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.