Endoglin in Amniotic Fluid as a Risk Factor for the Subsequent Development of Bronchopulmonary Dysplasia.

Objective Cross-talk between inflammation and angiogenesis pathways has been recently reported. The objectives of this study were to: (i) examine whether amniotic fluid ( AF) concentrations of soluble endoglin (sEng), a protein with anti-angiogenic properties, change during pregnancy, parturition, or intra-amniotic infection and/or inflammation ( IAI); (ii) determine whether an increase in sEng in the AF of patients with preterm labor ( PTL) and preterm prelabor rupture of membranes ( PROM) is associated with adverse neonatal outcomes; and (iii) investigate potential sources of sEng in AF. Study design A cross-sectional study was conducted to include patients in the following groups: (i) mid-trimester ( n = 20); (ii) PTL with term delivery ( n = 95); (iii) PTL leading to preterm delivery with ( n = 40) and without IAI ( n = 46); (iv) preterm PROM with ( n = 37) and without IAI ( n = 37); (v) term in labor ( n = 48) and not in labor ( n = 44). AF concentrations of sEng were determined by enzyme-linked immunosorbent assay. Chorioamniotic membranes, umbilical cord blood, and AF macrophages were examined for the expression of endoglin. Results (i) Patients with IAI had a higher median AF concentration of sEng than those without IAI ( P = 0.02 for PTL and 0.06 for preterm PROM); (ii) AF concentrations of sEng in the 3rd and 4th quartiles were associated with IAI ( OR 2.5 and 7.9, respectively); (iii) an AF sEng concentration ≥779.5 pg/mL was associated with bronchopulmonary dysplasia (BPD) ( OR 7.9); (iv) endoglin was co-localized with CD14+ macrophages in AF pellets of patients with IAI by immunofluorescence and flow cytometry; and (v) the concentration of sEng in the supernatant was significantly increased after the treatment of macrophages with endotoxin or TNF-α. Conclusions Soluble endoglin participates in the host response against IAI. Activated macrophages may be a source of sEng concentrations in the AF of patients with IAI. An increase of sEng in the AF is associated with BPD and adverse neonatal outcomes. [ABSTRACT FROM AUTHOR]