OP10.03: sFlt‐1/PlGF ratio at diagnosis of previable fetal growth restriction and expected time to delivery

Abstract Purpose The study aimed to assess the course of the soluble Fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio in pregnant women with fetal growth restriction (FGR) and to evaluate potential associations between the sFlt-1/PlGF ratio and feto-maternal Doppler parameters, fetal biometric measurements and the time between study inclusion and birth (“time to delivery”). Methods This was a retrospective longitudinal single center study including 52 FGR cases. The serum levels of sFlt-1 and PlGF were measured by using the BRAHMS Kryptor Compact PLUS. Fetal biometric and Doppler parameters, as well as the sFlt-1/PlGF ratio, were obtained both upon study inclusion and upon birth. Results Various associations between the levels of the biomarkers in maternal blood upon study inclusion and upon birth and sonographic parameters were observed in FGR cases: umbilical artery (p < 0.01), uterine arteries (p < 0.01), ductus venosus (p < 0.05), cerebroplacental ratio (CPR) (p < 0.01), femur length (p < 0.01) and birth weight (p < 0.01). The higher the sFlt-1/PlGF ratio upon study inclusion, the shorter the “time to delivery” (p < 0.01). The multivariate regression analysis showed that the greater the daily percentage increase of the angiogenic markers, the shorter the “time to delivery” (p < 0.01). Conclusion The fetal well-being, as measured by feto-maternal Doppler parameters such as CPR and the severity of the placental dysfunction, as measured by the urgency of birth and birth weight, is reflected by the level of the sFlt-1/PlGF ratio in the maternal serum. A rapid daily increase of the sFlt-1/PlGF ratio is significantly associated with the clinical progression of the disease.

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Screening for fetal growth restriction using ultrasound and the sFLT1/PlGF ratio in nulliparous women: a prospective cohort study

The Lancet Child & Adolescent Health ◽

10.1016/s2352-4642(18)30129-9 ◽

2018 ◽

Vol 2 (8) ◽

pp. 569-581 ◽

Cited By ~ 38

Author(s):

Francesca Gaccioli ◽

Ulla Sovio ◽

Emma Cook ◽

Martin Hund ◽

D Stephen Charnock-Jones ◽

...

Keyword(s):

Cohort Study ◽

Prospective Cohort Study ◽

Fetal Growth ◽

Fetal Growth Restriction ◽

Prospective Cohort ◽

Growth Restriction ◽

Nulliparous Women ◽

Plgf Ratio

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Fetal growth restriction and perinatal adverse outcomes associated with extremely high values of the sFlt-1/PlGF ratio

Pregnancy Hypertension ◽

10.1016/j.preghy.2019.08.151 ◽

2019 ◽

Vol 17 ◽

pp. S28-S29

Author(s):

C. Villalaín ◽

L. Valle ◽

M. Mendoza ◽

M. Vázquez-Fernández ◽

A. Fernández Oliva ◽

...

Keyword(s):

Fetal Growth ◽

Fetal Growth Restriction ◽

Adverse Outcomes ◽

Growth Restriction ◽

Plgf Ratio

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Diagnosis of preeclampsia and fetal growth restriction with the sFlt-1/PlGF ratio: Diagnostic accuracy of the automated immunoassay Kryptor®

Pregnancy Hypertension ◽

10.1016/j.preghy.2017.02.005 ◽

2017 ◽

Vol 8 ◽

pp. 31-36 ◽

Cited By ~ 8

Author(s):

Lisa Antonia Dröge ◽

Alice Höller ◽

Laura Ehrlich ◽

Stefan Verlohren ◽

Wolfgang Henrich ◽

...

Keyword(s):

Diagnostic Accuracy ◽

Fetal Growth ◽

Fetal Growth Restriction ◽

Growth Restriction ◽

Automated Immunoassay ◽

Plgf Ratio

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Correlation of Kryptor and Elecsys® immunoassay sFlt-1/PlGF ratio on early diagnosis of preeclampsia and fetal growth restriction: A case-control study

Pregnancy Hypertension ◽

10.1016/j.preghy.2020.03.002 ◽

2020 ◽

Vol 20 ◽

pp. 44-49 ◽

Cited By ~ 1

Author(s):

Elisa Simón ◽

Ignacio Herraiz ◽

Cecilia Villalaín ◽

Paula Isabel Gómez-Arriaga ◽

María Soledad Quezada ◽

...

