A first-trimester mechanistic framework integrating three Physiopathologic biomarker domains for pre-eclampsia...

Area of Science:

• Perinatal Medicine
• Biomarker Discovery
• Predictive Modeling in Obstetrics

Background:

• Pre-eclampsia (PE) poses significant risks to maternal and fetal health.
• Early and accurate prediction of PE is crucial for timely intervention.
• Existing prediction models have limitations in capturing the pathophysiologic complexity of PE.

Purpose of the Study:

• To develop and validate a mechanistic, three-domain framework for early PE classification and prediction.
• To utilize first-trimester angiogenic, uteroplacental, and maternal vascular biomarkers.
• To assess the framework's ability to predict PE, fetal growth restriction (FGR), and their composite.

Main Methods:

• Prospective cohort study of 1925 singleton pregnancies.
• Measured first-trimester placental growth factor (PGF), uterine artery pulsatility index (UtA-PI), and mean arterial pressure (MAP).
• Developed a three-domain model (molecular, hemodynamic, tensional) and assessed its predictive performance using logistic regression, AUC, and decision-curve analysis.

Main Results:

• The three-domain model demonstrated improved discrimination for PE (AUC 0.81) compared to the clinical model (AUC 0.68).
• Risk of PE increased stepwise with the number of abnormal domains, from 3.9% (normo) to 80.0% (triple).
• The model showed good discrimination for isolated FGR (AUC 0.75) and high discrimination for early-onset PE (AUC 0.99).

Conclusions:

• A first-trimester mechanistic three-domain framework accurately stratifies early PE risk.
• This model captures the pathophysiologic continuum of placental insufficiency.
• Internal validation supports the framework's clinical utility; external validation is recommended, especially for early-onset PE.