Introduction: Early pulmonary vascular disease in preterm infants is associated with the subsequent development of bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH), however, mechanisms that contribute to or identify infants with increased susceptibility for BPD and/or PH are incompletely understood. Therefore, we tested if changes in circulating angiogenic peptides during the first week of life are associated with the later development of BPD and/or PH. We further sought to determine alternate peptides and related signalling pathways with the risk for BPD or PH. 

Methods: We prospectively enrolled infants with gestational age <34 weeks gestation and collected blood samples during their first week of life.  BPD and PH were assessed at 36 weeks postmenstrual age. Samples were assayed for each of the 1121 peptides included in the SOMAscan^TM technology, with subsequent pathway analysis. 

Results: Of 102 study infants, 82 had BPD and 13 had PH. Multiple angiogenic proteins  (PF-4, VEGF121, ANG-1, BMP10, HGF, ANG2) were associated with the subsequent diagnosis of BPD, and FGF-19,  PF-4, CTAP-III and PDGF-AA levels were associated with BPD severity. Early increases in BMP10 was strongly associated with the late risk for BPD and PH.

Conclusion: We found that early alterations of circulating angiogenic peptides and others were associated with the subsequent development of BPD. We further identified  peptides that were associated with BPD severity and BPD-associated PH, including BMP10. We speculate that proteomic biomarkers during the first week of life may identify infants at risk for BPD and/or PH to enhance care and research. 

Supplemental tables and figures