HbA1c Measured in the First Trimester of Pregnancy and the Association with Gestational Diabetes

We aimed to examine the prospective association between first trimester HbA(1c) and gestational diabetes (GDM) and explore the utility of HbA(1c) for prediction of GDM. We used data from a case-control study within the prospective NICHD Fetal Growth Studies-Singleton Cohort (2009-2013), which enrolled 2,802 women at 12 U.S. clinical centers. HbA(1c) was measured in GDM cases (n = 107) and matched controls (n = 214) targeted at 8-13, 16-22, 24-29, and 34-37 gestational weeks. We excluded women with HbA(1c) >= 6.5% (48 mmol/mol) at enrollment (n = 3) or who had a hemoglobin variant (n = 6). At 8-13 gestational weeks, women who later developed GDM had significantly higher HbA(1c) (5.3[standard deviation 0.3]%; 34[4] mmol/mol) than women without GDM (5.1[0.3]%; 32[3] mmol/mol) (P <= 0.001); this difference remained significant throughout pregnancy. Each 0.1% (1 mmol/mol) HbA(1c) increase at 8-13 weeks was associated with an adjusted 22% increased GDM risk (95% confidence interval 1.09-1.36). First trimester HbA(1c) significantly improved GDM prediction over conventional risk factors (AUC 0.59 vs 0.65; P = 0.04). In conclusion, women who develop GDM may have impaired glucose homeostasis early in or prior to pregnancy, as indicated by their elevated first trimester HbA(1c). First trimester HbA(1c) may aid in early identification of at risk women.