An Elevated Maternal Plasma Soluble Fms-Like Tyrosine Kinase-1 to Placental Growth Factor Ratio at Midtrimester Is a Useful Predictor for Preeclampsia

Overview

Journal Obstet Gynecol Int

Publisher Wiley

Specialty Gynecology & Obstetrics

Date 2013 Dec 25

PMID 24367379

Citations 12

Authors

Mahmoud Fathy Hassan

Nancy Mohamed Ali Rund

Ahmed Husseiny Salama

Affiliations

Soon will be listed here.

Abstract

Background. To assess the ability of mid-trimester sFlt-1/PlGF ratio for prediction of preeclampsia in two different Arabic populations. Methods. This study measured levels of sFlt-1, PlGF, and sFlt-1/PlGF ratio at midtrimester in 83 patients who developed preeclampsia with contemporary 250 matched controls. Results. Women subsequently developed preeclampsia had significantly lower PlGF levels and higher sFlt-1 and sFlt-1/PlGF ratio levels than women with normal pregnancies (P < 0.0001 for all). Women who with preterm preeclampsia had significantly higher sFlt-1 and sFlt-1/PlGF ratio than term preeclamptic women (P = 0.01, 0.003, resp.). A cutoff value of 3198 pg/mL for sFlt-1 was able to predict preeclampsia with sensitivity, specificity, and accuracy of 88%, 83.6%, and 84.7%, respectively, with odds ratio (OR) 37.2 [95% confidence interval (CI) 17.7-78.1]. PIGF at cutoff value of 138 pg/mL was able to predict preeclampsia with sensitivity, specificity, and accuracy of 85.5%, 77.2%, and 79.3%, respectively, with OR 20 [95% CI, 10.2-39.5]. The sFlt-1/PIGF ratio at cutoff value of 24.5 was able to predict preeclampsia with sensitivity, specificity, and accuracy of 91.6%, 86.4%, and 87.7%, respectively with OR 67 [95% CI, 29.3-162.1]. Conclusion. Midtrimester sFlt-1/PlGF ratio displayed the highest sensitivity, specificity, accuracy, and OR for prediction of preeclampsia, demonstrating that it may stipulate more effective prediction of preeclampsia development than individual factor assay.

Citing Articles

Maternal angiogenic factor disruptions prior to clinical diagnosis of preeclampsia: insights from the REVAMP study.

Nema J, Sundrani D, Randhir K, Deshpande J, Lalwani S, Wagh G Hypertens Res. 2024; 47(9):2532-2548.

PMID: 38965425 DOI: 10.1038/s41440-024-01775-8.

Association of angiogenic factors (placental growth factor and soluble FMS-like tyrosine kinase-1) in preeclamptic women of African ancestry comorbid with HIV infection.

Mlambo Z, Sebitloane M, Naicker T Arch Gynecol Obstet. 2024; 311(2):259-274.

PMID: 38910142 PMC: 11890319. DOI: 10.1007/s00404-024-07590-3.

Correlation of sFlt/PlGF ratio with severity of preeclampsia in an Indian population.

Kumar N, Das V, Agarwal A, Agrawal S AJOG Glob Rep. 2023; 3(2):100177.

PMID: 36911235 PMC: 9992748. DOI: 10.1016/j.xagr.2023.100177.

Placental growth factor for the prognosis of women with preeclampsia (fullPIERS model extension): context matters.

Ukah U, Payne B, Hutcheon J, Chappell L, Seed P, Conti-Ramsden F BMC Pregnancy Childbirth. 2020; 20(1):668.

PMID: 33153436 PMC: 7643272. DOI: 10.1186/s12884-020-03332-w.

The Role of Placental Growth Factor, Soluble Endoglin, and Uterine Artery Diastolic Notch to Predict the Early Onset of Preeclampsia.

Lubis M, Hariman H, Lumbanraja S, Bachtiar A Open Access Maced J Med Sci. 2019; 7(7):1153-1159.

PMID: 31049099 PMC: 6490477. DOI: 10.3889/oamjms.2019.154.

