Association between umbilical cord oxidative stress and early neonatal outcomes in gestational diabetes mellitus

Gestational diabetes (GDM) is frequently associated with adverse neonatal outcomes, but the underlying mechanisms linking maternal hyperglycemia to fetal harm are not fully understood. Oxidative stress has been suggested as a key pathway; however, studies simultaneously evaluating multiple oxidative and antioxidant biomarkers in umbilical cord blood are limited. This study aimed to investigate the impact of GDM on the fetus by comprehensively evaluating oxidative stress and antioxidant defense mechanisms in umbilical cord blood and to examine their potential associations with neonatal clinical outcomes. Umbilical cord blood samples were analyzed for malondialdehyde (MDA), membrane attack complex (MAC), total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), ischemia-related modified albumin (IMA), 8-hydroxy-2’-deoxyguanosine (8-OHdG), advanced glycation end products (AGEs), reduced glutathione (GSH), and glutathione peroxidase (GPx). Neonatal clinical outcomes were recorded and compared between pregnancies with and without GDM. After correction for multiple biomarker comparisons, MAC, 8-OHdG, and TOS differed significantly between the GDM and non-GDM groups. MAC and 8-OHdG levels were higher in the GDM group, whereas TOS was lower. OSI was higher in the Mann–Whitney analysis but did not remain significant after BH-FDR correction. Exploratory multivariate analyses supported a group-level difference in the combined oxidative-stress biomarker profile, as confirmed by MANOVA and permutation testing. The Spearman heatmap showed that maternal HbA1c was most prominently associated with OSI and also correlated positively with 8-OHdG and GSH. Although neonatal complications were more frequent in the GDM group, oxidative-stress markers were not consistently associated with specific neonatal complications. These findings suggest that GDM is associated with a selective fetal redox-related biomarker pattern rather than a uniform global increase in oxidative stress. The combined biomarker profile and HbA1c-related heatmap correlations indicate that long-term maternal glycemic exposure may influence fetal oxidant–antioxidant balance and oxidative DNA-damage signals, while antioxidant-related responses may remain partially preserved. The comprehensive evaluation of multiple oxidative and antioxidant biomarkers, particularly the inclusion of rarely studied AGEs and IMA, provides a broader perspective on fetal exposure to GDM and its pathophysiological mechanisms.