Low-dose aspirin in pregnancy: 81 mg vs 162 mg - Is there a role for personalized medicine?

Hypertensive disorders of pregnancy (HDP), including preeclampsia, remain major contributors to maternal and perinatal morbidity and mortality worldwide. Low-dose aspirin is the primary pharmacologic strategy for preeclampsia prevention in high-risk pregnancies; however, uncertainty persists regarding the optimal dose. In the United States, 81 mg daily remains standard practice, whereas emerging international evidence supports higher-dose strategies, including 150-162 mg. This review examines the biologic rationale, clinical evidence, and implementation considerations surrounding aspirin dosing in pregnancy, with emphasis on the potential role of personalized medicine. Mechanistically, aspirin exerts pleiotropic effects beyond platelet inhibition, including modulation of inflammatory and angiogenic pathways implicated in preeclampsia pathogenesis. Increasing evidence suggests that aspirin responsiveness may vary according to patient-level factors such as obesity, multifetal gestation, chronic hypertension, prior severe preeclampsia, and biologic variability in platelet turnover. Randomized trials and meta-analyses demonstrate a consistent signal toward improved efficacy with higher-dose aspirin in selected high-risk populations without clear increases in major adverse safety outcomes. Emerging biomarker-based screening models and implementation strategies, including electronic health record-supported risk stratification, may further enable individualized prophylaxis approaches. Future large pragmatic trials are needed to define optimal dosing strategies and ensure equitable implementation across diverse populations.