Effect of gestational diabetes on maternal artery function

Endothelial dysfunction has been observed systemically in women with gestational diabetes (GDM). Important cardiovascular adaptations occur during pregnancy, including enhanced endothelium-dependent vasodilation in systemic and uterine arteries, which are necessary to ensure the health of both mother and fetus. The effects of GDM, however, on uterine artery function and the possible mechanisms that mediate endothelial dysfunction remain unknown. The aim of this study was to utilize a mouse model of GDM to investigate (a) effects on uteroplacental flow, (b) endothelial function of uterine and mesenteric arteries, and (c) possible mechanisms of any dysfunction observed. Pregnant mice heterozygous for a leptin receptor mutation (Lepr(db) (/+); He) spontaneously develop GDM and were compared to wild-type (WT) mice at day 18.5 of gestation. Uterine artery flow was assessed using ultrasound biomicroscopy. Uterine and mesenteric artery function was assessed using wire myography. Arterial superoxide production was measured using oxidative fluorescence microphotography. In vivo uteroplacental perfusion was impaired in mice with GDM, indicated by a significant increase in uterine artery resistance index. Maximal endothelium-dependent relaxation to methacholine was significantly impaired in mesenteric arteries from mice with GDM, while sensitivity was significantly reduced in uterine arteries. Both uterine and mesenteric arteries from mice with GDM exhibited a greater dependence on nitric oxide and increased superoxide production compared with those from mice with a healthy pregnancy. A significant source of superoxide in GDM mice was uncoupled nitric oxide synthase. These changes may contribute to the development of some of the fetal and maternal complication associated with GDM.     

The role of maternal mitochondria during oogenesis,fertilization and embryogenesis

This review examines the place of mitochondria in the life cycle through oogenesis, ovulation and early embryogenesis. Mitochondria are semi-autonomous organelles responsible for the bulk of oxidative energy production in the body. They play central roles in ageing, in apoptosis and in many non-Mendelian-inherited bioenergetic and neurological diseases. Originating as free alpha-proteobacteria that entered into a symbiotic relationship with the ancestral eukaryotic organisms, they now have a highly restricted genome of ~16 kb, encoding for 37 genes of the oxidative phosphorylation pathway. Mitochondria are inherited through the mother and special mechanisms have evolved to eliminate the contribution of the spermatozoon in early embryonic development. Most mitochondrial genes have become translocated to the nucleus, and nuclear and mitochondrial genes have co-evolved. This, coupled with a high mutation rate in the remaining mitochondrial DNA, has resulted in a high degree of concordance between them. Disharmony between nuclear and mitochondrial genes is thus likely to complicate cloning technology and the experimental reconstruction of chimeric embryos by cytoplasmic or nuclear transfer.     

Effect of maternal diabetes on human and rat fetal development

Diabetes is a genetically determined metabolic disease with fasting hyperglycemia due to relative or absolute absence of insulin. With the use of exogenous insulin, successful gestations are now possible. Nevertheless, there are still severe problems associated, such as spontaneous abortion, perinatal mortality and congenital malformations. Caudal regression syndrome, disclosure of the neural tube and cardiovascular alterations are the most common malformations. Gestational diabetes can induce increased fetal corporal fat and macrosomia with hyperinsulinemia, hypoglycemic, hypoxia, metabolic acidosis and perinatal death. During adult life, diabetic mothers' children can develop obesity, glucose intolerance and type 2 diabetes. In order to study fetuses' alterations during diabetic gestations we now have animal models of diabetes. Maternal diabetes in rats alters fetal development in a very similar manner to that of humans. Although we do not accurately know the pathogenic mechanism by which diabetes produces fetuses' abnormal development, hyperglycemia and hyperketonemia had been mentioned to have predominant roles. Hyperglycemia damages DNA and increases oxidative stress and hyperketonemia increases the rate of embryo malformations. The addition of antioxidants such as C and E vitamins can reduce this damage. During adult life, diabetic rats' cubs have alterations in glucose metabolism and in reproductive function. The understanding of mechanisms by which maternal diabetes affects fetuses development, can help us to prevent complications and improve mothers' and children's life quality.     

Effects of twin gestation on maternal morbidity

As the incidence of twin gestation increases, it is important to consider the maternal risks associated with carrying multiples. Compared with singleton gestation, there are increased risks to the mother during the antepartum, intrapartum, and postpartum periods. Certain pregnancy complications are more likely to occur during a twin gestation, including preeclampsia and other hypertensive disorders, antepartum hospitalization for preterm labor or abnormal bleeding, nutritional deficiencies, cesarean delivery, and postpartum hemorrhage. Women carrying twins may benefit from early education regarding these issues, close maternal monitoring as well as physical therapy sessions, and nutrition counseling during their pregnancies.     

Neonatal risk in early manifested maternal diabetes

Neonatal risk in 172 women with early manifested maternal diabetes mellitus (manifestation less than or equal to 18 years) has been estimated in an analysis of 10 years. We found a tendency towards an increased rate of mortality and malformations, but there are no statistic significant differences compared with the White B group as well as with the C/D-group of late manifestation. An increased risk of morbidity (rate of fetopathy , immaturity, disturbed adaptation) could be demonstrated, but it exists also in the newborns of diabetic mothers of the White group B. Using the recent literature the causes have been discussed and conclusions have been made.     

