title: Endoglin in amniotic fluid as a risk factor for the subsequent development of bronchopulmonary dysplasia.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD and Detroit, MI 48201, USA.
authors.forename: Sun K
authors.initials: SK
authors.lastname: Kim
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Zeynep A
authors.initials: ZA
authors.lastname: Savasan
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.forename: Zhong
authors.initials: Z
authors.lastname: Dong
authors.forename: Deug-Chan
authors.initials: DC
authors.lastname: Lee
authors.forename: Lami
authors.initials: L
authors.lastname: Yeo
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Hassan
authors.forename: Tinnakorn
authors.initials: T
authors.lastname: Chaiworapongsa
mesh_terms: D000328:Adult; D000653:Amniotic Fluid / Q000737:chemistry* / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D001997:Bronchopulmonary Dysplasia / Q000276:immunology / Q000378:metabolism*; D003430:Cross-Sectional Studies; D000071063:Endoglin; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000276:immunology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007231:Infant, Newborn; D007239:Infections; D007249:Inflammation; D007752:Obstetric Labor, Premature / Q000276:immunology; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface