Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access


Preeclampsia is one of the main causes of maternal mortality and leads to 50-60 thousand deaths annually worldwide, its prevalence in the world is 5-8%. Moreover, this complication is associated with an increased risk of the development of cardiovascular diseases and diabetes in the mother and child. Preeclampsia is a multi-systemic syndrome including hereditary and environmental factors in its pathogenesis and pathophysiology, and the only effective method of the treatment is still delivery. Regardless of the time of debut, preeclampsia is often characterized by the relative well-being of a pregnant woman, right up to the development of severe pre-eclampsia. This review is devoted to biochemical markers of the high risk of pre-eclampsia. Of particular interest there is the balance of proangiogenic (PIGF) and anti-angiogenic (sFlt) growth factors at different gestational ages; both the correct interpretation of the sFlt/PIGF balance and the correlation with the history data already allow us to expand the criteria for the prevention of preeclampsia and open up prospects for optimizing obstetric tactics in the third trimester of pregnancy.

Full Text

Restricted Access

About the authors

I. V Ignatko

I.M. Sechenov First Moscow State Medical University

119991, Moscow, Russian Federation

Violetta S. Florova

I.M. Sechenov First Moscow State Medical University

119991, Moscow, Russian Federation
MD, post-graduate student of the Department of Obstetrics, Gynecology and Perinatology of the Medical Faculty of the I.M. Sechenov First Moscow State Medical University, Moscow, 119991, Russian Federation

