First-trimester two-hour post-challenge glucose and HbA1c as early predictors of gestational diabetes mellitus: A prospective cohort study

Background and objectives Traditional gestational diabetes mellitus (GDM) screening at 24-28 wk occurs after foetal exposure to maternal hyperglycemia during critical developmental windows. Our objective was to investigate whether first-trimester glycaemic parameters within currently accepted normal ranges could predict subsequent GDM development. Methods In this prospective cohort (May 2023-December 2024), 270 women with singleton pregnancies were enrolled at 8-12 wk gestation with normal glycaemic values (FPG <92 mg/dL, 1-h <180 mg/dL, 2-h <153 mg/dL, HbA1c <5.9%). All underwent a 75 g OGTT and HbA1c testing in the first trimester and repeat OGTT at 24-28 wk for GDM diagnosis (IADPSG criteria). Results GDM prevalence was 15.9%. Women who developed GDM had significantly higher first-trimester 2-h post-challenge glucose [116.7±15.4 vs. 99.0±16.6 mg/dL (6.5±0.9 vs. 5.5±0.9 mmol/L), P<0.001] and HbA1c [5.30±0.30% vs. 4.90±0.37% (34±3.3 vs. 30±4.0 mmol/mol), P<0.001] compared to those who maintained normal glucose tolerance. ROC analysis identified optimal cut-offs: 2-h glucose ≥112 mg/dL (6.2 mmol/L) (sensitivity 79.1%, specificity 81.9%, AUC 0.799) and HbA1c ≥5.4% (36 mmol/mol) (sensitivity 60.5%, specificity 88.4%, AUC 0.805). A combined model incorporating 2-h glucose, HbA1c, and family history achieved the highest performance (AUC 0.866, sensitivity 69.8%, specificity 89.0%, diagnostic accuracy 85.9%). Newborns of GDM mothers had significantly higher birth weights (3366.4±399.0g vs. 2935.8±427.0g, P<0.001). Interpretation and conclusions First-trimester 2-h glucose ≥112 mg/dL and HbA1c ≥5.4%, even within normal ranges, effectively predict GDM. Combined assessment improves predictive accuracy, supporting early first-trimester risk stratification and timely intervention to enhance maternal and neonatal outcomes.