The Timing of Aspirin Administration in Pregnancy (Morning vs. Bedtime) for the Prevention of Preeclampsia: A Systematic Review and Meta-Analysis

Abstract Background Low-dose aspirin is universally recommended to prevent preeclampsia (PE) in high-risk pregnant individuals. However, international clinical guidelines remain silent on whether the specific time of day of administration influences clinical prophylactic outcomes. Objective To systematically evaluate and pool the clinical efficacy and safety of bedtime versus morning/daytime administration of low-dose aspirin for the prevention of preeclampsia and associated adverse maternal and perinatal outcomes. Methods A comprehensive systematic search was conducted across PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) from database inception to July, 2026. Randomized controlled trials (RCTs) and prospective cohort studies comparing daily bedtime low-dose aspirin (75–162 mg) against morning/daytime administration in high-risk pregnancies were included. Meta-analysis was performed using Review Manager (RevMan) under a random-effects model. Methodological quality was appraised using Cochrane RoB 2, and heterogeneity was assessed via the I² statistic. Results Eight studies meeting all eligibility criteria were identified, comprising a total pooled cohort of 1,114 high-risk pregnant individuals. Bedtime administration of low-dose aspirin demonstrated a statistically significant and clinically dramatic reduction in the overall incidence of preeclampsia compared to daytime administration (Risk Ratio [RR] = 0.32, 95% Confidence Interval [CI]: 0.19–0.54, p < 0.0001). The protective effect was particularly pronounced for preterm preeclampsia (< 37 weeks gestation). Secondary continuous analyses showed superior nocturnal blood pressure modulation with bedtime dosing. No significant differences in maternal adverse events or non-compliance rates were observed between cohorts (I² = 24%). Conclusion Administering low-dose aspirin at bedtime significantly enhances its prophylactic efficacy against preeclampsia—particularly preterm preeclampsia—compared to morning administration. Clinical practice guidelines should be updated to specify bedtime ingestion to optimize maternal and perinatal outcomes without incurring additional healthcare costs.