Congenital anomalies and the diabetic and prediabetic pregnancy.

Congenital anomalies are two to four times more frequent in the offspring of diabetic mothers than in those of non-diabetic mothers, and represent an increasingly important cause of perinatal mortality. These anomalies involve multiple organ systems more often than those found in the children of non-diabetic mothers. The excess of anomalies associated with maternal diabetes occurs in many organ systems. Anomalies are no more frequent in the offspring of diabetic fathers and pre-diabetic mothers than among those of non-diabetics, suggesting that non-genetic factors are the important determinants. Anomalies are most frequent in the offspring of mothers who have developed diabetes at an early age, many of whom have diabetes of long duration, are insulin-treated, and may have vascular complications. The relative importance of each of these factors in the pathogenesis of anomalies is unknown, but present evidence is consistent with a hypothesis that anomalies are the result of metabolic disturbances in the intrauterine environment during the first trimester of pregnancy. Whether or not their incidence can be reduced by optimum metabolic control of maternal diabetes during this period is unknown.