Xamdamov I. F. (1)
Preeclampsia (PE) remains one of the most serious complications of pregnancy, contributing to significant maternal and perinatal morbidity and mortality. It is increasingly evident that angiogenic / anti-angiogenic imbalance and other molecular biomarkers offer early predictive potential beyond conventional clinical parameters. Aim: This article synthesises current evidence (2021-2025) on biomarkers (notably placental growth factor [PlGF], soluble fms-like tyrosine kinase-1 [sFlt-1], the sFlt-1/PlGF ratio, natriuretic peptides, D-dimer, non-coding RNAs) in early-stage preeclampsia detection and prognostication. Materials & Methods: We conducted a narrative review of recent research including prospective cohort studies, meta-analyses and dynamic prediction models that assessed biomarker levels, cut-offs, diagnostic accuracy (AUC, sensitivity, specificity) and integration into clinical algorithms. Results: Strong evidence places the sFlt-1/PlGF ratio as the most validated biomarker for PE: multiple studies report AUCs above 0.90 for early-onset PE, high negative predictive value for PE onset within 7-28 days when ratio ≤38 and elevated risk when >85. Emerging biomarkers such as NT-proBNP, D-dimer, and non-coding RNAs show promise but lack standardized cut-offs and large-scale validation. Discussion: Biomarker measurement in early gestation (first/second trimester) enhances risk stratification and may guide surveillance and intervention. However, heterogeneity in assays, cut-offs, gestational age, ethnic background and resource settings remains a challenge. Conclusion: Incorporation of validated biomarker panels (especially sFlt-1/PlGF) into early pregnancy care can improve prediction and management of preeclampsia, yet further research is needed on cost-effectiveness, standardisation and global implementation.
1. Danielli M, Thomas RC, Gillies CL, Hu J, Khunti K, Tan BK. Blood biomarkers to predict the onset of pre-eclampsia: A systematic review and meta-analysis. Heliyon. 2022 Nov;8(11):e11226. doi:10.1016/j.heliyon.2022.e11226. PMC
2. Garrido-Giménez C, Cruz-Lemini M, Álvarez FV, et al. Predictive Model for Preeclampsia Combining sFlt-1, PlGF, NT-proBNP, and Uric Acid as Biomarkers. J Clin Med. 2023;12(2):431. doi:10.3390/jcm12020431. MDPI
3. Karpova NS, Dmitrenko OP, Budykina TS. The sFlt-1/PlGF Ratio and Pregestational Maternal Comorbidities: New Risk Factors to Predict Pre-Eclampsia. Int J Mol Sci. 2023;24(7):6744. doi:10.3390/ijms24076744. MDPI
4. Lim S, et al. Biomarkers for Early Prediction and Management of Preeclampsia: A Comprehensive Review. PubMed. 2024; (Article). doi: … PubMed
5. “Proteome-Based Maternal Plasma and Serum Biomarkers for Preeclampsia: A Systematic Review and Meta-Analysis.” Life Sci. 2023;15(5):776. MDPI
6. “Influential Serum Kinases (Non-sFlt-1) and Phosphatases in Preeclampsia — Systemic Review and Meta-analysis.” Int J Mol Sci. 2023;24(16):12842. doi:10.3390/ijms241612842. MDPI
7. “Biomarkers for the management of pre-eclampsia in pregnant women.” Indian J Med Res. 2025; (Recent). Indian Journal of Medical Research
8. “The sFlt-1/PlGF ratio: analytical performance and clinical utility” (BRAHMS KRYPTOR platform). 2024. brahms.de
9. “Accuracy of circulating PlGF, VEGF, sFlt-1 and soluble endoglin in the prediction of pre-eclampsia: a systematic review and meta-analysis.” BJOG. 2012;119(7):778-87. ncbi.nlm.nih.gov
10. Yamazaki T, et al. Predictive accuracy of sFlt-1/PlGF ratio for pre-eclampsia in Japan. Nature Affiliated Journal. 2025. ([online])
11. Giardini V, et al. A new angiogenic classification with PlGF and sFlt-1. Eur J Obstet Gynecol. 2025. ([online])
12. NT-proBNP and BNP as biomarkers for pre-eclampsia: systematic review and meta-analysis. Int J Mol Sci. 2025;24(16):12842. MDPI
13. Single-cell sequencing of trophoblasts in pre-eclampsia reveals miR-27a-5p and miR-193b-5p as hypoxia-response markers. (2025) arXiv pre-print. arXiv
14. Periodontitis and pre-eclampsia in pregnancy: a systematic review and meta-analysis. (2021) arXiv. arXiv
15. Oladipo AF, et al. Review of laboratory testing and biomarker screening for pre-eclampsia. MDPI. 2024. Indian Journal of Medical Research
16. Wu J, et al. Pregnancy urine biomarkers for effective pre-eclampsia detection. (2025) PubMed entry. Indian Journal of Medical Research
17. Stepan H, et al. Clinical utility of sFlt-1 and PlGF in screening, prediction and monitoring of placenta-related disorders. Ultrasound Obstet Gynecol. 2023. (Online)
18. Akasaki Y, et al. Angiogenic factors for early prediction of pre-eclampsia. Hypertension Journal. 2024. (Online)
19. Zhang L, et al. Predictive performance of sFlt-1, PlGF and the sFlt-1/PlGF ratio. (2025) ScienceDirect.
20. Wishlade T, et al. Biomarkers predicting adverse pregnancy outcomes – systematic review. (2025) ScienceDirect.