Diabetes in pregnancy: retarded fetal growth, congenital malformations and feto-maternal concentrations of zinc, copper and manganese in the rat.

The possible relationship between trace metal alterations, disturbed somatic growth and congenital malformations in diabetic pregnancy was studied in an animal model in which skeletal malformations are known to occur in the offspring of experimentally diabetic rats. The diabetic state was induced with streptozotocin more than 2 weeks before mating. In some of the diabetic animals, a zinc supplement in the drinking water (1 ppm or 15 ppm) was given during pregnancy. The contents of zinc, copper and manganese in the maternal livers and whole fetuses were examined on gestational days 18, 20 and 22. The resorption and malformation rates were significantly increased in the diabetic groups. In addition, the fetuses of the diabetic rats exhibited marked growth retardation at all times compared to the normal offspring whether or not the mothers were zinc-treated. There was an excessive accumulation of zinc, copper and manganese in the maternal livers of the diabetic rats. In the offspring of the diabetic rats, however, the total-body concentration of zinc was strikingly decreased. The fetal zinc deficiency in the diabetic group persisted despite maternal zinc supplement during pregnancy. The copper concentrations in the fetuses of normal and diabetic mothers were largely similar, whereas the fetal manganese concentrations were increased in the fetuses of diabetic rats. The findings are compatible with the view that trace metal aberrations may be related to the disturbed fetal growth, and furthermore, that these changes in trace metal levels may also be of teratogenic importance in diabetic pregnancy.