Early initiation of low-dose aspirin before 12 weeks improves pregnancy outcomes in women with moderate-risk factors for preeclampsia.

BACKGROUND: Preeclampsia is thought to originate from abnormal placentation during early pregnancy. Low-dose aspirin reduces the risk of preeclampsia, but most clinical guidelines recommend initiation at 12 weeks of gestation because evidence supporting earlier use remains limited. OBJECTIVE: To evaluate whether initiation of low-dose aspirin before 12 weeks of gestation improves maternal and neonatal outcomes compared with initiation between 12 and 20 weeks among women with multiple moderate-risk factors for preeclampsia. STUDY DESIGN: This retrospective cohort study included singleton pregnancies delivered at ≥20 weeks between 2015 and 2025 at a single academic center. Eligible women had at least two moderate-risk factors for preeclampsia and received daily low-dose aspirin during pregnancy. Women with high-risk conditions for preeclampsia were excluded. Women were categorized according to aspirin initiation timing: early initiation before 12 weeks (n=1802) and late initiation between 12 and 20 weeks (n=473). Multivariable logistic regression analyses adjusted for maternal age, body mass index, parity, and method of conception. RESULTS: Early aspirin initiation was associated with significantly lower risks of gestational hypertension (110/1802 [6.1%] vs 118/473 [24.9%]; adjusted odds ratio [aOR] 0.24, 95% confidence interval [CI] 0.18-0.33), preeclampsia (75/1802 [4.2%] vs 74/473 [15.6%]; aOR 0.29, 95% CI 0.20-0.42), and gestational diabetes (273/1802 [15.1%] vs 136/473 [28.8%]; aOR 0.49, 95% CI 0.38-0.63). Early initiation was also associated with lower risks of preterm birth before 32 weeks (5/1802 [0.3%] vs 33/473 [7.0%]; aOR 0.04, 95% CI 0.01-0.10). Neonatal outcomes were improved, including lower risks of low Apgar score at 5 minutes (15/1802 [0.8%] vs 19/473 [4.0%]; aOR 0.26, 95% CI 0.13-0.56) and neonatal intensive care unit admission (338/1797 [18.8%] vs 147/462 [31.8%]; aOR 0.52, 95% CI 0.41-0.67). CONCLUSION: Initiation of low-dose aspirin before 12 weeks of gestation was associated with reduced risks of hypertensive disorders of pregnancy, preterm birth, and neonatal morbidity compared with initiation between 12 and 20 weeks.