Early angiogenic proteins associated with high risk for bronchopulmonary dysplasia and pulmonary hypertension in preterm infants

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 SOMAscanTM 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.