Prevention of perinatal death and adverse perinatal outcome using low-dose aspirin: a meta-analysis.

OBJECTIVE To compare early vs late administration of low-dose aspirin on the risk of perinatal death and adverse perinatal outcome. METHODS Databases were searched for keywords related to aspirin and pregnancy. Only randomized controlled trials that evaluated the prophylactic use of low-dose aspirin (50-150 mg/day) during pregnancy were included. The primary outcome combined fetal and neonatal death. Pooled relative risks (RR) with their 95% CIs were compared according to gestational age at initiation of low-dose aspirin (≤ 16 vs > 16 weeks of gestation). RESULTS Out of 8377 citations, 42 studies (27 222 women) were included. Inclusion criteria were risk factors for pre-eclampsia, including: nulliparity, multiple pregnancy, chronic hypertension, cardiovascular or endocrine disease, prior gestational hypertension or fetal growth restriction, and/or abnormal uterine artery Doppler. When compared with controls, low-dose aspirin started at ≤ 16 weeks' gestation compared with low-dose aspirin started at >16 weeks' gestation was associated with a greater reduction of perinatal death (RR = 0.41 (95% CI, 0.19-0.92) vs 0.93 (95% CI, 0.73-1.19), P = 0.02), pre-eclampsia (RR = 0.47 (95% CI, 0.36-0.62) vs 0.78 (95% CI, 0.61-0.99), P < 0.01), severe pre-eclampsia (RR = 0.18 (95% CI, 0.08-0.41) vs 0.65 (95% CI, 0.40-1.07), P < 0.01), fetal growth restriction (RR = 0.46 (95% CI, 0.33-0.64) vs 0.98 (95% CI, 0.88-1.08), P < 0.001) and preterm birth (RR = 0.35 (95% CI, 0.22-0.57) vs 0.90 (95% CI, 0.83-0.97), P < 0.001). CONCLUSION Low-dose aspirin initiated at ≤ 16 weeks of gestation is associated with a greater reduction of perinatal death and other adverse perinatal outcomes than when initiated at >16 weeks.