Preeclampsia: The Modern State of the Problem

For citation: Syundyukova E.G., Chulkov V.S., Ryabikina M.G. Preeclampsia: The Modern State of the Problem. Doctor.Ru. 2021; 20(1): 11–16. (in Russian). DOI: 10.31550/1727-2378-2021-20-1-11-16
12 March 17:07

Objective of the Review: To conduct a systematic analysis of the available data from the Russian and foreign literature on the pathogenesis of preeclampsia, possible prognosis and pathology prevention.

Key Points. The generally accepted theory is that preeclampsia is caused by defective spiral artery remodelling during early gestation associated with reduced placenta perfusion; however, such changes in spiral arteries are not unique for preeclampsia. It is not impossible that increased resistivity of uterine vessels with defective uterine perfusion can lead to abnormal invasion and trophoblast dysfunction; therefore, preeclampsia is discussed secondary to maternal cardiovascular symptoms.

Conclusion. Analysis of maternal system and local uterine hemodynamics, molecular gestational sac pathology, its interaction with the environment and modifiable risk factors will facilitate biological understanding of the basis of preeclampsia; therefore, we will be more able to predict, prevent and manage this pathology.

Contributions: Syundyukova, E.G. — review of critically important material, assistance with manuscript preparation, approval of the manuscript for publication; Chulkov, V.S. — review of critically important material, assistance with manuscript preparation; Ryabikina, M.G. — literature review, translation of sources from English into Russian, manuscript preparation.

Conflict of interest: The authors declare that they do not have any conflict of interests.

E.G. Syundyukova (Corresponding author) — South Ural State Medical University of the Ministry of Health of the Russian Federation; 64 Vorovskiy Str., Chelyabinsk, Russian Federation 454091. E-mail:

V.S. Chulkov — South Ural State Medical University of the Ministry of Health of the Russian Federation; 64 Vorovskiy Str., Chelyabinsk, Russian Federation 454091. E-mail:

M.G. Ryabikina — South Ural State Medical University of the Ministry of Health of the Russian Federation; 64 Vorovskiy Str., Chelyabinsk, Russian Federation 454091. E-mail:


