Цереброваскулярные и нейрокогнитивные риски преэклампсии: патогенез, острые осложнения и отдаленные последствия для матери и плода

Преэклампсия является одной из наиболее значимых медико-социальных проблем современного акушерства. Данное осложнение беременности не только угрожает жизни матери и плода во время беременности, но и служит предиктором тяжелых цереброваскулярных и сердечно-сосудистых осложнений в отдаленном периоде. Преэклампсия вызывает как острые, так и хронические цереброваскулярные заболевания, которые обусловлены повышенной проницаемостью гематоэнцефалического барьера, нарушением церебральной ауторегуляции, гиперкоагуляцией и воспалением. В данном литературном обзоре проанализированы публикации за период с января 2010 г. по июнь 2025 г. с использованием информационных баз PubMed, Scopus, MEDLINE и eLibrary. Описаны особенности регуляции мозгового кровотока во время нормальной беременности и при преэклампсии. Цереброваскулярные осложнения преэклампсии во время беременности включают синдром задней обратимой энцефалопатии, синдром обратимой церебральной вазоконстрикции, геморрагический и ишемический инсульт, тромбоз церебральных венозных синусов. В отдаленный послеродовый период у женщин с анамнезом преэклампсии повышается риск нейрокогнитивных расстройств, включающих нарушение исполнительной функции и памяти. Также отмечаются значительные психосоциальные последствия в виде снижения качества жизни и социального функционирования, повышенный уровень тревожности, депрессии, что снижает адаптацию в стрессовых ситуациях повседневной жизни. Хроническая дисфункция гематоэнцефалического барьера может вызывать не только функциональные нейроваскулярные нарушения, но и морфологические изменения. В долгосрочной перспективе преэклампсия связана с повышением риска развития сосудистой деменции, болезни Альцгеймера и инсульта. Потомство, рожденное от матерей с преэклампсией, имеет повышенный риск неврологических заболеваний, включая когнитивные нарушения, синдром дефицита внимания и гиперактивности, расстройства аутистического спектра, депрессивные расстройства, эпилепсию и церебральный паралич.

1. Miller EC, Vollbracht S. Neurology of preeclampsia and related disorders: an update in neuro-obstetrics. Curr Pain Headache Rep. 2021;25(6):40. https://doi.org/10.1007/s11916-021-00958-z

2. McDermott M, Miller EC, Rundek T, Hurn PD, Bushnell CD. Preeclampsia: association with posterior reversible encephalopathy syndrome and stroke. Stroke. 2018;49(3):524530. https://doi.org/10.1161/STROKEAHA.117.018416

3. Torres-Torres J, Espino-Y-Sosa S, Martinez-Portilla R, Borboa-Olivares H, Estrada-Gutierrez G, Acevedo-Gallegos S, et al. A narrative review on the pathophysiology of preeclampsia. Int J Mol Sci. 2024;25(14):7569. https://doi.org/10.3390/ijms25147569

4. Michalczyk M, Celewicz A, Celewicz M, Woźniakowska-Gondek P, Rzepka R. The role of inflammation in the pathogenesis of preeclampsia. Mediators Inflamm. 2020;2020:3864941. https://doi.org/10.1155/2020/3864941

5. Таскина Е. С., Кибалина И. В., Мудров В. А., Давыдов С. О. Церебральные маркеры нейровоспаления и нейродегенерации при гипертензивных расстройствах во время беременности. Медицинская иммунология. 2025;27(4):301–310. https://doi.org/10.15789/1563-0625-CMO-3169 [Taskina ES, Kibalina IV, Mudrov VA, Davydov SO. Сerebral markers of neuroinflammation and neurodegeneration in hypertensive disorders during pregnancy. Medical Immunology. 2025;27(4):301–310. (In Russ.) https://doi.org/10.15789/1563-0625-CMO-3169]

6. Ijomone OK, Osahon IR, Okoh COA, Akingbade GT, Ijomone OM. Neurovascular dysfunctions in hypertensive disorders of pregnancy. Metab Brain Dis. 2021;36(6):1109–1117. https://doi.org/10.1007/s11011-021-00710-x

