Clinical utility of sFlt ‐1 and PlGF in screening, prediction, diagnosis and monitoring of pre‐eclampsia and fetal growth restriction
Open accessAbstract
Pre‐eclampsia (PE) is characterized by placental and maternal endothelial dysfunction, and associated with fetal growth restriction (FGR), placental abruption, preterm delivery and stillbirth. The angiogenic factors soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and placental growth factor (PlGF) are altered in pregnancies complicated by placenta‐related disorders. In this Review, we summarize the existing knowledge, examining the performance of maternal PlGF, sFlt‐1 and the sFlt‐1/PlGF ratio for screening PE, predicting development of PE in the short term, diagnosing PE, monitoring established PE and predicting other placenta‐related disorders in singleton pregnancy. We also discuss the performance of PlGF and the sFlt‐1/PlGF ratio for predicting PE in twin pregnancy. For first‐trimester screening in singleton pregnancy, a more accurate way of identifying high‐risk women than current practice is to combine maternal PlGF levels with clinical risk factors and ultrasound markers. Later in pregnancy, the sFlt‐1/PlGF ratio has advantages over PlGF because it has a higher pooled sensitivity and specificity for diagnosing and monitoring PE. It has clinical value because it can rule out the development of PE in the 1–4‐week period after the test. Once a diagnosis of PE is established, repeat measurement of sFlt‐1 and PlGF can help monitor progression of the condition and may inform clinical decision‐making regarding the optimal time for delivery. The sFlt‐1/PlGF ratio is useful for predicting FGR and preterm delivery, but the association between stillbirth and the angiogenic factors is unclear. The sFlt‐1/PlGF ratio can be used to predict PE in twin pregnancy, although different sFlt‐1/PlGF ratio cut‐offs from those for singleton pregnancy should be applied for optimal performance. In summary, PlGF, sFlt‐1 and the sFlt‐1/PlGF ratio are useful for screening, diagnosing, predicting and monitoring placenta‐related disorders in singleton and twin pregnancy. We propose that tests for these angiogenic factors are integrated more fully into clinical practice.© 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Traditional approaches relying on maternal characteristics and serum markers such as PAPP-A and PlGF offer only modest predictive power.
“Traditional approaches rely on maternal characteristics and serum markers such as pregnancy-associated plasma protein A (PAPP-A) and placental growth factor (PlGF), which offer only modest predictive power.9,12–14”
From Early detection of severe fetal growth restriction using multimodal deep learning based on ultrasound and prenatal biomarkers (2026) · cites this paper as [13]
In “Using PlGF in the first trimester to screen for PE” (page unavailable), the review says screening often relies on clinical risk factors alone and that adding PlGF and other measures may identify high-risk women more accurately. Its screening diagram (“Additional information,” page unavailable) includes PAPP-A as an option when PlGF is unavailable. These passages support the description of screening inputs, but not the blanket claim that approaches using PAPP-A or PlGF have only modest predictive power. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIdentifying FGR risk at 20-24 weeks - before overt restriction - creates opportunities for proactive management.
“Identifying FGR risk at 20–24 weeks – before overt restriction – creates opportunities for proactive management.2,13,31,32”
From Early detection of severe fetal growth restriction using multimodal deep learning based on ultrasound and prenatal biomarkers (2026) · cites this paper as [13]
The 'Using PlGF and the sFlt-1/PlGF ratio to predict FGR' section says maternal biomarkers may help predict pregnancies that will develop FGR. 'Additional information' describes risk assessment at 20–22 weeks in asymptomatic women and using the result to guide monitoring. It does not specifically establish FGR risk identification throughout 20–24 weeks or describe proactive management of FGR before overt restriction; the monitoring pathway shown is framed around pre-eclampsia risk. Page numbers are unavailable in our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 101 · Cited by 245
Research works printed but not linked: 6
- Savchev S, Figueras F, Sanz-Cortes M, Cruz-Lemini M, Triunfo S, Botet F, Gratacos E. Evaluation of an optimal gestational age cut-off for the definition of early-and late-onset fetal growth restriction. Fetal Diagn Ther 2014; 36: 99-105.
- Tranquilli AL, Brown MA, Zeeman GG, Dekker G, Sibai BM. The definition of severe and early- onset preeclampsia. Statements from the International Society for the Study of Hypertension in Pregnancy (ISSHP). Pregnancy Hypertens 2013; 3: 44-47.
- Roberge S, Nicolaides KH, Demers S, Villa P, Bujold E. Prevention of perinatal death and adverse perinatal outcome using low-dose aspirin: a meta-analysis. Ultrasound Obstet Gynecol 2013; 41: 491-499.
- National Collaborating Centre for Women's and Children's Health (UK). Hypertension in pregnancy: the management of hypertensive disorders during pregnancy. RCOG Press: London, 2010.
- Spanish Society of Gynaecology and Obstetrics (SEGO): Practical assistance guide: hypertensive disorders in pregnancy. Prog en Obstet y Ginecol 2020; 63: 244-272.
- NICE. Evidence review for prediction of complications in pre-eclampsia: Hypertension in pregnancy: diagnosis and management: Evidence review C. https://www.ncbi.nlm.nih.gov/books/NBK577929/ [17 May 2022].
- Authors
- Stepan, H., Galindo, A., Hund, M., Schlembach, D., Sillman, J., Surbek, D., & Vatish, M.
- Affiliations
- University Hospital Leipzig (DE)
- Hospital Universitario 12 De Octubre (ES)
- F. Hoffmann-La Roche AG (CH)
- Vivantes Klinikum (DE)
- University of Bern (CH)
- University of Oxford (GB)
- Corresponding author
- Stepan, H.
- Venue
- Ultrasound in Obstetrics & Gynecology
- Publisher
- Wiley
- Published
- 2023-02
- Volume
- 61
- Issue
- 2
- Pages
- 168-180
- ISSN
- 0960-7692 (ISSN-L)
- 1469-0705
- OpenAlex
- W4285012668
- Cited by
- 245
- References
- 101
- Citations by year
- 2026: 79 · 2025: 79 · 2024: 58 · 2023: 28 · 2022: 1
- FWCI
- 8.35
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Ultrasound in Obstetrics and Gynecology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Health Sciences › Medicine › Psychiatry and Mental health › Neurological Complications and Syndromes
- Health Sciences › Medicine › Epidemiology › Preterm Birth and Chorioamnionitis
- Keywords
- preeclampsia, fetal growth restriction, soluble fms-like tyrosine kinase-1, placental growth factor, sFlt-1/PlGF ratio, angiogenic factors, twin pregnancy, first-trimester screening, preterm birth, stillbirth, endothelial dysfunction, biomarkers
- MeSH terms
- Placenta Growth Factor, Female, Fetal Growth Retardation, Humans, Infant, Newborn, Placenta, Pre-Eclampsia, Predictive Value of Tests, Pregnancy, Biomarkers, Vascular Endothelial Growth Factor Receptor-1, Vascular Endothelial Growth Factor A, Premature Birth, Stillbirth
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
