scholarly journals Prognostic Value of Angiogenic Markers in Pregnant Women With Chronic Hypertension

2021 ◽  
Author(s):  
Julia Binder ◽  
Pilar Palmrich ◽  
Erkan Kalafat ◽  
Petra Pateisky ◽  
Ebru Öztürk ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Growth Factor ◽  
Prognostic Value ◽  
Placental Growth Factor ◽  
Chronic Hypertension ◽  
Increased Risk ◽  
Angiogenic Markers ◽  
Time To Delivery ◽  
Plgf Ratio ◽  
Angiogenic Marker

Background Women with chronic hypertension face a 5‐ to 6‐fold increased risk of developing preeclampsia compared with normotensive women. Angiogenic markers, especially soluble fms‐like kinase 1 (sFlt‐1) and placental growth factor (PlGF), were identified as clinically useful markers predicting the development of preeclampsia, but data on the prediction of superimposed preeclampsia are scarce. Therefore, we aimed to evaluate the predictive value of the sFlt‐1/PlGF ratio for delivery because of superimposed preeclampsia in women with chronic hypertension. Methods and Results This retrospective study included 142 women with chronic hypertension and suspected superimposed preeclampsia. Twenty‐seven women (19.0%) delivered because of maternal indications only, 17 women (12.0%) because of fetal indications primarily, and 98 women (69.0%) for other reasons. Women who both delivered because of maternal indications and for fetal indications had a significantly higher sFlt‐1/PlGF ratio (median 99.9 and 120.2 versus 7.3, respectively, P <0.001 for both) and lower PlGF levels (median 73.6 and 53.3 versus 320.0 pg/mL, respectively, P <0.001 for both) compared with women who delivered for other reasons. SFlt‐1/PlGF ratio and PlGF were strong predictors for delivery because of superimposed preeclampsia, whether for maternal or fetal indications ( P <0.05). Half of women with angiogenic imbalance (sFlt‐1/PlGF ratio ≥85 or PlGF levels <100 pg/mL) delivered because of maternal or fetal indications within 1.6 weeks (95% CI, 1.0–2.4 weeks). Conclusions Angiogenic marker imbalance in women with suspected superimposed preeclampsia can predict delivery because of maternal and fetal indications related to superimposed preeclampsia and is associated with a significantly shorter time to delivery interval.

scholarly journals Effect of Low-Dose Aspirin on Soluble FMS-Like Tyrosine Kinase 1/Placental Growth Factor (sFlt-1/PlGF Ratio) in Pregnancies at High Risk for the Development of Preeclampsia

2019 ◽  
Vol 8 (9) ◽  
pp. 1429 ◽  
Author(s):  
Karoline Mayer-Pickel ◽  
Vassiliki Kolovetsiou-Kreiner ◽  
Christina Stern ◽  
Julia Münzker ◽  
Katharina Eberhard ◽  
...  
Keyword(s):  
Growth Factor ◽  
High Risk ◽  
Tyrosine Kinase ◽  
Serum Levels ◽  
First Trimester ◽  
Placental Growth Factor ◽  
Chronic Hypertension ◽  
First Trimester Screening ◽  
Trimester Screening ◽  
Plgf Ratio

Background: Soluble FMS-like Tyrosine Kinase 1 (sFlt-1) and placental growth factor (PlGF) have been reported to be highly predictive several weeks before the onset of preeclampsia. Objective: To investigate longitudinal changes of serum levels sFlt-1 and PlGF in pregnant women at high risk for the development of preeclampsia and to reveal an impact of aspirin on maternal serum concentrations of sFlt-1 and PlGF. Methods: This was a prospective longitudinal study in 394 women with various risk factors for the development of preeclampsia (chronic hypertension, antiphospholipid syndrome/APS or systemic lupus erythematosus/SLE, thrombophilia, women with a history of preeclampsia, pathologic first trimester screening for preeclampsia) and 68 healthy women. Serum levels of sFlt-1 and PlGF were measured prospectively at 4-week intervals (from gestational weeks 12 until postpartum). Results: The sFlt-1/PlGF ratio was significantly higher in women with an adverse obstetric outcome compared to women with a normal pregnancy, starting between 20 and 24 weeks of gestation. There was no effect of aspirin on sFlt-1/PlGF ratio in women with chronic hypertension, APS/SLE, thrombophilia and controls. The use of aspirin showed a trend towards an improvement of the sFlt-1/PlGF ratio in women with preeclampsia in a previous pregnancy and a significant effect on the sFlt-1/PlGF ratio in women with a pathologic first trimester screening for preeclampsia. Conclusions: Our findings reveal an impact of aspirin on sFlt-1/PlGF ratio in women with a pathologic first trimester screening for preeclampsia, strongly supporting its prophylactic use.

