Abstract
Background/Objectives: This study aimed to evaluate the relationship between maternal systemic inflammatory indices, hematological parameters, and fetal thymus size, as measured by the thymus-thoracic ratio (TTR), among diabetic pregnancies, and to establish predictive cut-off values for reduced thymus size. Methods: This prospective cohort study enrolled 532 pregnant women, divided into four groups: pregestational diabetes mellitus (PGDM, n = 44), diet-controlled gestational diabetes mellitus (GDM, n = 73), insulin-treated GDM (n = 49), and normoglycemic controls (n = 366). Fetal thymus size, alongside serum levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), aggregate index of systemic inflammation (AISI), fibrinogen-to-albumin ratio (FAR), and C-reactive protein (CRP)-to-albumin ratio, were assessed in the third trimester. Results: All maternal diabetes subgroups demonstrated significantly reduced fetal thymus size compared with controls, with the most pronounced reduction observed in the PGDM group (p < 0.001). NLR, PLR, MLR, SIRI, AISI, and MPV were significantly elevated in the PGDM cohort, whereas CAR, FAR, and fibrinogen levels were markedly increased in the insulin-treated GDM group. Albumin levels were significantly decreased in both the PGDM and the insulin-treated GDM groups (p < 0.001). Among the evaluated biomarkers, AISI and FAR exhibited the highest diagnostic accuracy for predicting reduced fetal thymus size, with optimal cut-off values of 640.3 (sensitivity 82.3%, specificity 86.7%) and 0.114 (sensitivity 74.3%, specificity 88.7%), respectively. Conclusions: Maternal systemic inflammatory burden, as indicated by hematological biomarkers, is significantly associated with reduced fetal thymic size in diabetic pregnancies. These findings suggest that readily accessible blood-derived biomarkers, particularly AISI and FAR, may complement ultrasonographic evaluation, offering a cost-effective, non-invasive approach to predict compromised fetal immune development, especially in settings where direct thymic imaging is impractical.