Gestational diabetes and maternal third-trimester blood count

OBJECTIVE: To examine the effect of gestational diabetes mellitus (GDM) in the third trimester on the maternal blood count in nonanemic women with singleton pregnancies. STUDY DESIGN: In a prospective, observational study, consecutive women without preexisting anemia or hemoglobinopathies, endocrine disorders or diabetes were recruited for blood sampling for complete blood count at 28-30 weeks' gestation, when they were screened for GDM, and again at 36-38 weeks' gestation. The management of pregnancy or GDM was not influenced by the study. After delivery, the blood count results were compared between women with and without GDM. RESULTS: Of the 462 women recruited, 64 (13.8%) were diagnosed with GDM. This group had similar blood counts at 28-30 weeks but significantly higher hemoglobin, red cell count and hematocrit and lower white cell count at 36-38 weeks as compared with the controls. Except for the lower platelet count, these differences appeared to represent an accentuation of the gestation-related changes that were found in the controls. CONCLUSION: The development of GDM in the third trimester is associated with significant changes in blood counts beyond the effect of advancing gestation alone, probably related to the pathologic effect of diabetes.     

Effects of maternal hyperglycemia on fetal growing mechanism

The aim of this study was to clarify the effects of maternal hyperglycemia on fetal growth in rats. In streptozotocin (STZ)-induced diabetic rats, maternal serum glucose levels during pregnancy were controlled by daily injection of NPH insulin or saline from day 3 to 21 of pregnancy. The body weight, hepatic glycogen content and serum concentrations of insulin and Insulin-like Growth Factor-I (IGF-I) in fetuses from these rats were measured on Day 21 of pregnancy. Fetal body weight positively correlated with maternal mean blood glucose (MBG) during pregnancy in the groups of diabetic mothers whose MBG was less than 220 mg/dl, whereas a negative correlation was observed in the groups whose MBG was more than 220 mg/dl. In addition, a similar correlation between hepatic glycogen content, serum concentrations of insulin or IGF-I and maternal MBG was observed. On the other hand, in the culture of fetal rat hepatocytes, glycogen content indicated a dose-related increase according to the increase in glucose concentration in the medium. These results suggest that the growth retardation observed in rats whose maternal mean glucose level is higher than 220 mg/dl is not caused by abnormalities in the metabolic function of the fetal metabolic organ (liver), but it is caused by a decrease in the production and/or secretion of growth-promoting factors (for example insulin and IGF-I) in the fetuses.     

Frequency of diabetes mellitus in mothers of probands with gestational diabetes: possible maternal influence on the predisposition to gestational diabetes

Interviews for genetic histories were conducted prior to delivery in 166 pregnant diabetic probands and 83 control gravidas with normal carbohydrate metabolism throughout gestation. A significant association was observed between parental diabetic phenotypes and type of diabetes in the probands (chi 2(12)) = 32.413; p less than 0.001). In particular a higher than expected number of mothers with diabetes was encountered in 91 probands with gestational diabetes mellitus. The findings are examined in relationship to the hypothesis that vulnerability to gestational diabetes may be increased by exposure to an abnormal environment during intrauterine development.     

The influence of maternal insulin-dependent diabetes on fetal nuchal translucency thickness and first-trimester maternal serum biochemical markers of aneuploidy

OBJECTIVE: To evaluate the influence of maternal insulin dependent diabetes mellitus (IDDM) on maternal serum free beta-hCG, PAPP-A and fetal nuchal translucency (NT), thickness at 11 to 13(+6) weeks of gestation in a large cohort of women screened prospectively for chromosomal anomalies. METHODS: Information on maternal IDDM status, maternal serum biochemical marker levels and fetal NT were collected from the prenatal screening computer records in two first-trimester screening centres. In total the control group included 33 301 pregnancies of which 16 366 had NT and maternal serum biochemistry results and 16 305 with NT only. The IDDM group included 195 pregnancies of which 79 had NT and maternal serum biochemistry results and 127 with NT only. The median maternal weight corrected free beta-hCG and PAPP-A, expressed as multiple of the median (MoM), and fetal NT, expressed as delta values, in the IDDM and non-IDDM groups were compared. RESULTS: There were no significant differences between the IDDM and non-IDDM groups in median maternal weight corrected free beta-hCG (IDDM 0.87 MoM, 95% Confidence Interval 0.75 to 1.16 MoM, non-IDDM 1.00 MoM), median maternal weight corrected PAPP-A (IDDM 1.02 MoM, 95% Confidence Interval 0.83 to 1.05 MoM, non-IDDM 1.01 MoM), or mean delta NT (IDDM 0.0358 mm, non-IDDM 0.0002 mm). CONCLUSIONS: In pregnancies with maternal IDDM, first-trimester screening for chromosomal defects does not require adjustments for the measured fetal NT. However, more data are required before the possible reduction in maternal serum free beta-hCG and the reduction of PAPP-A suggested by the published world series can be considered sufficiently important to take into account in the calculation of risks for chromosomal defects.