A. C Kuznetsov

I.M. Sechenov First Moscow State Medical University

119991, Moscow, Russian Federation

E. Yu Kuzina

Ltd «Laboratory of the Center for Immunology and Reproduction

125171, Moscow, Russian Federation


  1. Abalos E., Cuesta C., Carroli G. et al. WHO Multicountry Survey on Maternal and Newborn Health Research Network. Pre-eclampsia, eclampsia and adverse maternal and perinatal outcomes: a secondary analysis of the World Health Organization Multicountry Survey on Maternal and Newborn Health. BJOG. 2014; 121(Suppl. 1): S14-24. doi: 10.1111/1471-0528.12629.
  2. ACOG Committee on Practice Bulletins - Obstetrics. ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. Obstet. Gynecol. 2002; 99(1): 159-67.
  3. American College of Obstetricians and Gynecologists; Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet. Gynecol. 2013; 122(5): 1122-31. doi: 10.1097/01.AOG.0000437382.03963.88.
  4. Савельева Г.М., Краснопольский В.И., Стрижаков А.Н., Радзинский В.Е., Курцер М.А., Шалина Р.И. Гестоз и преэклампсия. StatusPraesens. Гинекология, акушерство, бесплодный брак. 2013; 1: 9-14
  5. Vigil-De Gracia P., Reyes Tejada O., Calle Minaca A. et al. Expectant management of severe preeclampsia remote from term: the MEXPRE Latin Study, a randomized multicenter clinical trial. Am. J. Obstet. Gynecol. 2013; 209(5): 425. e1-8. doi: 10.1016/j.ajog.2013.08.016.
  6. Zuleta-Tobon J.J., Pandales-Perez H., Sanchez S. et al. Errors in the treatment of hypertensive disorders of pregnancy and their impact on maternal mortality. Int. J. Gynaecol. Obstet. 2013; 121(1): 78-81. doi: 10.1016/j.ijgo.2012.10.031.
  7. Aylamazyan E.K., Repina M.A. Comments on the clinical protocol «Hypertension during pregnancy, preeclampsia, eclampsia». Zhurnal akusherstva i zhenskikh bolezney. 2012; 61(5): 3-9. (in Russian)
  8. Стрижаков А.Н., Тимохина Е.В., Пицхелаури Е.Г., Белоусова В.С., Якушина Н.И. Преэклампсия сегодня: патогенез и возможности прогнозирования и лечения. Вопросы гинекологии, акушерства и перинатологии. 2016; 15(2): 24-31
  9. Valensise H., Vasapollo B., Gagliardi G., Novelli G.P. Early and late preeclampsia: two different maternal hemodynamic states in the latent phase of the disease. Hypertension. 2008; 52(5): 873-80. doi: 10.1161/HYPERTENSIONAHA.108.117358.
  10. Noori M., Donald A.E., Angelakopoulou A., Hingorani A.D, Williams D.J. Prospective study of placental angiogenic factors and maternal vascular function before and after preeclampsia and gestational hypertension. Circulation. 2010; 122(5): 478-87. doi: 10.1161/CIRCULATIONAHA.109.895458.
  11. Nelson D.B., Ziadie M.S., McIntire D.D. Rogers B.B., Leveno K.J. Placental pathology suggesting that preeclampsia is more than one disease. Am. J. Obstet. Gynecol. 2014; 210(1): 66. e1-7. doi: 10.1016/j.ajog.2013.09.010.
  12. Pijnenborg R. The placental bed. Hypertens. Pregnancy. 1996; 15(1): 7-23.
  13. Akolekar R., Syngelaki A., Sarquis R., Zvanca M., Nicolaides K.H. Prediction of early, intermediate and late pre-eclampsia from maternal factors, biophysical and biochemical markers at 11-13 weeks. Prenat. Diagn. 2011; 31(1): 66-74. doi: 10.1002/pd.2660.
  14. Bilano V.L., Ota E., Ganchimeg T., Mori R., Souza J.P. Risk factors of pre-eclampsia/eclampsia and its adverse outcomes in low- and middle-income countries: a WHO secondary analysis. PLoS One. 2014; 9(3): e91198. doi: 10.1371/journal.pone.0091198.
  15. Wright D., Akolekar R., Syngelaki A., Poon L.C., Nicolaides K.H. Competing risks model in early screening for pre-eclampsia. Fetal Diagn. Ther. 2012; 32(3): 171-8. doi: 10.1159/000338470.
  16. Akolekar R., Syngelaki A., Poon L., Wright D., Nicolaides K.H. Competing risks model in early screening for pre-eclampsia by biophysical and biochemical markers. Fetal Diagn. Ther. 2013; 33(1): 8-15. doi: 10.1159/000341264.
  17. Rolnik D.L., Wright D., Poon L.C., O’Gorman N., Syngelaki A. et al. Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia. N. Engl. J. Med. 2017; 377(7): 613-22. doi: 10.1056/NEJMoa1704559.
