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

Guo-bao Liang; Lian Wang; Sheng-qian Huang; Bao-ying Feng; Mu-lin Yao; Xu-fang Fan; Meng-jiao Wang; Lu Zhu; Jing Zhang; Zhi Zheng; Yao Zhu; Wei Shen; Wen-li Duan; Jian Mao; Fan Wu; Zhan-kui Li; Fa-lin Xu; Li Ma; Qiu-fen Wei; Ling Liu; Xin-zhu Lin

doi:10.1055/a-2419-0021

American Journal of Perinatology, Table of Contents

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^#

¹Department of Neonatology, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, China

,

Lian Wang^#

¹Department of Neonatology, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, China

,

Sheng-qian Huang^#

²Department of Neonatology, Guiyang Maternal and Child Health Care Hospital, Guiyang Children's Hospital, Guiyang, Guizhou, China

,

Bao-ying Feng^#

³Department of Neonatology, Maternal and Child Health Hospital of the Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China

,

Mu-lin Yao^#

⁴Department of Neonatology, Children's Hospital of Hebei Province, Shijiazhuang, Hebei, China

,

Xu-fang Fan^#

⁵Department of Neonatology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China

,

Meng-jiao Wang^#

⁶Department of Neonatology, Northwest Women's and Children's Hospital, Xi'an, Shanxi, China

,

Lu Zhu^#

⁷Department of Neonatology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China

,

Jing Zhang^#

⁸Department of Neonatology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.

,

Zhi Zheng

¹Department of Neonatology, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, China

,

Yao Zhu

¹Department of Neonatology, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, China

,

Wei Shen

¹Department of Neonatology, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, China

,

Wen-li Duan

⁵Department of Neonatology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China

,

Jian Mao^*

⁸Department of Neonatology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.

,

Fan Wu^*

⁷Department of Neonatology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China

,

Zhan-kui Li^*

⁶Department of Neonatology, Northwest Women's and Children's Hospital, Xi'an, Shanxi, China

,

Fa-lin Xu ^*

⁵Department of Neonatology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China

,

Li Ma^*

⁴Department of Neonatology, Children's Hospital of Hebei Province, Shijiazhuang, Hebei, China

,

Qiu-fen Wei^*

³Department of Neonatology, Maternal and Child Health Hospital of the Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China

,

Ling Liu^*

²Department of Neonatology, Guiyang Maternal and Child Health Care Hospital, Guiyang Children's Hospital, Guiyang, Guizhou, China

,

Xin-zhu Lin^*

¹Department of Neonatology, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, China

› Author Affiliations

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

Full Text

References

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