title: A role of the anti-angiogenic factor sVEGFR-1 in the 'mirror syndrome' (Ballantyne's syndrome).
abstract: BACKGROUND
  'Mirror syndrome' (Ballantyne's syndrome) refers to the association of fetal hydrops with placentomegaly and severe maternal edema. Preeclampsia occurs in approximately 50% of these cases. Soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), an anti-angiogenic factor, has been implicated in the pathophysiology of preeclampsia (PE).
  
  
  OBJECTIVE
  The objective of this study was to determine if the maternal plasma concentration of sVEGFR-1 is elevated in patients with mirror syndrome.
  
  
  METHODS
  This case-control study included patients with uncomplicated pregnancies (n = 40) and those with mirror syndrome (n = 4) matched for gestational age. Mirror syndrome was defined as fetal hydrops and severe maternal edema. Maternal plasma sVEGFR-1 concentrations were determined using specific enzyme-linked immunosorbent assays. Immunohistochemistry of sVEGFR-1 on villous trophoblasts was also performed in samples from one patient with mirror syndrome and compared with those from a patient with spontaneous preterm delivery matched for gestational age. Non-parametric statistics were used for analysis (p < 0.05).
  
  
  RESULTS
  (1) The median maternal plasma concentration of sVEGFR-1 was significantly higher in patients with mirror syndrome than in the control group (median: 3974 pg/mL, range: 3083-10 780 vs. median: 824 pg/mL, range: 260-4712, respectively; p < 0.001). (2) All patients with mirror syndrome had sVEGFR-1 concentrations above the 95th percentile for gestational age. Syncytiotrophoblast, especially syncytial knots, showed strong staining with antibodies against sVEGFR-1 in placental samples from the patient with mirror syndrome, but not in those from the patient with spontaneous preterm delivery.
  
  
  CONCLUSIONS
  High maternal plasma concentrations of sVEGFR-1 were observed in mirror syndrome. We propose that this anti-angiogenic factor may participate in the pathophysiology of this syndrome. Thus, maternal plasma determination of sVEGFR-1 may help to identify the hydropic fetus that places the mother at risk for preeclampsia.
authors.affiliation: Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland, Michigan, Detroit, USA.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Espinoza
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Jyh Kae
authors.initials: JK
authors.lastname: Nien
authors.forename: Juan Pedro
authors.initials: JP
authors.lastname: Kusanovic
authors.forename: Karina
authors.initials: K
authors.lastname: Richani
authors.forename: Ricardo
authors.initials: R
authors.lastname: Gomez
authors.forename: Chong Jai
authors.initials: CJ
authors.lastname: Kim
authors.forename: Pooja
authors.initials: P
authors.lastname: Mittal
authors.forename: Francesca
authors.initials: F
authors.lastname: Gotsh
authors.forename: Offer
authors.initials: O
authors.lastname: Erez
authors.forename: Tinnakorn
authors.initials: T
authors.lastname: Chaiworapongsa
authors.forename: Sonia
authors.initials: S
authors.lastname: Hassan
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004487:Edema / Q000378:metabolism*; D005260:Female; D005865:Gestational Age; D006801:Humans; D015160:Hydrops Fetalis / Q000378:metabolism*; D010920:Placenta / Q000473:pathology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood* / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood* / Q000378:metabolism*
chemical_list: D040281:Vascular Endothelial Growth Factor Receptor-1