Is HbA1c (hemoglobin A1c) affected by illness in a pregnant woman with hyperglycemia?

HbA1c is Affected by Illness in Pregnancy

Yes, HbA1c is physiologically altered during pregnancy due to increased red blood cell turnover, resulting in levels that are naturally lower than in non-pregnant individuals, and this physiological change means HbA1c should be used only as a secondary measure of glycemic control—not the primary metric—in pregnant women with hyperglycemia. 1

Physiological Changes to HbA1c in Pregnancy

Red Blood Cell Turnover Effects

• Due to increased red blood cell turnover during normal pregnancy, HbA1c levels fall physiologically below non-pregnant values. 1
• This alteration in red blood cell kinetics occurs throughout pregnancy and affects the interpretation of HbA1c values. 1
• The normal pregnancy HbA1c range is naturally lower, with reference intervals in healthy pregnant women being approximately 4.5-5.7% across trimesters. 2

Time Course During Pregnancy

• HbA1c levels significantly decrease in the second trimester and may increase slightly in the third trimester. 2
• Research shows HbA1c levels change dynamically: decreasing toward mid-pregnancy, then rising again in late pregnancy. 2

Clinical Implications for Glycemic Monitoring

Primary vs. Secondary Monitoring

• Self-monitoring of blood glucose (fasting and postprandial) must remain the primary method for achieving optimal glycemic control during pregnancy, with HbA1c serving only as a secondary measure. 1, 3
• HbA1c may not fully capture postprandial hyperglycemia, which is the primary driver of macrosomia and adverse fetal outcomes. 1

Monitoring Frequency

• HbA1c should be monitored more frequently during pregnancy than in non-pregnant individuals—specifically monthly—due to altered red blood cell kinetics and the need for close glycemic surveillance. 1, 3, 4

Target HbA1c Values in Pregnancy

Optimal Targets

• The ideal HbA1c goal is <6% (42 mmol/mol) throughout pregnancy if achievable without significant hypoglycemia. 1, 3, 4
• If the <6% target cannot be achieved safely without significant hypoglycemia, the target may be relaxed to <7% (53 mmol/mol). 1
• HbA1c <6% is associated with the lowest risk of large-for-gestational-age infants, preterm delivery, and preeclampsia. 1, 3

Evidence Supporting Strict Control

• Research demonstrates that in pregnant women with type 1 diabetes, glucose levels measured by continuous glucose monitoring were significantly better in patients with HbA1c ≤6.0% compared to those with HbA1c >6.0%. 5
• Treatment should be aimed at achieving HbA1c levels within the normal range (≤6.0%) rather than accepting levels up to 7.0%. 5

Additional Factors Affecting HbA1c Interpretation

Confounding Conditions

• Proteinuria during pregnancy is associated with lower glycated albumin levels and higher HbA1c levels, which can confound interpretation. 2
• Obesity (higher BMI) is associated with lower glycated albumin levels and higher HbA1c levels in pregnant women. 2
• Ferritin levels decrease as pregnancy progresses, which may influence HbA1c measurements. 6

Critical Pitfall to Avoid

Do Not Use Estimated HbA1c Calculations

• Commonly used estimated HbA1c and glucose management indicator calculations should NOT be used in pregnancy as estimates of HbA1c due to the physiological changes that occur. 1
• Use of CGM-reported mean glucose is superior to estimated HbA1c calculations given the changes to HbA1c that occur in pregnancy. 1

Recommended Monitoring Strategy

Blood Glucose Targets (Primary Monitoring)

• Fasting glucose: 70-95 mg/dL (3.9-5.3 mmol/L) 1, 3, 4
• 1-hour postprandial: 110-140 mg/dL (6.1-7.8 mmol/L) 1, 3, 4
• 2-hour postprandial: 100-120 mg/dL (5.6-6.7 mmol/L) 1, 3, 4

Monitoring Approach

• Both fasting and postprandial self-monitoring of blood glucose are essential for all pregnant women with diabetes. 1, 4
• Postprandial monitoring is associated with better glycemic control and lower risk of preeclampsia. 1, 4
• Continuous glucose monitoring can be used as an adjunct but should not substitute for self-monitoring of blood glucose to achieve optimal pre- and postprandial targets. 1