7. Brusse IA, Kluivers ACM, Zambrano MD, Shetler K, Miller EC. Neuro-obstetrics: a multidisciplinary approach to care of women with neurologic disease. Handb Clin Neurol. 2020;171:143–160. https://doi.org/10.1016/B978-0-444-64239-4.00007-2

8. Jones-Muhammad M, Warrington JP. Cerebral blood flow regulation in pregnancy, hypertension, and hypertensive disorders of pregnancy. Brain Sci. 2019;9(9):224. https://doi.org/10.3390/brainsci9090224

9. Fantini S, Sassaroli A, Tgavalekos KT, Kornbluth J. Cerebral blood flow and autoregulation: current measurement techniques and prospects for noninvasive optical methods. Neurophotonics. 2016;3(3):031411. https://doi.org/10.1117/1.NPh.3.3.031411

10. Morales-Roccuzzo D, Sabahi M, Obrzut M, Najera E, Monterroso-Cohen D, Bsat S, et al. A primer to vascular anatomy of the brain: an overview on anterior compartment. Surg Radiol Anat. 2024;46(6):829–842. https://doi.org/10.1007/s00276-024-03359-0

11. Armstead WM. Cerebral blood flow autoregulation and dysautoregulation. Anesthesiol Clin. 2016;34(3):465–477. https://doi.org/10.1016/j.anclin.2016.04.002

12. Batur Caglayan HZ, Nazliel B, Cinar M, Ataoglu E, Moraloglu O, Irkec C. Assessment of maternal cerebral blood flow velocity by transcranial Doppler ultrasound before delivery and in the early postpartum period. J Matern Fetal Neonatal Med. 2019;32(4):584–589. https://doi.org/10.1080/14767058.2017.1387529

13. Iadecola C. The neurovascular unit coming of age: a journey through neurovascular coupling in health and disease. Neuron. 2017;96(1):17–42. https://doi.org/10.1016/j.neuron.2017.07.030

14. Cipolla MJ, Bishop N, Chan SL. Effect of pregnancy on autoregulation of cerebral blood flow in anterior versus posterior cerebrum. Hypertension. 2012;60(3):705–711. https://doi.org/10.1161/HYPERTENSIONAHA.112.198952

15. Bergman L, Cluver C, Carlberg N, Belfort M, Tolcher MC, Panerai RB, et al. Cerebral perfusion pressure and autoregulation in eclampsia-a case control study. Am J Obstet Gynecol. 2021;225(2):185.e1–185.e9. https://doi.org/10.1016/j.ajog.2021.03.017

16. van Veen TR, Panerai RB, Haeri S, Singh J, Adusumalli JA, Zeeman GG, et al. Cerebral autoregulation in different hypertensive disorders of pregnancy. Am J Obstet Gynecol. 2015;212(4):513. e1–7. https://doi.org/10.1016/j.ajog.2014.11.003

17. Nation DA, Sweeney MD, Montagne A, Sagare AP, D’Orazio LM, Pachicano M, et al. Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction. Nat Med. 2019;25(2):270–276. https://doi.org/10.1038/s41591-018-0297-y

18. Cornelius DC. Preeclampsia: from inflammation to immunoregulation. Clin Med Insights Blood Disord. 2018;11: 1179545X17752325. https://doi.org/10.1177/1179545X17752325

19. Ciampa E, Li Y, Dillon S, Lecarpentier E, Sorabella L, Libermann TA, et al. Cerebrospinal fluid protein changes in preeclampsia. Hypertension. 2018;72(1):219–226. https://doi.org/10.1161/HYPERTENSIONAHA.118.11153

20. Burwick RM, Togioka BM, Speranza RJ, Gaffney JE, Roberts VHJ, Frias AE, et al. Assessment of blood-brain barrier integrity and neuroinflammation in preeclampsia. Am J Obstet Gynecol. 2019;221(3):269.e1–269.e8. https://doi.org/10.1016/j.ajog.2019.06.024

