Dynamic Lipid–Glycaemic Index and Inflammation—Endothelial Shifts and Fetal Aortic Wall Thickening: A Repeated-Measures Gestational Phenotyping Study

Abstract

Background and Objectives: Maternal dyslipidaemia and low-grade inflammation are recognised drivers of in utero vascular remodelling, yet composite dynamic markers that integrate lipid–glycaemic, inflammatory and endothelial signals have not been evaluated. We investigated whether eight-week trajectories in the triglyceride–glucose index (TyG), interleukin-6 (IL-6) and flow-mediated dilation (FMD) outperform single-timepoint lipids for predicting fetal aortic remodelling. Materials and Methods: In a prospective repeated-measures study, 90 singleton pregnancies were examined at 24–26 weeks (Visit-1) and 32–34 weeks (Visit-2). At each visit, we obtained fasting lipids, TyG index, hsCRP, IL-6, oxidative-stress markers (MDA, NOx), brachial flow-mediated dilation (FMD), carotid IMT and uterine-artery Doppler, together with advanced fetal ultrasonography (abdominal-aorta IMT, ventricular strain, Tei-index, fetal pulse-wave velocity). Mothers were grouped by k-means clustering of the visit-to-visit change (Δ) in TG, TyG, hsCRP, IL-6 and FMD into three Metabolic-Inflammatory Response Phenotypes (MIRP-1/2/3). Linear mixed-effects models and extreme-gradient-boosting quantified associations and predictive performance. Results: Mean gestational TG rose from 138.6 ± 14.1 mg/dL to 166.9 ± 15.2 mg/dL, TyG by 0.21 ± 0.07 units and FMD fell by 1.86 ± 0.45%. MIRP-3 (“Metabolic + Inflammatory”; n = 31) showed the largest change (Δ) Δ-hsCRP (+0.69 mg/L) and Δ-FMD (–2.8%) and displayed a fetal IMT increase of +0.17 ± 0.05 mm versus +0.07 ± 0.03 mm in MIRP-1 (p < 0.001). Mixed-effects modelling identified Δ-TyG (β = +0.054 mm per unit), Δ-IL-6 (β = +0.009 mm) and Δ-FMD (β = –0.007 mm per %) as independent determinants of fetal IMT progression. An XGBoost model incorporating these Δ-variables predicted high fetal IMT (≥90th percentile) with AUROC 0.88, outperforming logistic regression (AUROC 0.74). Conclusions: A short-term surge in maternal TyG, IL-6 and endothelial dysfunction delineates a high-risk phenotype that doubles fetal aortic wall thickening and impairs myocardial performance. Composite dynamic indices demonstrated superior predictive value compared with individual lipid markers.