References

Kim S, Ryu H, Yang J, Kim M, Han J, Kim J . Increased sFlt-1 to PlGF ratio in women who subsequently develop preeclampsia. J Korean Med Sci. 2007; 22(5):873-7. PMC: 2693856. DOI: 10.3346/jkms.2007.22.5.873. View

Noori M, Donald A, Angelakopoulou A, Hingorani A, Williams D . Prospective study of placental angiogenic factors and maternal vascular function before and after preeclampsia and gestational hypertension. Circulation. 2010; 122(5):478-87. DOI: 10.1161/CIRCULATIONAHA.109.895458. View

Noris M, Perico N, Remuzzi G . Mechanisms of disease: Pre-eclampsia. Nat Clin Pract Nephrol. 2006; 1(2):98-114. DOI: 10.1038/ncpneph0035. View

Koga K, Osuga Y, Yoshino O, Hirota Y, Ruimeng X, Hirata T . Elevated serum soluble vascular endothelial growth factor receptor 1 (sVEGFR-1) levels in women with preeclampsia. J Clin Endocrinol Metab. 2003; 88(5):2348-51. DOI: 10.1210/jc.2002-021942. View

Venkatesha S, Toporsian M, Lam C, Hanai J, Mammoto T, Kim Y . Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med. 2006; 12(6):642-9. DOI: 10.1038/nm1429. View

Chaiworapongsa T, Romero R, Espinoza J, Bujold E, Kim Y, Goncalves L . Evidence supporting a role for blockade of the vascular endothelial growth factor system in the pathophysiology of preeclampsia. Young Investigator Award. Am J Obstet Gynecol. 2004; 190(6):1541-7. DOI: 10.1016/j.ajog.2004.03.043. View

Vatten L, Eskild A, Nilsen T, Jeansson S, Jenum P, Staff A . Changes in circulating level of angiogenic factors from the first to second trimester as predictors of preeclampsia. Am J Obstet Gynecol. 2007; 196(3):239.e1-6. DOI: 10.1016/j.ajog.2006.10.909. View

Kendall R, Thomas K . Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor. Proc Natl Acad Sci U S A. 1993; 90(22):10705-9. PMC: 47846. DOI: 10.1073/pnas.90.22.10705. View

Lam C, Lim K, Karumanchi S . Circulating angiogenic factors in the pathogenesis and prediction of preeclampsia. Hypertension. 2005; 46(5):1077-85. DOI: 10.1161/01.HYP.0000187899.34379.b0. View

10.

Ferrara N . Role of vascular endothelial growth factor in regulation of physiological angiogenesis. Am J Physiol Cell Physiol. 2001; 280(6):C1358-66. DOI: 10.1152/ajpcell.2001.280.6.C1358. View

11.

Maynard S, Min J, Merchan J, Lim K, Li J, Mondal S . Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest. 2003; 111(5):649-58. PMC: 151901. DOI: 10.1172/JCI17189. View

12.

Sibai B, Dekker G, Kupferminc M . Pre-eclampsia. Lancet. 2005; 365(9461):785-99. DOI: 10.1016/S0140-6736(05)17987-2. View

13.

. ACOG committee opinion. Antenatal corticosteroid therapy for fetal maturation. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet. 2002; 78(1):95-7. View

14.

Kupferminc M, Daniel Y, Englender T, Baram A, Many A, Jaffa A . Vascular endothelial growth factor is increased in patients with preeclampsia. Am J Reprod Immunol. 1997; 38(4):302-6. DOI: 10.1111/j.1600-0897.1997.tb00519.x. View

15.

Wolf M, Shah A, Lam C, Martinez A, Smirnakis K, Epstein F . Circulating levels of the antiangiogenic marker sFLT-1 are increased in first versus second pregnancies. Am J Obstet Gynecol. 2005; 193(1):16-22. DOI: 10.1016/j.ajog.2005.03.016. View

16.

. ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet. 2002; 77(1):67-75. View

17.

Shibata E, Rajakumar A, Powers R, Larkin R, Gilmour C, Bodnar L . 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. J Clin Endocrinol Metab. 2005; 90(8):4895-903. DOI: 10.1210/jc.2004-1955. View

18.

He Y, Smith S, Day K, Clark D, Licence D, Charnock-Jones D . Alternative splicing of vascular endothelial growth factor (VEGF)-R1 (FLT-1) pre-mRNA is important for the regulation of VEGF activity. Mol Endocrinol. 1999; 13(4):537-45. DOI: 10.1210/mend.13.4.0265. View

19.

Levine R, Maynard S, Qian C, Lim K, England L, Yu K . Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004; 350(7):672-83. DOI: 10.1056/NEJMoa031884. View

20.

Levine R, Thadhani R, Qian C, Lam C, Lim K, Yu K . Urinary placental growth factor and risk of preeclampsia. JAMA. 2005; 293(1):77-85. DOI: 10.1001/jama.293.1.77. View