Validating an early pregnancy HbA1c as the screening test for gestational diabetes mellitus: findings from PRISMA Pakistan cohort

Abstract Background Early identification of gestational diabetes mellitus (GDM) is critical to improving maternal and neonatal outcomes, particularly in resource-constrained settings where universal oral glucose tolerance testing (OGTT) is burdensome. We assessed whether early-pregnancy HbA1c alone or combined with common risk factors can predict GDM and reduce the burden of OGTT requirements in a peri-urban cohort in Karachi, Pakistan. Methods We conducted a secondary analysis of the Pregnancy Risk Infant Surveillance and Measurement Alliance (PRISMA) Pakistan cohort. Women enrolled before 20 weeks’ gestation with available early-pregnancy HbA1c and a 2-hour 75g OGTT at 24–28 weeks were included. We externally validated GDM prediction models originally developed in the STRiDE-India cohort. Model performance was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). We assessed four models: HbA1c alone (Model 1a); age, BMI, and family history of diabetes mellitus (FH DM) (Model 1b); HbA1c combined with age, BMI, and FH DM (Model 2); and an extended model, i.e., Model 2 combined with socioeconomic status, gestational age, parity, systolic and diastolic blood pressure (Model 3). A dual-threshold approach was applied to assess rule-in and rule-out performance. Results Among 2,489 women, GDM incidence was 7.5% (n=186). Models with a broader set of predictors demonstrated higher AUC values, with Model 2 achieving an AUC of 0.61 (95% CI: 0.57–0.66). Including additional factors (Model 3) did not further improve predictive ability (AUC: 0.62; 95% CI: 0.58–0.66). In addition, at predefined thresholds, Model 2 achieved sensitivity of 73.7% (rule-out) and specificity of 83.5% (rule-in), with potential to reduce OGTT requirements (58.5%). Conclusions Early-pregnancy risk stratification using HbA1c combined with simple clinical predictors offers a pragmatic approach to streamline GDM screening among high-risk pregnant women. A dual-threshold strategy using Model 2 could reduce reliance on universal OGTT while prioritizing high-risk women for confirmatory testing. What is already known on this topic Studies have indicated that HbA1c may be an acceptable biomarker for identifying high-risk pregnant women with GDM and hence reducing the unnecessary burden of OGTT in resource-constrained settings. However, its ability to predict Pakistani women at high risk of GDM is unclear. What this study adds Early pregnancy HbA1c, together with age, BMI, and family history of diabetes achieved an AUC of 0.61 (95% CI: 0.57–0.66), with 58.5% of OGTTs could be avoided using this method. How this study might affect research, practice or policy Early pregnancy HbA1c-based prediction model is best positioned as pragmatic triage strategies to prioritize women for OGTT rather than replacing it. Such approaches may optimize resource use, particularly in settings where access to diagnostic testing is limited.