An elevated maternal plasma, but not amniotic fluid, soluble fms-like tyrosine kinase-1 (sFlt-1) at the time of mid-trimester genetic amniocentesis is a risk factor for preeclampsia

Park, Chan-Wook; Park, Joong Shin; Shim, Soon Sup; Jun, Jong Kwan; Yoon, Bo Hyun; Romero, Roberto

doi:10.1016/j.ajog.2005.06.033

Cited by 88 publications

(63 citation statements)

References 20 publications

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“…The contribution of sVEGFR-1 to the maternal syndrome of preeclampsia is thought to be, at least in part, related to its inhibition of VEGF stimulation of the endothelium-dependent nitric oxide system (through VEGFR-2) [86]. Plasma sVEGFR-1 concentration has been found to be elevated in preeclampsia both prior to [87][88][89][90][91][92][93][94] and after clinical diagnosis [84,87,[95][96][97][98][99]. In contrast, studies of plasma sVEGFR-1 concentration in women with SGA fetuses have yielded conflicting results-either no change [100] or an increase [99].…”

Section: Introductionmentioning

confidence: 99%

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

Chaiworapongsa

Romero

Gotsch

et al. 2008

The Journal of Maternal-Fetal & Neonatal Medicine

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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.

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Section: Introductionmentioning

confidence: 99%

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

Chaiworapongsa

Romero

Gotsch

et al. 2008

The Journal of Maternal-Fetal & Neonatal Medicine

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“…Two nested case-control studies from the Calcium for Preeclampsia Prevention trial conducted by Levine et al [12,25] reported promising ORs for the diagnosis of preeclampsia, but specifically for preterm preeclampsia, based on the maternal serum concentrations of sFlt1 and sEng (highest quartile) and PlGF (lowest quartile) in the second trimester. Since then, several studies have reported on the predictive accuracy of angiogenic factors in the first [14] and second trimester [16,32,37,41,42,45,46,[82][83][84][85][86] of pregnancy. Overall, the sensitivity, specificity, positive and negative likelihood ratios of PlGF, sVEGFR-1 and sEng for all cases of preeclampsia ranged between 59% and 100%, 43% and 100%, 1.4 to infinity, and 0.0 to 0.7, respectively (Conde-Agudelo A., Romero R., and Lindheimer M., in press).…”

Section: Angiogenic and Anti-angiogenic Factors In The Prediction Of mentioning

confidence: 99%

A prospective cohort study of the value of maternal plasma concentrations of angiogenic and anti-angiogenic factors in early pregnancy and midtrimester in the identification of patients destined to develop preeclampsia

Kusanovic¹,

Romero²,

Chaiworapongsa³

et al. 2009

DJMF

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OBJECTIVE-Changes in the maternal plasma concentrations of angiogenic (such as PlGF and VEGF) and anti-angiogenic factors (such as sEng and sVEGFR-1) precede the clinical presentation of preeclampsia. This study was conducted to examine the role of maternal plasma PlGF, sEng and sVEGFR-1 concentrations in early pregnancy and midtrimester in the identification of patients destined to develop preeclampsia.METHODS-This longitudinal cohort study included 1,622 consecutive singleton pregnant women. Plasma samples were obtained in early pregnancy (6-15 weeks) and midtrimester (20-25 weeks). Maternal plasma PlGF, sEng and sVEGFR-1 concentrations were determined using sensitive and specific immunoassays. The primary outcome was the development of preeclampsia. Secondary outcomes included term, preterm and early-onset preeclampsia. Receiving operating characteristic (ROC) curves, sensitivity, specificity, positive and negative likelihood ratios, and multivariable logistic regression were used for statistical analyses. A p-value of <0.05 was considered significant. RESULTS-1)The prevalence of preeclampsia, term, preterm (<37 weeks) and early-onset preeclampsia (<34 weeks) was 3.8% (62/1,622), 2.5% (40/1,622), 1.4% (22/1,622) and 0.6% (9/1,622), respectively; 2) Higher likelihood ratios were provided by ratios of midtrimester plasma concentrations of PlGF, sEng, and sVEGFR-1 than single analytes; 3) Individual angiogenic and anti-angiogenic factors did not perform well in the identification of preeclampsia as a whole; in particular, they perform poorly in the prediction of term preeclampsia; 4) In contrast, a NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript combination of these analytes such as the PlGF/sEng ratio, its delta and slope had the best predictive performance with a sensitivity of 100%, a specificity of 98%-99%, and likelihood ratios for a positive test of 57.6, 55.6 and 89.6, respectively, for predicting early-onset preeclampsia. CONCLUSIONS-1)The PlGF/sEng ratio and its delta and slope had an excellent predictive performance for the prediction of early-onset preeclampsia, with very high likelihood ratios for a positive test result and very low likelihood ratios for a negative test result; and 2) Although the positive likelihood ratios are high and the positive predictive values low, the number of patients needed to be closely followed is 4:1 for the PlGF/sEng ratio and 3:1 for the slope of PlF/sEng.

