Circulating soluble fms-like tyrosine kinase-1 and placental growth factor from 10 to 40 weeks’ pregnancy in normotensive women

2017 ◽  
Vol 45 (7) ◽  
Author(s):  
Tuangsit Wataganara ◽  
Busadee Pratumvinit ◽  
Piyaporn Lahfahroengron ◽  
Julaporn Pooliam ◽  
Pattarawalai Talungchit ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Gestational Age ◽  
Serum Levels ◽  
Reproductive Technologies ◽  
Placental Growth Factor ◽  
Low Risk ◽  
Placental Weight ◽  
Reference Ranges ◽  
Gestational Age At Delivery

AbstractIntroduction:Circulating soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are potential markers for preeclampsia. The objective was to construct and analyse the reference ranges of serum levels of sFlt-1 and PlGF throughout the course of pregnancy in low-risk Thai pregnant women.Methods:We enrolled 110 low-risk, Thai women singleton pregnancy from 10 to 40 gestational weeks. Serum concentrations of sFlt-1 and PlGF were measured with an automated assay. The reference ranges of serum levels of sFlt-1, PlGF and sFlt-1/PlGF ratio were constructed and assessed for possible correlations with gestational age, maternal factors [age, parity, tobacco use, artificial reproductive technologies (ARTS) and body mass index (BMI)], and pregnancy outcomes (gestational age at delivery, development of preeclampsia, neonatal birth weight and placental weight).Results:None of the subjects developed preeclampsia. Serum sFlt-1 concentrations significantly elevated from 20 to 40 gestational weeks (P=0.003). Significant elevation and dropping of serum PlGF levels and sFlt-1/PlGF ratios were observed at 10 to 29 and 30 to 40 weeks of gestation, respectively (P<0.001). There was an inversed correlation between serum PlGF levels at 20 to 29 gestational weeks and neonatal birth weights (r=−0.48, P<0.05). There were no associations between serum levels of sFlt-1, PlGF, or sFlt-1/PlGF ratios and maternal BMI, gestational age at delivery, or placental weight (P>0.05). Effects from parity, smoking and ARTS were inconclusive.Conclusion:Robust change of serum PlGF levels suggests for its broader clinical application compared to sFlt-1. Prediction of preeclampsia using serum analytes may be gestational period specific.

scholarly journals Soluble fms-Like Tyrosine Kinase 1 Is Increased in Preeclampsia But Not in Normotensive Pregnancies with Small-for-Gestational-Age Neonates: Relationship to Circulating Placental Growth Factor

2005 ◽  
Vol 90 (8) ◽  
pp. 4895-4903 ◽  
Author(s):  
Eiji Shibata ◽  
Augustine Rajakumar ◽  
Robert W. Powers ◽  
Robert W. Larkin ◽  
Carol Gilmour ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Vascular Dysfunction ◽  
Normal Pregnancy ◽  
Maternal Serum ◽  
Placental Growth Factor ◽  
Gestational Age At Delivery ◽  
Placental Protein

Context: An excess of the soluble receptor, fms-like tyrosine kinase 1 (sFlt-1) may contribute to maternal vascular dysfunction in women with preeclampsia by binding and thereby reducing concentrations of free vascular endothelial growth factor and placental growth factor (PlGF) in the circulation. The putative stimulus for increased sFlt-1 during preeclampsia, placental hypoxia due to poor perfusion, is common to both preeclampsia and idiopathic intrauterine growth restriction. However, the latter condition occurs without maternal vascular disease. Objective: We asked whether, as with preeclampsia, sFlt-1 is increased and free PlGF is decreased in villous placenta and maternal serum of normotensive women with small-for-gestational-age (SGA) neonates. Study Design: This was a case-control study using banked samples. Groups of women with SGA neonates (birth weight centile &lt; 10th) and women with preeclampsia were matched to separate sets of normal pregnancy controls based on gestational age at blood sampling (serum) or gestational age at delivery (placenta). Results: sFlt-1 levels were higher in preeclamptics than controls (serum, P &lt; 0.0001; placental protein, P = 0.03; placental mRNA, P = 0.007) but not increased in SGA pregnancies. PlGF was lower in both preeclampsia (serum, P &lt; 0.0001; placental protein, P = 0.05) and SGA (serum, P = 0.0008; placental protein, P = 0.03) compared with their controls. PlGF in preeclampsia and SGA groups did not differ. Conclusions: These data are consistent with a role for sFlt-1 in the maternal manifestations of preeclampsia. In contrast to preeclampsia, sFlt-1 does not appear to contribute substantially to decreased circulating free PlGF in SGA pregnancies in the absence of a maternal syndrome.

scholarly journals Maternal Serum Placental Growth Factor, Soluble Fms-Like Tyrosine Kinase-1, and Soluble Endoglin in Twin Gestations and the Risk of Preeclampsia—A Systematic Review

2020 ◽  
Vol 9 (1) ◽  
pp. 183 ◽  
Author(s):  
Katarzyna Kosinska-Kaczynska ◽  
Magdalena Zgliczynska ◽  
Szymon Kozlowski ◽  
Lukasz Wicherek
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Serum Levels ◽  
Maternal Serum ◽  
Placental Growth Factor ◽  
Cochrane Library ◽  
Original Research ◽  
Multiple Gestation ◽  
Soluble Endoglin ◽  
Twin Pregnancies

