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.
Pediatr Pulmonol. 2024 Dec;59(12):3435-3445. doi: 10.1002/ppul.27228. Epub 2024 Aug 27.
To investigate the use of inhaled nitric oxide (iNO) in hospitalized preterm infants in China over 10 years and its clinical outcomes.
A total of 616 premature infants who were administered iNO in the Neonatology Departments of 5 Class A tertiary hospitals in China for ten years from January 2013 to December 2022 were included retrospectively. Based on their enrollment periods, the patients were divided into two groups: Group 1 from January 2013 to December 2017 and Group 2 from January 2018 to December 2022, respectively. The perinatal characteristics, short-term clinical outcomes, and mortality rates were compared between these two groups.
The utilization of iNO in preterm infants grew annually over the past10 years; the utilization of iNO in Group 2 infants increased approximately one-fold when compared with Group 1 (1.52% vs. 0.80%, p < .001), and the increase was greater in gestational age (GA) < 34 weeks compared with 34-36 weeks preterm infants. Moreover, the iNO usage in Group 1 infants with GA < 34 weeks increased from 1.14% to 2.46% and 0.60% to 0.99% in 34-36 weeks preterm infants (p < .001) in Group 2, respectively. Apart from a smaller GA (32.9 w vs. 33.5 w, p < .001) and birth weight (BW, 1900 g vs. 2141 g, p < .001), the initial [14 parts per million (ppm) versus 10 ppm, p < .001] and maximum (15 ppm vs. 10 ppm, p < .001) doses of Group 2 were larger; however, their recent clinical outcomes did not improve with increasing iNO utilization (p > .05)as compared to Group 1, respectively. Although the overall iNO preterm mortality rates over the past 10 years were 25.8%, the mortality rates for preterm infants at 34-36 weeks were significantly lower than for preterm infants at GA < 34 weeks (15.4% vs. 33.8%, p < .001). Nonetheless, no improvement in mortality was observed in Group 2 preterm infants with GA < 34 weeks for the past 5 years when compared with Group 1 (32.9% vs. 35.8%, p > .05) infants, and significantly lower mortality rates were noticed in preterm infants with 34-36 weeks (11.2% vs. 22.7%, p < .001). Patients with hypoxic respiratory failure (HRF) or persistent pulmonary hypertension of the newborn (PPHN) iNO preterm infants did not show lower mortality rates with the increase of iNO use rate (p > .05). The overall mortality rates of preterm PPHN infants with iNO were lower than that of HRF (20.2% vs. 36.5%, p < .001), while the mortality rates of Group 2 preterm PPHN infants with iNO significantly lower than that of HRF (17.7% vs 36.0%, p < .001).
The iNO has been extensively used in Chinese preterm infants over the past 10 years, this increase was more significant in preterm infants with GA < 34 weeks. Moreover, preterm infants using iNO have lower GA and BW, larger initial and maximum doses, and more aggressive strategies in the last past 5 years. Although iNO use in preterm infants with GA of 34-36 weeks has significantly reduced mortality, mortality rates and short-term clinical outcomes of iNO in preterm infants <34 weeks of GA has no obvious improvement. Further studies are required to investigate the efficacy and safety of iNO in preterm infants <34 weeks of GA.
研究中国 10 年来吸入一氧化氮（iNO）在住院早产儿中的应用及其临床结局。
回顾性分析 2013 年 1 月至 2022 年 12 月期间，5 家 A 级三甲医院新生儿科收治的 616 例接受 iNO 治疗的早产儿。根据纳入时间，将患者分为两组：2013 年 1 月至 2017 年 12 月为第 1 组，2018 年 1 月至 2022 年 12 月为第 2 组。比较两组患儿的围产期特征、短期临床结局和死亡率。
过去 10 年来，早产儿中 iNO 的使用呈逐年增加趋势；第 2 组患儿 iNO 的使用率较第 1 组增加约 1 倍（1.52%比 0.80%，p<0.001），且 34 周以下早产儿的增加幅度大于 34-36 周早产儿。此外，第 1 组 34 周以下早产儿的 iNO 使用率从 1.14%增加到 2.46%，34-36 周早产儿的 iNO 使用率从 0.60%增加到 0.99%（p<0.001）；第 2 组的情况类似，34 周以下早产儿的 iNO 使用率从 1.14%增加到 2.46%，34-36 周早产儿的 iNO 使用率从 0.60%增加到 0.99%（p<0.001）。除了胎龄（GA）（32.9 w 比 33.5 w，p<0.001）和出生体重（BW）（1900 g 比 2141 g，p<0.001）较小外，第 2 组患儿的初始[14 ppm 比 10 ppm，p<0.001]和最大[15 ppm 比 10 ppm，p<0.001]剂量均较大，但随着 iNO 使用的增加，患儿的近期临床结局并没有改善（p>0.05）。尽管过去 10 年中，所有接受 iNO 治疗的早产儿的总体死亡率为 25.8%，但 34-36 周早产儿的死亡率明显低于 34 周以下早产儿（15.4%比 33.8%，p<0.001）。然而，与第 1 组相比，过去 5 年中，34 周以下早产儿的死亡率并没有明显改善（32.9%比 35.8%，p>0.05），而 34-36 周早产儿的死亡率明显降低（11.2%比 22.7%，p<0.001）。患有缺氧性呼吸衰竭（HRF）或新生儿持续性肺动脉高压（PPHN）的 iNO 早产儿的死亡率并未随着 iNO 使用率的增加而降低（p>0.05）。接受 iNO 治疗的早产儿 PPHN 患儿的总体死亡率低于 HRF（20.2%比 36.5%，p<0.001），而第 2 组接受 iNO 治疗的早产儿 PPHN 患儿的死亡率明显低于 HRF（17.7%比 36.0%，p<0.001）。
过去 10 年来，iNO 在我国早产儿中的应用广泛，34 周以下早产儿的使用增加更为显著。此外，使用 iNO 的早产儿胎龄和体重较小，初始和最大剂量较大，过去 5 年的治疗策略更为激进。虽然 34-36 周早产儿使用 iNO 可显著降低死亡率，但 34 周以下早产儿使用 iNO 后死亡率和短期临床结局无明显改善。需要进一步研究以评估 iNO 在 34 周以下早产儿中的疗效和安全性。
