Is diabetes mellitus a teratogen or a coteratogen?

The risk of major and minor congenital malformations was compared in the offspring of diabetic (n = 2,639) and nondiabetic (n = 2,144) women who delivered at the Johns Hopkins Hospital in Baltimore, Maryland, between January 1, 1946 and December 31, 1970. In spite of ample power, there was little evidence of an increased malformation risk in offspring born prior to the onset of overt diabetes in the mother. In offspring born after onset, the overall malformation risk was not increased, but severe multi-organ birth defects occurred at approximately twice the control group rate. It is postulated, therefore, that diabetes may act as a coteratogen enhancing the teratogenic effect of other insults but may not itself cause malformations. That some of its effects may be specific is suggested by the especially high risk of vertebral, lower limb, and urogenital defects, a pattern similar to that reported for the caudal dysgenesis syndrome. To better understand the teratogenic effects associated with diabetes, it may be necessary to consider interactions with other factors and to explore the association between maternal diabetes and caudal dysgenesis.