SUN-533 Prothymosin-alpha in the Early Shaping of Fetal Growth: It's Not All About Glucose

Abstract Disclosure: M. Mirabelli: None. M. Greco: None. F.S. Brunetti: None. E. Chiefari: None. D.P. Foti: None. A. Brunetti: None. Background: Prothymosin-alpha (ProT-α), an immunomodulatory protein, has recently gained attention as a biomarker of obesity-driven insulin resistance (IR), particularly among women. Although its significance in metabolic disorders is increasingly recognized, its specific role in gestational diabetes mellitus (GDM) and fetal growth (FG) remains less understood. Known contributors to GDM—such as maternal hyperglycemia, obesity, and placental dysfunction—can affect FG, yet pinpointing which pregnancies are most at risk is often challenging. In this observational study, we explored the associations among maternal metabolic parameters, inflammatory cytokines (including ProT-α), and early FG, acknowledging that adverse intrauterine conditions may begin to influence fetal development as early as 20 weeks of gestation (wg). Methods: Forty-six singleton pregnant women were included, fulfilling IADPSG criteria for either GDM (n=8) or normal glucose tolerance (NGT; n=38) at 24-28 wg. During the 75-g OGTT, we measured serum maternal glucose, insulin, inflammatory cytokines, and ProT-α levels. FG was evaluated via ultrasound at 20 wg, focusing on abdominal circumference (AC) and estimated fetal weight (EFW) percentiles. Factors affecting FG were determined through correlation and regression analyses. Results: Compared with NGT, women with GDM were significantly older and had higher BMI. They also displayed higher glucose readings at each OGTT time point, coupled with hyperinsulinemic responses, and tended to carry fetuses with larger AC and EFW. Notably, levels of IL-8 (p=0.034), TNFα (p=0.046), and IL-1α (p=0.007) were lower in the GDM group. Although ProT-α values were also lower in GDM, this difference was not statistically significant. Nonetheless, ProT-α exhibited a significant inverse correlation with EFW percentiles (β = -0.431, p=0.022). Regression analyses further revealed that 2-h post-load glucose (β = 0.545, p=0.010), VEGF (β = 0.380, p=0.021), and EGF (β = 0.374, p=0.047) positively predicted accelerated FG, whereas IL-10 (β = -0.416, p=0.030) and ProT-α were negative predictors. Conclusions: These findings underscore the interplay between maternal glucose metabolism, inflammatory pathways, and angiogenic factors in shaping early FG. ProT-α emerges as a novel biomarker that is inversely associated with FG, warranting deeper investigation into its mechanistic underpinnings and its potential as a therapeutic target in GDM, maternal obesity, and IR. Presentation: Sunday, July 13, 2025