The Road to Low-Dose Aspirin Therapy for the Prevention of Preeclampsia Began with the Placenta

The road to low-dose aspirin therapy for the prevention of preeclampsia began in the 1980s with the discovery that there was increased thromboxane and decreased prostacyclin production in placentas of preeclamptic women. At the time, low-dose aspirin therapy was being used to prevent recurrent myocardial infarction and other thrombotic events based on its ability to selectively inhibit thromboxane synthesis without affecting prostacyclin synthesis. With the discovery that thromboxane was increased in preeclamptic women, it was reasonable to evaluate whether low-dose aspirin would be effective for preeclampsia prevention. The first clinical trials were very promising, but then two large multi-center trials dampened enthusiasm until meta-analysis studies showed aspirin was effective, but with caveats. Low-dose aspirin was most effective when started 100 mg/day. It was effective in reducing preterm preeclampsia, but not term preeclampsia, and patient compliance and patient weight were important variables. Despite the effectiveness of low-dose aspirin therapy in correcting the placental imbalance between thromboxane and prostacyclin and reducing oxidative stress, some aspirin-treated women still develop preeclampsia. Alterations in placental sphingolipids and hydroxyeicosatetraenoic acids not affected by aspirin, but with biologic actions that could cause preeclampsia, may explain treatment failures. Consideration should be given to aspirin's effect on neutrophils and pregnancy-specific expression of protease-activated receptor 1, as well as additional mechanisms of action to prevent preeclampsia.

Automated summary

The path to low-dose aspirin therapy for preventing preeclampsia started with the discovery of imbalanced thromboxane and prostacyclin levels in the placentas of affected women in the 1980s. Despite the effectiveness of low-dose aspirin in correcting this imbalance and reducing oxidative stress, some women still develop preeclampsia, possibly due to alterations in placental sphingolipids and hydroxyeicosatetraenoic acids. Further research on aspirin's effects on neutrophils and pregnancy-specific expression of protease-activated receptor 1 is needed for prevention strategies.