Biomarker PlGF/sFlt-1 sebagai Pendeteksi Dini Preeklampsia
Abstract
Program Millenium Development Goals (MDGs) yang dilakukan sejak tahun 2003 belum berhasil mencapai tujuannya, termasuk untuk meningkatkan kesehatan ibu dengan target menurunkan Angka Kematian Ibu (AKI) sebesar tiga perempatnya antara tahun 1990 sampai 2015. Program ini kemudian dilanjutkan menjadi Sustainable Development Goals (SDGs) dengan salah satu fokusnya yaitu menurunkan AKI hingga di bawah 70 per 100.000 kelahiran hidup serta mengurangi sepertiga kematian bayi prematur akibat penyakit tidak menular. Angka kematian ibu di Indonesia cukup tinggi apabila dibandingkan dengan negara-negara lainnya di wilayah Asia Tenggara. Pada umumnya penyebab utama kematian ibu adalah pendarahan (28%), preeklampsia (PE)/eklampsia (24%), infeksi (11%), komplikasi persalinan (5%) dan abortus (5%). Preeklampsia (PE) merupakan penyakit hipertensi yang disertai dengan proteinuria yang terjadi pada saat usia kehamilan mencapai 20 minggu (trimester kedua). Penyakit ini umumnya tidak terdiagnosis namun terlihat setelah berdampak pada gangguan ibu dan janin dan apabila tidak ditangani dengan segera, maka dapat menyebabkan kematian bagi ibu pada proses persalinan. Dilaporkan bahwa rata-rata insiden kejadia PE di seluruh dunia adalah 2–10%. Berbagai upaya terus dilakukan untuk menurunkan angka kematian Ibu, salah satunya adalah dengan pencarian metode deteksi dini. Tujuan penulisan review ini adalah untuk mengkaji metode deteksi dini apa yang paling efektif dan efisien untuk mengatasi PE. Metode dalam review ini adalah penelusuran data berbasis Pubmed, Scopus dan Google Scholar dan tanpa pembatasan index factor dengan menggunakan kata kunci “biomarker, preeclampsia”, “early detection, preeclampsia”. Hasil review menunjukkan bahwa biomarker placental growth gactor (PlGF) dan soluble Fms-like tyrosine kinase 1 (sFlt-1) merupakan biomarker spesifik dengan sensitivitas dan spesifisitas yang tinggi dalam pendeteksian PE.
Kata kunci: Biomarker PlGF/sFlt-1, deteksi dini, preeklampsia
PlGF/sFlt-1 as Early Detection Biomarker for Preeclampsia
Abstract
Millennium Development Goals (MDGs) had been conducted since 2003 with uncomplished outcome target, particularly improving maternal health and lowering maternal mortality until one-fourth of population from 1990 until 2015. Then, this program was continued through Sustainable Development Goals (SDGs) in 2015 with lowering maternal mortality below 70 per 100,000 live births and reducing premature mortality due to one-third because of uncommunicable diseases. Maternal mortality in Indonesia is quite high compared with the other countries in the Southeast Asia. Generally, the main causes of maternal death are haemorrhage (28%), preeclampsia (PE)/eclampsia (24%), infection (11%), complications from birth delivery (5%), and unsafe abortion (5%). Preeclampsia (PE) is a hypertension disease accompanied with proteinuria that occuring in 20 weeks of pregnancy (second trimester). The disease is commonly unvisible and underdiagnosed until clinical manifestations were presented (e.g. maternal and fetal disorders). However, it can lead to maternal death during childbirth if this problem not addressed seriously. It was reported that the average incidence of PE reached 2–10% worldwide. Various efforts have been undertaken to lowering maternal mortality that is early detection of PE. The purpose of this review was to analyze the most effective early detection method to overcome PE based on literaure review. The methods of this review were data-based searching based on Pubmed, Scopus and Google Scholar, without limitation of index factor by using the keyword “biomarkers, preeclampsia”, “early detection, preeclampsia.” The results of the review showed that placental growth factor biomarkers (PlGF) and soluble Fms-like tyrosine kinase 1 (sFlt-1) is the specific biomarkers with high sensitivity and specificity in detection of PE.
Keywords: Biomarker PlGF/sFlt-1, early detection, preeclampsia
Keywords
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Bappenas. Laporan pencapaian tujuan pembangunan milenium di Indonesia. 2012 [diunduh Januari 2017]. Tersedia dari: http://www.bappenas.go.id/files/191 3/5229/9628/laporan-pencapaian-tujuan -pembangunan-milenium-di-indonesia-2011__20130517105523__ 3790__0.pdf.