Validation of Soluble Fms-Like Tyrosine Kinase-1 (sFlt-1) and Placental Growth Factor (PlGF) Assays on Cobas e602 System

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S12-S13
Author(s):  
Nga Yeung Tang ◽  
Sarosh Rana ◽  
Kiang-Teck J Yeo
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Medical Center ◽  
Placental Growth Factor ◽  
Analytical Performance ◽  
Hypertensive Disorder ◽  
Limit Of Quantitation ◽  
Roche Diagnostics ◽  
Interference Studies ◽  
Plgf Ratio

Abstract Background Preeclampsia is a leading hypertensive disorder in pregnant women. The angiogenic biomarkers, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) ratio, have been shown to be associated with diagnosis and prediction of preeclampsia. The objective of this study is to validate the analytical performance of sFlt-1 and PlGF on the Cobas e602 system (Roche Diagnostics Corporation). Method Intra-day and inter-day precisions for both sFlt-1 and PlGF assays were assessed using quality control materials provided from Roche Diagnostics. The accuracies for both assays were assessed by running 60 patient samples, which have been previously analyzed on the Elecsys 411 analyzer (Roche Diagnostics Corporation) at the Beth Israel Deaconess Medical Center. Linearity studies for both assays were performed using patient plasma spiked with recombinant sFlt-1 and PlGF proteins (R&D systems). Hemolysis, icterus, lipemia and biotin interference studies were performed by spiking hemolysate, bilirubin, intralipid or biotin into either pooled patient plasma with detectable levels of sFlt-1 and PlGF or otherwise, patient plasma spiked with recombinant sFlt-1 and PlGF proteins. Results Total precisions for both assays demonstrated CVs of &lt;5.0%. The sFlt-1 and PlGF assays demonstrated analytical measuring ranges of 3060,000 pg/mL and 79,000 pg/mL, respectively (r2 &gt; 0.98). Lower limit of quantitation (10% CV) was 30 pg/mL for sFlt-1 and 7 pg/mL for PlGF, respectively. Interference studies showed sFlt-1 and PlGF were not significantly affected by hemolysis up to H-indices of 500 and 1000 respectively; both assays were not affected by bilirubin up to an I-index of 60, and lipemia up to an L-index of 2800. Biotin at concentrations &gt;30 ng/mL caused significant negative bias for both sFlt-1 and PlGF assays. Comparison studies showed the following: Cobas e602 sFLT-1 = 1.09 [Elecsys 411 sFLT-1] +203 (r2=0.97, Sy/x=1234, n=58); Cobas e602 PlGF = 1.10 [Elecsys 411 PlGF] +47 (r2=0.99, Sy/x=22.1, n=58); Cobas e602 sFLT-1/PlGF ratio = 0.94 [Elecsys 411 sFLT-1/PlGF ratio] +3.5 (r2=0.91, Sy/x=50, n=58). Conclusion sFlt-1 and PlGF measured on Roche Diagnostics Cobas e602 system demonstrated excellent analytical performance and are acceptable for clinical use once approved in the US.

scholarly journals Applying the concept of uncertainty to the sFlt-1/PlGF cut-offs for diagnosis and prognosis of preeclampsia

2021 ◽  
Vol 59 (4) ◽  
pp. 681-686
Author(s):  
Pacifique Lévy ◽  
Safouane Hamdi ◽  
Jean Guiboudenche ◽  
Marie Clothilde Haguet ◽  
Sophie Bailleul ◽  
...  
Keyword(s):  
Quality Control ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Error Propagation ◽  
Placental Growth Factor ◽  
Internal Quality ◽  
Diagnosis And Prognosis ◽  
Diagnosis By Exclusion ◽  
Using Data ◽  
Plgf Ratio

