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.