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CC BY-NC-ND 4.0 · Am J Perinatol 2025; 42(06): 732-741
DOI: 10.1055/a-2419-0021
Original Article

Clinical Analysis of Inhaled Nitric Oxide Therapy in Preterm Infants at Different Gestational Ages: A National Retrospective Multicenter Study

Guo-bao Liang   #
1   Department of Neonatology, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, China
,
Lian Wang   #
1   Department of Neonatology, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, China
,
Sheng-qian Huang   #
2   Department of Neonatology, Guiyang Maternal and Child Health Care Hospital, Guiyang Children's Hospital, Guiyang, Guizhou, China
,
Bao-ying Feng   #
3   Department of Neonatology, Maternal and Child Health Hospital of the Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China
,
Mu-lin Yao   #
4   Department of Neonatology, Children's Hospital of Hebei Province, Shijiazhuang, Hebei, China
,
Xu-fang Fan   #
5   Department of Neonatology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
,
Meng-jiao Wang   #
6   Department of Neonatology, Northwest Women's and Children's Hospital, Xi'an, Shanxi, China
,
Lu Zhu   #
7   Department of Neonatology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
,
Jing Zhang   #
8   Department of Neonatology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
,
Zhi Zheng
1   Department of Neonatology, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, China
,
Yao Zhu
1   Department of Neonatology, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, China
,
Wei Shen
1   Department of Neonatology, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, China
,
Wen-li Duan
5   Department of Neonatology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
,
Jian Mao   *
8   Department of Neonatology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
,
Fan Wu   *
7   Department of Neonatology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
,
Zhan-kui Li   *
6   Department of Neonatology, Northwest Women's and Children's Hospital, Xi'an, Shanxi, China
,
Fa-lin Xu    *
5   Department of Neonatology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
,
Li Ma   *
4   Department of Neonatology, Children's Hospital of Hebei Province, Shijiazhuang, Hebei, China
,
Qiu-fen Wei   *
3   Department of Neonatology, Maternal and Child Health Hospital of the Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China
,
Ling Liu   *
2   Department of Neonatology, Guiyang Maternal and Child Health Care Hospital, Guiyang Children's Hospital, Guiyang, Guizhou, China
,
Xin-zhu Lin   *
1   Department of Neonatology, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, China
› Author Affiliations
Funding This study was supported by the Project of Clinical Key Specialty of Fujian Province (Specialty in Neonatology) and Xiamen Key Laboratory of Perinatal-Neonatal Infection.
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Abstract

Objective

This study aimed to investigate clinical features of inhaled nitric oxide (iNO) in preterm infants with a gestational age (GA) < 34 weeks in China.

Study Design

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.

Results

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 p < 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 p < 0.05), but there was no statistically significant difference in mortality between HRF and documented PPHN treated with iNO (all p > 0.05).

Conclusion

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.

Keywords

preterm infants - inhaling nitric oxide - clinical features - gestational age

# Co-first author.


* Co-corresponding author; the authors ranked first in different units are listed as equally contributing authors of this paper.




Publication History

Received: 04 June 2024

Accepted: 05 September 2024

Article published online:
08 October 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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