Trimester-specific reference intervals for haemoglobin A_1c (HbA_1c) in pregnancy

Background: Diabetes in pregnancy imposes additional risks to both mother and infant. These increased risks are considered to be primarily related to glycaemic control which is monitored by means of glycated haemoglobin (HbA _1c). The correlation of HbA_1c with clinical outcomes emphasises the need to measure HbA_1c accurately, precisely and for correct interpretation, comparison to appropriately defined reference intervals. Since July 2010, the HbA_1c assay in Irish laboratories is fully metrologically traceable to the IFCC standard. The objective was to establish trimester-specific reference intervals in pregnancy for IFCC standardised HbA 1 in non-diabetic Caucasian women. Methods: The authors recruited 311 non-diabetic Caucasian pregnant (n = 246) and non-pregnant women (n =65). A selective screening based on risk factors for gestational diabetes was employed. All subjects had a random plasma glucose < 7.7 mmol/L and normal haemoglobin level. Pregnancy trimester was defined as trimester 1 (T1, n = 40) up to 12 weeks + 6 days, trimester 2 (T2, n =106) 13-27 weeks + 6 days, trimester 3 (T3, n =100) > 28 weeks to term. Results: The normal HbA_1c reference interval for Caucasian non-pregnant women was 29-37 mmol/mol (Diabetes Control and Complications Trial; DCCT:4.8%-5.5%), T1:24-36 mmol/mol (DCCT:4.3%-5.4%), T2:25-35 mmol/mol (DCCT:4.4%-5.4%) and T3:28-39 mmol/mol (DCCT:4.7%-5.7%). HbA1 was significantly decreased in trimesters 1 and 2 compared to non-pregnant women. Conclusions: HbA1c trimester-specific reference intervals are required to better inform the management of pregnancies complicated by diabetes.