Thromboinflammatory biomarkers in obstetric pathophysiology: Predictive insights into placental insufficiency and feto-maternal adverse outcomes

Abstract

Background

Placental insufficiency is a key pathological process underlying major obstetric complications, including pre-eclampsia, fetal growth restriction (FGR), placental abruption, recurrent pregnancy loss, preterm birth and stillbirth. Emerging evidence identifies thromboinflammation—the interplay between coagulation, inflammation, endothelial dysfunction, platelet activation and complement pathways—as a central contributor to these adverse outcomes.

Objective

To critically evaluate the current evidence on thromboinflammatory biomarkers associated with placental insufficiency and adverse feto-maternal outcomes, emphasising their biological relevance, predictive value and clinical applicability.

Methods

A narrative review of literature from PubMed, Scopus, Web of Science, Embase and Google Scholar was conducted. Priority was given to systematic reviews, meta-analyses, prospective studies and international guidelines. Evidence on coagulation, inflammatory, angiogenic, endothelial, complement and emerging molecular biomarkers was synthesised.

Results

Among available biomarkers, the soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio demonstrates the strongest clinical utility for predicting and managing placental dysfunction and pre-eclampsia. Conventional markers, including D-dimer, fibrinogen, platelet indices, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio, provide additional prognostic information, but show variable predictive performance. Emerging biomarkers such as neutrophil extracellular traps, extracellular vesicles, complement activation products, cell-free DNA and circulating microRNAs offer mechanistic insights but remain investigational due to limited standardisation and validation. Multimarker approaches appear superior to individual biomarkers for risk prediction.

Conclusion

Thromboinflammatory biomarkers provide valuable insights into placental dysfunction and adverse pregnancy outcomes. While angiogenic biomarkers currently have the greatest clinical utility, integrated multimarker models may enhance future precision obstetric care. Further large-scale validation studies are required for clinical translation.