21. Miller EC, Gatollari HJ, Too G, Boehme AK, Leffert L, Marshall RS, et al. Risk factors for pregnancy-associated stroke in women with preeclampsia. Stroke. 2017;48(7):1752–1759. https://doi.org/10.1161/STROKEAHA.117.017374

22. Camargo EC, Singhal AB. Stroke in pregnancy: a multidisciplinary approach. Obstet Gynecol Clin North Am. 2021;48(1):75–96. https://doi.org/10.1016/j.ogc.2020.11.004

23. Lee S, Kim Y, Navi BB, Abdelkhaleq R, Salazar-Marioni S, Blackburn SL, et al. Risk of intracranial hemorrhage associated with pregnancy in women with cerebral arteriovenous malformations. J Neurointerv Surg. 2021;13(8):707–710. https://doi.org/10.1136/neurintsurg-2020-016838

24. Meeks JR, Bambhroliya AB, Alex KM, Sheth SA, Savitz SI, Miller EC, et al. Association of primary intracerebral hemorrhage with pregnancy and the postpartum period. JAMA Netw Open. 2020;3(4):e202769. https://doi.org/10.1001/jamanet-workopen.2020.2769

25. Leffert LR, Clancy CR, Bateman BT, Bryant AS, Kuklina EV. Hypertensive disorders and pregnancy-related stroke: frequency, trends, risk factors, and outcomes. Obstet Gynecol. 2015;125(1):124–131. https://doi.org/10.1097/AOG.0000000000000590

26. Fishel Bartal M, Sibai BM. Eclampsia in the 21st century. Am J Obstet Gynecol. 2022;226(2S):S1237–S1253. https://doi.org/10.1016/j.ajog.2020.09.037

27. Yu E, Green JM, Aberle LS, Mandelbaum RS, Brueggmann D, Ouzounian JG, et al. Posterior reversible encephalopathy syndrome following eclampsia: assessment of clinical and pregnancy characteristics. Am J Obstet Gynecol. 2024;231(1):e19–e25. https://doi.org/10.1016/j.ajog.2024.02.298

28. Mayama M, Uno K, Tano S, Yoshihara M, Ukai M, Kishigami Y, et al. Incidence of posterior reversible encephalopathy syndrome in eclamptic and patients with preeclampsia with neurologic symptoms. Am J Obstet Gynecol. 2016;215(2):239.e1–5. https://doi.org/10.1016/j.ajog.2016.02.039

29. Liman TG, Bohner G, Heuschmann PU, Scheel M, Endres M, Siebert E. Clinical and radiological differences in posterior reversible encephalopathy syndrome between patients with preeclampsia-eclampsia and other predisposing diseases. Eur J Neurol. 2012;19(7):935–943. https://doi.org/10.1111/j.1468-1331.2011.03629.x

30. Vgontzas A, Robbins MS. A hospital based retrospective study of acute postpartum headache. Headache. 2018;58(6):845–851. https://doi.org/10.1111/head.13279

31. Raffaelli B, Neeb L, Israel-Willner H, Korner J, Liman T, Reuter U, et al. Brain imaging in pregnant women with acute headache. J Neurol. 2018;265(8):1836–1843. https://doi.org/10.1007/s00415-018-8924-6

32. Janzarik WG, Jacob J, Katagis E, Markfeld-Erol F, Sommerlade L, Wuttke M, et al. Preeclampsia postpartum: impairment of cerebral autoregulation and reversible cerebral hyperperfusion. Pregnancy Hypertens. 2019;17:121–126. https://doi.org/10.1016/j.preghy.2019.05.019

33. Janzarik WG, Gerber AK, Markfeld-Erol F, Sommerlade L, Allignol A, Reinhard M. No long-term impairment of cerebral autoregulation after preeclampsia. Pregnancy Hypertens. 2018;13:171–173. https://doi.org/10.1016/j.preghy.2018.06.009

34. Bergman L, Akerud H, Wikstrom AK, Larsson M, Naessen T, Akhter T. Cerebral biomarkers in women with preeclampsia are still elevated 1 year postpartum. Am J Hypertens. 2016;29(12):1374–1379. https://doi.org/10.1093/ajh/hpw097

