Diagnostic and prognostic significance of serum soluble endoglin levels in preeclampsia and eclampsia

Sachan, Rekha; Patel, Munna Lal; Dhiman, Soniya; Gupta, Pooja; Sachan, Pushplata; Shyam, Radhey

Diagnostic and prognostic significance of serum soluble endoglin levels in preeclampsia and eclampsia

Authors

¹ Department of Obstetrics and Gynaecology, King George Medical University, Lucknow, Uttar Pradesh, India

² Department of Medicine, King George Medical University, Lucknow, Uttar Pradesh, India

³ Department of Physiology, Career Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

⁴ Department of Geriatric Intensive Care Unit, King George Medical University, Lucknow, Uttar Pradesh, India

Abstract

Background: Preeclampsia is a multisystem disorder of unknown etiology that affects 4–5% of all pregnancies. The aim of the study was to evaluate the diagnostic accuracy of serum soluble endoglin (sEng) in preeclampsia and eclampsia and also to evaluate its prognostic significance.
Materials and Methods: This prospective case–control study carried out over a period of 1 year in the Department of Obstetrics and Gynaecology, King George Medical University, Lucknow. After written informed consent and ethical clearance, total 90 subjects were enrolled. Among them, 30 subjects of eclampsia, 15 of nonsevere preeclampsia, 15 of severe preeclampsia served as cases, and 30 healthy pregnant normotensive women served as controls. Levels were estimated by enzyme-linked immunosorbent assay technique in both cases and controls.

Results: Mean level was highest in eclampsia group (14.96 ± 1.96 ng/mL) and lowest in controls (2.08 ± 0.56 ng/mL). At cut-off value of sEng levels of ≥6.26 ng/mL, it was found to be 100% sensitive and 100% specific for the diagnosis of preeclampsia (area under curve =1) at 95% confidence interval. sEng levels were strongly correlated with systolic (r = 0.928) and diastolic blood pressure (r = 0.916), serum lactate dehydrogenase (r = 0.791) and serum uric acid (r = 0.722). All four maternal deaths were reported within eclampsia group, in whom the mean sEng level was significantly higher (17.84 ± 0.22) as compared to other subjects (9.50 ± 5.80).
Conclusion: sEng is a novel marker for diagnosis of preeclampsia, and it can also be used as a prognostic marker to predict the severity of preeclampsia.

Keywords

References

1.	Prakash J, Pandey LK, Singh AK, Kar B. Hypertension in pregnancy: Hospital based study. J Assoc Physicians India 2006;54:273-8.
2.	Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet 2005;365:785-99.
3.	Redman CW, Sargent IL. Latest advances in understanding preeclampsia. Science 2005;308:1592-4.
4.	Hagmann H, Thadhani R, Benzing T, Karumanchi SA, Stepan H. The promise of angiogenic markers for the early diagnosis and prediction of preeclampsia. Clin Chem 2012;58:837-45.
5.	Sibai BM, Sarinoglu C, Mercer BM. Eclampsia. VII. Pregnancy outcome after eclampsia and long-term prognosis. Am J Obstet Gynecol 1992;166 (6 Pt 1):1757-61.
6.	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;123:2856-69.
7.	Mutter WP, Karumanchi SA. Molecular mechanisms of preeclampsia. Microvasc Res 2008;75:1-8.
8.	Maynard SE, Min JY, Merchan J, Lim KH, Li J, Mondal S, ssss. 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.
9.	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;12:642-9.
10.	Raab U, Velasco B, Lastres P, Letamendía A, Calés C, Langa C, et al. Expression of normal and truncated forms of human endoglin. Biochem J 1999;339 (Pt 3):579-88.
11.	López-Casillas F, Cheifetz S, Doody J, Andres JL, Lane WS, Massagué J. Structure and expression of the membrane proteoglycan betaglycan, a component of the TGF-beta receptor system. Cell 1991;67:785-95.
12.	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;2:47-51.
13.	Sachan R, Patel ML, Sachan P, Gaurav A, Singh M, Bansal B. Outcomes in hypertensive disorders of pregnancy in the North Indian population. Int J Womens Health 2013;5:101-8.
14.	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.
15.	El-Said MH, Abd El-Ghaffar MN, Eldin ELashmawi HS, Saad GR. Role of serum soluble endoglin in patients with preeclampsia. J Appl Sci Res 2013;9:1249-55.
16.	Caniggia I, Grisaru-Gravnosky S, Kuliszewsky M, Post M, Lye SJ. Inhibition of TGF-beta 1 restores the invasive capability of extravillous trophoblasts in preeclamptic pregnancies. J Clin Invest 1999;103:1641-50.
17.	Zhou Y, McMaster M, Woo K, Janatpour M, Perry J, Karpanen T, et al. Vascular endothelial growth factor ligands and receptors that regulate human cytotrophoblast survival are dysregulated in severe preeclampsia and hemolysis, elevated liver enzymes, and low platelets syndrome. Am J Pathol 2002;160:1405-23.
18.	Gaber K, Hamdy E, Hanafy A. Soluble endoglin as a new marker for prediction of pre-eclampsia in early pregnancy. Middle East Fertil Soc J 2010;15:42-6.
19.	Salahuddin 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.e1-6.
20.	Elhawary TM, El-Bendary AS, Demerdash H. Maternal serum endoglin as an early marker of pre-eclampsia in high-risk patients. Int J Womens Health 2012;4:521-5.
21.	Toporsian M, Gros R, Kabir MG, Vera S, Govindaraju K, Eidelman DH, et al. A role for endoglin in coupling eNOS activity and regulating vascular tone revealed in hereditary hemorrhagic telangiectasia. Circ Res 2005;96:684-92.
22.	Rana S, Cerdeira AS, Wenger J, Salahuddin S, Lim KH, Ralston SJ, et al. Plasma concentrations of soluble endoglin versus standard evaluation in patients with suspected preeclampsia. PLoS One 2012;7:e48259.

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