Effect of first-trimester aspirin initiation timing on obstetric outcomes: A comparative study

This study aims to evaluate the association between the timing of low-dose aspirin (LDA) initiation in the first trimester and obstetric outcomes, including uterine artery pulsatility index (UtA PI), fetal growth parameters, pregnancy-associated plasma protein-A (PAPP-A) levels, and delivery outcomes in a high-risk population for preeclampsia (PE). This prospective cohort study compared pregnant women at high risk for PE who initiated LDA before 11 weeks of gestation (early aspirin group) with those who initiated LDA between 11 and 14 weeks (late aspirin group). Outcomes included first- and second-trimester UtA PI measurements, PAPP-A multiples of median values, estimated fetal weight, fetal growth restriction, preterm birth, and delivery characteristics. Among 1062 pregnant women evaluated, 139 met the inclusion criteria; 55 initiated LDA before 11 weeks and 50 between 11 and 14 weeks of gestation. At least one high-risk factor for PE was present in 43.8% of participants, while more than 96% had at least one moderate-risk factor. PE developed in 3 cases (one in the early group and 2 in the late group). Mean PAPP-A multiples of median values at 11 to 14 weeks were significantly higher in the early aspirin group. No statistically significant differences were observed between groups in UtA PI values at either 11 to 14 or 20 to 24 weeks of gestation. Within the early aspirin group, women who delivered preterm had significantly higher mean UtA PI and UtA PI percentile values at 20 to 24 weeks compared with those who delivered at term (P = .003 and P = .007, respectively). Early initiation of LDA before 11 weeks of gestation was associated with higher first-trimester PAPP-A levels but was not associated with significant differences in uterine artery Doppler indices or major obstetric outcomes at the group level. Elevated UtA PI values were consistently associated with adverse pregnancy outcomes, independent of aspirin initiation timing, suggesting that uterine artery Doppler parameters more likely reflect the severity of underlying placental pathology rather than a treatment-related effect. Given the low incidence of PE and fetal growth restriction in the study population, the study may be underpowered for definitive conclusions regarding clinical outcomes; therefore, the findings should be interpreted cautiously and considered hypothesis-generating.