Tailoring low-dose aspirin to prevent preeclampsia: translational and biomarker insights

Abstract

Background: Low-dose aspirin is the only pharmacological intervention with consistent evidence for reducing the risk of preeclampsia in high-risk pregnancies. However, substantial interindividual variability in response has prompted interest in biomarkers that may improve understanding of aspirin responsiveness and disease heterogeneity. Methods: This narrative review synthesizes translational, observational, and clinical literature examining genetic, platelet, and angiogenic biomarkers in the context of aspirin prophylaxis for preeclampsia. Relevant studies were identified through targeted searches of major biomedical databases to provide a conceptual overview of current evidence. Results: Genetic variants related to aspirin metabolism and platelet function, platelet indices and aggregation assays, and angiogenic biomarkers such as soluble fms-like tyrosine kinase-1 and placental growth factor have been investigated as potential tools to refine risk stratification and elucidate variability in aspirin response. While these biomarkers offer important mechanistic insight, most evidence derives from association studies and observational cohorts. Genetic testing and platelet function assays lack validation in pregnant populations, standardized thresholds, and randomized evidence, supporting their use to guide aspirin initiation, dosing, or monitoring. Angiogenic biomarkers have an established diagnostic and prognostic role later in pregnancy but remain investigational for first-trimester risk stratification and are not used to modify aspirin therapy. Conclusions: Biomarkers provide valuable insight into the biological heterogeneity underlying preeclampsia and aspirin response; however, biomarker-guided aspirin strategies remain investigational. In the absence of randomized trials, aspirin prophylaxis should continue to follow established guideline-based risk assessment, with biomarker-informed approaches reserved for future research.