Received: 09.12.2020
Accepted: 11.01.2021

12 March 17:07
  1. Regitz-Zagrosek V., Roos-Hesselink J.W., Bauersachs J. et al. 2018 ESC guidelines for the management of cardiovascular diseases during pregnancy. Eur. Heart J. 2018; 39(34): 3165–241. DOI: 10.1093/eurheartj/ehy340
  2. Burton G.J., Redman C.W., Roberts J.M. et al. Pre-eclampsia: pathophysiology and clinical implications. BMJ. 2019; 366: l2381. DOI: 10.1136/bmj.l2381
  3. Alexandrova G.A., Golubev N.A., Tyurina E.M. et al. Key indicators of material and baby health. Child welfare and obstetrics services in the Russian Federation. 2018. М.; 2019. 172 p. (in Russian)
  4. Poon L.C., Shennan A., Hyett J.A. et al. The International Federation of Gynecology and Obstetrics (FIGO) initiative on pre-eclampsia: a pragmatic guide for first-trimester screening and prevention, 2019. Int. J. Gynecol. Obstet. 2019; 145(suppl.1): S1–33. DOI: 10.1002/ijgo.12802
  5. Ridder A., Giorgione V., Khalil A. et al. Preeclampsia: the relationship between uterine artery blood flow and trophoblast function. Int. J. Mol. Sci. 2019; 20(13): 3263. DOI: 10.3390/ijms20133263
  6. Adamyan L.V., Artymuk N.V., Bashmakova N.V. et al. Hypertensive disorders during pregnancy, delivery and postpartum period. Preeclampsia. Eclampsia. Clinical recommendations (treatment regimen). М.; 2016. 72 p. (in Russian)
  7. Kobalava Z.D., Konradi A.O., Nedogoda S.V. et al. Arterial hypertension in adults. Clinical guidelines 2020. Russian Journal of Cardiology. 2020; 25(3): 3786. (in Russian). DOI: 10.15829/1560-4071-2020-3-3786
  8. James J.L., Saghian R., Perwick R. et al. Trophoblast plugs: impact on utero-placental haemodynamics and spiral artery remodelling. Hum. Reprod. 2018; 33(8): 1430–41. DOI: 10.1093/humrep/dey225
  9. Staff A.C, Fjeldstad H.E., Fosheim I.K. et al. Failure of physiological transformation and spiral artery atherosis: their roles in preeclampsia. Am. J. Obstet. Gynecol. 2020; S0002-9378(20): 31116–9. DOI: 10.1016/j.ajog.2020.09.026
  10. Leslie K., Whitley G.St., Herse F. et al. Increased apoptosis, altered oxygen signaling, and antioxidant defenses in first-trimester pregnancies with high-resistance uterine artery blood flow. Am. J. Pathol. 2015; 185(10): 2731–41. DOI: 10.1016/j.ajpath.2015.06.020
  11. Chang C.W., Wakeland A.K., Parast M.M. Trophoblast lineage specification, differentiation and their regulation by oxygen tension. J. Endocrinol. 2018; 236(1): 43–56. DOI: 10.1530/JOE-17-0402
  12. Chulkov V.S., Medvedev B.I., Syundyukova E.G. et al. P 24 Cell renovation markers, apoptotic markers and placental expression of erythropoietin in preeclampsia. Pregnancy Hypertension. 2017; 9: 48. DOI: 10.1016/j.preghy.2017.07.102
  13. Redman C.W., Staff A.C. Preeclampsia, biomarkers, syncytiotrophoblast stress, and placental capacity. Am. J. Obstet. Gynecol. 2015; 213(4 suppl.): S9.e1–11. DOI: 10.1016/j.ajog.2015.08.003
  14. Staff A.C. The two-stage placental model of preeclampsia: an update. J. Reprod. Immunol. 2019; 134–135: 1–10. DOI: 10.1016/j.jri.2019.07.004
  15. Moghaddas Sani H., Zununi Vahed S., Ardalan M. Preeclampsia: a close look at renal dysfunction. Biomed. Pharmacother. 2019; 109: 408–16. DOI: 10.1016/j.biopha.2018.10.082
  16. Lu H.Q., Hu R. The role of immunity in the pathogenesis and development of pre-eclampsia. Scand. J. Immunol. 2019; 90(5): e12756. DOI: 10.1111/sji.12756
  17. Boeldt D.S., Bird I.M. Vascular adaptation in pregnancy and endothelial dysfunction in preeclampsia. J. Endocrinol. 2017; 232(1): 27–44. DOI: 10.1530/JOE-16-0340
  18. Alnaes-Katjavivi P., Roald B., Staff A.C. Uteroplacental acute atherosis in preeclamptic pregnancies: rates and clinical outcomes differ by tissue collection methods. Pregnancy Hypertens. 2020; 19: 11–17. DOI: 10.1016/j.preghy.2019.11.007
  19. Binder J., Monaghan C.A., Carta S. et al. OP17.07: Worsening of the uterine artery Doppler is associated with the development of hypertensive disorders of pregnancy. Ultrasound Obstet. Gynecol. 2017; 50(suppl.1): 104. DOI: 10.1002/uog.17856
  20. Kalafat E., Laoreti A., Khalil A. et al. Ophthalmic artery Doppler for prediction of pre-eclampsia: systematic review and meta-analysis. Ultrasound Obstet. Gynecol. 2018; 51(6): 731–7. DOI: 10.1002/uog.19002
  21. Dolgushina N.V., Artymuk N.V., Belokrinitskaya T.E. et al. Physiological pregnancy. Clinical recommendations. М.; 2020. 80 p. (in Russian)
  22. Osman M.W., Nath M., Breslin E. et al. Association between arterial stiffness and wave reflection with subsequent development of placental-mediated diseases during pregnancy: Findings of a systematic review and meta-analysis. J. Hypertens. 2018; 36(5): 1005–14. DOI: 10.1097/HJH.0000000000001664
  23. Falco M.L., Sivanathan J., Laoreti A. et al. Placental histopathology associated with pre-eclampsia: systematic review and meta-analysis. Ultrasound Obstet. Gynecol. 2017; 50(3): 295–301. DOI: 10.1002/uog.17494
  24. Benschop L., Duvekot J.J., Versmissen J. et al. Blood pressure profile 1 year after severe preeclampsia. Hypertension. 2018; 71(3): 491–8. DOI: 10.1161/HYPERTENSIONAHA.117.10338
  25. Romundstad P.R., Magnussen E.B., Smith G.D. et al. Hypertension in pregnancy and later cardiovascular risk: Common antecedents? Circulation. 2010; 122(6): 579–84. DOI: 10.1161/CIRCULATIONAHA.110.943407
