Sensitive Objective Markers for Measuring Aspirin Responsiveness in Pregnancy: an Explorative Scoping Review

Background Aspirin is frequently used in pregnancy to decrease the risk of developing preeclampsia. Studies have highlighted this potential benefit which in theory happens by inhibition of platelet function. However, questions remain on the appropriate dosing and the reliability of serum markers in determining aspirin responsiveness in pregnancy (ARP). Objective review the literature on ARP and identify the gaps, followed by investigating the objective biomarkers used to assess ARP. This includes the factors associated such as aspirin formulations, doses, and patient comorbidities. Methods A comprehensive search was conducted using keywords such as ‘aspirin’, ‘pregnancy’, and ‘responsiveness’ in relevant databases such as PubMed, SCOPUS, Cochrane from inception to March 2024. Our inclusion criteria enrolled pregnant women aged 18 years old and above, irrespective of their trimester status, who were prescribed aspirin for any medical indication. Results The research findings encompass three key areas. Firstly, examination of the impact of different aspirin formulations on responsiveness revealed no significant differences between different formulations. Secondly, nine papers were identified with varied dosages of administered aspirin, highlighting a need for standardized approach to dosing, and investigating higher dosing and its impact. Thirdly, there is a lack of consensus on biomarkers used to assess ARP. Finally, this synthesis sheds light on prognostic factors of developing aspirin non-responsiveness, such as medical comorbidities. Conclusion This scoping review identifies several residual uncertainties on ARP. The main gaps are validation of serum markers, understanding the influence of underlying morbidity on ARP, and determining appropriate aspirin dosing in pregnancy. Unstructured Abstract This scoping review examines the current knowledge on objective measures of aspirin responsiveness in pregnancy (ARP) and associated factors. It includes data extracted from PubMed, SCOPUS, Cochrane, and others up to March 2024. Key findings are summarized, and major gaps were found, especially the lack of consensus on objective biomarkers with residual uncertainties on standard approaches with aspirin for the prevention of pre-eclampsia. Additionally, many weaknesses exist in the current evidence on the impact of patient and medication factors. Finally, despite the lack of a standard approach, thromboxane B2 remains widely used as a biomarker for ARP with aspirin-triggered lipotoxins emerging as a potential novel marker.