World Health Organization. Maternal deaths fell 44% since 1990–UN: Report from WHO, UNICEF, UNFPA, World Bank Group and the United Nations Population Division highlights progress. 2015 [diunduh Januari 2017]. Tersedia dari: http://www.who.int/mediacentre/ne ws/releases/2015/maternal-mortality/en/.
Kementerian Kesehatan Republik Indonesia. Laporan Dirjen Bina Gizi KIA: Kesehatan dalam kerangka SDGs. In: Anak DJBGKId, editor. Jakarta: Kementerian Kesehatan Republik Indonesia; 2015.
Faiqoh E, Hendrati LY. Hubungan karakteristik ibu, ANC, dan kepatuhn perawatan ibu hamil dengan terjadinya pereklampsia. Jurnal Berkala Epidemiologi. 2014;2(2):216–26.
Kahnamouei-aghdam F, Amani F, Hamidimoghaddam S. Prevalence of pre- eclampsia and eclampsia risk factors among pregnant women, 2011–2013. Int J Adv Med. 2015;2(2):128–32. doi: 10.5455/2349-3933.ijam20150510
UNICEF. Ringkasan kajian: Kesehatan ibu dan anak, 2012 [diunduh 2017 Januari]. Tersedia dari: https://www.unic ef.org/indonesia/id/A5_-_B_Ringkasan_Kajian_Kesehatan_REV.pdf.
Roeshardi R. Upaya menurunkan angka kesakitan dan angka kematian ibu pada penderita preeklampsia dan eklampsia. Indones J Obstetrics Gynecology. 2007;31(3):123–33.
Cerdeira AS, Karumanchi SA. Angiogenic factors in preeclampsia and related disorders. Cold Spring Harb Perspect Med. 2012;2(11): a006585. doi: 10.1101/cshperspect.a006585
Aeni N. Faktor risiko kematian ibu. National Public Health J. 2013;7(10):453–9.
Lindheimer MD, Taler SJ, Cunningham FG. Hypertension in pregnancy. J Am Soc Hypertens. 2008;2(6):484–94. doi: 10.1016/j.jash.2008.10.001.
Uzan J, Carbonnel M, Piconne O, Asmar R, Ayoubi JM. Pre-eclampsia: Pathophysiology, diagnosis, and management. Vasc Health Risk Manag. 2011;7:467–74. doi: 10.2147/VHRM.S2 0181
Park HJ, Shim SS, Cha DH. Combined screening for early detection of pre-eclampsia. Int J Mol Sci. 2015;16(8):17952–74. doi: 10.3390/ijms160817952
Kar M. Role of biomarkers in early detection of preeclampsia. J Clin Diagn Res. 2014;8(4):Be01–4. doi: 10.7860/JCDR/2014/7969.4261
Departemen Kesehatan RI. Pedoman pelayanan antenatal. In: Dasar DBPM. Jakarta: Direktorat Jenderal Bina Pelayanan Medik Dasar, Departemen Kesehatan Republik Indonesia; 2007.
Mauri EM, Nespoli A, Persico G, Zobbi VF. Domestic violence during pregnancy: Midwives’ experiences. Midwifery. 2015; 31(5):498–504. doi: 10.1016/j.midw.2015.02.002
Osungbade KO, Ige OK. Public health perspectives of preeclampsia in developing countries: Implication for health system strengthening. Journal of Pregnancy. 2011; 2011:6. doi: 10.1155/2011/481095
UNICEF. The situation of children and women in Indonesia 2000–2010 (working towards progress with equity under decentralisation). 2011 [diunduh Januari 2017]. Tersedia dari: https://www.unicef.org/sitan/files/Indonesia_SitAn_2010.pdf.
Petla LT, Chikkala R, Ratnakar K, Kodati V, Sritharan V. Biomarkers for the management of pre-eclampsia in pregnant women. Indian J Med Res. 2013;138(1):60–7.
