Correlation of serum soluble endoglin to the severity of pre-eclampsia and its effect on the pregnancy outcome

Tamer Mamdouh Abd El-Dayem, Ahmed Samy Elagwany, Mohammed Yosry Khamis, Eman Soliman Kamha, Ahmed Mohammed Mohammed Hassan


Background: Preeclampsia is a major obstetric problem and a significant source of maternal and neonatal morbidity and mortality. Preeclampsia  is associated with  increased  risks of  placental  abruption,  acute renal  failure,  cerebrovascular and  cardiovascular complications, disseminated intravascular  coagulation,  and  maternal death. Consequently, early diagnosis of preeclampsia and  close  observation are imperative. In these cases of preeclampsia, combination of Doppler flowmetry and circulating angiogenic factors levels are recorded. Stepan et al examined endoglin, a cell-surface co-receptor for transforming growth factor in patients with Doppler flow patterns of preeclampsia at 19-24 weeks. Soluble endoglin levels were elevated in second trimester pregnancies with abnormal uterine perfusion in women who experienced preeclampsia. The aim of this study was to test if there is correlation between the level of serum endoglin in pregnant women with severe preeclampsia to the maternal and fetal outcome.

Methods: This study was conducted on a group of 90 pregnant women attended to the Antenatal clinic and selected from the preeclampsia unit of EL- Shatby Maternity University Hospital, The selected patients were subdivided in two groups. Group A (control group): 30 cases of normotensive pregnant ladies. Group B (case group): 60 cases of severe preeclamptic pregnant ladies. Routine investigations, maternal serum soluble endoglin and ultrasound results were analysed and compared for both groups.

Results: Significant correlation was found between severe preeclampsia and high level soluble endoglin. Significant correlation was found between high level of soluble endoglin and the occurrence of IUGR among the severe preeclamptic patients. Positive correlation was found between serum level of soluble endoglin and uterine artery PI and uterine artery RI, the higher the serum level of soluble endoglin the higher the uterine artery pulsatility and resistance index. Significant correlation was found between high level of soluble endoglin and the occurrence of specific complications, the higher the level of soluble endoglin the higher the risk of exposure to preeclampsia complications as the occurrence of eclamptic fits, the development of HELLP syndrome, the admission to the ICU, the admission of the baby to the NICU, and the fetal death.

Conclusions: From our study, it is evident that serum endoglin rises during  normal  as  well  as  preeclamptic  pregnancy  and that  the  rise  in  preeclampsia  is  much  higher, the rise in endoglin levels may  occur  as  early  as  the  first  trimester  in  pregnancies  which  later  develop  preeclampsia.   Hence, used alone or in combination with uterine artery Doppler flowmetry, the measurement of soluble serum endoglin has the potential for use as a predictive clinical test for preeclampsia risk assessment and could potentially improve the outcome of pregnancy.


Serum soluble endoglin, Pre-eclampsia, Pregnancy outcome

Full Text:



Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet. 2005;365:785-99.

Ghulmiyyah L, Sibai B. Maternal mortality from preeclampsia/eclampsia. Seminars in Perinatology 2012; 36(1):56-9.

WHO Recommendations for prevention and treatment of preeclampsia and eclampsia, WHO Department of Maternal and Child Health, Geneva, Switzerland. World Health Organization (WHO). 2011;38.

Irgens HU, Reisaeter L, Irgens LM, Lie RT. Long-term mortality of mothers and fathers after pre-eclampsia: population based cohort study. BMJ. 2001;323:1213-7.

Roberts JM, Taylor RN, Musci TJ, Rodgers GM, Hubel CA, McLaughlin MK. Preeclampsia: an endothelial cell disorder. Am J Obstet Gynecol. 1989;161:1200-4.

Chambers JC, Fusi L, Malik IS, Haskard DO, De Swiet M, Kooner JS. Association of maternal endothelial dysfunction with preeclampsia. JAMA. 2001;285:1607-12.

Conrad KP, Benyo DF. Placental cytokines and the pathogenesis of preeclampsia. Am J Reprod Immunol. 1997;37:240-9.

Fisher SJ, Roberts JM. Defects in placentation and placental perfusion. In: Chelsey’s Hypertensive Disorders in Pregnancy. by Lindheimer MD, Roberts JM, and Cunningham FG. Stanford, CT: Appleton & Lange. 1999;377-94.

Maynard SE, Min JY, Merchan J, Lim KH, Li J, Mondal S, et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest. 2003;111:649-58.

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

Levine RJ, Lam C, Qian C, Yu KF, Maynard SE, Sachs BP, et al. Soluble endoglin and other circulating antiangiogenic factors in preeclampsia. N Engl J Med. 2006;355:992-1005.

Rana S, Karumanchi SA, Levine RJ, Venkatesha S, Rauh-Hain JA, Tamez H, et al. Sequential changes in antiangiogenic factors in early pregnancy and risk of developing preeclampsia. Hypertension. 2007;50:137-42.

