Importance  Bronchopulmonary dysplasia (BPD) occurs in approximately 40% of infants born at younger than 30 weeks’ gestation and is associated with adverse pulmonary and neurodevelopmental outcomes.

Objective  To test whether administration of inhaled nitric oxide to preterm infants requiring positive pressure respiratory support on postnatal days 5 to 14 improves the rate of survival without BPD.

Design, Setting, and Participants  This intent-to-treat study was a randomized clinical trial performed at 33 US and Canadian neonatal intensive care units. Participants included 451 neonates younger than 30 weeks’ gestation with birth weight less than 1250 g receiving mechanical ventilation or positive pressure respiratory support on postnatal days 5 to 14. Enrollment spanned from December 23, 2009, to April 23, 2012, and neurodevelopmental outcome studies were completed by April 4, 2014.

Interventions  Placebo (nitrogen) or inhaled nitric oxide initiated at 20 ppm was decreased to 10 ppm between 72 and 96 hours after starting treatment and then to 5 ppm on day 10 or 11. Infants remained on the 5-ppm dose until completion of therapy (24 days).

Main Outcomes and Measures  The primary outcome was the rate of survival without BPD at 36 weeks’ postmenstrual age (PMA). Secondary outcomes included BPD severity, postnatal corticosteroid use, respiratory support, survival, and neurodevelopmental outcomes at 18 to 24 months’ PMA.

Results  In total, 222 infants (52.3% male [n = 116]) received placebo, and 229 infants (50.2% male [n = 115]) received inhaled nitric oxide. Their mean (SD) gestation was 25.6 (1.5) vs 25.6 (1.4) weeks, and their mean (SD) birth weight was 750 (164) vs 724 (160) g. Survival without BPD at 36 weeks’ PMA was similar between the placebo and inhaled nitric oxide groups (31.5% [n = 70] vs 34.9% [n = 80]) (odds ratio, 1.17; 95% CI, 0.79-1.73). Rates for severe BPD (26.6% [55 of 207] vs 20.5% [43 of 210]) and postnatal corticosteroid use for BPD (41.0% [91 of 222] vs 41.5% [95 of 229]) and the mean (SD) days of positive pressure respiratory support (55 [40] vs 54 [42]), oxygen therapy (88 [41] vs 91 [59]), and hospitalization (105 [37] vs 108 [54]) were equivalent between the 2 groups. No differences in the incidence of common morbidities were observed. Respiratory outcomes on discharge to home, at 1 year, and at age 18 to 24 months’ PMA and neurodevelopmental assessments at 18 to 24 months’ PMA did not differ between groups.

Conclusions and Relevance  Inhaled nitric oxide, initiated at 20 ppm on postnatal days 5 to 14 to high-risk preterm infants and continued for 24 days, appears to be safe but did not improve survival without BPD at 36 weeks’ PMA or respiratory and neurodevelopmental outcomes at 18 to 24 months’ PMA.

Trial Registration  clinicaltrials.gov Identifier: NCT00931632

重要性  支气管肺发育不良（BPD）发生在妊娠30周以下的婴儿中，约40％发生，并与不良的肺和神经发育结果相关。

目的  探讨出生后5至14天需要正压呼吸支持的早产儿吸入一氧化氮是否可以改善无BPD的存活率。

设计，环境和参与者  本意向治疗研究是一项在33个美国和加拿大新生儿重症监护室进行的随机临床试验。参与者包括451名小于30周妊娠，出生体重小于1250 g的新生儿，在出生后5至14天接受机械通气或正压呼吸支持。入组时间为2009年12月23日至2012年4月23日，以及神经发育结局研究已于2014年4月4日完成。

干预  在开始治疗后的72至96小时内，以20 ppm起始的安慰剂（氮气）或吸入一氧化氮降至10 ppm，然后在第10天或第11天降至5 ppm。直到治疗完成，婴儿仍以5 ppm的剂量服用（ 24天）。

主要结果和措施  主要结果是月经后36周（PMA）时无BPD的存活率。次要结局指标包括BPD严重程度，出生后使用皮质类固醇激素，呼吸支持，生存率以及PMA在18到24个月时的神经发育结局。

结果  总共有222例婴儿（52.3％的男性[n = 116]）接受了安慰剂，并且有229例婴儿（50.2％的男性[n = 115]）接受了吸入一氧化氮。他们的平均（SD）妊娠为25.6（1.5）周，相对于25.6（1.4）周，他们的平均（SD）出生体重为750（164）对724（160）g。安慰剂组和吸入一氧化氮组在PMA第36周时无BPD生存率相似（分别为31.5％[n = 70]和34.9％[n = 80]）（赔率，1.17； 95％CI，0.79-1.73）。严重BPD发生率（26.6％[207 of 55] vs 20.5％[43 of 210]）和产后皮质类固醇激素使用率（41.0％[91 of 222] vs 41.5％[95 of 229]）和平均值（SD）在这2天之间，正压呼吸支持的天数（55 [40] vs 54 [42]），氧疗（88 [41] vs 91 [59]）和住院治疗（105 [37] vs 108 [54]）相等。组。没有观察到常见发病率的差异。

结论和相关性  吸入一氧化氮在高危早产儿出生后第5天至第14天以20 ppm的浓度开始，并持续24天，似乎是安全的，但在36周PMA或无呼吸和神经发育结局时没有BPD不能改善生存。在18至24个月的PMA。

试验注册  临床试验.gov标识符：NCT00931632