What does uterine artery Doppler reflect in late pregnancy? Insights from angiogenic, hemodynamic, and vascular markers in preeclampsia.

Abstract

Preeclampsia is a complex disorder arising from abnormal placentation and maternal vascular maladaptation. Uterine artery Doppler is widely used to assess placental perfusion in early pregnancy. However, in late pregnancy its role remains unclear. To investigate the mechanisms linking uterine artery Doppler findings at 35-36 weeks' gestation with preeclampsia by quantifying the contribution of placental angiogenic, hemodynamic, and vascular pathways. This prospective observational study included 11,962 singleton pregnancies undergoing routine assessment at 35+0 to 36+6 weeks' gestation in a tertiary center in London, UK, between 2021 and 2024. Uterine artery pulsatility index, placental angiogenic biomarkers [placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1)], hemodynamic indices [ophthalmic artery peak systolic velocity ratio], and arterial stiffness [carotid to femoral pulse wave velocity (cfPWV)] were measured. Mediation analysis quantified indirect (average causal mediation effect) and direct effects. Multivariable logistic regression assessed independent associations with preeclampsia. Preeclampsia occurred in 349 (2.9%) pregnancies. Mediation analysis demonstrated that placental angiogenic imbalance accounted for the largest proportion of the association between uterine artery Doppler and preeclampsia, with PlGF mediating approximately 40% and sFlt-1 approximately 9% of the total effect. The ophthalmic artery ratio mediated approximately 15% of the association. In contrast, cfPWV did not demonstrate significant mediation. In multivariable models incorporating angiogenic, hemodynamic, and vascular parameters, uterine artery Doppler was no longer independently associated with preeclampsia (β=0.11, p=0.13). Higher sFlt-1, higher ophthalmic artery ratio, and increased arterial stiffness were independently associated with increased risk, whereas higher PlGF was strongly protective (all p<0.001). Uterine artery Doppler in late pregnancy appears to reflect biological processes related to placental and hemodynamic dysfunction, predominantly placental.