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

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.

Pregnancy History at 40 Years of Age as a Marker of Cardiovascular Risk

“…For example, blood glucose levels that are elevated within the normal range have been associated with increased risk of preeclampsia and preterm delivery, even after controlling for BMI and other risk factors. 50 Pregnancy complications can also indicate the imminent onset of established CVD risk factors. A Dutch study that measured blood pressure, lipids, and fasting glucose after pregnancy found that new hypertension and diabetes developed sooner in women after hypertensive disorders of pregnancy than in women without pregnancy complications.…”

Early HbA1c Levels as a Predictor of Adverse Obstetric Outcomes: A Systematic Review and Meta-Analysis

“…Carlsen et al showed that, among women with no recorded diabetes, higher HbA1c levels at 18 gestational weeks were associated with an increased risk of pre-eclampsia. Pre-eclampsia increased by 20% per unit increase of HbA1c (95% CI: 5%, 37%) [ 51 ] and, within the highest quartile of HbA1c (35mmol/mol or greater), increasing HbA1c was related to shorter pregnancy durations and an increased risk of pre-eclampsia and preterm delivery. Conversely, the occurrence of macrosomia was not significantly related to whether studies used an HbA1c threshold > or <39 mmol/mol (5.7%) (OR 1.20, 95% CI 0.98–1.47 and OR 2.06, 95% CI 0.93–4.55, respectively).…”

Effect of body mass index on pregnancy outcomes: a prospective observational study from a rural south Indian tertiary care setting

“…Obese women and their newborns appear to have more occurrences of miscarriage, pregnancy and labor difficulties, postnatal morbidity, and short and long-term negative health effects on their M a n u s c r i p t a c c e p t e d f o r p u b l i c a t i o n 3 offspring than childbearing women of normal weight [6,7]. The traditional treatment for GDM is mostly based on maternal blood glucose levels and stringent blood glucose control along with strict monitoring is essential to avoid negative pregnancy outcomes [8,9]. Insulin resistance increases with gestational age in normal pregnancy and it is identified as a major contributor to GDM along with B-cell dysfunctions [10,11].…”