The core clinical proposal tests the hypothesis that meticulous control of insulin-dependent diabetes mellitus during pregnancy, beginning in the first nine weeks of gestation, to levels approximating the normoglycemic state will lessen the risk of maternal complications, both acute and chronic, spontaneous early fetal losses, fetal malformations, and neonatal morbidity and mortality. Endpoints of maternal medical and obstetrical morbidity to be studied include retinal and renal microvascular disease and hypertension. Endpoints of fetal morbidity to be studied include birth asphyxia, macrosomia, intrauterine growth retardation, respiratory distress syndrome, cardiomyopathy, hypoglycemia, polycythemia, hyperbilirubinemia, hypocalcemia, hypomagnesemia, and malformations. Three groups of pregnant insulin-dependent diabetic subjects will be studied. Groups I and II are prospectively randomized groups. Group I includes subjects managed with "strict control" of diabetes beginning in the first trimester. Group 11 includes subjects managed with "Customary control" of diabetes beginning in the first trimester. Group III are pregnant insulin-dependent diabetic subjects managed with customary control after the first trimester, a "late entry" group A nondiabetic group, Group IV, will serve as a "control" comparison group for metabolic studies. The clinical core is an interdisciplinary study involving endocrinologists, obstetricians, geneticists, and neonatologists. It seeks to understand and prevent maternal, fetal, and neonatal pathology through appropriate control of diabetes and employment of state of the art techniques in obstetrical and neonatal management, forms a central core for other clinical projects in the proposal, and provides a clinical impetus for relevant basic studies of diabetes in pregnancy.