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

Int J Epidemiol. 2022 Jun 13;51(3):759-768. doi: 10.1093/ije/dyab270.

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.

Keywords: Birthweight; HbA1c; MoBa; diabetes; glucose; preeclampsia; pregnancy; pregnancy complications; preterm.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Birth Weight
  • Cohort Studies
  • Diabetes, Gestational* / epidemiology
  • Female
  • Glycated Hemoglobin / analysis
  • Humans
  • Infant, Newborn
  • Norway
  • Pre-Eclampsia* / epidemiology
  • Pregnancy
  • Pregnancy Outcome / epidemiology
  • Premature Birth* / epidemiology

Substances

  • Glycated Hemoglobin A