This prospective observational study examined what uterine artery pulsatility index (UtA-PI) at 35–36 weeks reflects biologically in 11,962 singleton pregnancies, using mediation analysis to quantify contributions of placental angiogenic markers (PlGF, sFlt-1), hemodynamic indices (ophthalmic artery peak systolic velocity ratio), and arterial stiffness (cfPWV) to the UtA-PI–preeclampsia association.
Preeclampsia occurred in 349 pregnancies (2.9%). PlGF mediated ~40% and sFlt-1 ~9% of the UtA-PI–preeclampsia association; ophthalmic artery ratio mediated ~15%; cfPWV showed no significant mediation. In multivariable models, UtA-PI was no longer independently associated with preeclampsia (β=0.11, p=0.13), while higher sFlt-1, higher ophthalmic artery ratio, and greater arterial stiffness each independently raised risk, and higher PlGF was strongly protective (all p<0.001).
Single tertiary center in London limits generalizability. Observational design precludes causal inference despite mediation framing. Preeclampsia rate of 2.9% may reflect referral bias at a specialist center.
In late pregnancy, UtA-PI alone adds little independent predictive value for preeclampsia once angiogenic and hemodynamic markers are available — clinicians should prioritize PlGF, sFlt-1, and ophthalmic artery ratio for risk stratification at 35–36 weeks. High sFlt-1, elevated ophthalmic artery ratio, and increased arterial stiffness signal independent risk even when UtA-PI appears unremarkable.
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