Elevated Maternal Glycated Albumin is Associated with Large for Gestational Age Infants: Results from a Prospective Longitudinal Study

Aims/hypothesis Glycated albumin (GA) has been shown to be a moderate predictor of gestational diabetes mellitus (GDM), while evidence supporting its role in predicting adverse pregnancy outcomes remains limited. Here, we aimed to perform a comparative study of GA and haemoglobin A1c (HbA1c) for predicting GDM and large-for-gestational-age (LGA) infants in a prospective cohort. Methods We developed a rapid liquid chromatography-tandem mass spectrometry method for measuring site-specific albumin glycation. GA was quantified at two glycation sites, GA (KQT) and GA (KLV), as well as their sum, GA-total. GA was measured in stored serum samples collected at 11-14 and 23-31 gestational weeks from 465 participants in the single-centre observational cohort. HbA1c was measured routinely at each visit. Linear mixed-effects models were used to compare GA between participants with and without GDM (n=100) or LGA (n=57). Logistic regression was used to estimate odds ratios (ORs) for GDM and LGA according to GA and HbA1c. Results GA was lower in women who developed GDM during early pregnancy compared to non-GDM controls (GA-total; p=0.004), while in mid-late pregnancy, only GA (KQT) was lower in women with GDM (p=0.036). In contrast, HbA1c was higher in women with GDM at both timepoints compared to non-GDM controls (p<0.001) and higher HbA1c was associated with increased odds of GDM (OR=2.20, p<0.001; OR=2.30, p<0.001, respectively). GA was higher in the LGA group, in both early (GA-total; p=0.032) and mid-late pregnancy (GA-total; p=0.030) and associated with increased odds of LGA (GA-total; OR=1.59, p=0.009; GA-total; OR=1.46, p=0.019, respectively). HbA1c was not associated with LGA at either timepoint. Conclusions/interpretation Higher GA in early and mid-late pregnancy were associated with an increased risk of LGA, whereas no significant association was observed for HbA1c. GA may therefore provide risk assessment beyond HbA1c for identifying pregnancies at risk of fetal overgrowth.