Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study

Associations of Maternal A1c and Glucose With Pregnancy Outcomes

Lynn P. Lowe, PHD; Boyd E. Metzger, MD; Alan R. Dyer, PHD; Julia Lowe, MBCHB; David R. Mccance, MD; Terence R.J. Lappin, PHD; Elisabeth R. Trimble, MD; Donald R. Coustan, MD; David R. Hadden, MD; Moshe Hod, MD; Jeremy J.N. Oats, MD; Bengt Persson, MD, PHD;


Diabetes Care. 2012;35(3):574-580. 

In This Article

Abstract and Introduction


Objective—To compare associations of maternal glucose and A1C with adverse outcomes in the multinational Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and determine, based on those comparisons, if A1C measurement can provide an alternative to an oral glucose tolerance test (OGTT) in pregnant women.
Research Design and Methods—Eligible pregnant women underwent a 75-g OGTT at 24–32 weeks' gestation. A sample for A1C was also collected. Neonatal anthropometrics and cord serum C-peptide were measured. Associations with outcomes were assessed using multiple logistic regression with adjustment for potential confounders.
Results—Among 23,316 HAPO Study participants with glucose levels blinded to caregivers, 21,064 had a nonvariant A1C result. The mean ± SD A1C was 4.79 ± 0.40%. Associations were significantly stronger with glucose measures than with A1C for birth weight, sum of skinfolds, and percent body fat >90th percentile and for fasting and 1-h glucose for cord C-peptide (all P < 0.01). For example, in fully adjusted models, odds ratios (ORs) for birth weight >90th percentile for each measure higher by 1 SD were 1.39, 1.45, and 1.38, respectively, for fasting, 1-, and 2-h plasma glucose and 1.15 for A1C. ORs for cord C-peptide >90th percentile were 1.56, 1.45, and 1.35 for glucose, respectively, and 1.32 for A1C. ORs were similar for glucose and A1C for primary cesarean section, preeclampsia, and preterm delivery.
Conclusions—On the basis of associations with adverse outcomes, these findings suggest that A1C measurement is not a useful alternative to an OGTT in pregnant women.


The American Diabetes Association recently endorsed recommendations to use hemoglobin A1C (A1C) to diagnose diabetes and to identify people at increased risk for developing diabetes.[1] They noted that A1C does not require a fasting state, reflects the usual level of glycemia for a period of 3–4 months, has low intraindividual variability, and is a good predictor of diabetes-related complications. However, these recommendations stipulate that the diagnosis of diabetes during pregnancy requires glucose testing since changes in erythrocyte turnover make the A1C assay problematic.[2]

In overt diabetes, measurements of A1C are highly correlated with average glucose concentrations assessed by multiple daily measurements of capillary blood.[3] Historically, A1C concentrations in preexisting diabetes have been associated with the risk of chronic complications and of adverse events during pregnancy, such as miscarriage, congenital malformations, or macrosomia.[3] However, it has been shown that A1C measurements[4,5] and fructosamine levels[6,7] do not adequately separate women with normal pregnancy from those with gestational diabetes mellitus (GDM), even though A1C levels decline in normal pregnancy.[8]

The objective of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study was to clarify the risk of adverse outcomes associated with degrees of glucose intolerance in pregnancy less severe than overt diabetes. Glucose tolerance was measured by a 75-g 2-h oral glucose tolerance test (OGTT) in a large, heterogeneous, international, ethnically diverse cohort of women at 24–32 weeks' gestation. Results of the HAPO Study on associations of maternal glucose levels below those diagnostic of diabetes with pregnancy outcomes have been reported.[9]

The purpose of this report is to compare associations of maternal glucose and A1C measured at 24–32 weeks' gestation with adverse outcomes and to determine, based on those comparisons, if A1C can be used as an alternative to measurement of glucose in pregnant women.


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