Complications of Pregnancy and Fetal Development

Abstract

Although the outcome of pregnancy for women with diabetes meilitus has improved in recent years, the infant of the diabetic mother has an increased risk of major clinical problems, particularly in the early neonatal period. These include birth injury due to macrosomia, neonatal hypoglycemia, respiratory distress syndrome, and serious congenital anomalies. Because of the great difficulties encountered during attempts to investigate these problems in clinical research protocols, there is a continuing need to establish appropriate animal models of the diabetic pregnancy. Studies carried out over the past decade, primarily with chemically-induced diabetes have suggested techniques which might be useful. In general, the choice of the animal to be studied will depend on the hypotheses being addressed. For instance, small animals such as rabbits and rats made diabetic with streptozotocin have been successfully used for investigation of fetal lung development. Furthermore, the rat model has been helpful for evaluation of fetal anomalies associated with maldevelopment of the spine and central nervous system. Larger animals, such as the nonhuman primate, are more appropriate for studying placental function and amniotic fluid composition in diabetic pregnancies. The task group on pregnancy and fetal development recommends that animal models of diabetes meilitus be used for a more extensive hormonal and metabolic characterization of diabetic mothers during pregnancy, for investigation of placental physiology with respect to the transfer of substrates from mother to fetus, for systematic and comprehensive study of mechanisms controlling fetal lung development, and for delineation of the pathophysiology of neonatal hypoglycemia. it is further recommended that animal models of spontaneous diabetes such as the BB/W rat be used in future studies dealing with pregnancy and fetal development. Because females with spontaneous diabetes show reduced conception rates, there is a pressing need to enhance the fertility of these animals in order to intensify studies on fetal development.

Influence of streptozotocin‐diabetes on the pharmacokinetics, placental transfer and tissue localization of dexamethasone in rats

“…Streptozotocin-diabetes in rats has been viewed as an appropriate model for studies on foetal and placental development (Farrell et al, 1982). Effects of a moderate dose of streptozotocin used in this study on the mother, foetus and placenta (Table 1) are similar to those reported elsewhere (Mulay & Solomon, 1983).…”

Delayed Lung Maturation in the Macrosomic Offspring of Genetically Determined Diabetic (db/+) Mice1

“…For example, the "diabetic" state may have been artificially arrived at by either eliminating maternal insulin production or by giving large amounts of glucose or insulin to mother or fetus (2). Fetuses of some of these models (notably the streptozotocin-treated rat with profound maternal and fetal hyperglycemia) are actually small for gestational age rather than macrosomic (18).…”

“…Infants of diabetic mothers whose hyperglycemia is inadequately controlled late in gestation appear to have an increased risk of lung immaturity, as manifested by RDS at birth (I). Animal models in which maternal glucose intolerance and consequent fetal hyperglycemia are artificially induced have been developed to study this phenomenon (2). However, important questions concerning maternal-fetal interactions in diabetes and the consequent effects on fetal organ growth and development might be more appropriately addressed by using a model in which the diabetes is genetically determined, therefore occuning spontaneously in the mother (2).…”

Effect of Acute Insulin-Induced Hypoglycemia on Fetal versus Adult Brain Fuel Utilization, Assessed by ¹³C MRS Isotopomer Analysis of [U-¹³C]Glucose Metabolites

“…The reason for this is not clear, although it has been suggested that the altered hormonal levels, mainly lower glucagon secretion, are responsible [7]. Since insulin does not cross the placenta [8], the fetus of the insulin-induced hypoglycemic mother is subjected to periods of hypoglycemia, and consequent hypoinsulinemia. The damage to the fetus caused by hypoglycemia has been suggested to stem from the total dependence of the fetus on glycolysis for energy during early neurulation; thus, the harmful effect of hypoglycemia is greatly diminished once the capacity for aerobic glucose metabolism is developed during late neurulation [5].…”

“…This suppression in turn leads to the necessity of replenishing TCA cycle intermediates via the anaplerotic PC pathway, active only in the glial compartment [27, for review]. This direct effect of insulin on the brain would not be found in the fetus, since insulin does not cross the placenta [8], and thus, the fetus is only hypoglycemic but not hyperinsulinemic.…”