TY - JOUR
T1 - Fetal death
T2 - A condition with a dissociation in the concentrations of soluble vascular endothelial growth factor receptor-2 between the maternal and fetal compartments
AU - Chaiworapongsa, Tinnakorn
AU - Kusanovic, Juan Pedro
AU - Savasan, Zeynep Alpay
AU - Mazaki-Tovi, Shali
AU - Kim, Sun Kwon
AU - Vaisbuch, Edi
AU - Tarca, Adi L.
AU - Mittal, Pooja
AU - Ogge, Giovanna
AU - Madan, Ichchha
AU - Dong, Zhong
AU - Yeo, Lami
AU - Hassan, Sonia S.
AU - Romero, Roberto
PY - 2010/9
Y1 - 2010/9
N2 - Objective. An anti-angiogenic state has been implicated in the pathophysiology of preeclampsia, fetal growth restriction and fetal death. Vascular endothelial growth factor (VEGF), an indispensible angiogenic factor for embryonic and placental development exerts its angiogenic properties through the VEGF receptor (VEGFR)-2. A soluble form of this protein (sVEGFR-2) has been recently detected in maternal blood. The aim of this study was to determine if fetal death was associated with changes in the concentrations of sVEGFR-2 in maternal plasma and amniotic fluid. Study Design.Maternal plasma was obtained from patients with fetal death (n = 59) and normal pregnant women (n = 134). Amniotic fluid was collected from 36 patients with fetal death and the control group consisting of patients who had an amniocentesis and delivered at term (n = 160). Patients with fetal death were classified according to the clinical circumstances into the following groups: (1) unexplained; (2) preeclampsia and/or placental abruption; (3) chromosomal and/or congenital anomalies. Plasma and amniotic fluid concentrations of sVEGFR-2 were determined by ELISA. Non-parametric statistics and logistic regression analysis were applied. Results. (1) Patients with a fetal death had a significantly lower median plasma concentration of sVEGFR-2 than normal pregnant women (p<0.001). The median plasma concentration of sVEGFR-2 in patients with unexplained fetal death and in those with preeclampsia/abruption, but not that of those with congenital anomalies, was lower than that of normal pregnant women (p = 0.006, p<0.001 and p = 0.2, respectively); (2) the association between plasma sVEGFR-2 concentrations and preterm unexplained fetal death remained significant after adjusting for potential confounders (OR: 3.2; 95 CI: 1.4-7.3 per each quartile decrease in plasma sVEGFR-2 concentrations); (3) each subgroup of fetal death had a higher median amniotic fluid concentration of sVEGFR-2 than the control group (p<0.001 for each); (4) the association between amniotic fluid sVEGFR-2 concentrations and preterm unexplained fetal death remained significant after adjusting for potential confounders (OR: 15.6; 95 CI: 1.5164.2 per each quartile increase in amniotic fluid sVEGFR-2 concentrations); (5) among women with fetal death, there was no relationship between maternal plasma and amniotic fluid concentrations of sVEGFR-2 (Spearman Rho: 0.02; p0.9). Conclusion.Pregnancies with a fetal death, at the time of diagnosis, are characterized by a decrease in the maternal plasma concentration of sVEGFR-2, but an increase in the amniotic fluid concentration of this protein. Although a decrease in sVEGFR-2 concentration in maternal circulation depends upon the clinical circumstances of fetal death, an increase in sVEGFR-2 concentration in amniotic fluid seems to be a common feature of fetal death. It remains to be determined if the perturbation in sVEGFR-2 concentrations in maternal and fetal compartments observed herein preceded the death of a fetus.
AB - Objective. An anti-angiogenic state has been implicated in the pathophysiology of preeclampsia, fetal growth restriction and fetal death. Vascular endothelial growth factor (VEGF), an indispensible angiogenic factor for embryonic and placental development exerts its angiogenic properties through the VEGF receptor (VEGFR)-2. A soluble form of this protein (sVEGFR-2) has been recently detected in maternal blood. The aim of this study was to determine if fetal death was associated with changes in the concentrations of sVEGFR-2 in maternal plasma and amniotic fluid. Study Design.Maternal plasma was obtained from patients with fetal death (n = 59) and normal pregnant women (n = 134). Amniotic fluid was collected from 36 patients with fetal death and the control group consisting of patients who had an amniocentesis and delivered at term (n = 160). Patients with fetal death were classified according to the clinical circumstances into the following groups: (1) unexplained; (2) preeclampsia and/or placental abruption; (3) chromosomal and/or congenital anomalies. Plasma and amniotic fluid concentrations of sVEGFR-2 were determined by ELISA. Non-parametric statistics and logistic regression analysis were applied. Results. (1) Patients with a fetal death had a significantly lower median plasma concentration of sVEGFR-2 than normal pregnant women (p<0.001). The median plasma concentration of sVEGFR-2 in patients with unexplained fetal death and in those with preeclampsia/abruption, but not that of those with congenital anomalies, was lower than that of normal pregnant women (p = 0.006, p<0.001 and p = 0.2, respectively); (2) the association between plasma sVEGFR-2 concentrations and preterm unexplained fetal death remained significant after adjusting for potential confounders (OR: 3.2; 95 CI: 1.4-7.3 per each quartile decrease in plasma sVEGFR-2 concentrations); (3) each subgroup of fetal death had a higher median amniotic fluid concentration of sVEGFR-2 than the control group (p<0.001 for each); (4) the association between amniotic fluid sVEGFR-2 concentrations and preterm unexplained fetal death remained significant after adjusting for potential confounders (OR: 15.6; 95 CI: 1.5164.2 per each quartile increase in amniotic fluid sVEGFR-2 concentrations); (5) among women with fetal death, there was no relationship between maternal plasma and amniotic fluid concentrations of sVEGFR-2 (Spearman Rho: 0.02; p0.9). Conclusion.Pregnancies with a fetal death, at the time of diagnosis, are characterized by a decrease in the maternal plasma concentration of sVEGFR-2, but an increase in the amniotic fluid concentration of this protein. Although a decrease in sVEGFR-2 concentration in maternal circulation depends upon the clinical circumstances of fetal death, an increase in sVEGFR-2 concentration in amniotic fluid seems to be a common feature of fetal death. It remains to be determined if the perturbation in sVEGFR-2 concentrations in maternal and fetal compartments observed herein preceded the death of a fetus.
KW - Amniotic fluid
KW - angiogenesis
KW - angiogenic factor
KW - congenital anomaly
KW - intrauterine demise
KW - maternal plasma
KW - preeclampsia
KW - sKDR
KW - stillbirth
KW - unexplained fetal death, sVEGF-R2
UR - http://www.scopus.com/inward/record.url?scp=77955899231&partnerID=8YFLogxK
U2 - 10.3109/14767050903410664
DO - 10.3109/14767050903410664
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C2 - 20158395
AN - SCOPUS:77955899231
SN - 1476-7058
VL - 23
SP - 960
EP - 972
JO - Journal of Maternal-Fetal and Neonatal Medicine
JF - Journal of Maternal-Fetal and Neonatal Medicine
IS - 9
ER -