35. Brzan Simenc G, Ambrozic J, Osredkar J, Gersak K, Lucovnik M. Correlation between cerebral biomarkers and optic nerve sheath diameter in patients with severe preeclampsia. Hypertens Pregnancy. 2021;40(1):9–14. https://doi.org/10.1080/10641955.2020.1849275

36. Bergman L, Zetterberg H, Kaihola H, Hagberg H, Blennow K, Åkerud H. Blood-based cerebral biomarkers in preeclampsia: plasma concentrations of NfL, tau, S100B and NSE during pregnancy in women who later develop preeclampsia — a nested case control study. PLoS. One. 2018;13(5):e0196025. https://doi.org/10.1371/journal.pone.0196025

37. Tan Z, Jiang J, Tian F, Peng J, Yang Z, Li S, et al. Serum visinin-like protein 1 is a better biomarker than neuron-specific enolase for seizure-induced neuronal injury: a prospective and observational study. Front. Neurol. 2020;11:567587. https://doi.org/10.3389/fneur.2020.567587

38. Elharram M, Dayan N, Kaur A, Landry T, Pilote L. Long-term cognitive impairment after preeclampsia: a systematic review and meta-analysis. Obstet Gynecol. 2018;132(2):355–364. https://doi.org/10.1097/AOG.0000000000002686

39. Ibarra AJ, Butters MA, Lim G, Jeyabalan A, Li R, Balasubramani GK, et al. Longitudinal cognitive evaluation before and after delivery among people with preeclampsia. Am J Obstet Gynecol MFM. 2023;5(7):100966. https://doi.org/10.1016/j.ajogmf.2023.100966

40. Adank MC, Hussainali RF, Oosterveer LC, Ikram MA, Steegers EAP, Miller EC, et al. hypertensive disorders of pregnancy and cognitive impairment: a prospective cohort study. Neurology. 2021;96(5):e709–e718. https://doi.org/10.1212/WNL.0000000000011363

41. Birnie K, Catov J, Anderson EL, Lapidaire W, Kilpi F, Lawlor DA, et al. Hypertensive disorders of pregnancy and midlife maternal cognition in a prospective cohort study. J Clin Hypertens. 2024;26(2):166–176. https://doi.org/10.1111/jch.14765

42. Alers RJ, Ghossein-Doha C, Canjels LPW, Muijtjens ESH, Brandt Y, Kooi ME, et al. Attenuated cognitive functioning decades after preeclampsia. Am J Obstet Gynecol. 2023;229(3):294.e1–294. e14. https://doi.org/10.1016/j.ajog.2023.02.020

43. Fields JA, Garovic VD, Mielke MM, Kantarci K, Jayachandran M, White WM, et al. Preeclampsia and cognitive impairment later in life. Am J Obstet Gynecol. 2017;217(1):74.e1–74. e11. https://doi.org/10.1016/j.ajog.2017.03.008

44. Kokori E, Aderinto N, Olatunji G, Komolafe R, Abraham IC, Babalola AE, et al. Maternal and fetal neurocognitive outcomes in preeclampsia and eclampsia; a narrative review of current evidence. Eur J Med Res. 2024;29(1):470. https://doi.org/10.1186/s40001-024-02070-5

45. Postma IR, Bouma A, Ankersmit IF, Zeeman GG. Neurocognitive functioning following preeclampsia and eclampsia: a long-term follow-up study. Am J Obstet Gynecol. 2014;211(1):37. e1–9. https://doi.org/10.1016/j.ajog.2014.01.042

46. Siepmann T, Boardman H, Bilderbeck A, Griffanti L, Kenworthy Y, Zwager C, et al. Long-term cerebral white and gray matter changes after preeclampsia. Neurology. 2017;88(13):1256–1264. https://doi.org/10.1212/WNL.0000000000003765

47. Kaur S, Darden CJ, Adegbola GM, Warrington JP. History of hypertensive disorders of pregnancy and risk of Alzheimer’s disease and vascular dementia. Front Neuroendocrinol. 2025;78:101198. https://doi.org/10.1016/j.yfrne.2025.101198

