title: Late-onset preeclampsia is associated with an imbalance of angiogenic and anti-angiogenic factors in patients with and without placental lesions consistent with maternal underperfusion.
abstract: OBJECTIVE
  An imbalance between maternal angiogenic/anti-angiogenic factors concentrations has been observed in preeclampsia (PE) and other obstetrical syndromes. However, the frequency of pathologic findings in the placenta and the changes in maternal plasma angiogenic/anti-angiogenic factor concentrations differ between late- and early-onset PE. The aim of this study was to determine if the maternal plasma concentrations of placental growth factor (PlGF), soluble endoglin (sEng), and soluble vascular endothelial growth factor receptor-1 and 2 (sVEGFR-1 and sVEGFR-2) are different in late-onset PE with and without placental pathologic findings consistent with maternal underperfusion.
  
  
  METHODS
  A cross-sectional study was conducted including 64 uncomplicated women and 66 women with late-onset PE (>34 weeks) who had blood samples and placenta available for pathologic examination. Patients with late-onset PE were divided into those with and without placental histologic findings consistent with maternal underperfusion as proposed by the Society for Pediatric Pathology. Maternal plasma concentrations of PlGF, sEng, sVEGFR-1 and sVEGRF-2 were determined by ELISA. Non-parametric statistics were used for analysis.
  
  
  RESULTS
  1) the prevalence of placental histological findings consistent with maternal underperfusion among women with late-onset PE was higher than that of those with an uncomplicated pregnancy (47% (31/66) vs. 7.8% (5/64), respectively; p < 0.01); 2) patients with late-onset PE and histological findings consistent with maternal underperfusion had a significantly lower median plasma concentration of PlGF, plasma PlGF/sVEGFR-1 ratio and plasma PlGF/sEng ratio than those with late-onset PE without placental underperfusion lesions (each p < 0.05); 3) the most common pathological findings in the placenta of patient with PE were lesions consistent with villous changes (77%, 24/31); and 4) isolated vascular lesions in the placenta were found only in 2 cases (6.5%), and the rest had a combination of villous and vascular lesions.
  
  
  CONCLUSIONS
  Nearly half of the patients with late-onset PE have placental lesions consistent with maternal underperfusion. These lesions are associated with an imbalance in the maternal concentration of angiogenic/anti-angiogenic factors. We propose that there is a link between maternal underperfusion and an anti-angiogenic state characterized by the changes in the concentrations of angiogenic and anti-angiogenic factors in women with late onset PE.
authors.affiliation: Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA.
authors.forename: Eleazar
authors.initials: E
authors.lastname: Soto
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Juan Pedro
authors.initials: JP
authors.lastname: Kusanovic
authors.forename: Giovanna
authors.initials: G
authors.lastname: Ogge
authors.forename: Youssef
authors.initials: Y
authors.lastname: Hussein
authors.forename: Lami
authors.initials: L
authors.lastname: Yeo
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Hassan
authors.forename: Chong Jai
authors.initials: CJ
authors.lastname: Kim
authors.forename: Tinnakorn
authors.initials: T
authors.lastname: Chaiworapongsa
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D015703:Antigens, CD / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D000071063:Endoglin; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007511:Ischemia / Q000175:diagnosis / Q000209:etiology; D010920:Placenta / Q000098:blood supply* / Q000473:pathology; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood*; D011956:Receptors, Cell Surface / Q000097:blood*; D012189:Retrospective Studies; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood*; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; C064206:ENG protein, human; D000071063:Endoglin; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D011956:Receptors, Cell Surface; D000072483:Placenta Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2