Ранні маркери прееклампсії: сучасний стан, аналіз та перспективи застосування

G. I. Ishchenko

doi:10.14739/2310-1210.2026.2.342079

Authors

G. I. Ishchenko State Institution “Ukrainian Center of Maternity and Childhood of the National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine https://orcid.org/0000-0003-0700-4517

DOI:

https://doi.org/10.14739/2310-1210.2026.2.342079

Keywords:

preeclampsia, biomarkers, diagnosis, pregnancy complications

Abstract

Preeclampsia (PE) complicates 2 % to 8 % of pregnancies and remains the leading cause of perinatal maternal and neonatal mortality worldwide. Early identification of high-risk pregnancies allows for the reduction of complications and the implementation of preventive measures.

Aim. To assess the current state of research on early biomarkers of PE, analyze their prognostic value, and determine the prospects for implementation in clinical practice.

Materials and methods. The article analyzes the current state of research regarding early biomarkers of PE, analyze their diagnostic accuracy, and determine the prospects for their integration into routine clinical practice. A systematic review (incorporating meta-analysis elements) of publications was conducted covering the period from 2000 to 30.06.2024. Databases searched included PubMed / MEDLINE, Embase, Scopus, Web of Science and Cochrane Library; additionally, Google Scholar (first 200 results), ClinicalTrials.gov and ProQuest Dissertations & Theses. MeSH / Emtree and free keywords were used: preeclampsia, biomarker, placental growth factor, PlGF, sFlt-1, sFlt-1/PlGF, PP-13, PAPP-A, microRNA, first trimester, prediction, screening. Human studies (prospective / retrospective cohorts, case-control), systematic reviews and meta-analyses that evaluated biomarkers in the I–II trimesters were included; cases, works without primary data and studies with n < 10 were excluded. The presented data substantiate the role of biomarker combinations in increasing the accuracy of early diagnosis, and the prospects for their implementation in clinical practice are discussed.

Results. The synthesis of data confirms a consistent early decrease in PlGF and an increase in sFlt-1 in pregnant women who subsequently develop PE. The sFlt-1/PlGF ratio emerged as the most robust predictor. Pooled diagnostic performance indices were: PlGF – sensitivity ~78 %, specificity ~85 %; sFlt-1 – sensitivity ~82 %, specificity ~80 %; sFlt-1/PlGF – sensitivity ~85 %, specificity ~88 %. The main limitations include population heterogeneity, differences in laboratory methods, and the absence of universally standardized cutoff values for different gestational ages.

Conclusions. PlGF, sFlt-1 and their ratios are promising early markers for PE screening. To facilitate clinical implementation, there is an urgent need for standardization of laboratory methods, identification of clinically validated thresholds, development of affordable rapid tests, and large multicenter validation studies. Integrating these biomarkers with clinical risk factors remains the most effective strategy for early-onset PE prediction.

Author Biography

G. I. Ishchenko, State Institution “Ukrainian Center of Maternity and Childhood of the National Academy of Medical Sciences of Ukraine”, Kyiv

MD, PhD, Senior Researcher at the Department of Prevention and Treatment of Purulent-Inflammatory Diseases in Obstetrics

References

Akbari R, Hantoushzadeh S, Panahi Z, Bahonar S, Ghaemi M. A bibliometric review of 35 years of studies about preeclampsia. Front Physiol. 2023;14:1110399. doi: https://doi.org/10.3389/fphys.2023.1110399

Valdés G. Focus on today's evidence while keeping an eye on the future: lessons derived from hypertension in women. J Hum Hypertens. 2022;36(10):882-6. doi: https://doi.org/10.1038/s41371-021-00652-y

Liu M, Niu Y, Ma K, Leung P, Chen ZJ, Wei D, et al. Identification of novel first-trimester serum biomarkers for early prediction of preeclampsia. J Transl Med. 2023;21(1):634. doi: https://doi.org/10.1186/s12967-023-04472-1

Shahid R, Bari MF, Hussain M. Serum biomarkers for the prediction and diagnosis of preeclampsia: A meta-analysis. J Taibah Univ Med Sci. 2021;17(1):14-27. doi: https://doi.org/10.1016/j.jtumed.2021.07.003

Xu L, Wang X, Wang C, Li W, Liu H. l-arginine supplementation improved neonatal outcomes in pregnancies with hypertensive disorder or intrauterine growth restriction: A systematic review and meta-analysis of randomized controlled trials. Clin Nutr. 2022;41(7):1512-22. doi: https://doi.org/10.1016/j.clnu.2022.05.014

Tong S, Kaitu'u-Lino TJ, Hastie R, Brownfoot F, Cluver C, Hannan N. Pravastatin, proton-pump inhibitors, metformin, micronutrients, and biologics: new horizons for the prevention or treatment of preeclampsia. Am J Obstet Gynecol. 2022;226(2S):S1157-70. doi: https://doi.org/10.1016/j.ajog.2020.09.014

Freimane KZ, Kerrigan L, Eastwood KA, Watson CJ. Pre-Eclampsia Biomarkers for Women With Type 1 Diabetes Mellitus: A Comprehensive Review of Recent Literature. Front Bioeng Biotechnol. 2022;10:809528. doi: https://doi.org/10.3389/fbioe.2022.809528

Ives CW, Sinkey R, Rajapreyar I, Tita AT, Oparil S. Preeclampsia-Pathophysiology and Clinical Presentations: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020;76(14):1690-02. doi: https://doi.org/10.1016/j.jacc.2020.08.014

Magee LA, Nicolaides KH, von Dadelszen P. Preeclampsia. N Engl J Med. 2022;386(19):1817-32. doi: https://doi.org/10.1056/NEJMra2109523

