Abstract
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]%; 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) 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.
Highlights
Gestational diabetes (GDM) is a common pregnancy complication associated with adverse maternal and fetal outcomes including an increased risk for type 2 diabetes and cardiovascular disease later in life in mothers and an increased risk for macrosomia and obesity in offspring[1]
The primary aims of the NICHD Fetal Growth Study were to develop fetal growth standards and enrollment was restricted to non-obese women without preexisting chronic diseases or medical conditions, including diabetes before pregnancy or GDM in a prior pregnancy, and without lifestyle risk factors including smoking (n = 2,334)
We observed significant improvement (P = 0.04) to the base prediction model based on conventional risk factors with the inclusion of HbA1c measured at enrollment (AUC = 0.65) (Supplementary Fig. S1). In this prospective study among women without pre-existing medical conditions, we systematically examined HbA1c measured across pregnancy starting in the first trimester and its relation with GDM risk
Summary
Gestational diabetes (GDM) is a common pregnancy complication associated with adverse maternal and fetal outcomes including an increased risk for type 2 diabetes and cardiovascular disease later in life in mothers and an increased risk for macrosomia and obesity in offspring[1]. A few prior studies have examined if HbA1c measured in the first trimester is useful for early predication of GDM3–6; these studies have been among high-risk populations only[4,5], evaluated an HbA1c threshold only of 5.7% (39 mmol/mol), corresponding to prediabetes outside of pregnancy[6], or used GDM diagnosed in the first trimester only as the outcome[3]. Research remains limited on HbA1c measured in the first trimester and its relation with GDM among a population based sample. This is important as early risk prediction may offer a unique opportunity for earlier interventions. This study aimed to comprehensively examine of HbA1c across pregnancy and its relation with GDM. The third exploratory aim of this study was to evaluate the predictive utility of using first trimester HbA1c to predict GDM and potentially identify an ideal cut-off for GDM screening in the first trimester
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