Makris A, Thornton C, Thompson J, Thomson S, Martin R, Ogle R et al. Uteroplacental isch- emia results in proteinuric hypertension and elevated sFLT-1. Kidney Int. 2007;71:977-84.

Park JE, Chen HH, Winer J, Houck KA, Ferrara N. Placenta growth factor. Potentiation of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but not to Flk-1/KDR. J Biol Chem. 1994;269:25646-54.

Venkatesha S, Toporsian M, Lam C, Hanai J, Mammoto T, Kim YM et al, Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med. 2006;12:642-6.

Carty DM, Delles C, Dominiczak AF. Nov-el biomarkers for predicting preeclampsia. Trends Cardiovasc Med. 2008;18:186-94.

Levine RJ, Lam C, Qian C, Yu KF. Soluble endoglin and other circulating antiangiogenic factors in preeclampsia. N Engl J Med. 2006;355:992-1005.

Venkatesha S, Toporsian M, Lam C. Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med. 2006;12:642-9.

Dallas NA, Samuel S, Xia L. Endoglin (CD105): a marker of tumor vasculature and potential target for therapy. Clin Cancer Res. 2008;14:1931-7.

Toporsian M, Gros R, Kabir MG. A role for endoglin in coupling eNOS activity and regulating vascular tone revealed in hereditary hemorrhagic telangiectasia. Circ Res. 2005;96:684-92.

American College of Obstetricians and Gynecologists (ACOG) Committee on Obstetric Practice: ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. sInt J Gynecol Obtet. 2002;77:67-75.

Kotz S, Balakrishnan N, Read CB, Vidakovic B. Encyclopedia of statistical sciences. 2nd ed. Hoboken, N.J: Wiley-Interscience; 2006.

Kirkpatrick LA, Feeney BC. A simple guide to IBM SPSS statistics for version 20.0. Student ed. Belmont, Calif. Wadsworth, Cengage Learning; 2013.

Levine RJ, Maynard SE, Qian C, Lim KH, Lucinda J, Yu KF. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004:350:672-83.

Dugas G, Fuller J, Singh S, Watson J. Pheochromocytoma and pregnancy: a case report and review of anesthetic management. Can J Anaesth. 2004;51:134-8.

Venkatesha S, Toporsian M, Lam C. Soluble endoglin contributes to the pathogenesis of pre-eclampsia. Nat Med. 2006;12:642-9.

Masuyama H, Nakatsukasa H, Takamoto N. Correlation between soluble endoglin, vascular endothelial growth factor receptor-1, and adipocytokines in pre-eclampsia. J Clin Endocrinol Metab. 2009;92:2672-9.

Hirashima C, Ohkuchi A, Arai F. Establishing reference values for both total soluble fms-like tyrosine kinase 1 and free placental growth factor in pregnant women. Hypertens Res. 2009;28:727-32.

Razieh DF, Mahdyeh M, Saedeh A, Reza NM. Uterine Artery Doppler Sonography in Predicting Preeclampsia and IUGR at 14-16. WASJ. 2013;22(2):197-201.

Kofinas AD, Penry M, Nelson LH, Meis PJ, Swain M. Flow velocity waveform analysis. Southeren medical journal. 1990;83(2):150-5.

Duhan N, Sharma D, Garg N, Dahiya K, Sirohiwal D. Comparative evaluation of serum soluble endoglin level in preeclampsia and normotensive pregnant women. J Physiol Pathophysiol. 2011;2(4):47-51.

Slahuddin S, Lee Y, Vadnais M, Sachs BP, Karumanchi SA, Lim KH. Diagnostic utility of soluble fms-like tyrosine kinase 1 and soluble endoglin in hypertensive diseases of pregnancy. Am J Obstet Gynecol. 2007;197:28-9.

Lee HB, Kil KC, Nam SY, Shin JE, Cheon YJ, Lee Y. Clinical usefulness of soluble fms-like tyrosine kinase 1, soluble endoglin and placental growth factor in korean women with preeclampsia Korean J Obstet Gynecol. 2011;54(5):229-35.

K. Gaber, Hamdyb EC, Hanafy A. Soluble Endoglin as a new marker for prediction of pre-eclampsia in early pregnancy Middle East Fertility Society Journal. 2010;15:42-6.

Chaiworapongsa T, Romero R, Kusanovic JP, Mittal P, Kim SK, Gotsch F. Plasma soluble endoglin concentration in pre-eclampsia is associated with an increased impedance to flow in the maternal and fetal circulations. Ultrasound Obstet Gynecol. 2010;35(2):155-62.

Tobinaga CM , Torloni MR, Gueuvoghlanian-Silva BY, Pendeloski KPT, Akita PA, Sass N. Angiogenic factors and uterine Doppler velocimetry in early and late-onset preeclampsia. 2014;93(5):469-76.