48. Nakashima A, Shima T, Aoki A, Kawaguchi M, Yasuda I, Tsuda S, et al. Placental autophagy failure: a risk factor for preeclampsia. J. Obstet. Gynaecol. Res. 2020;46(12):2497–2504. https://doi.org/10.1111/jog.14489

49. Lederer W, Dominguez CA, Popovscaia M, Putz G, Humpel C. Cerebrospinal fluid levels of tau and phospho-tau-181 proteins during pregnancy. Pregnancy Hypertens. 2016;64:384–387. https://doi.org/10.1016/j.preghy.2016.08.243

50. Wang Y, Guo B, Zhao K, Yang L, Chen T. Correlation between cognitive impairment and serum phosphorylated tau181 protein in patients with preeclampsia. Front Aging Neurosci. 2023;15:1148518. https://doi.org/10.3389/fnagi.2023.1148518

51. Bokstrom-Rees E, Zetterberg H, Blennow K, Hastie R, Schell S, Cluver C, et al. Correlation between cognitive assessment scores and circulating cerebral biomarkers in women with preeclampsia and eclampsia. Pregnancy Hypertens. 2023;31:38–45. https://doi.org/10.1016/j.preghy.2022.12.001

52. Evers KS, Atkinson A, Barro C, Fisch U, Pfister M, Huhn EA, et al. Neurofilament as neuronal injury blood marker in preeclampsia. Hypertension. 2018;71:6:1178–1184. https://doi.org/10.1161/HYPERTENSIONAHA.117.10314

53. Andersson M, Oras J, Thorn SE, Karlsson O, Kalebo P, Zetterberg H, et al. Signs of neuroaxonal injury in preeclampsia — a case control study. PLoS One. 2021;16(2):e0246786. https://doi.org/10.1371/journal.pone.0246786

54. Fang X, Liang Y, Zhang W, Wang Q, Chen J, Chen J, et al. Serum neurofilament light: a potential diagnostic and prognostic bio-marker in obstetric posterior reversible encephalopathy syndrome. Mol Neurobiol. 2021;58(12):6460–6470. https://doi.org/10.1007/s12035-021-02562-z

55. An J, Kim K, Lim HJ, Kim HY, Shin J, Park I, et al. Early onset diagnosis in Alzheimer’s disease patients via amyloid-β oligomers-sensing probe in cerebrospinal fluid. Nat Commun. 2024;15(1):1004. https://doi.org/10.1038/s41467-024-44818-x

56. Palmqvist S, Tideman P, Mattsson-Carlgren N, Schindler SE, Smith R, Ossenkoppele R, et al. Blood biomarkers to detect Alzheimer disease in primary care and secondary care. JAMA. 2024:e2413855. https://doi.org/10.1001/jama.2024.13855

57. Schindler SE, Bollinger JG, Ovod V, Mawuenyega KG, Li Y, Gordon BA, et al. High-precision plasma β-amy-loid 42/40 predicts current and future brain amyloidosis. Neurology. 2019;93(17):e1647-e1659. https://doi.org/10.1212/WNL.0000000000008081

58. Buhimschi IA, Nayeri UA, Zhao G, Shook LL, Pensalfini A, Funai EF, et al. Protein misfolding, congophilia, oligomerization, and defective amyloid processing in preeclampsia. Sci Transl Med. 2014;6:245ra92. https://doi.org/10.1126/sci-translmed.3008808

59. Schliep KC, Mclean H, Yan B, Qeadan F, Theilen LH, de Havenon A, et al. Association between hypertensive disorders of pregnancy and dementia: a systematic review and meta-analysis. Hypertension. 2023;80(2):257–267. https://doi.org/10.1161/HY-PERTENSIONAHA.122.19399

60. Carey C, Mulcahy E, McCarthy FP, Jennings E, Kublickiene K, Khashan A, et al. Hypertensive disorders of pregnancy and the risk of maternal dementia: a systematic review and meta-analysis. Am J Obstet Gynecol. 2024;231(2):196–210. https://doi.org/10.1016/j.ajog.2024.01.013

