Why are hemoglobin (Hb) A1c levels lower in pregnancy?

Hemoglobin A1c Levels in Pregnancy

Hemoglobin A1c levels are lower in pregnancy primarily due to increased red blood cell turnover, which results in a physiological decrease in A1c values compared to non-pregnant women. 1, 2

Physiological Mechanisms Behind Lower A1c in Pregnancy

• Increased Red Blood Cell Turnover:

  • Pregnancy causes accelerated production and turnover of red blood cells
  • This shortens the exposure time of hemoglobin to glucose, resulting in less glycosylation
  • The American Diabetes Association explicitly acknowledges this physiological change 1

• Hemodilution Effect:

  • Plasma volume expansion during pregnancy contributes to relative anemia
  • Lower hemoglobin levels are associated with greater discrepancy between A1c and actual glucose levels 3

• Altered Glucose Dynamics:

  • Early pregnancy features enhanced insulin sensitivity and lower glucose levels 2
  • Later pregnancy shows insulin resistance with postprandial hyperglycemia due to placental hormones 1

Clinical Implications

• Interpretation Challenges:

  • A1c may underestimate actual glucose intolerance, particularly in the second trimester 3
  • The discrepancy between A1c-estimated average glucose and actual mean glucose widens at 24-30 weeks gestation 3
  • Lower hemoglobin levels correlate with greater underestimation of glycemia by A1c 3

• Monitoring Recommendations:

  • A1c should be used as a secondary measure of glycemic control in pregnancy, after self-monitoring of blood glucose 1
  • More frequent A1c monitoring (e.g., monthly) is recommended during pregnancy due to altered red blood cell kinetics 1
  • Standard A1c targets are adjusted for pregnancy: ideally <6% if achievable without significant hypoglycemia 1

• Limitations of A1c in Pregnancy:

  • A1c may not fully capture postprandial hyperglycemia, which is a key driver of macrosomia 1
  • Commonly used estimated A1c calculations should not be used during pregnancy 1
  • The relationship between A1c and adverse outcomes may be less straightforward in pregnancy 4

Clinical Pitfalls to Avoid

• Don't rely solely on A1c: A study showed that patients with "safe" A1c values (≤7.0%) still experienced significant glycemic excursions, with up to 52.8% of continuous glucose readings above target range 5

• Avoid misinterpreting "normal" A1c values: What appears to be good control based on A1c may mask significant glucose variability in pregnant women with diabetes 5

• Remember trimester variations: A1c accurately reflects glycemia in the first trimester but increasingly underestimates glucose intolerance as pregnancy progresses 3