Integrating Angiogenic, Inflamatory and Molecular Biomarkers for Early Prediction of Preeclampsia : A Comprehensive Systematic Review
Keywords:
Preeclampsia, biomarkers, sFlt-1/PlGF ratio, early prediction, multi-marker models, angiogenesisAbstract
Background: Preeclampsia (PE) is a leading cause of maternal and perinatal morbidity and mortality worldwide. Early prediction remains challenging due to its multifactorial pathophysiology. This systematic review evaluates the predictive performance of angiogenic, inflammatory, and molecular biomarkers for early PE prediction.
Methods: We screened 80 studies (that examined biomarkers in pregnant women, reported predictive accuracy, and included comparison groups. Data extraction focused on single and multi-marker performance, prediction timing, and clinical applicability.
Results: Angiogenic markers were most studied. Low PlGF and elevated sFlt-1 consistently predicted PE, with the sFlt-1/PlGF ratio showing pooled sensitivity 80%, specificity 92% (AUC 0.90–0.95). For short-term rule-out, sFlt-1/PlGF ≤38 had 99.3% negative predictive value for PE within one week. First-trimester multi-omics models (e.g., leptin/ceramide ratio, cell-free RNA panels) achieved AUC 0.85–0.94, detecting risk up to 18 weeks before onset. Inflammatory markers (CA-125, IL-6, TNF-α) and molecular markers (microRNAs, MMP-7, PAPP-A) showed moderate individual performance but improved in combination. Early-onset PE was more accurately predicted than late-onset disease. Machine learning and multi-marker integration consistently outperformed single biomarkers.
Discussion: The sFlt-1/PlGF ratio is the most clinically validated biomarker for short-term rule-out in symptomatic women. First-trimester multi-marker screening enables aspirin prophylaxis in high-risk women. However, standardization, cost-effectiveness, and population-specific validation remain challenges.
Conclusion: Integrating angiogenic, inflammatory, and molecular biomarkers significantly improves early PE prediction compared to single markers. The sFlt-1/PlGF ratio is ready for clinical use for short-term prediction. Future research should validate multi-omics panels in diverse populations and integrate placental pathology.
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