Glycosylated haemoglobin (HbA1c) and risk of congenital malformation in diabetes

• frequency of fetal developmental defects in diabetic pregnancies is significantly higher compared to uncomplicated gestations
  • in infants born to diabetic mothers, malformations are found in 2.7-16.8%, while in that born to healthy mothers they were only in 2-3% infants (1,2)
• early period of fetal development, i.e. the period of organogenesis (up to the 12th week of gestation), is especially vulnerable to teratogenic factors - teratogenic factors during this period cause mostly large congenital defects, mainly of the central nervous system (CNS), the cardiovascular (CVS), skeletal, and urogenital systems
  • results of numerous studies show that the occurrence of congenital defects is much more frequent in infants born to mothers who presented with increased glycaemia during the first trimester of pregnancy (3)
• risk of malformations in a group of newborns born to mothers in varied with respect to HbA1C (4)
  • if the HbA1C level during the first trimester of pregnancy did not exceed a value of 8.5% the risk of malformation was 3.4%
  • if the maternal HbA1C from the first trimester exceeded 9.5% then this was related to a 22.0% risk of malformation
• relating risk of malformations to mean glycaemia:
  • in a maternal diabetic female population with a mean glycemia 163 mg/dl (9.1 mmol/l), the risk of fetal malformation is 9.6%, while in that with a mean glycaemia 110 mg/dl (6.1 mmol/l) the risk is reduced to 3.9% (5)
  • keeping fasting glucose levels in first trimester below 5.8 mmol/l and postprandial glucose levels below 9.1 mmol/l can contribute to decreasing number of fetal malformations (3)
  • note that diabetic pregnancy, despite the improved metabolic control, is still a strong risk factor for alterations in fetal development, particularly in patients with a tendency to brittle glycaemia during first trimester of pregnancy (3)

Reference:

1. Lemons JA, Vargas P, Delaney JJ. Infant of the diabetic mother. Review of 225 cases. Obstet Gynecol 1981; 57: 187-92.
2. Key TC, Giuffrida R, Moore TR. Predictive value of early pregnancy glycohemoglobin in the insulin-treated diabetic patient. Am J Obstet Gynecol 1987; 156: 273-80.
3. Wender-Oegowska E et al. Acta Obstetricia et Gynecologica Scandinavica Volume 84 Issue 1 Page 17 - January 2005.
4. Miller E, Hare JW, Cloherty JP, Dunn PJ, Gleason RE, Soeldner JS et al. Elevated maternal hemoglobin A1c in early pregnancy and major congenital anomalies in infants of diabetic mothers. N Engl J Med 1981; 304: 1331-4.
5. Goldman JA, Dicker D, Feldberg D, Yeshaya A, Samuel N, Karp M. Pregnancy outcome in patients with insulin-dependent diabetes mellitus with preconceptional diabetic control: a comparative study. Am J Obstet Gynecol 1986; 155: 293-7