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

Authors

  • Sun K. Kim,

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD and Detroit, MI, USA
    2. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
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  • Roberto Romero,

    Corresponding author
    • Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD and Detroit, MI, USA
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  • Zeynep A. Savasan,

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD and Detroit, MI, USA
    2. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
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  • Yi Xu,

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD and Detroit, MI, USA
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  • Zhong Dong,

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD and Detroit, MI, USA
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  • Deug-Chan Lee,

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD and Detroit, MI, USA
    2. Department of Medical Biotechnology, College of Biomedical Science, Kangwon National University, Chunchon, Korea
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  • Lami Yeo,

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD and Detroit, MI, USA
    2. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
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  • Sonia S. Hassan,

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD and Detroit, MI, USA
    2. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
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  • Tinnakorn Chaiworapongsa

    1. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD and Detroit, MI, USA
    2. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
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Correspondence

Roberto Romero, Perinatology Research Branch, NICHD, NIH, DHHS, Wayne State University/Hutzel Women's Hospital, 3990 John R, Box 4, Detroit, MI 48201, USA.

E-mail: romeror@mail.nih.gov

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.

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.

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