An Early Pregnancy HbA1c ≥5.9% (41 mmol/mol) Is Optimal for Detecting Diabetes and Identifies Women at Increased Risk of Adverse Pregnancy Outcomes

Abstract

OBJECTIVEPregnant women with undiagnosed diabetes are a high-risk group that may benefit from early intervention. Extrapolating from nonpregnancy data, HbA 1c ‡6.5% (48 mmol/mol) is recommended to define diabetes in pregnancy. Our aims were to determine the optimal HbA 1c threshold for detecting diabetes in early pregnancy as defined by an early oral glucose tolerance test (OGTT) at <20 weeks' gestation and to examine pregnancy outcomes relating to this threshold. RESEARCH DESIGN AND METHODSDuring 2008-2010 in Christchurch, New Zealand, women were offered an HbA 1c measurement with their first antenatal bloods. Pregnancy outcome data were collected. A subset completed an early OGTT, and HbA 1c performance was assessed using World Health Organization criteria. RESULTSHbA 1c was measured at a median 47 days' gestation in 16,122 women. Of those invited, 974/4,201 (23%) undertook an early OGTT. In this subset, HbA 1c ‡5.9% (41 mmol/mol) captured all 15 cases of diabetes, 7 with HbA 1c <6.5% (<48 mmol/mol). This HbA 1c threshold was also 98.4% (95% CI 97-99.9%) specific for gestational diabetes mellitus (GDM) before 20 weeks (positive predictive value = 52.9%). In the total cohort, excluding women referred for GDM management, women with HbA 1c of 5.9-6.4% (41-46 mmol/mol; n = 200) had poorer pregnancy outcomes than those with HbA 1c <5.9% (<41 mmol/mol; n = 8,174): relative risk (95% CI) of major congenital anomaly was 2.67 (1.28-5.53), preeclampsia was 2.42 (1.34-4.38), shoulder dystocia was 2.47 (1.05-5.85), and perinatal death was 3.96 (1.54-10.16). CONCLUSIONSHbA 1c measurements were readily performed in contrast to the low uptake of early OGTTs. HbA 1c ‡5.9% ( ‡41 mmol/mol) identified all women with diabetes and a group at significantly increased risk of adverse pregnancy outcomes.

First-Trimester Placental Growth Factor in Screening for Gestational Diabetes

“…However, even after excluding PGDM, there remain some first-trimester metabolic changes in pregnancies that will develop GDM, as HbA1c was elevated in our and other studies [7,8]. The fact that we found no correlation between HbA1c and PlGF in the first trimester further lends support to the conclusion that PlGF in the first trimester is not a good marker for GDM.…”

“…Therefore, international and national societies have recommended screening for these pre-existing metabolic disorders at the first antenatal visit by a fasting glucose measurement, 75-g oGTT, or by assessment of glycosylated hemoglobin (HbA1c) [2,5,6]. Recently an association been first-trimester HbA1c and GDM was reported [7,8]. …”

Response to Comment on Hughes et al. An Early Pregnancy HbA1c ≥5.9% (41 mmol/mol) Is Optimal for Detecting Diabetes and Identifies Women at Increased Risk of Adverse Pregnancy Outcomes. Diabetes Care 2014;37:2953–2959

“…(1) on our recent article (2). We agree, as highlighted under our study limitations, that the low participation rate in the oral glucose tolerance test (OGTT) could affect the validity of the HbA 1c sensitivity and specificity calculations.…”

Early prediction of gestational diabetes: a practical model combining clinical and biochemical markers

“…While HbA 1c is lower during pregnancy than in the non-pregnant state [41], some studies showed that higher levels can be found in the first trimester in women who develop GDM and are associated with an increased risk of adverse pregnancy outcomes [29,32,42]. HbA 1c is a candidate marker of the glycemic status during first trimester, which seems to be slightly higher in women at increased risk of GDM even in the absence of overt diabetes.…”