We aimed to examine the prospective association between first trimester HbA1c and gestational diabetes (GDM) and explore the utility of HbA1c 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. HbA1c 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 HbA1c ≥ 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 HbA1c (5.3[standard deviation 0.3]%; 34mmol/mol) than women without GDM (5.1[0.3]%; 32 mmol/mol) (P ≤ 0.001); this difference remained significant throughout pregnancy. Each 0.1% (1 mmol/mol) HbA1c increase at 8–13 weeks was associated with an adjusted 22% increased GDM risk (95% confidence interval 1.09–1.36). First trimester HbA1c 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 HbA1c. First trimester HbA1c may aid in early identification of at risk women.
Bibliographical noteFunding Information:
This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development intramural funding and included American Recovery and Reinvestment Act funding via contract numbers HHSN275200800013C, HHSN275200800002I, HHSN27500006, HHSN275200800003IC, HHSN275200800014C, HHSN275200800012C, HHSN275200800028C, HHSN275201000009C, and HHSN275201000001Z.