First-year outcomes of very low birth weight preterm singleton infants with hypoxemic respiratory failure treated with milrinone and inhaled nitric oxide (iNO) compared to iNO alone: A nationwide retrospective study

Ya-Ting Chang; Jia-Rou Liu; Wei-Min Chen; Chi-Nan Tseng; Lai-Chu See

doi:10.1371/journal.pone.0297137

First-year outcomes of very low birth weight preterm singleton infants with hypoxemic respiratory failure treated with milrinone and inhaled nitric oxide (iNO) compared to iNO alone: A nationwide retrospective study

PLoS One. 2024 May 9;19(5):e0297137. doi: 10.1371/journal.pone.0297137. eCollection 2024.

Authors

Ya-Ting Chang¹, Jia-Rou Liu², Wei-Min Chen², Chi-Nan Tseng³, Lai-Chu See^{2

4

5}

Affiliations

¹ Department of Pediatrics, Chang Gung Memorial Hospital at Linkou, Taoyuan City, Taiwan.
² Department of Public Health, College of Medicine, Chang Gung University, Taoyuan City, Taiwan.
³ Department of Cardiac Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City, Taiwan.
⁴ Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital at Linkou, Taoyuan City, Taiwan.
⁵ Biostatistics Core Laboratory, Molecular Medicine Research Center, Chang Gung University, Taoyuan City, Taiwan.

Abstract

Background: Inhaled nitric oxide (iNO) has a beneficial effect on hypoxemic respiratory failure. The increased use of concurrent iNO and milrinone was observed. We aimed to report the trends of iNO use in the past 15 years in Taiwan and compare the first-year outcomes of combining iNO and milrinone to the iNO alone in very low birth weight preterm (VLBWP) infants under mechanical ventilation.

Methods: This nationwide cohort study enrolled preterm singleton infants with birth weight <1500g treated with iNO from 2004 to 2019. Infants were divided into two groups, with a combination of intravenous milrinone (Group 2, n = 166) and without milrinone (Group 1, n = 591). After propensity score matching (PSM), each group's sample size is 124. The primary outcomes were all-cause mortality and the respiratory condition, including ventilator use and duration. The secondary outcomes were preterm morbidities within one year after birth.

Results: After PSM, more infants in Group 2 needed inotropes. The mortality rate was significantly higher in Group 2 than in Group 1 from one month after birth till 1 year of age (55.1% vs. 13.5%) with the adjusted hazard ratio of 4.25 (95%CI = 2.42-7.47, p <0.001). For infants who died before 36 weeks of postmenstrual age (PMA), Group 2 had longer hospital stays compared to Group 1. For infants who survived after 36 weeks PMA, the incidence of moderate and severe bronchopulmonary dysplasia (BPD) was significantly higher in Group 2 than in Group 1. For infants who survived until one year of age, the incidence of pneumonia was significantly higher in Group 2 (28.30%) compared to Group 1 (12.62%) (p = 0.0153).

Conclusion: Combined treatment of iNO and milrinone is increasingly applied in VLBWP infants in Taiwan. This retrospective study did not support the benefits of combining iNO and milrinone on one-year survival and BPD prevention. A future prospective study is warranted.

Copyright: © 2024 Chang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Research Support, Non-U.S. Gov't
Comparative Study

MeSH terms

Administration, Inhalation
Female
Humans
Hypoxia / drug therapy
Infant
Infant, Newborn
Infant, Premature
Infant, Very Low Birth Weight*
Male
Milrinone* / administration & dosage
Milrinone* / therapeutic use
Nitric Oxide* / administration & dosage
Nitric Oxide* / therapeutic use
Respiration, Artificial
Respiratory Insufficiency / drug therapy
Respiratory Insufficiency / mortality
Retrospective Studies
Taiwan / epidemiology
Treatment Outcome

Substances

Milrinone
Nitric Oxide

Grants and funding

This study was partly supported by grants from Chang Gung Medical Foundation (CMRPD1K0352). The funding body of this study did not play any role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript. There was no additional external funding received for this study.