First-trimester biomarkers of gestational diabetes mellitus: A scoping review

Gestational diabetes mellitus (GDM) affects approximately 14% of pregnancies globally, with rising incidence depending on the diagnostic criteria used. In the UK, screening relies on risk factors at booking, followed by a diagnosis via an oral glucose tolerance test in the second trimester. This approach may lack sensitivity and has poor tolerability. Emerging evidence suggests that GDM pathophysiology begins in the first trimester, with biomarkers showing potential for early prediction. Identifying these could enable earlier risk stratification, improved diagnostic pathways, and better maternal-fetal outcomes. This scoping review maps the existing literature on first-trimester biomarkers of GDM to evaluate their clinical utility and integration into predictive models. A literature search was conducted using Medline, Embase, and PubMed to identify studies on first-trimester biomarkers of GDM. Inclusion criteria included (1) studies investigating biomarkers at <15 weeks' gestation; (2) studies that diagnosed GDM using an OGTT with recognized diagnostic guidelines or clearly stated glucose thresholds. A total of 133 studies were included, reporting a wide range of biomarkers (145 in total). PAPP-A was generally lower in GDM, with mixed findings for β-hCG and PlGF. Metabolic markers, including lipid profiles, fasting glucose, and HbA1c, were often elevated. Inflammatory markers, such as WCC, neutrophils, and CRP, were higher in those later diagnosed with GDM. First-trimester biomarkers highlight GDM's complex pathophysiology. PAPP-A shows predictive potential, while metabolic and inflammatory biomarkers suggest early systemic dysfunction. Emerging tools like 3D ultrasonography indicate placental structural changes. Larger studies are needed to validate these biomarkers and integrate them into predictive models to improve maternal-fetal outcomes.