Abstract Objectives Placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) assays and the corresponding ratios (sFlt-1/PlGF) have been proposed to aid in the diagnosis by exclusion and/or prognosis of preeclampsia (PE). A method for evaluating ratio uncertainties (RUs), based on the theory of error propagation, was applied to the sFlt-1/PlGF ratio. Methods RUs were calculated using data derived from sFlt-1 and PlGF Internal Quality Control (IQC) results collected from four centers using Elecsys (Roche) or Kryptor (Thermo Fisher) sFlt-1 and PlGF assays. The corresponding ratio uncertainties were defined for each ratio value. Results The RUs increased linearly with the sFlt-1/PlGF ratio values. The Elecsys RUs were lower than the Kryptor RUs. Although RUs cannot eliminate differences in ratio values observed among various immunoassays, it can affect interpretation of the sFlt-1/PlGF ratio, especially when results are within the range of predefined PE diagnosis or prognosis cut-offs. Conclusions Since RUs are only a function of PlGF and sFlt-1 precision, they can be calculated for each assay from each laboratory to adjust the interpretation of sFlt-1/PlGF ratio results in the context of PE.

scholarly journals Placental growth factor predicts time to delivery in women with signs or symptoms of early preterm preeclampsia: a prospective multicenter study

2020 ◽  
Vol 222 (3) ◽  
pp. 259.e1-259.e11 ◽  
Author(s):  
John R. Barton ◽  
Doug A. Woelkers ◽  
Roger B. Newman ◽  
C. Andrew Combs ◽  
Helen Y. How ◽  
...  
Keyword(s):  
Growth Factor ◽  
Multicenter Study ◽  
Placental Growth Factor ◽  
Prospective Multicenter Study ◽  
Time To Delivery

scholarly journals Usefulness of the sFlt-1/PlGF (Soluble fms-Like Tyrosine Kinase-1/Placental Growth Factor) Ratio in Diagnosis or Misdiagnosis in Women With Clinical Diagnosis of Preeclampsia

Hypertension ◽  
2020 ◽  
Vol 76 (3) ◽  
pp. 892-900 ◽  
Author(s):  
Alfredo Leaños-Miranda ◽  
Ana Graciela Nolasco-Leaños ◽  
Reyes Ismael Carrillo-Juárez ◽  
Carlos José Molina-Pérez ◽  
Liliana Janet Sillas-Pardo ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Clinical Diagnosis ◽  
Correct Diagnosis ◽  
Kidney Injury ◽  
Placental Growth Factor ◽  
Adverse Outcomes ◽  
Elevated Liver Enzymes ◽  
The Relationship ◽  
Plgf Ratio

Preeclampsia is characterized by angiogenic imbalance (AI), sFlt-1 (soluble fms-like tyrosine kinase-1)/PlGF (placental growth factor) is useful for its diagnosis and prediction of adverse outcomes, but the relationship among the degrees of AI as assessed by this ratio with the correct diagnosis, clinical characteristics, and outcomes in women with clinical diagnosis of preeclampsia are unclear. We studied 810 women with clinical diagnosis of preeclampsia. Patients were divided into 3 groups based on their degree of AI, evaluated by the sFlt-1/PlGF ratio: no AI (≤38), mild AI (>38–<85), and severe AI (≥85). Patients with no AI were more likely to have comorbidities and false significant proteinuria compared with patients with mild and severe AI ( P <0.001). The rates of preterm delivery, delivery within 14 days, and small-for-gestational-age infant were higher among patients with severe AI than in patients with no and mild AI ( P <0.001) and in patients with mild AI that in those with no AI ( P ≤0.01). The occurrence of any adverse maternal outcome (HELLP syndrome, elevated liver enzymes, thrombocytopenia, placental abruption, acute kidney injury) was only present in patients with severe AI. Interestingly, the frequency of misdiagnosis of preeclampsia was progressively lower as the degrees of AI increased (no AI: 100%, mild AI: 88.2%, and severe AI: 15.6%). We concluded that in women with clinical diagnosis of preeclampsia, severe AI is characterized by high frequency of true preeclampsia and preeclampsia-related adverse outcomes, in contrast, no and mild AI, are characterized by unnecessary early deliveries, often due to misdiagnosis.

scholarly journals Study of the relationship between the parameters of complex prenatal screening of the first trimester of pregnancy with a risk of the most common aneuploidies

2020 ◽  
Vol 5 ◽  
pp. 33-36
Author(s):  
V. I. Oshovskyy
Keyword(s):  
Blood Pressure ◽  
Growth Factor ◽  
Pregnant Women ◽  
Prenatal Screening ◽  
First Trimester ◽  
Placental Growth Factor ◽  
Type I ◽  
Uterine Arteries ◽  
Increased Risk ◽  
The Relationship