Keyword(s):

Early Diagnosis ◽

Fetal Growth ◽

Fetal Growth Restriction ◽

Case Control Study ◽

Case Control ◽

Growth Restriction ◽

Plgf Ratio ◽

Control Study

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sFlt ‐1/ PlGF ratio and timing of delivery in early‐onset fetal growth restriction with antegrade umbilical artery flow

Ultrasound in Obstetrics and Gynecology ◽

10.1002/uog.21949 ◽

2020 ◽

Vol 56 (4) ◽

pp. 549-556 ◽

Cited By ~ 2

Author(s):

M. S. Quezada ◽

J. Rodríguez‐Calvo ◽

C. Villalaín ◽

P. I. Gómez‐Arriaga ◽

A. Galindo ◽

...

Keyword(s):

Fetal Growth ◽

Fetal Growth Restriction ◽

Early Onset ◽

Umbilical Artery ◽

Growth Restriction ◽

Artery Flow ◽

Plgf Ratio

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181. Predictive value of the sFlt-1/PlGF ratio in preecalmpsia with or without fetal growth restriction

Pregnancy Hypertension ◽

10.1016/j.preghy.2018.08.275 ◽

2018 ◽

Vol 13 ◽

pp. S93

Author(s):

Qian Huang ◽

Xiaodan di ◽

Junjie Bao, Huishu Liu

Keyword(s):

Fetal Growth ◽

Predictive Value ◽

Fetal Growth Restriction ◽

Growth Restriction ◽

Plgf Ratio

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Clinical implementation of the sFlt-1/PlGF ratio to identify preeclampsia and fetal growth restriction: A prospective cohort study

Pregnancy Hypertension ◽

10.1016/j.preghy.2018.06.017 ◽

2018 ◽

Vol 13 ◽

pp. 279-285 ◽

Cited By ~ 15

Author(s):

I. Herraiz ◽

E. Simón ◽

P.I. Gómez-Arriaga ◽

M.S. Quezada ◽

A. García-Burguillo ◽

...

Keyword(s):

Cohort Study ◽

Prospective Cohort Study ◽

Fetal Growth ◽

Fetal Growth Restriction ◽

Prospective Cohort ◽

Growth Restriction ◽

Clinical Implementation ◽

Plgf Ratio

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Combining Biomarkers to Predict Pregnancy Complications and Redefine Preeclampsia

Hypertension ◽

10.1161/hypertensionaha.119.13763 ◽

2020 ◽

Vol 75 (4) ◽

pp. 918-926 ◽

Cited By ~ 6

Author(s):

Holger Stepan ◽

Martin Hund ◽

Theresa Andraczek

Keyword(s):

Fetal Growth ◽

Pregnancy Complications ◽

Fetal Growth Restriction ◽

Clinical Characteristics ◽

Angiogenic Factors ◽

Growth Restriction ◽

Placental Dysfunction ◽

Angiogenic Biomarkers ◽

Plgf Ratio ◽

New Onset

Placental dysfunction underlies a spectrum of perinatal pathologies, including preeclampsia and fetal growth restriction. Angiogenesis-related factors, including sFlt-1 (soluble fms-like tyrosine kinase 1) and PlGF (placental growth factor), play an important role in placental dysfunction; altered levels are detectable several weeks before onset of pregnancy complications. In vitro diagnostic tests for these biomarkers can improve early diagnosis and facilitate prediction of maternal and fetal outcomes. We assessed evidence for combining angiogenic biomarkers with other biomarkers or clinical parameters to predict maternal/fetal outcomes in pregnant women with placental dysfunction. Pooled information on placental perfusion (ultrasonography, mean arterial pressure), clinical characteristics, and biomarker levels (PlGF) can improve first-trimester prediction and preeclampsia diagnosis. Angiogenic factors (sFlt-1/PlGF ratio; PlGF alone) with or without clinical characteristics can facilitate second-/third-trimester prediction of early-onset and late-onset preeclampsia. A combination of increased sFlt-1/PlGF ratio and ultrasound can rule out early fetal growth restriction. The sFlt-1/PlGF ratio is also a reliable tool for discriminating between pregnancy-related hypertensive disorders, including superimposed preeclampsia and gestational hypertension. Analysis of angiogenic factors with or without uterine Doppler substantially improves sensitivity and specificity for predicting adverse outcomes and iatrogenic preterm delivery. We propose to extend the American College of Obstetricians and Gynecologists definition of preeclampsia in the future to include the combination of new-onset hypertension and new-onset of altered angiogenic factors (sFlt-1/PlGF ratio or PlGF alone). In summary, altered angiogenic biomarkers indicate placental dysfunction, and their implementation into clinical practice will help reduce the considerable burden of morbidity and mortality associated with adverse pregnancy outcomes as a consequence of angiogenic-placental syndrome.

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