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HbA1c Can Underestimate Maternal Glycemia During Pregnancy

Key findings

  • In this interim analysis of a prospective cohort study, Massachusetts General Hospital researchers assessed the relationship between hemoglobin (Hb)A1c and OGTT-based measures of glycemia for pregnancy and the postpartum period in women without pre-existing diabetes
  • HbA1c underestimated the degree of glucose intolerance in the late second trimester, the usual time of screening for gestational diabetes
  • Lower hemoglobin levels in the late second trimester were associated with greater HbA1c underestimation of glucose intolerance
  • HbA1c could provide false reassurance if it's used to measure glycemia in mid- to late-gestation without accounting for gestational age and maternal hemoglobin level

Hemoglobin A1c (HbA1c) is not recommended as a tool for diagnosing gestational diabetes, because compared with oral glucose tolerance testing (OGTT) and self-monitoring of blood glucose (SMBG), it's a less reliable marker of glycemia during pregnancy.

On the other hand, HbA1c is accepted for the screening of pre-existing diabetes in early pregnancy, confirming glycemic control in women performing SMBG and assessing glycemic control if SMBG is inadequate. Still, HbA1c is affected by conditions that alter the lifespan of red blood cells (RBC), and pregnancy is one of those. Pregnant women exhibit altered RBC kinetics, increased erythropoiesis and hemodilution.

Based on interim results from a prospective study, researchers at Massachusetts General Hospital suggest accounting for gestational age and maternal hemoglobin levels when interpreting HbA1c levels in pregnant women. P. Kaitlyn Edelson, MD, fellow in the Maternal-Fetal Medicine ProgramCamille E. Powe, MD, endocrinologist and co-director of the Diabetes in Pregnancy Program, and colleagues report the basis for this recommendation in the Journal of Clinical Endocrinology and Metabolism.

Study Details

The Study of Pregnancy Regulation of Insulin and Glucose (SPRING) is examining the longitudinal change in insulin physiology across pregnancy and the postpartum state in women who did not have diabetes but had risk factors for gestational diabetes.

Participants were enrolled between 2016 and 2019 if they had at least one of the following:

  • Body mass index ≥25 kg/m2 (≥23 kg/m2 in Asian women) plus one additional risk factor for diabetes as defined by the American Diabetes Association
  • Abnormal glucose testing during a prior pregnancy
  • History of diabetes (including gestational diabetes) in a first-degree relative

Participants had an OGTT and an HbA1c assay performed on the same day during each of three time periods:

  • 10–15 weeks of gestation
  • 24–30 weeks of gestation (the usual time of screening for gestational diabetes)
  • 6–24 weeks after delivery

An interim analysis of 102 participants was conducted on data available as of August 2019.

Key Results

  • Between the first trimester and late second trimester, average OGTT glucose increased by 8.1 mg/dL (P = .001), while HbA1c decreased by 0.13% (P < .001)
  • In the first trimester and the postpartum period, the discrepancy between average OGTT glucose and HbA1c-estimated average glucose was minimal (1.2 mg/dL in the first trimester; 0.16 mg/dL postpartum)
  • In the late second trimester, though, average OGTT glucose was 13.2 mg/dL higher than HbA1c-estimated average glucose (P < .001 compared with the discrepancy in the first trimester)
  • Lower hemoglobin was associated with a greater discrepancy in the late second trimester (P = .03 in a model adjusted for maternal age and gestational age)

Applying the Findings to Practice

According to these results, HbA1c can underestimate maternal glycemia in mid- to late-gestation, and underestimation is more likely in women with lower hemoglobin levels. Accounting for maternal hemoglobin level and gestational age may improve the interpretation of HbA1c levels during pregnancy.

Learn more about the Maternal-Fetal Medicine Program

Learn more about the Diabetes in Pregnancy Program

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