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

Author:

Carlsen Ellen Ø12,Harmon Quaker3ORCID,Magnus Maria C145,Meltzer Helle M6,Erlund Iris7,Stene Lars C8,Håberg Siri E1ORCID,Wilcox Allen J3

Affiliation:

1. Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway

2. Department of Community Medicine, Institute of Health and Society, University of Oslo, Oslo, Norway

3. Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC, USA

4. MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK

5. Population Health Sciences, Bristol Medical School, Bristol, UK

6. Division of Climate and Environment, Environment and Health, Norwegian Institute of Public Health, Oslo, Norway

7. Department of Government Services (Biomarkers Team), Finnish Institute for Health and Welfare, Helsinki, Finland

8. Department of Chronic Diseases and Ageing, Norwegian Institute of Public Health, Oslo, Norway

Abstract

Abstract Background Maternal 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. Methods We 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. Results Size 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). Conclusions 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 BMI.

Funder

Norwegian Ministry of Health and Care Services and the Ministry of Education and Research

Norwegian Research Council’s Centres of Excellence Funding

Medical Research Council Integrative Epidemiology

University of Bristol

National Institute of Environmental Health Sciences, National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

General Medicine,Epidemiology

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