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Angiogenic Factors and the Risk of Adverse Outcomes in Women With Suspected Preeclampsia
Open accessAbstract
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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“The increase of sVEGFR-1 causes a parallel decrease of maternal plasma concentrations of PIGF in preeclampsia(119, 143–150).”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [146]
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DeLong, E. R., DeLong, D. M., & Clarke-Pearson, D. L. (1988) · Biometrics · doi:10.2307/2531595 · Cited by 22,649
Maynard, S. E., Min, J.-Y., Merchan, J., Lim, K.-H., Li, J., Mondal, S., Libermann, T. A., Morgan, J. P., Sellke, F. W., Stillman, I. E., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17189 · Cited by 4,101
Self-citationCirculating angiogenic factors and the risk of preeclampsia
Levine, R. J., Maynard, S. E., Qian, C., Lim, K.-H., England, L. J., Yu, K. F., Schisterman, E. F., Thadhani, R., Sachs, B. P., Epstein, F. H., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa031884 · Cited by 3,720
Self-citationCirculating angiogenic factors and the risk of preeclampsia*
(2004) · Obstetrics and Gynecology · doi:10.1097/00006250-200405000-00028 · Cited by 2,623
Soluble Endoglin and Other Circulating Antiangiogenic Factors in Preeclampsia
Levine, R. J., Lam, C., Qian, C., Yu, K. F., Maynard, S. E., Sachs, B. P., Sibai, B. M., Epstein, F. H., Romero, R. J., Thadhani, R., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa055352 · Cited by 1,823
Kendall, R. L., & Thomas, K. A. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.22.10705 · Cited by 1,419
Eremina, V., Sood, M. M., Haigh, J. J., Nagy, A., Lajoie, G., Ferrara, N., Gerber, H. P., Kikkawa, Y., Miner, J. H., & Quaggin, S. E. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17423 · Cited by 1,308
Soluble Endoglin and Other Circulating Antiangiogenic Factors in Preeclampsia
(2006) · New England Journal of Medicine · doi:10.1056/nejmx060063 · Cited by 1,237
ACOG Practice Bulletin No. 33: Diagnosis and Management of Preeclampsia and Eclampsia
ACOG Committee on Obstetric Practice (2002) · Obstetrics and Gynecology · doi:10.1016/s0029-7844(01)01747-1 · Cited by 1,180
Wallis, A. B., Saftlas, A. F., Hsia, J., & Atrash, H. K. (2008) · American Journal of Hypertension · doi:10.1038/ajh.2008.20 · Cited by 759
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Rana (2019) · doi:10.1161/circresaha.118.313276 · Cited by 2,095
Brown, M. A., Magee, L. A., Kenny, L. C., Karumanchi, S. A., McCarthy, F. P., Saito, S., Hall, D. R., Warren, C. E., Adoyi, G., & Ishaku, S. (2018) · Hypertension · doi:10.1161/hypertensionaha.117.10803 · Cited by 2,089
“Measurement of angiogenic factors may play a role in this regard in the future but is still at a research stage.(56)”
BackgroundSelf-citationPredictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia
Zeisler, H., Llurba, E., Chantraine, F., Vatish, M., Staff, A. C., Sennström, M., Olovsson, M., Brennecke, S. P., Stepan, H., Allegranza, D., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1414838 · Cited by 1,872
Mol, B. W., Roberts, C. T., Thangaratinam, S., Magee, L. A., de Groot, C. J. M., & Hofmeyr, G. J. (2015) · The Lancet · doi:10.1016/s0140-6736(15)00070-7 · Cited by 1,667
Tranquilli, A. L., Dekker, G., Magee, L. A., Roberts, J. M., Sibai, B. M., Steyn, W., Zeeman, G. G., & Brown, M. A. (2014) · Pregnancy Hypertension · doi:10.1016/j.preghy.2014.02.001 · Cited by 1,419
Metadata
- 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
- Venue
- Circulation
- Published
- 2012-02-21
- Volume
- 125
- Issue
- 7
- Pages
- 911-919
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- 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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