Early treatment with low-dose aspirin is effective for the prevention of preeclampsia and related complications in high-risk patients selected by the analysis of their historic risk factors.

Brenner1 recently reviewed thrombophilia-related placental vascular complications, notably including preeclampsia and intrauterine growth restriction, and dealt baldly with the question of the potential benefit of aspirin in prevention of preeclampsia, claiming it was raised and refuted in the 1980s. Of course, when preeclampsia occurs in association with factor V (FV) Leiden mutation, factor II 20210G A, or methylenetetrahydrofolate reductase TT polymorphisms, a specific treatment is required. However, the efficacy of low-dose aspirin in prevention of preeclampsia and related complications was still recently confirmed,2 and an abundant literature contributed to define now the groups of women who can benefit from low-dose aspirin. This effect was first demonstrated in high-risk patients accurately selected by close analysis of their historic risk factors.3-5 In these first trials, the approach of the investigators was justified in view of the low mean birth weight or high preeclampsia incidence in the placebo groups, and the gain was substantial. Subsequently, several large-scale trials including heterogeneous groups of women at low or moderate risk aimed to test the preventive action of low-dose aspirin either in a high proportion or even in the whole population of the pregnant women. Moreover, gestational age at entry was very variable, until 32 weeks of gestation. Given the low incidence of preeclampsia and the normal mean birth weight in the placebo groups, these large trials not surprisingly either reported a mild benefit or were negative. However, some of them usefully determined that the specific risk attributable to such conditions as primiparity, twin pregnancy, and nonsevere diabetes or hypertension can probably not be avoided by means of low-dose aspirin.6 In the complex network of the mechanisms involved in the pathogenesis of preeclampsia and related disorders, thromboxane is probably one of the factors leading from defective placentation and placental ischemia to platelet aggregation and placental thrombosis and finally to the clinical stage of the disease. Low-dose aspirin selectively inhibits thromboxane production in the woman’s circulation, and this inhibition parallels the clinical effect.4,5 However, the abnormalities of the uteroplacental circulation development that constitute uteroplacental insufficiency are early established. So, the early excess of placental production of thromboxane reported in women with uteroplacental insufficiency may explain that low-dose aspirin only acts optimally when aspirin treatment is started before placentation is completed, and clinical data support this view.7 Thus, the baseline risk of preeclampsia or intrauterine growth retardation should be estimated and low-dose aspirin started early on the presence of significant historic risk factors, such as previous severe preeclampsia or moderate to severe renal insufficiency.8 A 2-stage Doppler artery screening in first and second trimester could also define a high-risk population,9 and promising results have been published for aspirin prevention with first-trimester uterine artery Doppler selection in high-risk pregnancies.10