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Peer-reviewedCC BY-NCPulmonary circulation

Early Tracheal and Salivary miRNAs in Extremely Preterm Infants Predict Bronchopulmonary Dysplasia-Related Pulmonary Hypertension.

  • Tang Li1
  • Shaoyi Zhang1
  • Vincent Aluquin2
  • Ann Donnelly3
  • Heather Stephens4
  • Shakshi Sharma5
  • Steven D Hicks2
  • Dajiang Liu1
  • Eric Austin6
  • Roopa Siddaiah2,5,7
7 affiliations
  1. 1Department of Public Health Sciences Penn State College of Medicine Hershey Pennsylvania USA.
  2. 2Department of Pediatrics Penn State Health Children's Hospital Hershey Pennsylvania USA.
  3. 3Department of Respiratory Care Penn State Health Milton S. Hershey Medical Center Hershey Pennsylvania USA.
  4. 4Department of Nursing Penn State Health Milton S. Hershey Medical Center Hershey Pennsylvania USA.
  5. 5Arkansas Childrens Research Institute Little Rock Arkansas USA.
  6. 6Department of Pediatrics Vanderbilt University Nashville Tennessee USA.
  7. 7Department of Pediatrics Arkansas Children's Hospital Little Rock Arkansas USA.
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Abstract

Pulmonary hypertension (BPD-PH) associated with bronchopulmonary dysplasia (BPD) in preterm infants associates with high morbidity and mortality within the first 2 years of life. In a previous unbiased study, we identified a panel of 16 miRNAs in tracheal aspirates (TA) that were differentially expressed in extremely low gestational age newborns (ELGANs) with BPD-PH compared to those with BPD but no PH. To explore the predictive potential of these candidate miRNAs, we studied them in TA exosomes from 7-day-old ELGANs and through logistic regression calculated the predictive area under the receiver operating characteristic curve (AUROC) to diagnose BPD-PH at 36 weeks post menstrual age (PMA). AUROC of TA miRNAs was 0.76 with sensitivity and specificity of 93% and 54%, respectively. Adding sex and gestational age to the variables improved the AUROC to 0.78 with sensitivity and specificity of 88% and 62%, respectively. Due to challenges of obtaining TA in noninvasively ventilated infants, we collected saliva samples from ELGANs at 7 days of age and compared the log expression of these target miRNAs in both biofluids and found a significant correlation in their expression (pearson r = 0.92, p < 0.001). We calculated the predictive AUROC of these candidate miRNAs to diagnose BPD-PH at 36 weeks PMA. AUROC of these miRNAs in saliva was = 0.85 with sensitivity and specificity of 72% and 82%, respectively; addition of biological sex and gestational age improved AUROC to 0.86 with sensitivity and specificity of 76% and 79%, respectively. Leave-one-sample-out sensitivity analysis demonstrated stable training performance with reduced performance in testing samples, supporting the need for validation in larger independent cohorts. In conclusion, early salivary miRNAs have great potential for risk stratification of ELGANs to develop BPD-PH, while also providing the opportunity to identify target molecules and mechanisms that modulate molecular function.

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Cite

BibTeXRIS
BibTeX
@article{li2026early,
  title = {{Early Tracheal and Salivary miRNAs in Extremely Preterm Infants Predict Bronchopulmonary Dysplasia-Related Pulmonary Hypertension.}},
  author = {Tang Li and Shaoyi Zhang and Vincent Aluquin and Ann Donnelly and Heather Stephens and Shakshi Sharma and Steven D Hicks and Dajiang Liu and Eric Austin and Roopa Siddaiah},
  journal = {Pulmonary circulation},
  year = {2026},
  month = oct,
  doi = {10.1002/pul2.70437},
  url = {https://europepmc.org/article/MED/42948566},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Early Tracheal and Salivary miRNAs in Extremely Preterm Infants Predict Bronchopulmonary Dysplasia-Related Pulmonary Hypertension.
AU  - Tang Li
AU  - Shaoyi Zhang
AU  - Vincent Aluquin
AU  - Ann Donnelly
AU  - Heather Stephens
AU  - Shakshi Sharma
AU  - Steven D Hicks
AU  - Dajiang Liu
AU  - Eric Austin
AU  - Roopa Siddaiah
PY  - 2026
DA  - 2026/10/27
JO  - Pulmonary circulation
DO  - 10.1002/pul2.70437
UR  - https://europepmc.org/article/MED/42948566
AB  - Pulmonary hypertension (BPD-PH) associated with bronchopulmonary dysplasia (BPD) in preterm infants associates with high morbidity and mortality within the first 2 years of life. In a previous unbiased study, we identified a panel of 16 miRNAs in tracheal aspirates (TA) that were differentially expressed in extremely low gestational age newborns (ELGANs) with BPD-PH compared to those with BPD but no PH. To explore the predictive potential of these candidate miRNAs, we studied them in TA exosomes from 7-day-old ELGANs and through logistic regression calculated the predictive area under the receiver operating characteristic curve (AUROC) to diagnose BPD-PH at 36 weeks post menstrual age (PMA). AUROC of TA miRNAs was 0.76 with sensitivity and specificity of 93% and 54%, respectively. Adding sex and gestational age to the variables improved the AUROC to 0.78 with sensitivity and specificity of 88% and 62%, respectively. Due to challenges of obtaining TA in noninvasively ventilated infants, we collected saliva samples from ELGANs at 7 days of age and compared the log expression of these target miRNAs in both biofluids and found a significant correlation in their expression (pearson r = 0.92, p < 0.001). We calculated the predictive AUROC of these candidate miRNAs to diagnose BPD-PH at 36 weeks PMA. AUROC of these miRNAs in saliva was = 0.85 with sensitivity and specificity of 72% and 82%, respectively; addition of biological sex and gestational age improved AUROC to 0.86 with sensitivity and specificity of 76% and 79%, respectively. Leave-one-sample-out sensitivity analysis demonstrated stable training performance with reduced performance in testing samples, supporting the need for validation in larger independent cohorts. In conclusion, early salivary miRNAs have great potential for risk stratification of ELGANs to develop BPD-PH, while also providing the opportunity to identify target molecules and mechanisms that modulate molecular function.
SN  - 2045-8932
SN  - 2045-8940
ER  -