How and why maternal metabolic disturbance affects embryonic development

Prevalence of congenital malformations in infants born to women with diabet es mellitus remains high (between 6 and 10 %), which is between 3 and 5 tim es higher than in the general population. Major congenital anomalies are 7 to 10 times more frequent in infants born to diabetics. Normal pregnancy is a state of metabolic stress that requires a high degree of maternal physio logical adaptation to help optimize fetal growth. Decreased insulin sensiti vity throughout pregnancy with reactional hyperinsulinism helps metabolic e fficiency. Changes are observed in glucose, lipid and protein metabolism du ring pregnancy with a rapid switch from anabolism to catabolism. Diabetic w omen have absolute or relative insulin deficiency and display abnormalities in carbohydrate, lipid and protein metabolism. These abnormalities can adv ersely affect embryo growth and explain the high prevalence of spontaneous abortions and congenital malformations. There is a multifactorial origin, o f which hyperglycemia in early embryo development is the most important. Hy perglycemia-induced malformations are mediated by sorbital accumulation, ar achidonic acid and myoinositol deficiencies and high concentrations of beta -hydroxybutyrate. Accumulation of free oxygen radicals by increased format ion and decreased clearance may serve as metabolic common denominators for teratogenic processes. Other factors such as zinc deficiency, the presence of somatomedin inhibitors and released TNF alpha are candidates. Human clin ical studies are not consistent with a genetic predisposition to diabetes-r elated malformations. Progress is needed in pre-conception care of diabetes and blood glucose must be strictly controlled during early pregnancy.