ArticleInternational journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics2026
A first-trimester mechanistic framework integrating three Physiopathologic biomarker domains for pre-eclampsia classification.
Article in International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Rethinking Risk Prediction in Preeclampsia: From Biomarkers to Mechanistic Phenotypes and Longitudinal Models.International journal of molecular sciences · 2026Review
- Oxidative dyslipidemia in early pregnancy: integrating atherogenic index of plasma (AIP) and uric acid (UA) to refine preeclampsia risk stratification.Frontiers in pharmacology · 2026Article
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9 authors.
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Abstract
objectiveTo develop and internally validate a mechanistic, three-domain framework for early classification and prediction of pre-eclampsia (PE) using first-trimester angiogenic, uteroplacental, and maternal vascular biomarkers.
methodsIn a prospective cohort of 1925 singleton pregnancies screened at 11 to 13.6 weeks, placental growth factor (PGF), uterine artery pulsatility index (UtA-PI), and mean arterial pressure (MAP) were log-transformed and standardized to gestational age-adjusted multiples of the median. Prespecified percentile thresholds (PGF <10th; UtA-PI >95th; MAP >95th) defined domain abnormalities and mechanistic phenotypes. Associations with PE, fetal growth restriction (FGR), and the composite of PE or FGR were assessed using logistic regression. Discrimination (area under the [receiver operating characteristic] curve [AUC]), calibration, and clinical utility were evaluated; bootstrap internal validation was used for optimism correction; and decision-curve analysis quantified net clinical benefit.
resultsPE occurred in 104 of 1925 pregnancies (5.4%). Phenotypes were distributed as normo (81.7%), molecular (7.6%), hemodynamic (3.2%), tensional (5.1%), dual (≥2 domains; 2.1%), and triple (3/3; 0.3%). The risk of PE increased stepwise from 3.9% (normo) to 80.0% (triple) (P for trend <0.001). The three-domain model improved discrimination to an AUC of 0.81 (95% confidence interval [CI], 0.77-0.86) versus the clinical model (AUC, 0.68; P < 0.001), achieved good discrimination for isolated FGR (AUC, 0.75 [95% CI, 0.70-0.81]), and provided higher net clinical benefit among 5% to 30% thresholds. In early-onset PE (n = 14), discrimination was high (AUC, 0.99 [95% CI, 0.98-1.00]); estimates should be interpreted cautiously given the small number of events.
conclusionA first-trimester, mechanistic three-domain framework captures the pathophysiologic continuum of placental insufficiency and supports accurate, clinically meaningful early risk stratification for PE. Findings were internally validated; external validation-particularly for early-onset PE-is warranted.
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