Predicting accelerated fetal growth in pregnancy: beyond maternal hyperglycemia - The role of prothymosin-α, inflammatory cytokines, and angiogenic factors

Abstract

Aim: This study investigates prothymosin-α (ProT-α), an immunomodulatory protein, as a potential biomarker for insulin resistance in gestational diabetes (GDM), and as a predictor of fetal growth by 20 weeks of gestation (wg). Methods: Forty-six women with singleton pregnancies were classified into GDM (n = 8) and normal glucose tolerance (NGT; n = 38) groups based on 75 g OGTT results. Maternal glucose, insulin, cytokines, and ProT-α levels were measured, and fetal growth was assessed by ultrasound at 20 wg, focusing on abdominal circumference (AC) and estimated fetal weight (EFW) percentiles. Results: Women with GDM were older, had a higher BMI, glucose, and insulin levels, with fetuses showing higher AC and EFW percentiles. IL-8, TNFα, and IL-1α were lower in the GDM group, while ProT-α was also lower but not significantly. ProT-α inversely correlated with EFW percentiles, independent of GDM. Regression analysis identified 2-hour post-load glucose, VEGF, and EGF as positive predictors of fetal growth acceleration, while IL-10 and ProT-α were negative predictors. Conclusions: Fetal growth is influenced by maternal glucose, inflammation, and angiogenesis. ProT-α may serve as an independent biomarker for predicting fetal growth in early pregnancy, suggesting further investigation into its role in GDM, obesity, and insulin resistance.

Keywords: Cytokines; Fetal growth; Insulin resistance; Pregnancy; Prothymosin-α.

Graphical abstract

Fig. 1

Spearman’s correlation analysis between fetal growth parameters, abdominal circumference (AC), and estimated fetal weight (EFW) percentiles, measured at the mid-trimester ultrasound screening (20 wg) and at a follow-up scan performed later into gestation, shortly before the OGTT at 24 wg. The intensity of the color reflects the absolute magnitude of the correlation coefficient (r). Statistically significant correlations are marked with asterisks: * p < 0.05; ** p < 0.01; *** p < 0.001. Corresponding scatter plots of the correlations between AC and EFW percentiles at the two timepoints are also included.

Fig. 2

Spearman’s correlation analysis between circulating ProT-α, inflammatory cytokines, and angiogenic factors. The blue shades represent positive correlations, the red shades indicate negative correlations, and the white color denotes no correlation. Statistically significant correlations are marked with asterisks: * p < 0.05; ** p < 0.01.