Urine Desmosine as a Novel Biomarker for Bronchopulmonary Dysplasia and Postprematurity Respiratory Disease in Extremely Preterm or Low Birth Weight Infants

Abstract

Objective This study aimed to evaluate whether elevated urine desmosine levels at 3 weeks of age were associated with severe radiological findings, bronchopulmonary dysplasia (BPD), and post-prematurity respiratory disease (PRD) in extremely preterm (EP) or extremely low birth weight (ELBW) infants.

Study Design This study recruited 37 EP (22–27 completed weeks) or ELBW (<1,000 g) infants. Urine was collected between 21 and 28 postnatal days, and desmosine was measured using an enzyme-linked immunosorbent assay kit; the urine creatinine level was also measured. Bubbly/cystic lungs were characterized by emphysematous chest X-rays on postnatal day 28. Furthermore, provision of supplemental oxygen or positive-pressure respiratory support at 40 weeks' postmenstrual age defined BPD, and increased medical utilization at 18 months of corrected age defined PRD. The desmosine/creatinine threshold was determined by receiver operating characteristic analysis. The adjusted risk and 95% confidence interval (CI) for elevated urine desmosine/creatinine levels were estimated by logistic regression analysis.

Results Elevated urine desmosine/creatinine levels higher than the threshold were significantly associated with bubbly/cystic lungs (8/13 [61.5%] vs. 2/24 [8.3%], p = 0.001), BPD (10/13 [76.9%] vs. 8/24 [33.3%], p = 0.02), and PRD (6/13 [46.2%] vs. 2/24 [8.3%], p = 0.01). After adjusting for gestational age, birth weight, and sex, the urine desmosine/creatinine levels were significantly higher in those who were highly at risk of bubbly/cystic lungs (odds ratio [OR], 13.2; 95% CI, 1.67–105) and PRD (OR, 13.8; 95% CI, 1.31–144).

Conclusion Elevated urine desmosine/creatinine levels on the third postnatal week were associated with bubbly/cystic lungs on day 28 and PRD at 18 months of corrected age in EP or ELBW infants.

Key Points

• Urine desmosine was prospectively measured in 3-week-old EP/ELBW infants.

• Elevated urine desmosine levels were associated with emphysematous radiological findings on day 28, PRD at 18 months of corrected age.

• Urine desmosine may be a promising biomarker indicating lung damage in EP/ELBW infants.

Keywords

biomarker - bronchopulmonary dysplasia - desmosine - extremely low birth - extremely preterm infant

Ethical Approval

This study protocol was reviewed and approved by the Osaka Women's and Children's Hospital Institutional Review Board (approval number: 1175). Written informed consent was obtained from the parents. This study was conducted following the Declaration of Helsinki.

Authors' Contributions

K. H. and M. F. conceptualized and designed the research. K. H., M. No., and K. W. collected and analyzed the data. K. H. wrote the manuscript. M. Ni., H. K., I. Y., and M. F. assisted with study design and reviewed the manuscript. M. F. reviewed and revised the manuscript. All authors read and approved the final manuscript.

Publication History

Received: 04 August 2022

Accepted: 08 November 2022

Accepted Manuscript online:
16 November 2022

Article published online:
21 December 2022

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