THE ROLE OF PREDICTOR PLACENTAL GROWTH FACTOR, SOLUBLE ENDOGLIN, SOLUBLE-FMS-LIKE-TYROSINE KINASE-1 AND PULSATIL UTERINA ARTERIAL INDEX TO PREDICT THE EARLY ONSET OF PREECLAMPSIA

Authors

  • MUARA P. LUBIS Fetomaternal Division, Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Sumatera Utara

DOI:

https://doi.org/10.22159/ijcpr.2020v12i3.38305

Keywords:

Preeclampsia, PlGF, sFlt1, Pulsatil Index, sEng

Abstract

Objective: In preeclampsia, there will be an increase in SFlt-1 and in and decrease in PlGF levels. This condition will cause disorders of vasculogenesis and angiogenesis in fetomaternal circulation, which will eventually lead to preeclampsia syndrome such as proteinuria, hypertension and endothelial dysfunction.

Methods: An observational study design with nested case-control. The study was conducted at Bunda Thamrin Hospital, Tanjung Mulia Medika Hospital, Sundari Hospital and private practice, from March to November 2018, with a sample of 64 research subjects.

Results: The results of this study indicate that there were significant values with p<0.05, namely the pulsatile value of the uterine artery index with a 1.228 cut-off point, Area Under Curve (AUC) of 78.2% (95% CI 59.3%-97%), sensitivity 80%, specificity 64.6%, PlGF level with 441 pg/ml cut-off point, Area Under Curve (AUC) of 82.5% (95% CI 61.5%-100%), sensitivity 80%, specificity 87.7%, sFlt-1 level with a cut-off point of 10087.5 pg/ml, Area Under Curve (AUC) of 81.2% (95% CI 63.6%-98.9%), sensitivity 80%, specificity 67.7% while sEng with p value>0.05 which means it is not significant.

Conclusion: From this study, no significant differences were found in sEng, whereas differences were found in the pulsatile value of the uterine artery index, PlGF levels, and sFlt-1 levels in the incidence of early-onset preeclampsia. From the multivariate analysis, an examination of PlGF levels alone is sufficient as a predictor of early-onset preeclampsia.

