pulmonary hemorrhage in the i NO treatment group.Common complications of premature infants were arterial duct closure,retinopathy of prematurity,and neonate There was no statistical difference in the incidence of necrotizing enterocolitis,and there was no statistical difference in the incidence of long-term neurodevelopmental disability in survivors from 12 to 30 months.There was no statistical difference in oxygen use time,mechanical ventilation time,and length of hospital stay(P> 0.05).Conclusion:According to the meta analysis of 19 RCT literatures,the treatment of inhaled nitric oxide in preterm infants has certain benefits,which can reduce the incidence of BPD,mortality and the comprehensive results of the incidence of BPD.Especially,the preterm infants with gestational age > 32 weeks and birth weight >1000 g are more likely to reduce the comprehensive results of the incidence of BPD and mortality.Inhaled nitric oxide did not increase the risk of severe intracranial hemorrhage,pulmonary hemorrhage and the common premature complications such as ROP,PDA,NEC.There was no effect on the time of oxygen use,mechanical ventilation and hospitalization.Combined with the advantages and disadvantages,we can recommend the treatment and prevention of BPD with inhaled nitric oxide.