Beyond aneuploidies: exploring the glycometabolic link to pregnancy-associated Plasma Protein A in pregestational diabetes

Pregnancy-associated plasma protein-A (PAPP-A) is a glycoprotein produced by the syncytiotrophoblast and the decidua during pregnancy, and other tissues, including vascular smooth muscle cells and fibroblasts. Type 2 diabetes is associated with chronically low PAPP-A levels. These low values contribute to vascular dysfunction and impaired metabolic health This retrospective study investigated whether PAPP-A levels are correlated with glycated hemoglobin (HbA1c), a marker of glycometabolic control, in pregnant women with type 1 and type 2 pre-GD who underwent first-trimester combined screening. Among the 96 women analyzed, a significant inverse correlation was observed in type 1 pre-GD between PAPP-A and both pregestational and first trimester HbA1c values (R = –0.69 and –0.49; p < 0.01). In type 2 pre-GD, multivariate analysis revealed that for each unit increase in HbA1c, PAPP-A decreased by 0.03 units in Caucasian women, but increased by 2.7 units in South American women. These findings suggest that glycometabolic compensation influences PAPP-A levels and should be considered when calculating aneuploidy risk. Rather than categorizing pre-GD history as a binary variable, incorporating HbA1c as a continuous parameter may improve the accuracy of risk assessment in first trimester screening for aneuploidies.