Acetylsalicylic Acid for the Prevention of Preeclampsia and Intra-uterine Growth Restriction in Women with Abnormal Uterine Artery Doppler: A Systematic Review and Meta-analysis

Background: Preeclampsia is a major global cause of maternal, neonatal and perinatal mortality. From studies of placental pathophysiology in women with preeclampsia, a potentially important role of low-dose acetylsalicylic acid (ASA) in the prevention of preeclampsia was expected, but the results from clinical trials have been disappointing. While recent evidence has shown that uterine Doppler can predict preeclampsia as early as in the first trimester of pregnancy, most clinical trials have evaluated ASA in the second and third trimesters. Objectives: We performed a meta-analysis to assess the influence of gestational age at the time of introduction of ASA on the incidence of preeclampsia in women at increased risk, on the basis of abnormal uterine artery Doppler. Methods: Computerized searches of randomized controlled trials were conducted to retrieve studies in which pregnant women at increased risk of preeclampsia had been identified on the basis of abnormal uterine Doppler measurements. The trials compared women who received ASA with a control group. The primary outcome was preeclampsia. Secondary outcomes included severe preeclampsia, gestational hypertension, preterm birth, intrauterine growth restriction, placental abruption, birth weight and gestational age at delivery. Statistical analyses used fixed effects of risk ratioRR) with the Mantel-Haenszel method and 95% confidence intervals. Results: Nine randomized controlled trials with a total of 1317 women met the inclusion criteria. ASA treatment beginning in early gestation was associated with a greater reduction in the incidence of preeclampsia than treatment beginning in late gestation: ASA treatment started at <= 16 weeks' gestation resulted in RR 0.48 (95% CI 0.33 to 0.68), at 17-19 weeks RR 0.55 (95% CI 0.17 to 1.76), and at >= 20 weeks RR 0.82 (95% CI 0.62 to 1.09). ASA treatment started before 16 weeks was also linked with a significant reduction in the incidence of severe preeclampsia (RR 0.10; 95% CI 0.01 to 0.74), gestational hypertension (RR 0.31; 95% CI 0.13 to 0.78) and IUGR (RR 0.51; 95% CI 0.28 to 0.92). Conclusion: ASA treatment initiated early in pregnancy is an efficient method of reducing the incidence of preeclampsia and its consequences in women with ultrasonographic evidence of abnormal placentation diagnosed by uterine artery Doppler studies.