Characterization of five marker levels of the hemostatic system and endothelial status in normotensive pregnancy and pre‐eclampsia

American Journal of Obstetrics and Gynecology

Korzeniewski

et al. 2013

130

OBJECTIVE To determine if maternal plasma concentrations of placental growth factor (PlGF), soluble endoglin (sEng), and soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) at 30–34 weeks can identify mothers at risk for preeclampsia (PE), stillbirth and small-for-gestational-age neonates (SGA). STUDY DESIGN A prospective cohort study included 1269 singleton pregnant women who had blood samples obtained at 30–34 weeks and delivered after 34 weeks of gestation. Plasma concentrations of PlGF, sEng, and sVEGFR-1 were determined by ELISA. RESULTS The prevalence of late (>34 weeks) PE, severe late PE, stillbirth and SGA was 3.2% (n=40), 1.8% (n=23), 0.4% (n=5) and 8.5% (n=108), respectively. A plasma concentration of PlGF/sEng <0.3 MoM was associated with severe late PE [adjusted odds ratio (aOR) 16]; addition of PlGF/sEng to clinical risk factors increased the area under the ROC curve (AUC) from 0.76 to 0.88 (p=0.03). The ratio of PlGF/sEng or PlGF/sVEGFR-1 in the third trimester outperformed those obtained in the first or second trimester and uterine artery Doppler velocimetry at 20–25 weeks for the prediction of severe late PE (comparison of AUC; each p≤0.02). Both PlGF/sEng and PlGF/sVEGFR-1 ratios achieved a sensitivity of 74% with a fixed false positive rate of 15% for the identification of severe late PE. A plasma concentration of PlGF/sVEGFR-1 <0.12 MoM at 30–34 weeks had a sensitivity of 80%, a specificity of 94%, and a likelihood ratio of a positive test of 14 for the identification of subsequent stillbirth. Similar findings (sensitivity 80% and specificity 93%) were observed in a separate case-control study. Integrating these biomarkers with clinical data did not improve the prediction of SGA. CONCLUSIONS Risk assessment for severe late PE and stillbirth in the third trimester is possible with the determination of maternal plasma concentrations of angiogenic and anti-angiogenic factors at 30–34 weeks of gestation.

Section: Introductionmentioning

confidence: 99%

Maternal plasma concentrations of angiogenic/antiangiogenic factors in the third trimester of pregnancy to identify the patient at risk for stillbirth at or near term and severe late preeclampsia

Chaiworapongsa

American Journal of Obstetrics and Gynecology

Korzeniewski

et al. 2013

130

“…Mechanisms of disease implicated in this syndrome [1][2][3][4] include uteroplacental ischemia [5][6][7][8][9][10][11], increased trophoblast deportation [12][13][14] with apoptosis/necrosis [15][16][17], oxidative stress [18][19][20][21][22][23][24][25][26][27], and an exaggerated systemic inflammatory response [28][29][30]. The abnormalities observed in patients with preeclampsia include increased insulin resistance [31][32][33][34], hyperlipidemia [35][36][37], excess thrombin generation [38][39][40][41][42][43], and widespread endothelial damage/dysfunction [44][45][46] resulting in multiple organ damage. Of interest, neonates delivered from mothers with preeclampsia are at higher risk to be small for gestational age (SGA) than those delivered from women with ...…”

Section: Introductionmentioning

confidence: 99%

Low maternal concentrations of soluble vascular endothelial growth factor receptor-2 in preeclampsia and small for gestational age

Chaiworapongsa

The Journal of Maternal-Fetal & Neonatal Medicine

Gotsch

et al. 2008

Objectives. Preeclampsia is considered an anti-angiogenic state. A role for the anti-angiogenic factors soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and soluble endoglin in preeclampsia has been proposed. Soluble vascular endothelial growth factor receptor-2 (sVEGFR-2) has been detected in human plasma, and the recombinant form of this protein has anti-angiogenic activity. There is a paucity of information about maternal plasma sVEGFR-2 concentrations in patients with preeclampsia and those without preeclampsia with small for gestational age (SGA) fetuses. This study was conducted to determine whether: (1) plasma sVEGFR-2 concentration changes throughout pregnancy; and (2) preeclampsia and SGA are associated with abnormalities in the maternal plasma concentration of sVEGFR-2. Study design. This cross-sectional study included non-pregnant women (n ¼ 40), women with normal pregnancies (n ¼ 135), women with an SGA fetus (n ¼ 53), and women with preeclampsia (n ¼ 112). SGA was defined as an ultrasoundestimated fetal weight below the 10 th percentile for gestational age that was confirmed by neonatal birth weight. Plasma concentrations of sVEGFR-2 were determined by ELISA. Results. (1) There was no significant difference in the mean plasma concentration of sVEGFR-2 between non-pregnant women and those with normal pregnancies ( p ¼ 0.8); (2) patients with preeclampsia and those without preeclampsia with SGA fetuses had a lower mean plasma concentration of sVEGFR-2 than that of women with normal pregnancies ( p 5 0.001 for both); and (3) there was no significant difference in the mean plasma concentration of sVEGFR-2 between patients with preeclampsia and those without preeclampsia with SGA ( p ¼ 0.9). Conclusions. Preeclampsia and SGA are associated with low plasma concentrations of sVEGFR-2. One interpretation of the findings is that plasma sVEGFR-2 concentration could reflect endothelial cell function.

“…In addition, the maternal plasma thrombin-antithrombin complex concentration increases further during labor [54] and after delivery [53,54] and decreases during the puerperium. Increased thrombin generation has been implicated as a mechanism of disease in several obstetrical syndromes including: PE [9,11,[55][56][57][58][59][60][61], delivery of small-for-gestational neonates age [11,62,63], preterm labor [64,65], and preterm prelabor rupture of membranes (PROM) [64,66]. However, the role of thrombin in these syndromes is probably not limited to the activation of the hemostatic system.…”

Section: Thrombin In Pregnancymentioning

confidence: 99%

Over-expression of the thrombin receptor (PAR-1) in the placenta in preeclampsia: A mechanism for the intersection of coagulation and inflammation

Erez

The Journal of Maternal-Fetal & Neonatal Medicine

Kim

et al. 2008

Placentas from pregnancies complicated by preterm PE had a significantly higher frequency of strong PAR-1 expression than placentas from women with spontaneous preterm labor. This observation is consistent with a role for PAR-1 as a mediator of the effect of thrombin on coagulation and inflammation in PE. We propose that the effects of thrombin in PE are due to increased thrombin generation and higher expression of PAR-1, the major receptor for this enzyme.