What is the role of HbA1c (Hemoglobin A1c) in managing diabetes during pregnancy?

Use of HbA1c in Pregnancy

HbA1c should be used as a secondary measure of glycemic control in pregnancy, with self-monitoring of blood glucose (SMBG) remaining the primary tool for achieving optimal pre- and postprandial glucose targets. 1

Why HbA1c Has Limited Primary Utility in Pregnancy

Physiological Changes Affect HbA1c Interpretation

• Red blood cell turnover increases during pregnancy, causing HbA1c levels to fall below non-pregnant values even in women with normal glucose metabolism 1
• HbA1c represents an integrated average of glucose levels and does not adequately capture postprandial hyperglycemia, which is the primary driver of macrosomia and other fetal complications 1
• Standard estimated A1C and glucose management indicator calculations should not be used in pregnancy as they are unreliable 1

Primary Role: SMBG Targets

Fasting and postprandial self-monitoring of blood glucose is the recommended primary method for achieving optimal glycemic control in both gestational diabetes mellitus (GDM) and preexisting diabetes 1

The glucose targets are:

• Fasting plasma glucose <95 mg/dL (5.3 mmol/L) 1
• 1-hour postprandial glucose <140 mg/dL (7.8 mmol/L) 1
• 2-hour postprandial glucose <120 mg/dL (6.7 mmol/L) 1

When and How to Use HbA1c in Pregnancy

Preconception Period

Women planning pregnancy should achieve HbA1c <6.5% (<48 mmol/mol) before conception to reduce the risk of congenital anomalies, preeclampsia, macrosomia, and preterm birth 1

• Observational studies demonstrate that HbA1c levels correlate directly with congenital malformations, particularly anencephaly, microcephaly, congenital heart disease, and renal anomalies occurring during the first 10 weeks of gestation 1, 2
• The lowest rates of adverse fetal outcomes occur with preconception HbA1c <6.5% (<48 mmol/mol) 1

During Pregnancy

The optimal HbA1c target during pregnancy is <6% (<42 mmol/mol) if achievable without significant hypoglycemia, but may be relaxed to <7% (<53 mmol/mol) if necessary to prevent hypoglycemia 1

• In the second and third trimesters, HbA1c <6% (<42 mmol/mol) has the lowest risk of large-for-gestational-age infants, preterm delivery, preeclampsia, and other complications 1
• HbA1c should be monitored more frequently than usual (e.g., monthly) given the altered red blood cell kinetics and physiological changes in glycemic parameters during pregnancy 1

Important Caveats

• The HbA1c goal must be achieved without hypoglycemia, which may increase the risk of low birth weight in addition to usual maternal adverse effects 1
• For women with type 1 diabetes and history of recurrent hypoglycemia or hypoglycemia unawareness, less stringent targets may be necessary 1

Role of Continuous Glucose Monitoring (CGM)

When used in addition to pre- and postprandial SMBG, CGM can help achieve HbA1c targets and reduce adverse outcomes in pregnancies complicated by type 1 diabetes 1

• The CONCEPTT trial demonstrated that real-time CGM in type 1 diabetes pregnancy improved HbA1c and time in range without increasing hypoglycemia, and reduced large-for-gestational-age births, neonatal hospital stays, and severe neonatal hypoglycemia 1
• CGM metrics should be used as an adjunct but not as a substitute for SMBG to achieve optimal pre- and postprandial targets 1
• CGM-reported mean glucose is superior to estimated A1C calculations for assessing glycemic control in pregnancy 1

HbA1c for Diagnosis in Pregnancy

HbA1c ≥6.5% (≥48 mmol/mol) can be used to diagnose preexisting diabetes in early pregnancy, but has significant limitations for detecting gestational diabetes 1

• An early pregnancy HbA1c cutoff of 5.7% has been identified as optimal for detecting diabetes in pregnancy diagnosed by oral glucose tolerance test (OGTT), though sensitivity remains only 64.6% 3
• HbA1c analysis is less useful than OGTT for detecting gestational diabetes in later pregnancy 4
• Women with HbA1c ≥5.7% in early pregnancy have increased risks of requiring insulin, macrosomia, and shoulder dystocia 3

Postpartum Follow-up

HbA1c analysis postpartum detects fewer women with abnormal glucose tolerance than OGTT, but the ease of testing may improve follow-up rates 4

• Combining HbA1c with fasting plasma glucose or waist circumference may improve detection rates of persistent glucose abnormalities postpartum 4