Whigham CA, Hastie R, Hannan NJ, Brownfoot F, Pritchard N, Cannon P, Nguyen TV, Kandel M, Masci J, Tong S, Kaitu'u-Lino TJ. Placental growth factor is negatively regulated by epidermal growth factor receptor (EGFR) signaling. Placenta. 2021;114:22-28. doi: https://doi.org/10.1016/j.placenta.2021.08.002

Reddy M, Rolnik DL, Poon L, Han A, Bujold E, Belizán M, et al. Preventing pre-eclampsia and its complications. In: Hanson C, Vousden N, editors. Glob Libr Women S Med. London, UK: 2022. Available from: http://doi.org/10.3843/GLOWM.416343

Sande AK, Dalen I, Torkildsen EA, Sande RK, Morken NH. Pregestational maternal risk factors for preterm and term preeclampsia: A population-based cohort study. Acta Obstet Gynecol Scand. 2023;102(11):1549-57. doi: https://doi.org/10.1111/aogs.14642

Beniuk VO, Komar VM, Kovaliuk TV, Lastovetska LD, Shcherba OA, Shapovaliuk OV. [Anamnestic predictors of preeclampsia risk: a modern view on the problem]. Reproductive health of woman. 2025;(3):104-12. Ukrainian. doi: https://doi.org/10.30841/2708-8731.3.2025.331554

Yip KC, Luo Z, Huang X, Lee W, Li L, Dai C, et al. The role of aspirin dose and initiation time in the prevention of preeclampsia and corresponding complications: a meta-analysis of RCTs. Arch Gynecol Obstet. 2022;305(6):1465-79. doi: https://doi.org/10.1007/s00404-021-06349-4

Jung E, Romero R, Yeo L, Gomez-Lo pez N, Chaemsaithong P, Jaovisidha A, et al. The etiology of preeclampsia. Am J Obstet Gynecol. 2022;226(2S):844-66. doi: https://doi.org/10.1016/j.ajog.2021.11.1356

Sutton EF, Rogan SC, Lopa S, Sharbaugh D, Muldoon MF, Catov JM. Early Pregnancy Blood Pressure Elevations and Risk for Maternal and Neonatal Morbidity. Obstet Gynecol. 2020;136(1):129-39. doi: https://doi.org/10.1097/AOG.0000000000003885

Chaemsaithong P, Gil MM, Chaiyasit N, Cuenca-Gomez D, Plasencia W, Rolle V, et al. Accuracy of placental growth factor alone or in combination with soluble fms-like tyrosine kinase-1 or maternal factors in detecting preeclampsia in asymptomatic women in the second and third trimesters: a systematic review and meta-analysis. Am J Obstet Gynecol. 2023;229(3):222-47. doi: https://doi.org/10.1016/j.ajog.2023.03.032

Townsend R, Khalil A, Premakumar Y, Allotey J, Snell K, Chan C, Chappell LC, et al. Prediction of pre-eclampsia: review of reviews. Ultrasound Obstet Gynecol. 2019;54(1):16-27. doi: https://doi.org/10.1002/uog.20117

Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin, Number 222. Obstet Gynecol. 2020;135(6):e237-60. doi: https://doi.org/10.1097/AOG.0000000000003891

Phoswa WN, Khaliq OP. The Role of Oxidative Stress in Hypertensive Disorders of Pregnancy (Preeclampsia, Gestational Hypertension) and Metabolic Disorder of Pregnancy (Gestational Diabetes Mellitus). Oxid Med Cell Longev. 2021;2021:5581570. doi: https://doi.org/10.1155/2021/5581570

Yang Y, Xu P, Zhu F, Liao J, Wu Y, Hu M, et al. The Potent Antioxidant MitoQ Protects Against Preeclampsia During Late Gestation but Increases the Risk of Preeclampsia When Administered in Early Pregnancy. Antioxid Redox Signal. 2021;34(2):118-36. doi: https://doi.org/10.1089/ars.2019.7891

Callbo PN, Junus K, Gabrysch K, Bergman L, Poromaa IS, Lager S, et al. Novel Associations Between Mid-Pregnancy Cardiovascular Biomarkers and Preeclampsia: An Explorative Nested Case-Control Study. Reprod Sci. 2024;31(5):1391-00. doi: https://doi.org/10.1007/s43032-023-01445-z

Tomkiewicz J, Darmochwał-Kolarz DA. Biomarkers for Early Prediction and Management of Preeclampsia: A Comprehensive Review. Med Sci Monit. 2024;30:e944104. doi: https://doi.org/10.12659/MSM.944104

Sulimenko OM, Romanenko TG. [Markers of angiogenesis and their role in prediction of preeclampsy in multiple pregnancy]. Ukrainian Journal Health of Woman. 2022;(3):9-15. Ukrainian. doi: https://doi.org/10.15574/HW.2022.160.9

Zhao R, Zhou L, Wang S, Xiong G, Hao L. Association between maternal vitamin D levels and risk of adverse pregnancy outcomes: a systematic review and dose-response meta-analysis. Food Funct. 2022;13(1):14-37. doi: https://doi.org/10.1039/d1fo03033g

US Preventive Services Task Force; Davidson KW, Barry MJ, Mangione CM, Cabana M, Caughey AB, et al. Aspirin Use to Prevent Preeclampsia and Related Morbidity and Mortality: US Preventive Services Task Force Recommendation Statement. JAMA. 2021;326(12):1186-91. doi: https://doi.org/10.1001/jama.2021.14781

Hoffman MK. The great obstetrical syndromes and the placenta. BJOG. 2023;130(Suppl 3):8-15. doi: https://doi.org/10.1111/1471-0528.17613