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References

1. Siddiq A, Mose JC, Irianti S. Perbandingan kadar soluble-fms-like tyrosine kinase 1 (sFlt1) serum kehamilan normal dengan preeklamsi berat serta hubungannya dengan tekanan darah dan derajat proteinuria. Bandung: Rumah Sakit Hasan Sadikin Bandung; 2015.
2. Kementerian Kesehatan RI dan WHO. Buku saku pelayanan kesehatan ibu di fasilitas kesehatan dasar dan rujukan. Jakarta: Kementerian Kesehatan RI; 2013.
3. Jido TA, Yakasai IA. Preeclampsia: a review of the evidence. Annals African Med 2013;12:3.
4. Barton JR, Sibai BM. Prediction and prevention of recurrent preeclampsia. Obstet Gynecol 2008;112:359-72.
5. Chaiworapongsa. Plasma soluble endoglin concentration in preeclampsia is associated with an increased impedance to flow in the maternal and fetal circulations. Ultrasound Obstet Gynecol 2010;35:155-62.
6. Alves. Reference range of uterine artery doppler parameters between the 11th and 14th pregnancy weeks in a population sample from North East Brazil. Rev Bras Ginecol Obstet 2013;32:128-32.
7. Tardif C, Dumontet E, Caillon H, Misbert E, Dochez V, Masson D, et al. Angiogenic factors sFlt-1 and PLGF in preeclampsia: prediction of risk and prognosis in a high-risk obstetric population. J Gynecol Obstet Hum Reprod 2018;47:17-21.
8. Hassan MF, Rund NM, Salama AH. An elevated maternal plasma soluble fms-like tyrosine kinase-1 to placental growth factor ratio at midtrimester is a useful predictor for preeclampsia. Obstet Gynecol Int 2013. Doi:10.1155/2013/202346
9. Birdir C, Droste L, Fox L, Frank M, Fryze J, Enekwe A, et al. Predictive vaue of sFlt-1, PlGF, sFlt-1/PlGF ratio and PAPP-A for late-onset preeclampsia and IUGR between 32 and 37 w of pregnancy. Pregnancy Hypertension 2018;12:124-8.
10. Doherty A, Carvalho JC, Drewlo S, EL-Khuffash A, Downey K, Dodds M, et al. Altered hemodynamics and hyperuricemia accompany an elevated sFlt-1/PLGF ratio before the onset of early severe preeclampsia. J Obstet Gynaecol Can 2014;36:692-700.
11. Andersen LB, Frederiksen Moller B, Havelund KW, Dechend R, Jorgensen JS, Jensen BL, et al. Diagnosis of preeclampsia with soluble Fms-like tyrosine kinase 1/placental growth factor ratio: an inter-assay comparison. J Am Soc Hypertens 2015;9:86-96.
12. Charkiewicz K, Jasinska E, Goscik J, Koc-Zorawska E, Zorawski M, Kuc P, et al. Angiogenic factor screening in women mild preeclampsia-new and significant proteins in plasma. Cytokine 2018;106:125-30.
13. Huppertz B, Kawaguchi R. First trimester serum markers to predict preeclampsia. Wien Med Wochenschr 2012;162/9-10:191-5.
14. Turpin CA, Sakyi SA, Owideru WKBA, Ephraim RKD, Anto EO. Association between adverse pregnancy outcome and imbalance in angiogenic regulators and oxidative stress biomarkers in gestational hypertension and preeclampsia. BMC Pregnancy Childbirth 2015;15:189.
15. Carty DM, Delles C, Dominiczak AF. Novel biomarkers for predicting preeclampsia. TCM 2008;18:5.
16. EL-Said MH, Mohammed NAG, EL-Ashmawi HS, Saad GR. Role of serum soluble endoglin in patients with preeclampsia. J Appl Sci Res 2013;2:1249-55.
17. Masuyama H, Nakatsukasa H, Takamoto N, Hiramatsu Y. Correlation between soluble endoglin, vascular endothelial growth factor receptor-1, and adipocytokines in preeclampsia. J Clin Endocrinol Metab 2007;92:2672-9.
18. Salahuddin S, Lee Y, Vadnais M, Sachs BP, Karumanchi SA, Lim KH. Diagnostic utility of soluble fms-like tyrosine kinase 1 and soluble endglin in hypertensive disease of pregnancy. Am J Obstet Gynecol 2007;197:28-6.
19. Cui L, Shu C, Liu Z, Tong W, Cui M, Wei C, et al. The expression of serum sEGFR, sFlt-1, sEndoglin and PLGF in preeclampsia. Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health; 2018.
