To determine whether alterations in second-trimester maternal serum cytokine concentrations can identify women at risk for developing severe, early-onset preeclampsia.
Patients with severe preeclampsia requiring delivery prior to 34 weeks (n = 20) were each matched by gestational age, gravidity, parity, and sample freezing time with three healthy controls who delivered at term (n = 60). By using second-trimester maternal sera originally collected for fetal aneuploidy screening, the concentrations of placental growth factor, vascular endothelial growth factor, granulocyte colony-stimulating factor, endothelin-1, and human chorionic gonadotropin were compared between patients and controls. Logistic regression analysis was used to estimate odds ratios for high versus low (median split) cytokine concentrations with respect to the development of severe, early-onset preeclampsia. Receiver operating characteristic (ROC) curves based on a second logistic regression, using actual cytokine values, were plotted to illustrate reciprocal impact on sensitivity and specificity.
Placental growth factor and vascular endothelial growth factor levels were significantly lower in patients than in controls. No significant differences were observed for the other cytokines. The odds ratios (with 95% confidence intervals) were 15.54 (3.29, 73.40) for vascular endothelial growth factor and 4.20 (1.35, 13.06) for placental growth factor. Receiver operating characteristic analysis of placental growth factor and vascular endothelial growth factor confirmed that both were useful in discriminating between patients and controls. Models combining both vascular endothelial growth factor and placental growth factor provided the best performance for identifying patients at risk for developing severe, early-onset preeclampsia, according to both odds ratios and ROC analyses.
Combined analysis of placental growth factor and vascular endothelial growth factor is potentially useful as a tool for early identification of patients at risk for developing severe, early-onset preeclampsia.
"Therefore, it appears that preeclampsia compromises the homeostasis between HGF and s-Met. Well-defined changes in preeclamptic patients include lowered level of vascular endothelial growth factor (VEGF) and placental growth factor (PIGF) and elevated level of pseudotyrosine kinase receptor (sFlt-1) and endoglin (sEng) which result in reduced angiogenic effects of VEGF/PIGF and abnormal function of endothelial cells in patients with PE [8, 9]. On the other hand, it appears that reduced s-Met in preeclampsia facilitates the angiogenic properties of HGF. "
[Show abstract][Hide abstract] ABSTRACT: Introduction. Preeclampsia (PE) is an important cause of mortality and morbidity for mothers, fetuses, and the newborns. Placenta plays a pivotal role in pathogenesis of PE. Hepatic growth factor (HGF) is a cytokine expressed by the mesenchymal stalk of placental villi during pregnancy and assumes a paracrine role in trophoblasts which express its receptor (c-MET). In the present study, we investigate the diagnostic value of s-Met (the soluble form of the receptor) in the first and second trimesters of pregnancy for early diagnosis of preeclampsia. Method and Materials. This is a case-control study conducted on 95 pregnant women. The serum level of s-Met was measured in the first and second trimesters, and the participants were followed until delivery. 44 individuals with preeclampsia (the case group) and 51 individuals without preeclampsia (the control group) were evaluated. Results. Serum level of s-Met in preeclamptic participants was lower than that of the control group in both the first and the second trimesters (P < 0.0001). In addition, serum levels of s-Met were significantly lower during the first and second trimesters in patients with early, severe preeclampsia compared to those with late, mild preeclampsia (P < 0.0001). The sensitivity and specificity of s-Met in the first and second trimesters were, respectively, (83%, 94%) and (77%, 94%) for early preeclampsia and (88%, 92%) and (86%, 98%) for severe preeclampsia. Conclusion. Considering our findings, serum level of s-Met may be used as a predictive factor for early detection of preeclampsia. Further research is required to corroborate the functional and therapeutic value of s-Met in preeclampsia.
ISRN obstetrics and gynecology 07/2013; 2013:925062. DOI:10.1155/2013/925062
"Our study is in line with most earlier studies in finding significant differences of sFlt-1 concentration between women who are destined to develop preeclampsia and controls not earlier than during the second half of pregnancy [15,20,25]. However, some studies have reported elevated sFlt-1 concentration already from thirteen to twenty weeks of gestation [18,26-28]. Analyses performed using first trimester serum samples have resulted in negative findings [19,21,22]. "
[Show abstract][Hide abstract] ABSTRACT: Background
To evaluate the soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and sFlt-1/PlGF ratio for the prediction of early- and late-onset preeclampsia in a high-risk cohort.
We studied serial serum samples collected prospectively at 12 + 0 - 14 + 0, 18 + 0 - 20 + 0, and 26 + 0 - 28 + 0 weeks + days of gestation in 6 women who developed early-onset preeclampsia (before 34 weeks of gestation) and in 21 women who developed late-onset preeclampsia (after 34 weeks of gestation) with automated ElecSys 2010 immunoanalyzer (Roche Diagnostics, Germany). Twenty-six high-risk women and 53 women without risk factors with normal pregnancies served as controls.
Serum PlGF concentrations were lower at 18 + 0 to 20 + 0, and 26 + 0 to 28 + 0 weeks of gestation in women who developed early-onset preeclampsia compared to women who developed late-onset preeclampsia and to controls (p < 0.05 for all comparisons). At 18 + 0 to 20 + 0 weeks of gestation area under the receiver-operating characteristic curve (AUC) for serum PlGF was 99.8% (p = 0.0007, 95% CI 99.0-100.0). At 26 + 0 to 28 + 0 weeks of gestation serum sFlt-1/PlGF ratio explicitly detects those women who developed early-onset preeclampsia (AUC 100.0%, p = 0.0007, 95% CI 100–100). Amongst women with late-onset preeclampsia, those who developed severe form of the disease (N = 8) had significantly higher serum sFlt-1 concentrations at all three timepoints (p = 0.004, p = 0.006, and p = 0.003, respectively) compared to women with non-severe form (N = 13).
Low serum PlGF concentration predicts early-onset preeclampsia from the second trimester and elevated serum sFlt-1/PlGF ratio from 26 to 28 weeks of gestation. Elevated serum sFlt-1 concentration in the first trimester in women who later develop late-onset, severe preeclampsia may suggest different etiology compared to the late-onset non-severe form of the disease.
"Angiogenic factors have been subject of intensive research in recent years, as they appear to be involved in the aetiology of PE. Several studies show a decrease in the concentration of PlGF (Polliotti et al., 2003; Levine et al., 2004) and an increase in circulating levels of sVEGFR-1 (McKeeman et al., 2004; Levine et al., 2004) in PEc women. Nevertheless, there is some controversy regarding the concentration of VEGF in pregnant women with PE (Simmons et al., 2000; McKeeman et al., 2004). "
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