Poon LCY, Akolekar R, Lachmann R, Beta J, Nicolaides KH. Hypertensive disorders in pregnancy: Screening by biophysical and biochemical markers at 11–13 weeks. Ultrasound Obstet Gynecol. 2010;35(6):662–70. doi: 10.1002/uog.7628
Plasencia W, Maiz N, Bonino S, Kaihura C, Nicolaides KH. Uterine artery Doppler at 11+0 to 13+6 weeks in the prediction of pre-eclampsia. Ultrasound Obstet Gynecol. 2007;30(5):742–9. doi: 10.1002/uog.5157
Spencer K, Cowans NJ, Chefetz I, Tal J, Meiri H. First-trimester maternal serum PP-13, PAPP-A and second-trimester uterine artery Doppler pulsatility index as markers of pre-eclampsia. Ultrasound Obstet Gynecol. 2007;29(2):128–34. doi: 10.1002/uog.3876
Poon LC, Nicolaides KH. Early prediction of preeclampsia. Obstet Gynecol Int. 2014;2014:1–11. doi: 10. 1155/2014/297397
Cnossen JS, Morris RK, ter Riet G, Mol BWJ, van der Post JAM, Coomarasamy A, et al. Use of uterine artery Doppler ultrasonography to predict pre-eclampsia and intrauterine growth restriction: A systematic review and bivariable meta-analysis. Can Med Assoc J. 2008;178(6):701–11. doi: 10.1503/cmaj.070430.
Herraiz I, Escribano D, Gómez-Arriaga PI, Herníndez-García JM, Herraiz MA, Galindo A. Predictive value of sequential models of uterine artery Doppler in pregnancies at high risk for pre-eclampsia. Ultrasound Obstet Gynecol. 2012;40(1):68–74. doi: 10.1002/uog.10147
Hata T, Tanaka H, Noguchi J, Hata K. Three-dimensional ultrasound evaluation of the placenta. Placenta. 2011;32(2):105–15. doi: 10.1016/j.placenta.2010.11.001
Odeh M, Ophir E, Maximovsky O, Grinin V, Bornstein J. Placental volume and three-dimensional power Doppler analysis in prediction of pre-eclampsia and small for gestational age between week 11 and 13 weeks and 6 days of gestation. Prenat Diagn. 2011;31(4):367–71. doi: 10.1002/pd.2697
Cnossen JS, Vollebregt KC, Vrieze Nd, Riet Gt, Mol BWJ, Franx A, et al. Accuracy of mean arterial pressure and blood pressure measurements in predicting pre-eclampsia: systematic review and meta-analysis. BMJ. 2008;336(7653):1117–20. doi: 10.1136/bmj.39540.522049.BE.
Gallo D, Poon LC, Fernandez M, Wright D, Nicolaides KH. Prediction of preeclampsia by mean arterial pressure at 11–13 and 20–24 weeks’ gestation. Fetal Diagn Ther. 2014;36(1):28–37. doi: 10.1159/000360287.
Scazzocchio E, Figueras F. Contemporary prediction of preeclampsia. Current Opinion in Obstetrics and Gynecology. 2011;23(2):65–71.
Nolen BM, Langmead CJ, Choi S, Lomakin A, Marrangoni A, Bigbee WL, et al. Serum biomarker profiles as diagnostic tools in lung cancer. Cancer Biomark. 2011;10(1):3–12. doi: 10.3233/CBM-2012-0229.
Kharb S. Serum markers in pre-eclampsia. Biomarkers. 2009;14(6):395–400. doi: 10.1080/13547500903033415
Strimbu K, Tavel JA. What are biomarkers? Curr Opin HIV AIDS. 2010;5(6):463–6. doi: 10.1097/COH.0b013e32833ed177
Carty DM, Delles C, Dominiczak AF. Novel biomarkers for predicting preeclampsia. Trends Cardiovasc Med. 2008;18(5–24):186–94. doi: 10.1016/j.tcm.2008.07.002
Akolekar R, Syngelaki A, Beta J, Kocylowski R, Nicolaides KH. Maternal serum placental protein 13 at 11–13 weeks of gestation in preeclampsia. Prenat Diagn. 2009;29(12):1103–8. doi: 10.1002/pd.2375.
Spencer K, Yu CKH, Cowans NJ, Otigbah C, Nicolaides KH. Prediction of pregnancy complications by first-trimester maternal serum PAPP-A and free β-hCG and with second-trimester uterine artery Doppler. Prenat Diagn. 2005;25(10):949–53. doi: 10.1002/pd.1251
Papantoniou N, Bagiokos V, Agiannitopoulos K, Kolialexi A, Destouni A, Tounta G, et al. RASSF1A in maternal plasma as a molecular marker of preeclampsia. Prenat Diagn. 2013;33(7):682–7. doi: 10.1002/pd.4093
Costa FdS, Murthi P, Keogh R, Woodrow N. Early screening for preeclampsia. Rev Bras Ginecol Obstet. 2011;33(11):367–75. doi: 10.1590/S0100-72032011001100008
Poon LC, Nicolaides KH. First-trimester maternal factors and biomarker screening for preeclampsia. Prenat Diagn. 2014;34(7):618–27. doi: 10.1002/pd.4397
Krantz D, Hallahan T, Janik D, Carmichael J. Maternal serum screening markers and adverse outcome: A new perspective. J Clin Med. 2014;3(3):693–712. doi: 10.3390/jcm3030693
Phillips JK, Janowiak M, Badger GJ, Bernstein IM. Evidence for distinct preterm and term phenotypes of preeclampsia. J Matern Fetal Neonatal Med. 2010;23(7):622–6. doi: 10.3109/14767050903258746.
