Preeclampsia causes maternal and perinatal morbidity and mortality and is defined as hypertension and proteinuria occurring at 20 weeks of gestation or greater in women with previously normal blood pressure. The disease is deemed severe when associated with even higher blood pressures greater than 160 mm Hg systolic or 110 mm Hg diastolic, evidence for liver damage with elevated liver function tests, thrombocytopenia, intrauterine fetal growth restriction, headache, visual disturbance, or right upper-quadrant pain. In addition, studies have found that women with preterm preeclampsia are at higher risk of severe preeclampsia and eclampsia. Studies have also indicated that low-dose aspirin therapy starting at 16 weeks of gestation or less can prevent preeclampsia and intrauterine fetal growth restriction and is associated with improvement in uterine artery blood flow resistance. The current systematic review and meta-analysis of randomized controlled trials assessed the benefits of low-dose aspirin prophylaxis to prevent severe preeclampsia.
EMBASE, PubMed, CENTRAL (Cochrane Central Register of Controlled Trials), and Web of Science databases were searched for articles published from 1965 to October 2011. Studies in which women were randomized at 16 weeks of gestation or less to low-dose aspirin versus placebo or no treatment were included. Low-dose aspirin was defined as 50 to 150 mg acetylsalicylic acid daily alone or combined with 300 mg dipyridamole or less. Pooled relative risks (RRs) with their 95% confidence intervals (CIs) were calculated. The primary outcome was the development of severe or mild preeclampsia, based on the definitions of the American College of Obstetricians and Gynecologists. Studies were combined and analyzed with Review Manager 5.0.25.
Of 7941 eligible studies, 352 were reviewed. The inclusion criteria were met by 15 studies, but only 4 were included (392 women) in the final analysis because they reported data on severe and mild preeclampsia. Women in 3 studies who randomized to the control group received placebo, whereas in the fourth study, they received no treatment. When aspirin was given at 16 weeks of gestation or less, the risks of overall preeclampsia and severe preeclampsia were significantly reduced (RR, 0.52; 95% CI, 0.38–0.76 [P < 0.01]; and RR, 0.22; 95% CI, 0.08–0.57 [P < 0.001], respectively), but not the risk for mild preeclampsia (RR, 0.81; 95% CI, 0.33–1.96 [P = 0.63]). For studies not included in the meta-analysis, the overall rate of preeclampsia showed a similar effect of aspirin on preeclampsia (RR, 0.22; 95% CI, 0.10–0.46 [P < 0.01]). In the included studies, the homogeneity for the reduction in RR of severe preeclampsia was high; homogeneity for the effect on RR of mild preeclampsia was moderate.
These results show a major beneficial effect of early-onset (7–16 weeks), low-dose aspirin in decreasing the overall risk of preeclampsia. This effect was especially noted for severe preeclampsia in which the RR was reduced by 90%. One reason for the reduction in the risk of severe preeclampsia could be the improvement in placentation resulting from low-dose aspirin therapy. Future studies should examine the role of low-dose aspirin in preventing the adverse outcomes of severe preeclampsia in high-risk women and should attempt to decrease the risk of adverse outcomes associated with severe rather than mild preeclampsia.
Department of Social and Preventive Medicine, Faculty of Medicine, Université Laval, Quebec, Canada (S.R., S.T.); Department of Molecular Biology, Medical Biochemistry and Pathology, Faculty of Medicine, Université Laval, Quebec, Canada (Y.G., J.-C.F.); Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland (P.V.); Harris Birthright Research Centre of Fetal Medicine, King’s College Hospital, London, United Kingdom (K.N.); Kanta-Häme Central Hospital, Hämeenlinna, Finland (M.V.); Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, British Columbia, Canada (P.v.D.); Genomics and Epigenetics of Human Reproduction, Institut Cochin, Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Paris Descartes, Paris, France (D.V.); and Department of Obstetrics and Gynecology, Faculty of Medicine, Université Laval, Quebec, Canada (E.B.).