Antecedents and early correlates of high and low concentrations of angiogenic proteins in extremely preterm newborns

Abstract

Background: To identify the antecedents and very early correlates of low concentrations of angiogenic proteins in the blood of extremely preterm newborns during the first postnatal month.

Methods: Using multiplex immunoassays we measured the concentrations of vascular endothelial growth factor A (VEGF), VEGF receptor-1 (VEGFR-1), VEGF receptor-2 (VEGFR-2), placenta growth factor (PIGF), and angiopoietins 1 and 2 (Ang-1, Ang-2), as well as 21 other proteins in blood spots collected on postnatal days 1 (N=1062), 7 (N=1087), 14 (N=989), 21 (N=940) and 28 (N=880) from infants born before the 28th week of gestation. We then sought the protein-concentration correlates of concentrations in the top and bottom quartile for gestational age and day the specimen was collected.

Results: Children who were delivered for medical indications and those who were severely growth restricted were more likely than others to have low day-1 blood concentrations of VEGF, VEGF-R2, Ang-1, and PIGF. Systemic inflammation accompanied top quartile concentrations of every one of the 6 angiogenic proteins.

Conclusions: Low day-1 concentrations of most angiogenic proteins are associated with disorders linked to placenta insufficiency/dysfunction. High concentrations, on the other hand, are associated with systemic inflammation throughout the first postnatal month.

Keywords: Angiogenesis; Cytokines; Infant, premature/blood; Inflammation; Neurotrophic factors.