Aspirin, in low oral doses of 50 to 150 mg daily, efectively inhibits platelet thromboxane A2 biosynthesis but has minimal efects on vascular prostacyclin production (Wallenburg, 1986). Still, several clinical trials have shown limited benefits in preeclampsia prevention. For example, a randomized trial from the MFMU Network found that risks for adverse outcomes were not significantly reduced with aspirin therapy (Caritis, 1998). Some combined reports, however, are more favorable. The Paris Collaborative Group performed a metaanalysis that included 31 randomized trials involving 32,217 women (Askie, 2007). For women assigned to receive antiplatelet agents, the relative risk for preeclampsia, superimposed preeclampsia, preterm delivery, or any adverse pregnancy outcome was significantly decreased by 10 percent. Other metaanalyses report marginal benefits of low-dose aspirin for prevention of severe preeclampsia (Roberge, 2012; Villa, 2013). Recently, one randomized trial of more than 1600 women at high risk for preterm preeclampsia provided low-dose aspirin from 11 to 14 weeks' gestation until 36 weeks to prevent recurrence. The rate of preterm recurrence was 1.6 percent in the aspirin group compared with 4.3 percent in the placebo arm (Rolnik, 2017).
In recent dueling metaanalyses, Roberge and colleagues (2017) found that aspirin prophylaxis initiated before 16 weeks' gestation was associated with a signiicant risk reductionabout 60 percent-for preeclampsia and fetal-growth restriction. Moreover, they found a dose-response efect. At the same time, Meher and associates (2017) performed an individual participant data metaanalysis and reported a much lower-about 10 percent-risk reduction that was significant whether therapy was initiated before or after 16 weeks.
Meanwhile, the U.S. Preventive Services Task Force recommends low-dose aspirin prophylaxis for women at high risk for preeclampsia (Henderson, 2014). Because of this, the American College of Obstetricians and Gynecologists (2016b) issued a Practice Advisory that recommends low-dose aspirin be given between 12 and 28 weeks' gestation to help prevent preeclampsia in high-risk women. This includes those with a history of preeclampsia and those with twins, chronic hypertension, overt diabetes, renal disease, and autoimmune disorders. These results have also raised the question as to whether al pregnant women should be given aspirin (Mone, 2017). At this time, our answer is "no."
Low-dose aspirin coupled with heparin mmgates thrombotic sequelae in women with lupus anticoagulant (Chap. 59, p. 1145). Because of a similarly high prevalence of placental thrombotic lesions found with severe preeclampsia, trials have assessed the possible merits of such treatments for women with prior preeclampsia. In two randomized trials, women with a history of early-onset preeclampsia were given an aspirin therapy or an enoxaparin plus aspirin regimen (Groom, 2017; Haddad, 2016). Outcomes were similar. From their reviews, Sergis and associates (2006) reported better pregnancy outcomes in women with prior severe preeclampsia given low-molecularweight heparin plus low-dose aspirin compared with those given low-dose aspirin alone. Similar indings were reported by de Vries and coworkers (2012).