Complex prenatal screening of the first trimester remains the most accessible and effective way of stratifying the risks of fetal chromosomal abnormalities in the general population, which has satisfactory sensitivity and specificity. Over the last decade, due to including additional parameters (average pulsation index of blood flow in the uterine arteries, average blood pressure, placental growth factor concentration, obstetric and somatic anamnesis data), it has also become a tool for determining obstetric risks. The objective: to study the effect of these additional parameters on the accuracy of predicting the most common aneuploidies was made. Materials and methods. The cohort included 2164 pregnant women at 11+0 – 13+6 weeks of gestation, who underwent extended complex screening of the first trimester, which aimed to determine the risk of trisomy on the 21st, 13th and 18th chromosomes in the fetus and calculation risk of perinatal complications, namely: premature birth, preeclampsia and fetal growth retardation. Results. It was found that the history of miscarriage at 13–22 weeks of pregnancy (P=0,0006), increased resistance in the uterine arteries (P=0,0307), decreased concentration of placental growth factor (P=<0,0001) and increased mean blood pressure (P=0,0125) correlate with a high risk of trisomy of chromosome 21. Type I diabetes mellitus in pregnant women (P=0,0477) correlates with an increased risk of trisomy on chromosome 18. The concentration of placental growth factor (P=<0,0001) correlates with an increased risk of trisomy on chromosome 13. Conclusions. The data obtained require detailed analysis in the context of the possibility of optimizing mathematical models for predicting aneuploidy, as well as studying the relationship between markers of trophoblast invasion and chromosomal pathology of the fetus to better understand the mechanisms of first trimester fetal loss and placental dysfunction in the second half of pregnancy.

scholarly journals Prediction of Preeclampsia-Related Adverse Outcomes With the sFlt-1 (Soluble fms-Like Tyrosine Kinase 1)/PlGF (Placental Growth Factor)-Ratio in the Clinical Routine

Hypertension ◽  
2020 ◽  
Author(s):  
Lisa Antonia Dröge ◽  
Frank Holger Perschel ◽  
Natalia Stütz ◽  
Anna Gafron ◽  
Lisa Frank ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Area Under The Curve ◽  
Placental Growth Factor ◽  
Adverse Outcomes ◽  
Low Risk ◽  
Cutoff Values ◽  
Elevated Liver Enzymes ◽  
Factor Ratio ◽  
Plgf Ratio

This retrospective real-world study investigated the clinical use of the sFlt-1 (soluble fms-like tyrosine kinase 1)/PlGF (placental growth factor) ratio alone or in combination with other clinical tests to predict an adverse maternal (maternal death, kidney failure, hemolysis elevated liver enzymes low platelets-syndrome, pulmonary edema, disseminated intravascular coagulation, cerebral hemorrhage, or eclampsia) or fetal (delivery before 34 weeks because of preeclampsia and/or intrauterine growth restriction, respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage, placental abruption or intrauterine fetal death or neonatal death within 7 days post natum) pregnancy outcome in patients with signs and symptoms of preeclampsia. We evaluated the sFlt-1/PlGF-ratio cutoff values of 38 and 85 and evaluated its integration into a multimarker model. Of 1117 subjects, 322 (28.8%) developed an adverse fetal or maternal outcome. Patients with an adverse versus no adverse outcome had a median sFlt-1/PlGF-ratio of 177 (interquartile range, 54–362) versus 14 (4–64). Risk-stratification with the sFlt-1/PlGF cutoff values into high- (>85), intermediate- (38–85), and low-risk (<38) showed a significantly shorter time to delivery in high- and intermediate- versus low-risk patients (4 versus 8 versus 29 days). When integrating all available clinical information into a multimarker model, an area under the curve of 88.7% corresponding to a sensitivity, specificity, positive and negative predictive value of 80.0%, 87.3%, 75.0%, and 90.2% was reached. The sFlt-1/PlGF-ratio alone was inferior to the full model with an area under the curve of 85.7%. As expected, blood pressure and proteinuria were significantly less accurate with an area under the curve of 69.0%. Combining biomarker measurements with all available information in a multimarker modeling approach increased detection of adverse outcomes in women with suspected disease.

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