Beyond Aneuploidies: Exploring the Glycometabolic Link to Pregnancy-Associated Plasma Protein A in Pregestational Diabetes

Introduction: Pregnancy-associated plasma protein A (PAPP-A) is a glycoprotein produced by the syncytiotrophoblast and decidua, as well as vascular smooth muscle cells. While type 2 diabetes is typically associated with chronically low PAPP-A levels – contributing to vascular dysfunction – the relationship between glycometabolic control and PAPP-A in pregestational diabetes (pre-GD) remains under-explored. This study investigated the correlation between PAPP-A levels and glycated hemoglobin (HbA1c) in pregnant women with type 1 and type 2 pre-GD. Methods: This retrospective study analyzed 96 pregnant women with pre-GD (type 1 and type 2) who underwent first-trimester combined screening. PAPP-A levels were correlated with both pregestational and first-trimester HbA1c values. In type 2 pre-GD, multivariate analysis was employed to assess the impact of HbA1c on PAPP-A levels while accounting for ethnic differences. Results: In women with type 1 pre-GD, a significant inverse correlation was observed between PAPP-A and both pregestational (R = −0.69; p < 0.01) and first-trimester HbA1c (R = −0.49; p < 0.01). In type 2 pre-GD, multivariate analysis showed divergent results based on ethnicity: 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. Conclusion: These findings suggest that glycometabolic compensation significantly influences PAPP-A levels. Clinical risk assessments for aneuploidy should consider HbA1c as a continuous parameter rather than treating pre-GD history as a binary variable. Incorporating specific glycometabolic data and ethnicity may improve the accuracy of first-trimester screening for women with pre-GD.