  26. Foo F.L., Mahendru A.A., Masini G. et al. Association between prepregnancy cardiovascular function and subsequent preeclampsia or fetal growth restriction. Hypertension. 2018; 72(2): 442–50. DOI: 10.1161/HYPERTENSIONAHA.118.11092
  27. Ambia A.M., Morgan J.L., Wells C.E. et al. Perinatal outcomes associated with abnormal cardiac remodeling in women with treated chronic hypertension. Am. J. Obstet. Gynecol. 2018; 218(5): 519.e1–7. DOI: 10.1016/j.ajog.2018.02.015
  28. Moe K., Alnaes-Katjavivi P., Størvold G.L. et al. Classical cardiovascular risk markers in pregnancy and associations to uteroplacental acute atherosis. Hypertension. 2018; 72(3): 695–702. DOI: 10.1161/HYPERTENSIONAHA.118.10964
  29. Duffy J.M.N., Cairns A.E., Richards-Doran D. et al. A core outcome set for pre-eclampsia research: an international consensus development study. BJOG. 2020; 127(12): 1516–26. DOI: 10.1111/1471-0528.16319
  30. Townsend R., Khalil A., Premakumar Y. et al. Prediction of pre-eclampsia: review of reviews. Ultrasound Obstet. Gynecol. 2019; 54(1): 16–27. DOI: 10.1002/uog.20117
  31. Dolgushina V.F., Chulkov V.S., Vereina N.K. et al. Assessing the relationship of clinical and genetic factors to pregnancy complications and outcomes in women with preeclampsia in the presence of chronic hypertension. Russian Bulletin of Obstetrician-Gynecologist. 2014; 14(6): 4–8. (in Russian)
  32. Giannakou K., Evangelou E., Papatheodorou S.I. Genetic and non-genetic risk factors for pre-eclampsia: umbrella review of systematic reviews and meta-analyses of observational studies. Ultrasound Obstet. Gynecol. 2018; 51(6): 720–30. DOI: 10.1002/uog.18959
  33. Belokrinitskaya T.E., Frolova N.I., Strambovskaya N.N. et al. Prevalence and gene-gene interactions of gene polymorphism associated with arterial hypertension, endothelial dysfunction, disorders of hemostasis and folate metabolism in patients with severe preeclampsia. ENI Transbaikalian Medical Bulletin. 2019; 1: 1–13. (in Russian)
  34. Wang X., Sun T., Chen G. et al. Association between vascular endothelial growth factor gene polymorphisms and pre-eclampsia susceptibility: an updated meta-analysis. Immunol. Invest. 2020; 49(1–2): 120–33. DOI: 10.1080/08820139.2019.1659812
  35. Medvedev B.I., Syundyukova E.G., Sashenkov S.L. et al. A clinical, laboratory and instrumental model for the early prognosis of preeclampsia. Russian Bulletin of Obstetrician-Gynecologist. 2019; 19(1): 12–17. (in Russian). DOI: 10.17116/rosakush20191901112
  36. Khodzhaeva Z.S., Kholin A.M., Chulkov V.S. et al. Aspirin in the prevention of preeclampsia and associated maternal and perinatal complications. Obstetrics and Gynecology. 2018; 8: 12–8. (in Russian). DOI: 10.18565/aig.2018.8.12-18
  37. Lopez-Jaramillo P., Barajas J., Rueda-Quijano S.M. et al. Obesity and preeclampsia: common pathophysiological mechanisms. Front. Physiol. 2018; 9: 1838. DOI: 10.3389/fphys.2018.01838
  38. Agarwal S., Kovilam O., Agrawal D.K. Vitamin D and its impact on maternal-fetal outcomes in pregnancy: a critical review. Crit. Rev. Food Sci. Nutr. 2018; 58(5): 755–69. DOI: 10.1080/10408398.2016.1220915
  39. De-Regil L.M., Palacios C., Lombardo L.K. et al. Vitamin D supplementation for women during pregnancy. Cochrane Database Syst. Rev. 2016; 1: CD008873. DOI: 10.1002/14651858.CD008873.pub3
  40. Syundyukova E.G., Medvedev B.I., Sashenkov S.L. et al. Ozone therapy technologies in the prevention and treatment of obstetric pathology. Russian Bulletin of Obstetrician-Gynecologist. 2020; 20(5): 33–7. (in Russian). DOI: 10.17116/rosakush20202005133
  41. Sobota-Grzeszyk A., Kuźmicki M., Szamatowicz J.J. Myoinositol in the prevention of gestational diabetes mellitus: is it sensible? Diabetes Res. 2019; 2019: 3915253. DOI: 10.1155/2019/3915253
  42. Martis R., Crowther C.A., Shepherd E. et al. Treatments for women with gestational diabetes mellitus: an overview of Cochrane systematic reviews. Cochrane Database Syst. Rev. 2018; 8(8): CD012327. DOI: 10.1002/14651858.CD012327.pub2
  43. D'Anna R., Santamaria A., Alibrandi A. et al. Myo-inositol for the prevention of gestational diabetes mellitus. A brief review. Nutr. Sci. Vitaminol. (Tokyo). 2019; 65(suppl.): S59–61. DOI: 10.3177/jnsv.65.S59


30 June 00:00
A New Issue of Doctor.Ru Neurology Psychiatry, Vol. 20, No. 5 (2021), Published

Find original articles and reviews covering various aspects of neurology, psychiatry and the interview with Professor Marina Arkadievna Kinkulkina

28 June 00:00
A New Issue of Doctor.Ru Internal Medicine, Vol. 20, No. 4 (2021), Published

Find original articles and reviews covering various aspects of cardiology, gastroenterology, internal medicine and the interview with Professor Elena Zelikovna Golukhova


3 May 17:06
A New Issue of Doctor.Ru Pediatrics, Vol. 20, No. 3 (2021), Published

Find original articles and reviews covering various aspects of pediatrics and the interview with Professor Evgeny Grigorievich Furman

3 May 17:06
A New Issue of Doctor.Ru Endocrinology, Vol. 20, No. 2 (2021), Published

Find original articles and reviews covering various aspects of endocrinology and the interview with Professor Valentin Viktorovich Fadeev

16 April 11:57
Igor Evgenievich Khatkov joined the American Surgical Association

Igor Evgenievich Khatkov, Head of A. S. Loginov Moscow Clinical Scientific and Practical Centre, Chief Oncologist in and for Moscow is now an honoured member of the American Surgical Association.

All news