Stepwise risk stratification of early-onset preeclampsia: integrating mid-trimester uterine artery doppler and maternal comorbidities

Abstract

Background: This study aimed to evaluate the association between mean uterine artery pulsatility index (UtA-PI) ≥ 95th percentile at 20–24 weeks and early-onset preeclampsia (EOPE, < 34 weeks) in pregnancies identified as high risk in first-trimester preeclampsia (PE) screening. Methods: This retrospective cohort study included 727 singleton pregnancies with high-risk first-trimester PE screening results (≥ 1/100) and mean UtA-PI measurements at 20–24 weeks. Patients were categorized into two groups: UtA-PI ≥ 95th percentile (n = 111) and < 95th percentile (n = 616). Gestational age-specific reference ranges were derived from a separate cohort of 1,012 low-risk pregnancies. The incidence of EOPE, gestational age at delivery, and birth weight were compared between groups. Multivariate logistic regression identified independent EOPE risk factors, presented as adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results: EOPE incidence was significantly higher in the UtA-PI ≥ 95th percentile group compared to the < 95th percentile group (13.5% vs. 2.1%, p < 0.001). In multivariate analysis, mean UtA-PI ≥ 95th percentile remained an independent predictor of EOPE (adjusted OR: 12.01, 95% CI: 4.89–29.50, p < 0.001), along with chronic hypertension (adjusted OR: 4.61, 95% CI: 1.76–12.06, p = 0.002) and renal disease (adjusted OR: 38.32, 95% CI: 8.93–164.27, p < 0.001). EOPE also developed in patients with normal UtA-PI, particularly in those with underlying medical comorbidities. Conclusions: In pregnancies identified as high risk in first-trimester PE screening and under aspirin prophylaxis, mean UtA-PI ≥ 95th percentile at 20–24 weeks is associated with a significantly increased EOPE risk. However, maternal comorbidities, such as chronic hypertension, pregestational diabetes, and renal disease, also contribute to EOPE risk even when UtA-PI remains within the normal range. These findings suggest that second-trimester risk stratification should incorporate both UtA-PI and maternal comorbidities rather than relying solely on Doppler parameters. Prospective studies are needed to validate these findings and assess whether aspirin discontinuation is safe in pregnancies with both normal UtA-PI and no additional medical comorbidities.