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

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.

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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

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2004-1955 ◽

2005 ◽

Vol 90 (8) ◽

pp. 4895-4903 ◽

Cited By ~ 178

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 < 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 < 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 < 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.

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The role of angiogenic factors in preeclampsia

Orvosi Hetilap ◽

10.1556/oh.2014.30042 ◽

2014 ◽

Vol 155 (47) ◽

pp. 1860-1866 ◽

Cited By ~ 3

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.

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Maternal serum placental growth factor and soluble fms-like tyrosine kinase 1 as early predictors of preeclampsia

Acta Obstetricia Et Gynecologica Scandinavica ◽

10.1080/00016340903289892 ◽

2009 ◽

pp. 1-4

Author(s):

Mahmoud Shokry ◽

Mohamed Bedaiwy ◽

Mohamed Fathalla ◽

Ali Alsemary ◽

Sahar Elwakil ◽

...

Keyword(s):

Growth Factor ◽

Tyrosine Kinase ◽

Maternal Serum ◽

Placental Growth Factor ◽

Early Predictors

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Clinical usefulness of serum levels of soluble fms-like tyrosine kinase 1/placental growth factor ratio to rule out preeclampsia in women with new-onset lupus nephritis during pregnancy

CEN Case Reports ◽

10.1007/s13730-018-0373-7 ◽

2018 ◽

Vol 8 (2) ◽

pp. 95-100 ◽

Cited By ~ 2

Author(s):

Chikako Hirashima ◽

Manabu Ogoyama ◽

Miyuki Abe ◽

Satoru Shiraishi ◽

Taro Sugase ◽

...

Keyword(s):

Growth Factor ◽

Lupus Nephritis ◽

Tyrosine Kinase ◽

Serum Levels ◽

Placental Growth Factor ◽

Clinical Usefulness ◽

Factor Ratio ◽

Rule Out ◽

New Onset

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Accuracy of Circulating Placental Growth Factor, Vascular Endothelial Growth Factor, Soluble fms-like Tyrosine Kinase-1, and Soluble Endoglin in the Prediction of Preeclampsia

Obstetric Anesthesia Digest ◽

10.1097/01.aoa.0000432382.59560.a1 ◽

2013 ◽

Vol 33 (3) ◽

pp. 160-161

Author(s):

C.E. Kleinrouweler ◽

M.M. Wiegerinck ◽

C. Ris-Stalpers ◽

P.M. Bossuyt ◽

J.A. van der Post ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Tyrosine Kinase ◽

Placental Growth Factor ◽

Vascular Endothelial ◽

Soluble Endoglin ◽

Endothelial Growth Factor

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Midgestation Maternal Serum 25-Hydroxyvitamin D Level and Soluble Fms-Like Tyrosine Kinase 1/Placental Growth Factor Ratio as Predictors of Severe Preeclampsia

Hypertension ◽

10.1161/hypertensionaha.111.179069 ◽

2011 ◽

Vol 58 (6) ◽

pp. 1120-1125 ◽

Cited By ~ 23

Author(s):

Padmashree Chaudhury Woodham ◽

Julia E. Brittain ◽

Arthur M. Baker ◽

D. Leann Long ◽

Sina Haeri ◽

...

Keyword(s):

Growth Factor ◽

Tyrosine Kinase ◽

Maternal Serum ◽

Placental Growth Factor ◽

Severe Preeclampsia ◽

Hydroxyvitamin D ◽

Factor Ratio ◽

25 Hydroxyvitamin D

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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

Journal of Clinical Medicine ◽

10.3390/jcm8091429 ◽

2019 ◽

Vol 8 (9) ◽

pp. 1429 ◽

Cited By ~ 5

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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