Omic-signature of bronchopulmonary dysplasia associated pulmonary hypertension in <1500g-birth-weight-infants with hemodynamically significant intracardiac shunt

Abstract

Background

PDA and ASD are common intracardiac shunts noted in prematurely born infants. While there is evidence of persistent PDA and ASD associated with a higher risk for developing bronchopulmonary dysplasia (ICS-BPD) and pulmonary hypertension (ICS-BPD-PH), the underlying pathogenesis is poorly understood and hence challenging to identify at-risk infants. Our study goal was to evaluate transcriptomic expression and associated pathways in tracheal aspirates (TAs) of low-birth-weight infants with hemodynamically significant cardiac shunt (ICS) that develop bronchopulmonary dysplasia (ICS-BPD) and pulmonary hypertension (ICS-BPD-PH).

Methods

TAs were collected from preterm infants with ICS and a diagnosis of BPD or BPD-PH from a single center. 36 TA samples including 19 ICS-BPD and 17 ICS-BPD-PH were analyzed. MiRNA expression was determined via PCR arrays, and mRNA expression via RNA seq. Data were analyzed using limma.

Results

11 miRNAs and 10 mRNAs were differentially expressed (adjusted p < 0.05) in ICS-BPD-PH group when compared to ICS-BPD. Ingenuity Pathway Analysis identified associations with cellular growth, proliferation, death, and cell function pathways.

Conclusion

TAs from preterm infants show differentially expressed miRNAs and mRNAs in ICS-BPD-PH when compared to ICS-BPD, an in-silico model identified target molecules that could be playing a role in BPD-PH pathogenesis in low-birth-weight infants with ICS.

Impact

Pulmonary hypertension associated with severe BPD (BPD-PH) is a distinct disease in preterm infants with severe BPD and the role of intracardiac shunt (ICS) in its development is controversial and often challenging for clinical management. Our pilot study, researching specific endotyping of infants with pulmonary hypertension associated with BPD using multiomics approach has identified molecular markers and potential underlying pathways associated with this condition. These markers could aid in stratifying high risk infants with ICS that are at risk for developing BPD-PH and aid clinical management.