  18. Roberge S., Villa P., Nicolaides K., Giguère Y., Vainio M. et al. Early administration of low-dose aspirin for the prevention of preterm and term preeclampsia: a systematic review and meta-analysis. Fetal Diagn. Ther. 2012; 31(3): 141-6. doi: 10.1159/000336662.
  19. Roberge S., Giguère Y., Villa P., Giguère Y., Vainio M. et al. Early administration of low-dose aspirin for the prevention of severe and mild preeclampsia: a systematic review and meta-analysis. Am. J. Perinatol. 2012; 29(7): 551-6. doi: 10.1159/000336662.
  20. Pinheiro C.C., Rayol P., Gozzani L., Reis L.M., Zampieri G. et al. The relationship of angiogenic factors to maternal and neonatal manifestations of early-onset and late-onset preeclampsia. Prenat. Diagn. 2014; 34(11): 1084-92. doi: 10.1002/pd.4432.
  21. Irving F.C. A study of five hundred consecutive cases of pre-eclampsia. Can. Med. Assoc. J. 1939; 40(2): 137-40.
  22. Yung H.W., Atkinson D., Campion-Smith T., Olovsson M., Charnock-Jones D.S., Burton G.J. Differential activation of placental unfolded protein response pathways implies heterogeneity in causation of early- and late-onset preeclampsia. J. Pathol. 2014; 234(2): 262-76. doi: 10.1002/path.4394.
  23. Granger J.P., Alexander B.T., Llinas M.T., Bennett W.A., Khalil R.A. Pathophysiology of hypertension during preeclampsia linking placental ischemia with endothelial dysfunction. Hypertension. 2001; 38(3, Pt 2): 718-22.
  24. Bonno M., Oxvig C., Kephart G.M. et al. Localization of pregnancy-associated plasma protein-А and colocalization of pregnancy-associated plasma protein-А messenger ribonucleic acid and eosinophil granule major basic protein messenger ribonucleic acid in placenta. Lab. Invest. 1994; 71(4): 560-6.
  25. Wright D., Syngelaki A., Bradbury I., Akolekar R., Nicolaides K.H. First-trimester screening for trisomies 21, 18 and 13 by ultrasound and biochemical testing. Fetal Diagn. Ther. 2014; 35(2): 118-26. doi: 10.1159/000357430.
  26. Lawrence J.B., Oxvig C., Overgaard M.T., Sottrup-Jensen L., Gleich G.J. et al. The insulin-like growthfactor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblastsis pregnancy-associated plasma protein-A. Proc. Natl. Acad. Sci. USA. 1999; 96(6): 3149-53.
  27. Bersinger N.A., Smárason A.K., Muttukrishna S., Groome N.P., Redman C.W. Women with preeclampsia have increased serum levels of pregnancy-associated plasma protein A (PAPP-A), inhibin A, activin A, and soluble E-selectin. Hypertens. Pregnancy. 2003; 22(1): 45-55.
  28. Bersinger N.A., Ødegård R.A. Second- and third-trimester serum levels of placental proteins in preeclampsia and small-for-gestational age pregnancies. Acta Obstet. Gynecol. Scand. 2004; 83(1): 37-45.
  29. Deveci K., Sogut E., Evliyaoglu O., Duras N. Pregnancy-associated plasma protein-A and C-reactive protein levels in pre-eclamptic and normotensive pregnant women at third trimester. J. Obstet. Gynaecol. Res. 2009; 35: 94-8. doi: 10.1111/j.1447-0756.2008.00835.x.
  30. Pilalis A., Souka A.P., Antsaklis P. et al. Screening for pre-eclampsia and fetal growth restriction by uterine artery Doppler and PAPP-A at 11-14 weeks gestation. Ultrasound Obstet. Gynecol. 2007; 29(2): 135-40. doi: 10.1002/uog.3881.
  31. Spencer K., Cowans N.J., 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.3881.
  32. Maynard S.E., Min J.Y., Merchan J. 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(5): 649-58. doi: 10.1172/JCI17189.
  33. Ahmad S., Ahmed A. Elevated placental soluble vascular endothelial growth factor receptor-1 inhibits angiogenesis in preeclampsia. Circ. Res. 2004; 95(9): 884-91. doi: 10.1161/01.RES.0000147365.86159.f5.
  34. Levine R.J., Maynard S.E., Qian C. et al. Circulating angiogenic factors and the risk of preeclampsia. N. Engl. J. Med. 2004; 350(7): 672-83.
  35. Stepan H., Unversucht A., Wessel N., Faber R. Predictive value of maternal angiogenic factors in second trimester pregnancies with abnormal uterine perfusion. Hypertension. 2007; 49(4): 818-24. doi: 10.1161/01.HYP.0000258404.21552.a3.
