Levels of molecular angiogenic and antiangiogenic in pregnant women with risk of preeclampsia


  • Diah Wulandari Department of Midwifery, Universitas Gadjah Mada, Yogyakarta, Indonesia http://orcid.org/0000-0002-3666-8382
  • Mohamad Sulchan Departement of Nutrition Science, Faculty of Medicine, Universitas Diponegoro, Semarang, Indonesia http://orcid.org/0000-0002-8321-3815
  • Syarief Thaufik Hidayat Departement of Obstetrics and Gynecology, Faculty of Medicine, Universitas Diponegoro, Semarang, Indonesia




Preeclampsia, PlGF, Risk factors, sFlt-1, VEGF


Background: Angiogenic and antiangiogenic imbalances play a major role in the pathogenesis of preeclampsia. Increased production of sFlt-1 by the placenta causes free circulating PIGF and VEGF concentrations to lower because it is bound by sFlt-1. Measuring levels of angiogenic and antiangiogenic proteins as biomarkers indicates placental dysfunction and distinguishes preeclampsia from other disorders. This study aims to analyze the levels of angiogenic and antiangiogenic molecules in pregnant women at risk for preeclampsia.

Methods: The study with a cross-sectional design was carried out in 11-15 weeks gestational age whom had a risk of preeclampsia with 30 samples in primary health care starting April-August 2018. Blood serum was measured by molecular levels of VEGF, PlGF, sFlt-1, and sFlt-1/PlGF ratio using the ELISA method. Data analysis used Pearson product moment test.

Results: The mean of VEGF levels are 15.5±21.6, PlGF 89.7±55.5, sFlt-1 11519.4±5126.0 and the ratio sFlt-1/PlGF 166.7±102.1. Correlation value of risk factors for preeclampsia with molecular levels of VEGF r= -0.05; p = 0.76, PlGF r= -0.21; p = 0.26, sFlt r= 0.01; p =0.99 and ratio sFlt-1/PlGF r = 0.10; p = 0.58.

Conclusions: The higher the total score of preeclampsia risk factor, the lower the molecular level of VEGF and PlGF is. Moreover, the higher the total score of preeclampsia risk factor, the higher the molecular level sFlt-1 and the sFlt-1/PlGF ratio is. There are no significant correlation between total score of preeclampsia risk factor and levels of molecule VEGF, PlGF, sFlt-1 and sFlt-1/PlGF ratio.


Magee L, Pels A, Helewa M, Rey E, von Dadelszen P. Diagnosis, evaluation, and management of the hypertensive disorders of pregnancy: executive summary. J Obs Gynaecol Can. 2014;36(5):416-38.

Wibowo N, Irwinda R, Frisdiantiny E, Kartaka M, Mose JC, Chalid MT, et al. Pedoman nasional pelayanan kedokteran diagnosis dan tata laksana preeklampsia. Jakarta: Perkumpulan Obstetri dan Ginekologi Indonesia Himpunan Kedokteran Feto Maternal. 2016:11-20.

Uzan J, Carbonnel M, Piconne O, Asmar R, Ayoubi JM. Pre-eclampsia: Pathophysiology, diagnosis, and management. Vasc Health Risk Manag. 2011;7(1):467-74.

Gathiram P, Moodley J. Pre-eclampsia: its pathogenesis and pathophysiolgy. Cardiovasc J Afr. 2016;27(2):71-8.

Esta M, Afdal P, Anggraini NW. Malondialdehyde levels are higher and glutathione levels are lower in preeclampsia than in normal pregnancies. Univ Med. 2017;36(3):179-86.

Lam C, Lim KH, Karumanchi SA. Circulating angiogenic factors in the pathogenesis and prediction of preeclampsia. Hypert. 2005;46(5):1077-85.

Levine RJ, Lam C, Qian C, Yu KF, Maynard SE, Sachs BP, et al. Soluble endoglin and other circulating antiangiogenic factors in preeclampsia, 2006. Available at: http://www.nejm.org/doi/pdf/10.1056/NEJMoa055352. Accessed on 2nd April 2019.

Thadhani RI, Johnson RJ, Karumanchi SA. Hypertension during pregnancy: a disorder begging for pathophysiological support. Hypert. 2005;46(6):1250-1.

National Institute for Health and Care Excellence. Preterm labour and birth, 2015. Available at: http://nice.org.uk/guidance/ng25. Accessed on 2nd April 2019.

