Body mass index adjusted aspirin dosing does not overcome pharmacokinetic and pharmacodynamic disadvantages in obese pregnant women at risk for preeclampsia: a prospective cohort study

Objective To assess if aspirin dosed based on a patient's body mass index (BMI) would yield similar pharmacokinetics and pharmacodynamics for obese compared to non-obese patients who are taking aspirin to prevent preeclampsia. Methods This prospective cohort study included 35 pregnant women at high-risk of developing preeclampsia from Haseki Training and Research Hospital, Istanbul, Türkiye. Participants were prospectively stratified (non-randomized) into two groups based on baseline BMI: Group 1 ( n = 17, BMI <30 kg/m 2 , 100 mg/day aspirin) and Group 2 ( n = 18, BMI ≥30 kg/m 2 , 150 mg/day aspirin). Blood salicylate levels, 11-dehydrothromboxane B2 (11-dTxB2) levels, uterine artery Doppler measurements, and diastolic notch presence were evaluated at both the baseline (weeks 12–16 of pregnancy) and follow up (weeks 16–20 of pregnancy). Biomarker analyses were available for 17 of 18 obese participants due to one missing sample. Results Although the obese group was administered 50% more aspirin, they had 17% lower serum salicylate levels at follow-up (mean ± SD 2.08 ± 0.23 vs. 2.52 ± 0.32 μg/mL, p < 0.001). Although the 100 mg group had a significant decrease in 11-dTxB2 ( p = 0.004), the 150 mg group did not have a significant decrease ( p = 0.379). BMI had a strong inverse correlation with salicylate levels (r = −0.648, p < 0.001). A multiple regression model was developed using study group (β = 16.368, p = 0.002) and BMI (β = −1.984, p = 0.003) as the independent variables, and the uterine artery resistance index (UtA-RI) as the dependent variable. Mediation analysis showed that 21.0% of the total effect was numerically attributable to salicylate levels; however, the indirect effect was not statistically significant (Sobel p = 0.524). Uterine artery resistance change was the most significant predictor of diastolic notch resolution (OR = 0.86, p = 0.009). Conclusion In this non-randomized cohort, a 150 mg aspirin dose did not appear to overcome the pharmacokinetic and pharmacodynamic disadvantages associated with obesity in pregnant women. Other dosing approaches, such as weight-based dosing or twice-daily administration, should be evaluated to optimize preeclampsia prophylaxis in obese pregnancies. These findings require confirmation in larger randomized trials.