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Early Tracheal and Salivary miRNAs in Extremely Preterm Infants Predict BPD-related Pulmonary Hypertension
Insights
Saliva microRNAs in preterm infants can predict bronchopulmonary dysplasia-pulmonary hypertension (BPD-PH). This non-invasive test shows high accuracy, aiding early risk stratification for better infant outcomes.
Area of Science:
- Neonatal Medicine
- Genomics
- Respiratory Medicine
Background:
- Bronchopulmonary dysplasia-pulmonary hypertension (BPD-PH) in preterm infants leads to high mortality.
- Previous studies identified microRNAs (miRNAs) in tracheal aspirates (TA) that differentiate BPD-PH.
- Tracheal aspirate collection poses challenges, especially for non-invasively ventilated infants.
Purpose of the Study:
- To evaluate the predictive potential of specific miRNAs in tracheal aspirates and saliva for diagnosing BPD-PH in extremely low gestational age newborns (ELGANs).
- To assess the correlation of miRNA expression between tracheal aspirates and saliva.
- To determine the efficacy of salivary miRNAs, with clinical factors, for early BPD-PH risk stratification.
Main Methods:
- Analyzed 16 specific miRNAs from tracheal aspirate exosomes of 7-day-old ELGANs using logistic regression.
- Collected saliva samples from the same infants at 7 days of age and compared miRNA expression with TA samples.
- Calculated the area under the receiver operating characteristic curve (AUROC) for diagnosing BPD-PH at 36 weeks postmenstrual age (PMA).
Main Results:
- Tracheal aspirate miRNAs showed an AUROC of 0.76 for BPD-PH prediction.
- Saliva miRNA expression significantly correlated with TA miRNA expression (Pearson r=0.92, p<0.001).
- Saliva miRNAs achieved a higher AUROC of 0.85 for BPD-PH prediction, improving to 0.86 when combined with sex and gestational age.
Conclusions:
- Early detection of BPD-PH in ELGANs is possible using non-invasive salivary miRNA analysis.
- Salivary miRNAs offer a promising tool for risk stratification, potentially improving clinical management of BPD-PH.
- Further validation in larger cohorts is necessary to confirm the diagnostic and prognostic value of salivary miRNAs.
Abstract:
Pulmonary hypertension (BPD-PH) associated with bronchopulmonary dysplasia (BPD) in preterm infants associates with high morbidity and mortality within the first two years of life. In a previous unbiased study, we identified a panel 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 miRNAs, we studied TA exosomes from 7 days old ELGANs and analysed a curated panel of 16 miRNAs through logistic regression and calculated the predictive AUROC to diagnose BPD-PH at 36 weeks PMA. AUROC of TA miRNAs was 0.76 with sensitivity and specificity of 53% and 93%, respectively. Adding sex and gestational age to the variables improved the AUROC to 0.78 with sensitivity and specificity of 61 and 87% respectively. Due to challenges of obtaining TA in non-invasively ventilated infants, we collected saliva samples from ELGANs at 7 days of age and compared the log expression of these 16 miRNAs in both biofluids and found significant correlation in their expression (pearson r=0.92, p<0.001). We calculated the predictive AUROC of the same miRNAs to diagnose BPD-PH at 36 weeks PMA. AUROC of these miRNAs in saliva was = 0.85 with sensitivity and specificity of 82% and 72%, respectively; addition of biological sex and gestational age improved AUROC to 0.86 with sensitivity and specificity of 79% and 76% 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.