  36. Akolekar R., Zaragoza E., Poon L.C.Y., Pepes S., Nicolaides K.H. Maternal serum placental growth factor at 11+0 to 13+6 weeks of gestation in the prediction of pre-eclampsia. Ultrasound Obstet. Gynecol. 2008; 32(6): 732-9. doi: 10.1002/uog.6244.
  37. Crispi F., Llurba E., Domínguez C., Martín-Gallán P., Cabero L., Gratacós E. Predictive value of angiogenic factors and uterine artery Doppler for early- versus late-onset pre-eclampsia and intrauterine growth restriction. Ultrasound Obstet. Gynecol. 2008; 31(3): 303-9. doi: 10.1002/uog.5184
  38. Erez O., Romero R., Espinoza J. et al. The change in concentrations of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters in risk assessment for the subsequent development of preeclampsia and small-for-gestational age. J. Matern. Fetal Neonatal Med. 2008; 21(5): 279-87. doi: 10.1080/14767050802034545.
  39. Verlohren S., Herraiz I., Lapaire O. New gestational phase-specific cutoff values for the use of the soluble fms-like tyrosine kinase-1/placental growth factor ratio as a diagnostic test for preeclampsia. Hypertension. 2014; 63(2): 346-52. doi: 10.1161/HYPERTENSIONAHA.113.01787.
  40. Poon L.C., Akolekar R., Lachmann R., Beta J., Nicolaides K.H. 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.
  41. Roberts J.M., Rajakumar A. Preeclampsia and soluble fms-like tyrosine kinase-1. J. Clin. Endocrinol. Metab. 2009; 94(7): 2252-4.
  42. Paré E., Parry S., McElrath T.F., Pucci D., Newton A., Lim K.H. Clinical risk factors for preeclampsia in the 21st century. Obstet. Gynecol. 2014; 124(4): 763-70. doi: 10.1097/AOG. 0000000000000451.
  43. Tsiakkas A., Duvdevani N., Wright A., Wright D., Nicolaides K.H. Serum placental growth factor in the three trimesters of pregnancy: effects of maternal characteristics and medical history. Ultrasound Obstet. Gynecol. 2015; 45(5): 591-8. doi: 10.1002/uog.14811.
  44. Park H.J., Kim S.H., Jung Y.W., Shim S.S., Kim J.Y. et al. Screening models using multiple markers for early detection of late-onset preeclampsia in low-risk pregnancy. BMC Pregnancy Childbirth. 2014; 14: 35. doi: 10.1186/1471-2393-14-35.
  45. Koopmans C.M., Bijlenga D., Groen H. et al. Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia after 36 weeks’ gestation (HYPITAT): a multicentre, open-label randomised controlled trial. Lancet. 2009; 374(9694): 979-88. doi: 10.1016/S0140-6736(09)60736-4.
  46. Verlohren S., Herraiz I., Lapaire O. et al. The sFlt-1/PlGF ratio in different types of hypertensive pregnancy disorders and its prognostic potential in preeclamptic patients. Am. J. Obstet. Gynecol. 2012; 206(1): 58. e1-8. doi: 10.1016/j.ajog.2011.07.037.
  47. Bdolah Y., Sukhatme V.P., Karumanchi S.A. Angiogenic imbalance in the pathophysiology of preeclampsia: newer insights. Semin. Nephrol. 2004; 24(6): 548-56.
  48. Zeisler H., Llurba E., Chantraine F., Velohren S. et al. Predictive value of the sFlt-1: PlGF ratio in women with suspected preeclampsia. N. Engl. J. Med. 2016; 374(1): 13-22. doi: 10.1056/NEJMoa1414838.
  49. Lai J., Garcia-Tizon Larroca S., Peeva G., Poon L.C., Wright D., Nicolaides K.H. Competing risks model in screening for preeclampsia by serum placental growth factor and soluble fms-like tyrosine kinase-1 at 30-33 weeks gestation. Fetal Diagn. Ther. 2014; 35(4): 240-8. doi: 10.1159/000359968.
  50. Bujold E., Roberge S., Lacasse Y. et al. Prevention of preeclampsia and intrauterine growth restriction with aspirin started in early pregnancy: a meta-analysis. Obstet. Gynecol. 2010; 116(2, Pt. 1): 402-14. doi: 10.1097/AOG.0b013e3181e9322a.
  51. Стрижаков А.Н., Игнатко И.В., Самсонян З.Л., Дуболазов В.Д. Дифференцированный подход к выбору терапии и акушерской тактики у беременных с артериальной гипертензией. Вопросы гинекологии, акушерства и перинатологии. 2004; 3(1): 7-15



Abstract - 115

PDF (Russian) - 0


Article Metrics

Metrics Loading ...


  • There are currently no refbacks.

Copyright (c) 2017 Eco-Vector

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies