Biomarkers associated with bronchopulmonary dysplasia/mortality in premature infants

Pediatr Res. 2017 Mar;81(3):519-525. doi: 10.1038/pr.2016.259. Epub 2016 Nov 28.


Background: Bronchopulmonary dysplasia (BPD) portends lifelong organ impairment and death. Our ability to predict BPD in first days of life is limited, but could be enhanced using novel biomarkers.

Methods: Using an available clinical and urine biomarker database obtained from a prospective 113 infant cohort (birth weight ≤1,200 g and/or gestational age ≤31 wk), we evaluated the independent association of 14 urine biomarkers with BPD/mortality.

Results: Two of the 14 urine biomarkers were independently associated with BPD/mortality after controlling for gestational age (GA), small for gestational age (SGA), and intubation status. The best performing protein was clusterin, a ubiquitously expressed protein and potential sensor of oxidative stress associated with lung function in asthma patients. When modeling for BPD/mortality, the independent odds ratio for maximum adjusted urine clusterin was 9.2 (95% CI: 3.3-32.8, P < 0.0001). In this model, clinical variables (GA, intubation status, and SGA) explained 38.3% of variance; clusterin explained an additional 9.2%, while albumin explained an additional 3.4%. The area under the curve incorporating clinical factors and biomarkers was 0.941.

Conclusion: Urine clusterin and albumin may improve our ability to predict BPD/mortality. Future studies are needed to validate these findings and determine their clinical usefulness.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albuminuria / diagnosis*
  • Albuminuria / mortality
  • Biomarkers / urine*
  • Birth Weight
  • Bronchopulmonary Dysplasia / diagnosis
  • Bronchopulmonary Dysplasia / mortality
  • Bronchopulmonary Dysplasia / urine*
  • Clusterin / urine
  • Female
  • Gestational Age
  • Humans
  • Infant
  • Infant, Newborn
  • Infant, Premature
  • Infant, Small for Gestational Age
  • Infant, Very Low Birth Weight
  • Intensive Care Units, Neonatal
  • Male
  • Odds Ratio
  • Risk Factors


  • Biomarkers
  • CLU protein, human
  • Clusterin