61. Wu P, Haththotuwa R, Kwok CS, Babu A, Kotronias RA, Rushton C, et al. Preeclampsia and future cardiovascular health: a systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes. 2017;10(2):e003497. https://doi.org/10.1161/CIRCOUT-COMES.116.003497

62. Simon E, Bechraoui-Quantin S, Tapia S, Cottenet J, Mariet AS, Cottin Y, et al. Time to onset of cardiovascular and cerebrovascular outcomes after hypertensive disorders of pregnancy: a nationwide, population-based retrospective cohort study. Am J Obstet Gynecol. 2023;229(3):296.e1–296.e22. https://doi.org/10.1016/j.ajog.2023.03.021

63. Brohan MP, Daly FP, Kelly L, McCarthy FP, Khashan AS, Kublickiene K, et al. Hypertensive disorders of pregnancy and long-term risk of maternal stroke - a systematic review and meta-analysis. Am J Obstet Gynecol. 2023;229(3):248–268. https://doi.org/10.1016/j.ajog.2023.03.034

64. Hung SK, Lee MS, Lin HY, Chen LC, Chuang CJ, Chew CH, et al. Impact of hypertensive disorders of pregnancy on the risk of stroke stratified by subtypes and follow-up time. Stroke. 2022;53(2):338–344. https://doi.org/10.1161/STROKEA-HA.121.034109

65. Barron A, McCarthy CM, O’Keeffe GW. Preeclampsia and neurodevelopmental outcomes: potential pathogenic roles for inflammation and oxidative stress? Mol Neurobiol. 2021;58(6):2734–2756. https://doi.org/10.1007/s12035-021-02290-4

66. Zhang H, Lin J, Zhao H. Impacts of maternal preeclampsia exposure on offspring neuronal development: recent insights and interventional approaches. Int J Mol Sci. 2024;25(20):11062. https://doi.org/10.3390/ijms252011062

67. Gumusoglu SB, Chilukuri ASS, Santillan DA, Santillan MK, Stevens HE. Neurodevelopmental outcomes of prenatal preeclampsia exposure. Trends Neurosci. 2020;43(4):253–268. https://doi.org/10.1016/j.tins.2020.02.003

68. Zhen Lim TX, Pickering TA, Lee RH, Hauptman I, Wilson ML. Hypertensive disorders of pregnancy and occurrence of ADHD, ASD, and epilepsy in the child: a meta-analysis. Pregnancy Hypertens. 2023;33:22–29. https://doi.org/10.1016/j.preghy.2023.06.002

69. Mak LE, Croy BA, Kay V, Reynolds JN, Ratsep MT, Forkert ND, et al. Resting-state functional connectivity in children born from gestations complicated by preeclampsia: a pilot study cohort. Pregnancy Hypertens. 2018;12:23–28. https://doi.org/10.1016/j.preghy.2018.02.004

70. Koparkar S, Srivastava L, Randhir K, Dangat K, Pisal H, Kadam V, et al. Cognitive function and behavioral problems in children born to mothers with preeclampsia: an Indian study. Child Neuropsychol. 2022;28(3):337–354. https://doi.org/10.1080/09297049.2021.1978418

71. Ratsep MT, Hickman AF, Maser B, Pudwell J, Smith GN, Brien D, et al. Impact of preeclampsia on cognitive function in the offspring. Behav Brain Res. 2016;302:175–181. https://doi.org/10.1016/j.bbr.2016.01.030

72. Sverrisson FA, Bateman BT, Aspelund T, Skulason S, Zoega H. Preeclampsia and academic performance in children: a nationwide study from Iceland. PLoS One. 2018;13(11):e0207884. https://doi.org/10.1371/journal.pone.0207884

73. Tuovinen S, Eriksson JG, Kajantie E, Lahti J, Pesonen AK, Heinonen K, et al. Maternal hypertensive disorders in pregnancy and self-reported cognitive impairment of the offspring 70 years later: the Helsinki Birth Cohort Study. Am J Obstet Gynecol. 2013;208(3):200.e1–9. https://doi.org/10.1016/j.ajog.2012.12.017