Role of Hba1c in pregnancy

Outline
• Introduction – what and why A1c?

• Normal A1c in pregnancy

• Role of A1c in diagnosis of diabetes in pregnancy

• Role in prognosis

• Current recommendations
Introduction
• Glycated hemoglobin is a series of glycated variants resulting from
attachment of various carbohydrates to N terminal valine of Hb

• HbA1c: -attachment of glucose to N terminal amino acid valine of the beta

chain of hemoglobin

• Glycation results in increased negative charge and hence runs fast on

electrophoresis systems

• Average exposure to glycemia over the lifespan of RBCs – 120 days

• ADAG study (A1c Derived Average Glucose ) - mathematical
relationship between A1c and average glucose levels

HbA1c (%) Glucose (mg/dl)

5 97
6 126
7 154
8 183
9 212
10 240
11 269
12 298

Translating the A1C Assay Into Estimated Average Glucose Values

Diabetes Care. 2008 Aug; 31(8): 1473–1478.
Factors affecting A1c
• Erythrocyte life span and turnover

• Falsely low – hemolytic anemia, blood loss, severe nephropathy

• Falsely elevated – Iron deficiency

• Affected by hemoglobin variants

Relative contribution of fasting and PP values

Monnier et al Diabetes Care 2003 Mar; 26(3): 881-885.

Plasma glucose Vs HbA1c
Plasma glucose HbA1c

Patient preparation

Processing of sample

Affected by hemoglobinopathy

Detection of glycemic
variability
Day to day variability High Low
Changes in pregnancy
• Biphasic response

• Reduction in plasma glucose (nadir at 20 weeks of gestation) , RBC

turnover

• Blood dilution–related anemia – Iron deficiency

Iron status and HbA1c

Diabetes Care 2008 Oct; 31(10): 1945-1948.

What is normal A1c in pregnancy?
• Limited data, various fallacies in available studies

• First trimester – HbA1c >5.7 abnormal

• Second trimester – mean A1c – 4.8% , HAPO

• 3rd trimester – 4.1-5.9%, various studies

Role of A1c in diagnosis
• Establish pre-gestational diabetes mellitus

• No specific cut-off is recommended in pregnancy by professional

bodies

• Study by Rajesh et al, India – second trimester – A1c > 5.4 %

sensitivity of 85.7%

• A1c > 5.9% speficity of 97%

Prognosis in pre-gestational diabetes
• First trimester A1c – risk of fetal anomalies/loss

• absolute increase in risk of anomaly of 2 % with every 1 % increase in

HbA1c

• Increased periconception A1c – lower birth weight / pre-eclampsia

• Increased A1c in later trimester – perinatal morbidity and mortality

A: Risk of a major or minor congenital
anomaly according to the number of SDs of
GHb above normal,
measured periconceptionally.

B:Risk of a major or minor anomaly

according to periconceptional A1C.

Diabetes Care 2007 Jul; 30(7): 1920-1925

• Increased odds of LGA ( OR 1.7 (95 % CI 1.0–3.0))– A1c > 6%

• Preterm delivery (OR – 2.5) , pre-eclampsia (4.3) and neonatal

hypoglycemia ( OR – 2.9) – A1c - > 6.5%

• Greater odds with higher A1c levels

• 3rd trimester A1c upto 7% - associated with increased birth weight

Prediction of GDM
• Most women have normal A1c during early trimester – cannot predict
GDM later

• HbA1c 5.8 -6.0% - predict development of GDM later

Role in postpartum period
• Current recommendation – reassess all women with GDM in the
postpartum period

• Poor correlation between A1c and OGTT – first 3 months post-

partum

• Red cell turn over, iron status, legacy effect of treatment during
pregnancy, blood loss
Current guidelines
• HbA1c – no role in diagnosis or monitoring GDM

• Pre-gestational diabetes mellitus – detection in first trimester

• Optimal HbA1c - < 6% if it can be achieved without undue

complications
Take home
• Normal cutoff values – not established

• Diagnosis and monitoring in GDM – based on plasma glucose and

OGTT

• Role in pre gestational diabetes mellitus

• Immediate post partum – unreliable – OGTT recommended

Thank you