Maternal Systemic Inflammation and Fetal Thymic Size in Diabetic Pregnancies: Predictive Role of Hematological Biomarkers.

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.