Low Dose Aspirin for Prevention of Early Pregnancy Loss

Pre-Eclampsia

Preeclampsia is a pregnancy-specific, multisystem disorder affecting 3% to 8% of pregnancies and remains a significant cause of maternal and neonatal morbidity and mortality worldwide. The World Health Organization estimates that approximately 76,000 maternal deaths annually are attributed to preeclampsia, accounting for 16% of global maternal mortality, with the majority occurring in low- and middle-income countries

The pathogenesis of preeclampsia (PE) is not fully understood, but it is believed to be associated with impaired early placental development, primarily attributed to defective trophoblast invasion and remodeling of the spiral arterioles . Various mechanisms have been proposed to contribute to the development of preeclampsia, including angiogenesis, endothelial injury, oxidative stress, and inflammation, which lead to clinical manifestations such as hypertension, proteinuria, and end organ damage . Preeclampsia is associated with severe short- and long-term maternal and neonatal morbidities, and its occurrence is influenced by risk factors such as diabetes, hypertension, multifetal gestation, as well as the severity and timing of previous preeclampsia episodes . While low-dose aspirin (LDA) has shown some benefit in preventing preeclampsia and fetal growth restriction when initiated before 16 weeks' gestation, there is no widely effective prophylactic therapy, and delivery remains the primary approach to prevent maternal morbidity and mortality. Recent research has indicated that LDA intervention, following firsttrimester screening of women at risk of developing preeclampsia, can significantly reduce the occurrence of preterm PE . As such, LDA's use is increasingly considered standard practice for women at high risk of developing preeclampsia . Nevertheless, the potential role of low-dose aspirin in preventing early pregnancy loss in this specific high-risk population remains underexplored. Given that abnormal placentation and inflammation are associated with both early and late pregnancy losses, low-dose aspirin therapy has the potential to mitigate these complications. However, current evidence on aspirin's efficacy in preventing early pregnancy loss is limited. Considering this, we propose a randomized, double-blind, placebocontrolled trial to investigate whether low-dose aspirin (81 mg daily) administered before 16 weeks of gestation can effectively reduce the rate of early pregnancy loss in women at high risk of developing preeclampsia.

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