Preeclampsia is defined as
hypertension arising after 20 weeks of gestational age with
proteinuria or other signs of end-organ damage and is an important cause of maternal and perinatal morbidity and mortality, particularly when of early onset. Although a significant amount of research has been dedicated in identifying preventive measures for
preeclampsia, the incidence of the condition has been relatively unchanged in the last decades. This could be attributed to the fact that the underlying pathophysiology of
preeclampsia is not entirely understood. There is increasing evidence suggesting that suboptimal trophoblastic invasion leads to an imbalance of angiogenic and antiangiogenic
proteins, ultimately causing widespread
inflammation and endothelial damage, increased platelet aggregation, and thrombotic events with placental
infarcts.
Aspirin at doses below 300 mg selectively and irreversibly inactivates the
cyclooxygenase-1 enzyme, suppressing the production of
prostaglandins and
thromboxane and inhibiting
inflammation and platelet aggregation. Such an effect has led to the hypothesis that
aspirin could be useful for preventing
preeclampsia. The first possible link between the use of
aspirin and the prevention of
preeclampsia was suggested by a case report published in 1978, followed by the first randomized controlled trial published in 1985. Since then, numerous randomized trials have been published, reporting the safety of the use of
aspirin in pregnancy and the inconsistent effects of
aspirin on the rates of
preeclampsia. These inconsistencies, however, can be largely explained by a high degree of heterogeneity regarding the selection of trial participants, baseline risk of the included women, dosage of
aspirin, gestational age of prophylaxis initiation, and
preeclampsia definition. An individual patient data meta-analysis has indicated a modest 10% reduction in
preeclampsia rates with the use of
aspirin, but later meta-analyses of aggregate data have revealed a dose-response effect of
aspirin on
preeclampsia rates, which is maximized when the medication is initiated before 16 weeks of gestational age. Recently, the
Aspirin for Evidence-Based
Preeclampsia Prevention trial has revealed that
aspirin at a daily dosage of 150 mg, initiated before 16 weeks of gestational age, and given at night to a high-risk population, identified by a combined first trimester screening test, reduces the incidence of preterm
preeclampsia by 62%. A secondary analysis of the
Aspirin for Evidence-Based
Preeclampsia Prevention trial data also indicated a reduction in the
length of stay in the neonatal intensive care unit by 68% compared with placebo, mainly because of a reduction in births before 32 weeks of gestational age with
preeclampsia. The beneficial effect of
aspirin has been found to be similar in subgroups according to different maternal characteristics, except for the presence of chronic
hypertension, where no beneficial effect is evident. In addition, the effect size of
aspirin has been found to be more pronounced in women with good compliance to treatment. In general, randomized trials are underpowered to investigate the treatment effect of
aspirin on the rates of other placental-associated adverse outcomes such as
fetal growth restriction and
stillbirth. This article summarizes the evidence around
aspirin for the prevention of
preeclampsia and its complications.