Cited by 668Pregnancy and preeclampsia studiesNeurological Complications and SyndromesNeonatal and fetal brain pathology

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Angiogenic Factors and the Risk of Adverse Outcomes in Women With Suspected Preeclampsia

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Rana, Sarosh, Powe, Camille E., Salahuddin, Saira, Verlohren, Stefan, Perschel, Frank H., Levine, Richard J., Lim, Kee-Hak, Wenger, Julia B., Thadhani, Ravi, Karumanchi, S. Ananth·2012·Circulation

DOI 10.1161/circulationaha.111.054361PMC PMC3319742

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Abstract

BACKGROUND: An imbalance in circulating angiogenic factors plays a central role in the pathogenesis of preeclampsia. METHODS AND RESULTS: We prospectively studied 616 women who were evaluated for suspected preeclampsia. We measured plasma levels of antiangiogenic soluble fms-like tyrosine kinase 1 (sFlt1) and proangiogenic placental growth factor (PlGF) at presentation and examined for an association between the sFlt1/PlGF ratio and subsequent adverse maternal and perinatal outcomes within 2 weeks. The median sFlt1/PlGF ratio at presentation was elevated in participants who experienced any adverse outcome compared with those who did not (47.0 [25th-75th percentile, 15.5-112.2] versus 10.8 [25th-75th percentile, 4.1-28.6]; P<0.0001). Among those presenting at <34 weeks (n=167), the results were more striking (226.6 [25th-75th percentile, 50.4-547.3] versus 4.5 [25th-75th percentile, 2.0-13.5]; P<0.0001), and the risk was markedly elevated when the highest sFlt1/PlGF ratio tertile was compared with the lowest (odds ratio, 47.8; 95% confidence interval, 14.6-156.6). Among participants presenting at <34 weeks, the addition of sFlt1/PlGF ratio to hypertension and proteinuria significantly improved the prediction for subsequent adverse outcomes (area under the curve, 0.93 for hypertension, proteinuria, and sFlt1/PlGF versus 0.84 for hypertension and proteinuria alone; P=0.001). Delivery occurred within 2 weeks of presentation in 86.0% of women with an sFlt1/PlGF ratio ≥85 compared with 15.8% of women with an sFlt1/PlGF ratio <85 (hazard ratio, 15.2; 95% confidence interval, 8.0-28.7). CONCLUSIONS: In women with suspected preeclampsia presenting at <34 weeks, circulating sFlt1/PlGF ratio predicts adverse outcomes occurring within 2 weeks. The accuracy of this test is substantially better than that of current approaches and may be useful in risk stratification and management. Additional studies are warranted to validate these findings.

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Circulating angiogenic factors and the risk of preeclampsia
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The value of angiogenic biomarkers in determining preeclampsia-related perinatal deaths: A cross-sectional study in a high burden setting of southern Mozambique
Chileshe, M. N., Rakislova, N., Carrilho, C., Fernandes, F., Nhampossa, T., Morató, A., Marimón, L., Peñuelas, N., Mendes, A., Luís, E., et al. (2026) · PLoS ONE · doi:10.1371/journal.pone.0339830
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Authors: Rana, S., Powe, C. E., Salahuddin, S., Verlohren, S., Perschel, F. H., Levine, R. J., Lim, K.-H., Wenger, J. B., Thadhani, R., & Karumanchi, S. A.
Affiliations: National Institutes of Health (US)
ORCID: Rana, Sarosh
Powe, Camille E.
Verlohren, Stefan
Perschel, Frank H.
Wenger, Julia B.
Thadhani, Ravi
Karumanchi, S. Ananth
Venue: Circulation
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2012-02-21
Volume: 125
Issue: 7
Pages: 911-919
ISSN: 0009-7322 (ISSN-L)
1524-4539
DOI: 10.1161/circulationaha.111.054361
PMC: PMC3319742
OpenAlex: W2134502189
Cited by: 668
References: 39
Citations by year: 2026: 30 · 2025: 51 · 2024: 40 · 2023: 46 · 2022: 50 · 2021: 52 · 2020: 49 · 2019: 48 · 2018: 49 · 2017: 48 · 2016: 49 · 2015: 42 · 2014: 49 · 2013: 41 · 2012: 20
FWCI: 58.66
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Circulation (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Howard Hughes Medical Institute
Topics: Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
Health Sciences › Medicine › Clinical Neurology › Neurological Complications and Syndromes
Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
Keywords: preeclampsia, angiogenic factors, soluble fms-like tyrosine kinase-1, placental growth factor, sFlt-1/PlGF ratio, adverse maternal outcomes, perinatal outcomes, early-onset preeclampsia, proteinuria, hypertension, adverse outcome prediction, preterm birth, placental insufficiency, endothelial dysfunction, maternal morbidity
MeSH terms: Placenta Growth Factor, Adult, Female, Humans, Pre-Eclampsia, Pregnancy, Pregnancy Proteins, Prospective Studies, Risk, ROC Curve, Systole, Logistic Models, Vascular Endothelial Growth Factor Receptor-1

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Angiogenic Factors and the Risk of Adverse Outcomes in Women With Suspected Preeclampsia

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