Glycated haemoglobin (HbA1c) in mid-pregnancy and perinatal outcomes.

Ellen Ø Carlsen,Allen J Wilcox,Lars C Stene,Helle M Meltzer,Siri E Håberg,Quaker Harmon,Iris Erlund,Maria C Magnus

doi:10.1093/ije/dyab270

Abstract

BackgroundMaternal diabetes is a well-known risk factor for pregnancy complications. Possible links between long-term maternal blood sugar in the normal range and pregnancy complications are less well described.MethodsWe assayed glycated haemoglobin (HbA1c) in blood samples collected around the 18th week of pregnancy for 2937 singleton pregnancies in the Norwegian Mother, Father and Child Cohort Study (2000–09). Perinatal outcomes (gestational length, birthweight, birth length and head circumference, large-for-gestational age, small-for-gestational age, congenital malformations, preterm delivery and preeclampsia) were obtained from medical records. We tested associations using linear and log-binomial regression, adjusting for maternal age, body mass index (BMI) and smoking.ResultsSize at birth increased modestly but linearly with HbA1c. Birthweight rose 0.10 standard deviations [95% confidence interval (CI): 0.03, 0.16], for each 5-mmol/mol unit increase in HbA1c, corresponding to about 40 g at 40 weeks of gestation. Large-for-gestational age rose 23% (95% CI: 1%, 50%) per five-unit increase. Other pregnancy complications increased in non-linear fashion, with strongest associations within the top quartile of HbA1c (>35 mmol/mol or >5.4%). Per unit HbA1c within the top quartile, preterm delivery increased by 14% (95% CI: 1%, 31%), preeclampsia increased by 20% (95% CI: 5%, 37%) and gestational duration decreased by 0.7 days (95% CI: −1.0, −0.3).ConclusionsAmong women with no recorded diabetes, higher HbA1c levels at 18 gestational weeks were associated with important perinatal outcomes independent of mother’s age, smoking or BMI.

Highlights

Glycated haemoglobin (HbA1c) provides an integrated measure of blood glucose levels across the previous 90– 120 days
Among women with no recorded diabetes, higher HbA1c levels at 18 gestational weeks were associated with important perinatal outcomes independent of mother’s age, smoking or body mass index (BMI)
We find that normal variations in long-term maternal blood sugar, as measured by glycated haemoglobin (HbA1c), are related to pregnancy complications even among pregnant women without diabetes

Summary

Introduction

Glycated haemoglobin (HbA1c) provides an integrated measure of blood glucose levels across the previous 90– 120 days. HbA1c assays are standard for monitoring glycaemic control in patients with diabetes.[1,2] monitoring blood glucose is important during pregnancy (because hyperglycaemia is a recognized risk factor in pregnancy),[3,4,5,6,7,8,9] HbA1c is not the preferred tool for pregnancy glucose monitoring This is because increased haemoglobin turnover during pregnancy can slightly reduce HbA1c levels, and because as an integrated measure of glucose, HbA1c may not adequately capture the short-term fluctuations regarded as important to diabetes management during pregnancy.[1,2,10,11,12,13,14,15,16]. Per unit HbA1c within the top quartile, preterm delivery increased by 14% (95% CI: 1%, 31%), preeclampsia increased by 20% (95% CI: 5%, 37%) and gestational duration decreased by 0.7 days (95% CI: À1.0, À0.3)

Results

Discussion

Conclusion