Comparison of Fetomaternal Outcomes Between Standard Versus High-Dose Aspirin in Patients with High Risk of Pre-Eclampsia

Abstract

Preeclampsia remains a leading cause of maternal and perinatal morbidity and mortality, particularly in low- and middle-income countries. Low-dose aspirin is recommended for prophylaxis in high-risk pregnancies; however, the optimal preventive dose remains uncertain. Objective: To compare fetomaternal outcomes between standard-dose and high-dose aspirin in pregnant women at high risk of developing preeclampsia. Methods: This single-center comparative study was conducted at a tertiary care hospital in Pakistan from March to August 2025. A total of 90 high-risk pregnant women enrolled in early pregnancy were allocated to receive either standard-dose aspirin (n = 45) or high-dose aspirin (n = 45) from the late first trimester until 36 weeks of gestation or delivery. The primary outcome was the incidence of preeclampsia. Secondary outcomes included early-onset and severe preeclampsia, medically indicated preterm birth, need for magnesium sulfate, fetal growth restriction, birth weight, NICU admission, and maternal safety outcomes. Effect estimates were expressed as relative risks with 95% confidence intervals. Multivariable logistic regression was used to identify independent predictors of preeclampsia. Results: Baseline characteristics were comparable between groups. The incidence of preeclampsia was significantly lower in the high-dose aspirin group compared with the standard-dose group (13.3% vs. 31.1%; RR 0.43, 95% CI: 0.20–0.92). High-dose aspirin was associated with lower rates of early-onset preeclampsia, severe disease, medically indicated preterm birth, and magnesium sulfate use. Preterm birth before 37 weeks was reduced in the high-dose group (20.0% vs. 37.8%; RR 0.53, 95% CI: 0.30–0.95), and mean birth weight was higher by 220 g. Safety profiles were comparable, with no significant increase in major adverse events. On multivariable analysis, high-dose aspirin remained independently associated with reduced odds of preeclampsia (aOR 0.33, 95% CI: 0.11–0.95). Conclusion: High-dose aspirin was more effective than standard-dose aspirin in reducing the incidence of preeclampsia and adverse perinatal outcomes in high-risk pregnancies, without a clinically significant increase in adverse effects. These findings support consideration of higher-dose aspirin prophylaxis in selected high-risk populations.