Congenital malformations in diabetic pregnancy: the clinical relevance of experimental animal studies.

The aim of this work was to present recent observations on the occurrence of malformations in the offspring of diabetic rats and to discuss these findings in the light of present clinical experience. Comparison of malformation rates between different substrains of Sprague-Dawley rats showed marked differences in the occurrence of diabetes-induced malformations. These findings suggest that congenital malformations in diabetic pregnancy may result from a teratological insult in genetically predisposed individuals. Recent clinical reports seem to link facial malformations to an increased incidence of sacral-caudal malformations in human diabetic pregnancy. The present rat model, which expresses both these aberrations--micrognathia and sacral dysgenesis--may therefore be a useful tool in studies of the aetiological relationships between disturbed maternal metabolism and skeletal malformations in the offspring. Malformations in fetuses of diabetic animals seem to arise from teratogenic insult(s) early in pregnancy. Hyperglycemia and hyperketonemia may both singly, and in combination, be of teratological significance. Insulin itself does not appear to be directly teratogenic. Furthermore, there is evidence to suggest that disturbed levels of trace metals, primarily zinc, may be a significant factor in the production of congenital malformations. The increased rate of malformations in diabetic pregnancy, therefore, appears to be multifactorial in origin.