Chappell LC, Enye S, Seed P, Briley AL, Poston L, Shennan AH. Adverse perinatal outcomes and risk factors for preeclampsia in women with chronic hypertension: A prospective study. Hypert. 2008;54:1002-9.

Verma MK, Kapoor P, Yadav R, Manohar RK. Risk factor assessment for preeclampsia: a case control study. Int J Med Public Heal. 2017;7(3):172-7.

Agrawal S, Millett C, Casas JP, Walia GK, Staines-Urias E. Prevalence of and risk factors for eclampsia in pregnant women in India. Fam Med Community Heal. 2017;5(4):225-44.

Esplin S, Ausett M, Fraser A, Kerber R, Mineau G, Carillo J, et al. Paternal and maternal components of the predisposition to preeclampsia. N Engl J Med. 2002;346(15):1105-12.

Duckitt K. Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies. BMJ. 2005;330(7491):565.

Dekker G, Robillard PY. The birth interval hypothesis - Does it really indicate the end of the primipaternity hypothesis. J Reprod Immunol. 2003;59(2):245-51.

Cunningham FG. Williams obstetrics. 24th edition. F. Gary Cunningham, Kenneth J. Leveno, Steven L. Bloom, Catherine Y. Spong, Jodi S. Dashe, Barbara L. Hoffman, Brian M. Casey JSS, editor. United States Publisher: New York : M: New York : McGraw-Hill Education/Medical; 2014.

Weiss JL, Malone FD, Emig D, Ball RH, Nyberg DA, Comstock CH, et al. Obesity, obstetric complications and cesarean delivery rate - A population-based screening study. Am J Obstet Gynecol. 2004;190(4):1091-7.

Sukhatme VP, Stillman IE, Epstein FH, Karumanchi SA, Maynard SE. Preeclampsia: a renal perspective. Kidney Int. 2005;67(6):2101-13.

Sibai BM. Diagnosis and management of gestational hypertension and preeclampsia. Obstet Gynecol. 2003;102(1):181-92.

Chen Y. Novel angiogenic factors for predicting preeclampsia: sFlt-1, PlGF, and soluble Endoglin. Open Clin Chem J. 2009;2:1-6.

Nikuei P, Malekzadeh K, Rajaei M, Nejatizadeh A, Ghasemi N. The imbalance in expression of angiogenic and anti-angiogenic factors as candidate predictive biomarker in preeclampsia. Iran J Reprod Med. 2015;13(5):251-62.

Agarwal R, Bills JE, Hecht TJW, Light RP. Role of home blood pressure monitoring in overcoming therapeutic inertia and improving hypertension control: A systematic review and meta-analysis. Hypert. 2011;57(1):29-38.

Powe CE, Levine RJ, Karumanchi SA. Preeclampsia, a disease of the maternal endothelium: The role of antiangiogenic factors and implications for later cardiovascular disease. Circulation. 2011;123(24):2856-69.

Sibiude J, Guibourdenche J, Dionne MD, Le Ray C, Anselem O, Serreau R, et al. Placental Growth Factor for the prediction of adverse outcomes in patients with suspected preeclampsia or intrauterine growth restriction. PLoS One. 2012;7(11):e50208.

Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, Yu KF, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004;350(7):672-83.

Poon LC, Nicolaides KH. Early Prediction of Preeclampsia. Obstet Gynecol Int. 2014;2014(2):1-11.

Shibuya M. Involvement of Flt-1 (VEGF receptor-1) in cancer and preeclampsia. Proc Japan Acad Ser B. 2011;87(4):167-78.

Maynard S, Epstein FH, Karumanchi SA. Preeclampsia and angiogenic imbalance. Annu Rev Med. 2008;59(1):61-78.

Yang Gu, Lewis YW. Placental productions and expressions of soluble Endoglin, soluble fms-Like tyrosine kinase receptor-1, and placental growth factor in normal and preeclamptic pregnancies. J Clin Endocrinol Metab. 2008;93(1):260-6.

Zeisler H, Llurba E, Chantraine F, Vatish M, Staff AC, Sennström M, et al. Predictive value of the sFlt-1:PlGF ratio in women with suspected preeclampsia. Obstet Gynecol Surv. 2016;71(5):273-4.






Original Research Articles