Early markers of preeclampsia: a current state, analysis, and clinical implementation prospects

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.