20. Acharya A, Brima W, Burugu S, Rege T. Prediction of preeclampsia-bench; 2014.
21. Kar M. Role of biomarkers in early detection of preeclampsia. J Clin Diagnosis Res 2014;8:BE01-BE04.
22. Thadhani R, Mutter WP, Wolf M, Levine RJ, Taylor RN, Sukhatme VP, et al. First trimester placental growth factor and soluble fms-like tyrosine kinase 1 and risk for preeclampsia. J Clin Endocrinol Metabolism 2004;89:770-5.
23. Wikstrom AK, Larsson A, Eriksson UJ, Nash P, Norden Lindeberg S, Olovsson M. Placental growth factor and soluble FMS-like tyrosine kinase-1 in early-onset and late-onset preeclampsia. Obstet Gynecol 2007;109:1368-74.
24. Radulescu C, Bacarea A, Hutanu A, Gabor R, Dobreanu M. Placental growth factor, soluble fms-like tyrosine kinase 1, soluble endoglin, IL-6, and IL-16 as biomarkers in preeclampsia. Mediators Inflammation 2016. DOI:10.1155/2016/3027363
25. Cardenas Mondragon MG, Vallejo Flores G, Delgado Dominguez J, Romero Arauz JF, Gomez Delgado A, Aguilar Madrid G, et al. Preeclampsia is associated with lower production of vascular endothelial growth factor by peripheral blood mononuclear cells. Arch Med Res 2014;45:561-9.
26. Karumanchi SA, Lindheimer MD. Preeclampsia pathogenesis: “triple a rating”–autoantibodies and antiangiogenic factors. Hypertension 2008;51:991–2.
27. Scazzocchio E, Figueras F. Contemporary prediction of preeclampsia. Curr Opinion Obstetrics Gynecol 2011;23:65–71.
28. Akolekar R, Syngelaki A, Beta J, Kocylowski R, Nicolaides KH. Maternal serum placental protein 13 at 11–13 w of gestation in preeclampsia. Prenat Diagn 2009;29:1103–8.
29. Harrington K. Early screening for pre-eclampsia and intrauterine growth restriction. Ultrasound Obstet Gynecol 2011;37:623–4.
30. Schnettler WT, Dmitry Dukhovny, Julia Wenger, Saira Salahuddin, Steven J Ralston, Dan Sarosh Rana. Cost and resource implications with serum angiogenic factor estimation in the triage of preeclampsia. BJOG 2013;120:1224–32.
31. Herraiz I, Simon E, Gomez Arriaga PI, Martinez Moratalla JM, Garcia Burguillo A, Lopez Jimenez EA, et al. Angiogenesis-related biomarkers (sFlt-1/PLGF) in the prediction and diagnosis of placental dysfunction: an approach for clinical integration. Int J Mol Sci 2015;16:19009–26.
32. 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. N Engl J Med 2016;374:13–22.
33. Klein E, Schlembach D, Ramoni A, Langer E, Bahlmann F, Grill S, et al. Influence of the sFlt-1/PlGF ratio on clinical decision-making in women with suspected preeclampsia. PLoS One 2016;11:e0156013.
34. Kushtagi P, Emani A. Arterial resistance in late first trimester as a predictor of subsequent pregnancy-related hypertension. Sultan Qaboos University Medical Journal 2016;16:e451-e457.
35. Vartun A, Flo K, Widnes C, Acharya G. Static and functional hemodynamic profiles of women with abnormal uterine artery doppler at 22-14 W of gestation. PLos One 2016. DOI:10.1371/journal.pone.0157916
36. Yu N, Cui H, Chen X, Chang Y. First trimester maternal serum analytes and second trimester uterine artery doppler in the prediction of preeclampsia and fetal growth restriction. Taiwanese J Obstetrics Gynecol 2017;56:358-61.
37. Narang S, Agarwal A, Das V, Pandey A, Agrawal S, Ali W. Prediction of pre-eclampsia at 11-14 w of pregnancy using mean arterial pressure, uterine artery Doppler and pregnancy-associated plasma protein-a. Int J Rep Contraception Obstetrics Gynecol 2016;5:3948-53.
38. Konishi I, Katabuchi H. Preeclampsia: Basic, Genomic, and Clinical. Toyama, Japan: Springer Nature; 2018.
39. Al-Jamcil N, Aziz Khan F, Farced Khan M, Tabassum H. A brief overview of preeclampsia. J Clin Med Res 2014;6:1-7.
40. Bian Z, Shixia C, Duan T. First-trimester maternal serum levels of sFLT1, PGF and ADMA predict preeclampsia. PLOS One 2015;10:e0124684.