Multiple gestation is one of the key risk factors for the occurrence of preeclampsia (PE). Soluble fms-like tyrosine kinase-1, placental growth factor, and soluble endoglin are molecules involved in the process of angiogenesis with a proven role in the pathogenesis of PE. The aim of the review was to summarize available data on maternal serum levels of the above-mentioned factors and their usefulness in predicting PE in twin pregnancies. Only original research articles written in English were considered eligible. Reviews, chapters, case studies, conference papers, experts’ opinions, editorials, and letters were excluded from the analysis. No publication date limitations were imposed. The systematic literature search using PubMed/MEDLINE, Scopus, Embase, and Cochrane Library databases identified 338 articles, 10 of which were included in the final qualitative analyses. The included studies showed significant differences in maternal serum levels of the discussed factors between women with twin pregnancies with PE and those who did not develop PE, and their promising performance in predicting PE, alone or in combination with other factors. The identification of the most effective algorithms, their prompt introduction to the clinical practice, and further assessment of the real-life performance should become a priority.

Abstract 28: Omeprazole Administration To Women With Preterm Preeclampsia: Effects On Circulating Soluble Fms-like Tyrosine Kinase-1, Placental Growth Factor And Endothelin-1 Secretion.

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Rugina I Neuman ◽  
Willy Visser ◽  
Jan H Danser
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Gestational Age ◽  
Controlled Trial ◽  
Placental Growth Factor ◽  
Potential Treatment ◽  
Perinatal Complications ◽  
Longitudinal Course ◽  
The Difference ◽  
Circulating Levels

Low soluble Fms-like tyrosine kinase (sFlt-1) has been reported in women with suspected or confirmed preeclampsia (PE) coincidentally using proton pump inhibitors (PPIs), suggesting a role for these agents as potential treatment for PE. Here, we examined whether administration of omeprazole to women with PE could acutely reduce their circulating levels of sFlt-1 or enhance their placental growth factor (PlGF) concentrations. We performed a randomized controlled trial in which women (≥ 18 years) with confirmed preeclampsia and a gestational age between 20 +0 and 34 +6 weeks were allocated to receive 40mg omeprazole once daily or no omeprazole. Blood was collected at baseline and days 1,2,4,8 followed by twice-weekly until delivery. Primary outcome was specified as the difference in sFlt-1 or PlGF 4 days after omeprazole initiation compared to the non-omeprazole group. Secondary outcomes were defined as between-group differences in longitudinal course of sFlt-1 and PlGF and pregnancy outcomes. Between Dec 2018 and June 2021, 50 women with PE were randomized, of which 40 women remained pregnant after 4 days. Mean maternal age was 30 years, and median gestational age was 31 weeks. Baseline sFlt-1 levels did not differ between non-omeprazole (n=20) and omeprazole group (n=20) (10743 vs. 7110pg/mL, p=0.11), neither did the levels of PlGF (p=0.14). After 4 days, sFlt-1 levels remained similar in women receiving omeprazole compared to women not receiving omeprazole (8364 vs. 13017pg/mL, p=0.14), and the same was true for PlGF (90 vs. 55pg/mL, p=0.14). Using linear mixed models, no difference in longitudinal course of sFlt-1 or PlGF could be attributed to the treatment group, when adjusted for baseline values and GA at enrollment (p=0.47). Women receiving omeprazole had a similar length of pregnancy compared with those not receiving this drug (median 15 vs. 14 days, p=0.70). Except for a higher neonatal intubation rate in the non-omeprazole group (31% vs 4%, p=0.02) there were no differences in maternal/perinatal complications between the two groups. Our findings suggest that daily administration of 40mg in women with PE do not alter their circulating levels of sFlt-1 and PlGF, arguing against a role for this drug as a potential treatment for this syndrome.

scholarly journals The role of angiogenic factors in preeclampsia

2014 ◽  
Vol 155 (47) ◽  
pp. 1860-1866 ◽  
Author(s):  
Bálint Alasztics ◽  
Nóra Gullai ◽  
Attila Molvarec ◽  
János Rigó Jr.
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Clinical Symptoms ◽  
Current Knowledge ◽  
Point Of Care ◽  
Serum Levels ◽  
Maternal Blood ◽  
Placental Growth Factor ◽  
Maternal Circulation ◽  
Early Onset Preeclampsia

Preeclampsia is one of the most common and most serious complications of pregnancy and the management of this condition still challenges obstetricians. Despite intensive research the etiology of preeclampsia still remains unclear. At the beginning of the 2000s preeclampsia-related research was directed towards factors that influence angiogenesis. Most studies have been carried out on the placental growth factor and soluble fms-like tyrosine kinase-1. Most publications confirm the increased concentrations of antiangiogenic factors and decreased concentrations of proangiogenic factors in maternal blood samples in preeclampsia even before the onset of clinical symptoms. According to our current knowledge antiangiogenic proteins are responsible for the endothelial dysfunction in the symptomatic stage of the disease. Placental growth factor and soluble fms-like tyrosine kinase-1 may have important roles in the prediction and treatment of the disease. The point of care detection of placental growth factor and soluble fms-like tyrosine kinase-1 may be used to predict preeclampsia. Rapid tests are available to determine the serum levels of the two proteins. Removal of soluble fms-like tyrosine kinase-1 from maternal circulation is a potential treatment option for early onset preeclampsia. Orv. Hetil., 2014, 155(47), 1860–1866.

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.

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.

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