A role of the anti-angiogenic factor sVEGFR-1 in the 'mirror syndrome' (Ballantyne's syndrome).
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.
Espinoza
Jimmy
J
Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland, Michigan, Detroit, USA.
Romero
Roberto
R
Nien
Jyh Kae
JK
Kusanovic
Juan Pedro
JP
Richani
Karina
K
Gomez
Ricardo
R
Kim
Chong Jai
CJ
Mittal
Pooja
P
Gotsh
Francesca
F
Erez
Offer
O
Chaiworapongsa
Tinnakorn
T
Hassan
Sonia
S
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*
D040281:Vascular Endothelial Growth Factor Receptor-1