Rebalancing prostanoids: How differential COX-1 and COX-2 inhibition explains the success and limitations of low-dose aspirin in pregnancy.

Preeclampsia presents a major health impact to the maternal-fetal dyad and poses a maternal mortality risk estimated to be 5-15% worldwide, with diagnosis rates for this disorder substantially increasing. This disorder continues to pose a substantial economic burden, with costs estimated at 2.18 billion dollars within the first year postpartum. Despite the dramatic annual impact of preeclampsia, the pathophysiology of this disorder remains poorly understood. Low-dose aspirin (LDA) is the sole primary therapy for the prevention of preeclampsia. The mechanism of action of LDA on the cyclooxygenase isoform, COX-1, and its limited interaction with COX-2 help explain its treatment approach and shortcomings. Important questions remain regarding LDA therapy with respect to its efficacy, optimal timing of initiation, and dosing regimens required to achieve maximal therapeutic benefit. In this review, we explore the pathophysiology of preeclampsia, with attention to the cyclooxygenase pathway as a means of refining understanding of aspirin's mechanism of action, informing potential dosing strategies, and discussing alternative therapies and future directions for preeclampsia treatment.