Investigation of factors determining resistance to low-dose aspirin prophylaxis initiated in pregnant women at high risk of developing preeclampsia/eclampsia

Objective: This study aimed to identify factors associated with aspirin resistance that may limit the efficacy of low-dose aspirin (LDA) prophylaxis in pregnant women at high risk for preeclampsia (PE). The prevention, early diagnosis, and treatment of PE are crucial for both maternal and fetal health. Our study seeks to elucidate the factors influencing aspirin resistance and reducing treatment efficacy. The findings obtained are expected to contribute to the individualization of aspirin prophylaxis and the more effective management of PE risk by enabling the predictability of aspirin resistance. Materials and Methods: Our study was designed as a retrospective cohort study including pregnant women who were initiated on low-dose aspirin for PE prophylaxis. Between July 2013 and July 2023, printed medical records and electronic health records (for completing missing information) of pregnant women who were prescribed prophylactic LDA (75–150 mg/day) and delivered at Zeynep Kâmil Maternity and Children's Training and Research Hospital were retrospectively reviewed. Thus, each birth record was screened twice to ensure access to reliable and accurate data. PE risk was determined according to the high- and moderate-risk criteria outlined in the American College of Obstetricians and Gynecologists (ACOG) practice guidelines. Aspirin resistance can be categorized into three main types: pharmacokinetic, pharmacodynamic, and clinical resistance. In our study, clinical resistance was used as the definition of aspirin resistance. Results: It was determined that 39%of the included pregnant women were in the risk group for PE. The number of patients who developed PE was 349, the number of patients using aspirin was 163, and the number of patients diagnosed with aspirin resistance was 82. The most significant factors associated with aspirin resistance were chronic hypertension (CHT), intrauterine growth restriction (IUGR), and maternal weight at delivery. A strong correlation was found between gestational hypertension (GHT) and chronic hypertension (CHT) with aspirin resistance. However, factors such as gestational diabetes mellitus (GDM), obesity, and smoking were not found to have a significant impact on aspirin resistance. The overall accuracy of the model predicting aspirin resistance was calculated as 67.5%, with a sensitivity of 67.1%and a specificity of 67.9%. Conclusion: Aspirin resistance is strongly associated with hypertension and IUGR, suggesting that aspirin prophylaxis should be implemented using an individualized approach. While obesity and increased BMI elevate PE risk, they were not found to be directly related to aspirin resistance. This suggests that the mechanism of aspirin resistance may be more closely linked to vascular dysfunction and hypertension. Pregnant women who develop aspirin resistance should be closely monitored. Particularly in pregnant women with risk factors such as hypertension and IUBK, aspirin efficacy should be regularly evaluated. However, the accuracy of predicting aspirin resistance could be further enhanced by incorporating additional biomarkers. Keywords: Aspirin resistance, maternal weight at delivery (maternal BMI), gestational hypertension, IUGR, preeclampsia