41. Gannoun MB, Bourrelly S, Raguema N, Zitouni H, Nouvellon E, Maleh W, et al. Placental growth factor and vascular endothelial growth factor serum levels in Tunisian Arab women with suspected preeclampsia. Cytokine 2016;79:1-6.
42. KE Duhig, AH Shennan. Recent advances in the diagnosis and management of pre-eclampsia. F1000 Prime Reports 2015;7:24.
43. Rezi E. Perbedaan kadar soluble endoglin pada preeklampsia awitan dini (PEAD) dengan preeklampsia awitan lambat (PEAL). Program Studi S2 Ilmu Kebidanan. Fakultas Kedokteran. Universitas Andalas Padang; 2017.
44. Magee LA, Peis A, Heiewa M, Rey E, von Dadelszen P. Canadian hypertensive disorders of pregnancy working g diagnosis evaluation, and management of the hypertension disorders of pregnancy; executive summary. J Obstet Gynaecol Can 2014;36:416-41.
45. Shu C, Liu Z, Cui L, Wei C, Wang S, Tang JJ, et al. Protein profiling of preeclampsia placental tissues. Plos One 2014;9:E112890.
46. 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;11:649-58.
47. N Ogorman, D Wright, IC Poon, CL Ralnik, A Syngelaki, A Wright, et al. Accuracy of competing-risks model in screening for pre-eclampsia by maternal factors and biomarkers at 11-13 w gestation. Ultrasound Obstet Gyneco 2017;49:751-5.
48. Chen Y. Novel angigenic factors for predicting preeclampsia: sFlt-1, PLGF, and soluble Endoglin. Open Clinical Chemistry J 2009;2:1-6.
49. 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.
50. Taylor RN, Grimwood J, Taylor RS. Longitudinal serum concentrations of placental growth factor: evidence for abnormal placental angiogenesis in pathologic pregnancies. Am J Obstet Gynecol 2003;188:177-82.
51. 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.
52. Liu Z, Afink GB, Dijke P. Soluble fms-like tyrosine kinase 1 and soluble endoglin are elevated circulating anti-angiogenic factors in pre-eclampsia. Pregnancy Hypertension: Int J Women’s Cardiovascular Health 2012;2:358-67.
53. Lee ES, Oh MJ, Jung JW, Lim JE, Seol Hj, Lee KJ, et al. The levels of circulating vascular endothelial growth factor and soluble flt-1 in pregnancies complicated by preeclampsia. J Korean Med Sci 2007;22:94-8.
54. Reddy A, Suri S, Sargent IL, Redman CW, Muttukhrisna S. Maternal circulating levels of activin a, inhibin a, sflt-1 and endoglin at parturition in normal pregnancy and pre-eclampsia. PLoS One 2009;4:e4453.
55. Noori M, Donald AE, Angelakopoulou A, Hingorani AD, Williams DJ. Prospective study of placental angiogenic factors and maternal vascular function before and after preeclampsia and gestational hypertension. Circulation 2010;122:478-87.
56. Govender L, Mackraj I, Gathiram P, Moodley J. The role of angiogenic, anti-angiogenic and vasoactive factors in pre-eclamptic african women: early-versus late-onset pre-eclampsia. Cardio Vascular J Africa 2012;23:153-9.
57. Eremina V, Sood M, Haigh J, Nagy A, Lajoie G, Ferrara N, et al. Glomerular-specific alterations of VEGF-a expression lead to distinct congenital and acquired renal diseases. J Clin Investigation 2003;111:707-16.
58. Luttun A, Carmeliet P. Soluble VEGF receptor Flt1: the elusive preeclampsia factor discovered? J Clin Investigation 2003;111:600-2.
59. Rahmi L, Herman RB, Yusrawati Y. Perbedaan rerata kadar sFlt-1 pada penderita early onset, late onset preeklampsia berat/eklampsia dan kehamilan normal. Jurnal Kesehatan Andalas.2016;5:3948-53.

Published

15-05-2020

How to Cite

LUBIS, M. P. “THE ROLE OF PREDICTOR PLACENTAL GROWTH FACTOR, SOLUBLE ENDOGLIN, SOLUBLE-FMS-LIKE-TYROSINE KINASE-1 AND PULSATIL UTERINA ARTERIAL INDEX TO PREDICT THE EARLY ONSET OF PREECLAMPSIA”. International Journal of Current Pharmaceutical Research, vol. 12, no. 3, May 2020, pp. 45-57, doi:10.22159/ijcpr.2020v12i3.38305.

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