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“…Plasma concentrations of the angiogenic factor, placental growth factor (PlGF), are decreased [69,70,92,93,96,[100][101][102], and the anti-angiogenic factors (soluble vascular endothelial growth factor receptor-1 [sVEGFR-1] and soluble endoglin [sEng]) are elevated both prior to [67,72,[119][120][121][122][123][124][125] and at the time of diagnosis [94,95,[97][98][99]. Moreover, the concentrations of these factors can be used to predict the outcome of the disease in patients presented to the obstetrical triage area [73,75,126,127].…”

Section: Introductionmentioning

confidence: 99%

Maternal plasma concentrations of sST2 and angiogenic/anti-angiogenic factors in preeclampsia

Stampalija

Chaiworapongsa

Romero

et al. 2013

The Journal of Maternal-Fetal & Neonatal Medicine

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Objectives: Angiogenic/anti-angiogenic factors have emerged as one of the promising biomarkers for the prediction of preeclampsia. Since not all patients with preeclampsia can be identified by these analytes, the search for additional biomarkers continues. The soluble form of ST2 (sST2), a protein capable of binding to interleukin (IL)-33 and thus contributing to a Th1-biased immune response, has been reported to be elevated in maternal plasma of women with preeclampsia. The aims of this study were to examine: (1) differences in maternal plasma concentrations of sST2 and IL-33 between women diagnosed with preeclampsia and those having uncomplicated pregnancies; (2) the relationship between sST2, umbilical and uterine artery Doppler velocimetry, and the severity of preeclampsia; and (3) the performance of sST2 and angiogenic/anti-angiogenic factors in identifying patients with preeclampsia at the time of diagnosis. Methods: This cross-sectional study included women with preeclampsia (n ¼ 106) and women with an uncomplicated pregnancy (n ¼ 131). Plasma concentrations of sST2, IL-33, soluble vascular endothelial growth factor receptor (sVEGFR)-1, soluble endoglin (sEng) and placental growth factor (PlGF) were determined by enzyme linked immune sorbent assay. Area under the receiver operating characteristic curve (AUC) for the identification of preeclampsia was examined for each analyte. Results: (1) Patients with preeclampsia had a higher mean plasma concentrations of sST2 than those with an uncomplicated pregnancy (p50.0001), while no significant difference in the mean plasma concentration of IL-33 between the two groups was observed; (2) the magnitude of this difference was greater in early-onset, compared to late-onset disease, and in severe compared to mild preeclampsia; (3) sST2 plasma concentrations did not correlate with the results of uterine or umbilical artery Doppler velocimetry (p ¼ 0.7 and p ¼ 1, respectively) among women with preeclampsia; (4) sST2 correlated positively with plasma concentrations of sVEGFR1-1 and sEng (Spearman's Rho ¼ 0.72 and 0.63; each p50.0001), and negatively with PlGF (Spearman's Rho ¼ À0.56, p50.0001); and (5) while the AUC achieved by sST2 and angiogenic/anti-angiogenic factors in identifying women with preeclampsia at the time of diagnosis were non-significantly different prior to term (537 weeks of gestation), thereafter the AUC achieved by sST2 was significantly less than that achieved by angiogenic/anti-angiogenic factors. Conclusions: Preeclampsia is associated with increased maternal plasma concentrations of sST2. The findings that sST2 concentrations do not correlate with uterine or umbilical artery Doppler velocimetry in women with preeclampsia suggest that elevated maternal plasma sST2 concentrations in preeclampsia are not related to the increased impedance to flow in the uteroplacental circulation. The performance of sST2 in identifying preeclampsia at the time of diagnosis prior to 37 weeks of gestation was comparable to that of angiogenic/anti-angiogenic f...

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An elevated maternal plasma, but not amniotic fluid, soluble fms-like tyrosine kinase-1 (sFlt-1) at the time of mid-trimester genetic amniocentesis is a risk factor for preeclampsia

Cited by 88 publications

References 20 publications

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

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

A prospective cohort study of the value of maternal plasma concentrations of angiogenic and anti-angiogenic factors in early pregnancy and midtrimester in the identification of patients destined to develop preeclampsia

Maternal plasma concentrations of sST2 and angiogenic/anti-angiogenic factors in preeclampsia

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