The Metabolic Basis for Birth Defects in Pregnancies Complicated by Diabetes Mellitus

Abstract

By the beginning of the 1980s, perinatal mortality in pregnancies complicated by diabetes at Northwestern University Medical Center (Freinkel 1980) and several other clinics (Coustan et al. 1980; Jovanovic et al. 1980) had declined to levels that were beginning to approximate those of non-diabetic gravida. Thus, an incidence of about 2% was being observed. However, the increased frequency of birth defects associated with diabetic pregnancies had not changed (Soler et al. 1976; Pedersen 1977; Freinkel 1980; Mills 1982) and approximated the values that had persisted worldwide throughout the two to three decades in which the enhanced teratogenicity of diabetic pregnancies had been well documented (Mølsted-Pedersen et al. 1964; Kucera 1971). Indeed, during 1977 to 1981, birth defects were encountered in 4.9% of the pregnancies in our patients with “carbohydrate intolerance . . . with onset or first recognition during pregnancy” (i.e. gestational diabetes mellitus) and in 10.9% of those with known pregestational diabetes, whereas malformations were present in only 2.4% of the offspring of our concurrently enrolled gravida with normal glucoregulation (Simpson et al. 1983). Thus, in our Center, as elsewhere, congenital anomalies had become the leading cause of perinatal death in pregnancies complicated by diabetes, and represented the most compelling unresolved problem in this condition.