Relationship Between Neonatal Blood Protein Concentrations and Placenta Histologic Characteristics in Extremely Low GA Newborns

Abstract

Amniotic fluid infection with chorioamnionitis is associated with increased risks of morbidity and mortality in children born prematurely. These risks depend on the presence of a fetal inflammatory response. We measured the concentrations of 25 proteins in the blood of 871 infants born before the 28th wk of gestation and examined their placentas for acute inflammation. Newborns who had inflammatory lesions of the placenta were much more likely than their peers (p < 0.01) to have elevated blood concentrations of cytokines (IL-1β, IL-6, and TNF-α), chemokines (IL-8, MIP-1β, RANTES, and I-TAC), adhesion molecules (ICAM-1, ICAM-3, and E-selectin), matrix metalloproteinases (MMP-1 and MMP-9), the angiogenic inflammatory factor VEGF and its receptor VEGF-R2, and acute phase proteins (SAA and CRP) during the first 3 d after birth. In contrast, newborns with poor placental perfusion had lower levels of inflammatory proteins (p < 0.01; IL-6, RANTES, ICAM-1, ICAM-3, VCAM-1, E-selectin, MMP-1, MMP-9, MPO, and VEGF). An inverse pattern was found between newborn levels of VEGF and its competitive inhibitor VEGF-R1 in both the inflamed and poorly perfused placenta categories. These results confirm the predictive value of placental histology for the presence or absence of elevated inflammatory response in newborns.