Liang Guo-Bao, Wang Lian, Huang Sheng-Qian, Feng Bao-Ying, Yao Mu-Lin, Fan Xu-Fang, Wang Meng-Jiao, Zhu Lu, Zhang Jing, Zheng Zhi, Zhu Yao, Shen Wei, Duan Wen-Li, Mao Jian, Wu Fan, Li Zhan-Kui, Xu Fa-Lin, Ma Li, Wei Qiu-Fen, Liu Ling, Lin Xin-Zhu
Department of Neonatology, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Department of Neonatology, Guiyang Maternal and Child Health Care Hospital, Guiyang Children's Hospital, Guiyang, Guizhou, China.
Am J Perinatol. 2025 Apr;42(6):732-741. doi: 10.1055/a-2419-0021. Epub 2024 Oct 8.
This study aimed to investigate clinical features of inhaled nitric oxide (iNO) in preterm infants with a gestational age (GA) < 34 weeks in China.The clinical data of 434 preterm infants with GA < 34 weeks, treated with iNO in the neonatology departments of eight Class A tertiary hospitals in China over a 10-year period from January 2013 to December 2022, were included in this retrospective multicenter investigation. The infants were divided into three groups based on GA: 24 to 27 weeks (extremely preterm infants), 28 to 31 weeks (very preterm infants), and 32 to 33 weeks (moderate preterm infants). The use of iNO, perinatal data, incidence and mortality of indication for iNO treatment, therapeutic effects of iNO, incidence of short-term complications for iNO treatment, and mortality were compared among these three groups.Over the past 10 years, the proportion of iNO use was highest in extremely preterm infants each year. The lower the GA, the higher the iNO use rate: 4.20% for GA 24 to 27 weeks, 1.54% for GA 28 to 31 weeks, and 0.85% for GA 32 to 33 weeks. There was no significant difference in the therapeutic effect of iNO among the three groups. The incidence of neonatal pulmonary hemorrhage, neonatal shock, late-onset diseases, retinopathy of prematurity requiring intervention, intracranial hemorrhage (grade 3 or 4), periventricular leukomalacia, neonatal necrotizing enterocolitis (≥stage II), and moderate to severe bronchopulmonary dysplasia was highest in extremely preterm infants and increased with decreasing GA. Mortality was negatively correlated with GA and birth weight. The highest rate of iNO treatment in 24 to 27 weeks' preterm infants was due to hypoxic respiratory failure (HRF), whereas the highest rate of iNO treatment in 32 to 33 weeks' preterm infants was due to documented persistent pulmonary hypertension of the newborn (PPHN). The rates of iNO treatment due to HRF and documented PPHN were 54.3 and 60.6%, respectively, in extremely preterm infants, significantly higher than in very preterm and moderate preterm infants (all < 0.05). Within the same GA group, the proportion of preterm infants treated with iNO for HRF was lower than that for documented PPHN (all < 0.05), but there was no statistically significant difference in mortality between HRF and documented PPHN treated with iNO (all > 0.05).Among preterm infants with GA < 34 weeks, the rate of iNO usage was highest in extremely preterm infants. However, iNO failed to improve the clinical outcome of extremely preterm infants with refractory hypoxemia, and there was no significant difference in the therapeutic effect of iNO among preterm infants with different GAs.
本研究旨在调查中国胎龄（GA）<34周的早产儿吸入一氧化氮（iNO）的临床特征。本项回顾性多中心研究纳入了2013年1月至2022年12月这10年间在中国8家三级甲等医院新生儿科接受iNO治疗的434例GA<34周的早产儿的临床资料。根据GA将这些婴儿分为三组：24至27周（极早产儿）、28至31周（非常早产儿）和32至33周（中度早产儿）。比较这三组在iNO使用情况、围产期数据、iNO治疗指征的发生率和死亡率、iNO的治疗效果、iNO治疗短期并发症的发生率以及死亡率等方面的差异。
在过去10年中，每年极早产儿使用iNO的比例最高。GA越低，iNO使用率越高：GA 24至27周为4.20%，GA 28至31周为1.54%，GA 32至33周为0.85%。三组中iNO的治疗效果无显著差异。极早产儿发生新生儿肺出血、新生儿休克、晚发型疾病、需要干预的早产儿视网膜病变、颅内出血（3级或4级）、脑室周围白质软化、新生儿坏死性小肠结肠炎（≥Ⅱ期）以及中重度支气管肺发育不良的发生率最高，且随GA降低而增加。死亡率与GA和出生体重呈负相关。24至27周早产儿接受iNO治疗的最主要原因是缺氧性呼吸衰竭（HRF），而32至33周早产儿接受iNO治疗的最主要原因是确诊的新生儿持续性肺动脉高压（PPHN）。极早产儿因HRF和确诊PPHN接受iNO治疗的比例分别为54.3%和60.6%，显著高于非常早产儿和中度早产儿（均<0.05）。在同一GA组内，因HRF接受iNO治疗的早产儿比例低于因确诊PPHN接受治疗的比例（均<0.05），但iNO治疗HRF和确诊PPHN的死亡率之间无统计学显著差异（均>0.05）。
在GA<34周的早产儿中，极早产儿iNO使用率最高。然而，iNO未能改善极早产难治性低氧血症患儿的临床结局，且不同GA的早产儿中iNO的治疗效果无显著差异。