Gram M, Anderson UD, Johansson ME, Edström-Hägerwall A, Larsson I, Jälmby M, et al. The human endogenous protection system against cell-gree hemoglobin and heme is overwhelmed in preeclampsia and provides potential biomarkers and clinical indicators. PLoS ONE. 2015;10(9):e0138111. doi: 10.1371/journal.pone.0138111
Verlohren S, Galindo A, Schlembach D, Zeisler H, Herraiz I, Moertl MG, et al. An automated method for the determination of the sFlt-1/PIGF ratio in the assessment of preeclampsia. Am J Obstet Gynecol. 2010;202(2):161.e1–.e11. doi: 10.1016/j.ajog.2009.09.016.
Robinson CJ, Johnson DD. Soluble endoglin as a second-trimester marker for preeclampsia. Am J Obstet Gynecol. 2007;197(2):174.e1–.e5.
Levine RJ, Maynard SE, Qian C, Lim K-H, England LJ, Yu KF, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004;350(7):672–83. doi: 10.1056/NEJMoa031884
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(5):837–45. doi: 10.1373/clinchem.2011.169094
Mutter WP, Karumanchi SA. Molecular mechanism of preeclampsia. Microvasc Res. 2008;75(1):1–8. doi: 10.1016/j.mvr.2007.04.009
Rajakumar A, Michael HM, Rajakumar PA, Shibata E, Hubel CA, Karumanchi SA, et al. Extra-placental expression of vascular endothelial growth factor receptor-1, (Flt-1) and soluble Flt-1 (sFlt-1), by peripheral blood Mmononuclear cells (PBMCs) in normotensive and preeclamptic pregnant women. Placenta. 2005;26(7):563–73. doi: 10.1016/j.placenta.2004.09.001
Salahuddin S, Lee Y, Vadnais M, Sachs BP, Karumanchi SA, Lim K-H. Diagnostic utility of soluble fms-like tyrosine kinase 1 and soluble endoglin in hypertensive diseases of pregnancy. Am J Obstet Gynecol. 2007;197(1):28.e1–.e6. doi: 10.1016/j.ajog.2007.04.010
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(10):992–1005. doi: 10.1056/NEJMoa055352
Karumanchi SA, Lindheimer MD. Preeclampsia pathogenesis: “triple a rating”–autoantibodies and antiangiogenic factors. 2008;51(4):991–2. doi: 10.1161/HYPERTENSIONAHA.107.100735
Harrington K. Early screening for pre-eclampsia and intrauterine growth restriction. Ultrasound Obstet Gynecol. 2011;37(5):623–4. doi: 10.1002/uog.9018
Schnettler WT, Dukhovny D, Wenger J, Salahuddin S, Ralston SJ, Rana S. Cost and resource implications with serum angiogenic factor estimation in the triage of preeclampsia. BJOG. 2013;120(10): 1224–32. doi: 10.1111/1471-052 8.1 2259
Herraiz I, Simón E, Gómez-Arriaga PI, Martínez-Moratalla JM, García-Burguillo A, López Jiménez 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(8):19009–26. doi: 10.3390/ijms160819009.
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. doi: 10.1056/NEJMoa1414838
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(5):e0156013. doi: 10.1371/journal.pone.0156013
Schiettecatte J, Russcher H, Anckaert E, Mees M, Leeser B, Tirelli AS, et al. Multicenter evaluation of the first automated Elecsys sFlt-1 and PlGF assays in normal pregnancies and preeclampsia. Clin Biochem. 2010;43(9):768–70. doi: 10.1016/j.clinbiochem.2010.02.010
Stepan H, Herraiz I, Schlembach D, Verlohren S, Brennecke S, Chantraine F, et al. Implementation of the sFlt-1/PlGF ratio for prediction and diagnosis of pre-eclampsia in singleton pregnancy: Implications for clinical practice. Ultrasound Obstet Gynecol. 2015;45(3):241–6. doi: 10.1002/uog.14799
DOI: https://doi.org/10.15416/ijcp.2017.6.2.123
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