Insulin-dependent Diabetic Pregnancies Research Articles

262: Relationship between increased fetal anabolism and thymic size: a study in insulin dependent diabetic pregnancies

Thymic involution can result from transitory activations of the fetal H-P-Axis by O2- stress during episodes of increased anabolism. We aimed at measuring the fetal thymus in Insulin Dependent Diabetes (ID) and control (C).

Diabetic Nephropathy and Pregnancy

Diabetic nephropathy, the most common etiology for end-stage renal disease, complicates approximately 5% of insulin-dependent diabetic pregnancies. Assessment for vasculopathy is important before pregnancy because nephropathy can increase perinatal risks including potential for preeclampsia and preterm birth. Counseling women receiving renoprotective medications including angiotensin converting enzyme inhibitors has recently become complicated in light of new information suggesting a teratogenic risk for these agents. Most reproductive age women with overt diabetic nephropathy have preserved renal function and do not seem to have the progression of their disease affected by pregnancy. Perinatal outcomes are excellent for these women who have received care in tertiary institutions. However, there are relatively few women with significant renal impairment included in case series of pregnancies complicated by diabetic nephropathy. For these women, adverse perinatal outcomes are more common, and the effect of pregnancy on the course of their disease is less certain.

The influence of tobacco smoking on humoral immune response in insulin dependent diabetic pregnancy

Tobacco smoking products have a heavy impact on the public health of developed as well as non-developed countries by being a main etiologic factor for the induction of cardiovascular diseases and tobacco-related cancer. The purpose of this study was to determine the influence of tobacco smoking on the measurement of the humoral immune response in Egyptian pregnant women with type 1 diabetes. Concentrations of serum immunoglobulin A, G and M in 35 smoking, 35 non-smoking pregnant women with type 1 diabetes and 35 matched normal women were measured by ELISA. Women were matched by age and working life with controls. Measurements suggested that diabetic smokers had decreased levels of IgG and IgM in their sera. It was found that normal individuals had mean IgA, IgG and IgM levels of 2.80 mg/ml, 9.33 mg/ml and 1.66 mg/ml, respectively while non-smoker women suffering from type 1 diabetes had mean levels of 3.47 mg/ml, 10.97 mg/ml and 2.05 mg/ml (p<0.0004,p<0.0001 andp<0.0002). However, the mean level of IgA, IgG and IgM in diabetic smoker sera was determined to be 3.33 mg/ml, 8.07 mg/ml and 1.31 mg/ml, respectively (p<0.003,p<0.0001 andp<0.0001). The obtained results suggest that toxic smoke components were immuno-suppressant and may well play a part in the complex immuno-pathogenesis interaction. The increased risk of smoking in insulin dependent diabetic pregnant women during pregnancy is a further reason to encourage pregnant women to quit tobacco smoking.

Villous Histomorphometry and Placental Bed Biopsy Investigation in Type I Diabetic Pregnancies

Insulin-dependent diabetes mellitus (Type I) is associated with disregulation of the glucose and oxygen metabolic pathways during pregnancy, both of which affect placental villous development. Term complete placentas and placental bed biopsies, between 37 and 40 weeks, from 12 singleton pregnancies complicated by Type I diabetes were collected following delivery by elective Caesarean section. The controls consisted of 10 term placentas from uncomplicated pregnancies delivered by elective Caesarean section. Villous morphology was investigated using unbiased histomorphometric techniques, in relation to the degree of transformation of the spiral arteries and the presence of fetal macrosomia. A significant increase in fetal and placental weights, placental volume, volumes of the intervillous space and the trophoblast was found in the diabetic group compared to the controls. A significant reduction in the villous membrane specific diffusing capacity was observed between the diabetic and control groups (1.32 vs 1.72 cm3 min(-1)mmHg(-1)kg(-1), P=0.032). A significant increase in the volume of the intermediate and terminal villi, the surface area of the villi and of the fetal capillaries, and the harmonic thickness of the villous membrane was found in the macrosomic subgroup compared to the controls. There were no differences between the hypertensive subgroup with histological evidence of partial transformation of the spiral arteries and the controls. These data indicate that placental development in insulin-dependent diabetic pregnancies is affected differentially when pregnancies complicated by fetal macrosomia are separated from those complicated by maternal hypertensive disorders with partial transformation of the spiral arteries. The reduction in the specific diffusing capacity of the villous membrane may contribute to the fetal hypoxia and increased fetal and neonatal morbidity associated with diabetes.

Maternal-fetal status of copper, iron, molybdenum, selenium and zinc in insulin-dependent diabetic pregnancies.

The objective was to assess the status of essential trace elements such as copper, iron, molybdenum, selenium and zinc in insulin-dependent diabetic pregnancies at term and to compare the data with a control group. Fetal-maternal ratios of the elements and copper:zinc ratio were also computed in the control and study populations. Samples from maternal vein, umbilical artery and umbilical vein of diabetic and control women were collected at the time of spontaneous delivery or cesarean section and activities of trace elements evaluated by atomic absorption spectrophotometry. Cu, Fe, Mo, Se and Zn concentrations in maternal venous blood averaged 2,156, 2,020, 13, 102 and 656 microg/l in control women (n=17) while in the diabetic group (n=14), the corresponding values for the trace elements averaged 3,135, 3,675, 15, 85 and 628 microg/l respectively. Values for copper and molybdenum were significantly higher (p<0.05) in the study group compared to control while those of zinc, iron and selenium were not significantly different (p>0.05). Iron and molybdenum values were significantly higher (p<0.05) and that of zinc significantly lower (p<0.05) in umbilical arterial samples of diabetic group compared to controls. In the case of molybdenum, copper the values were significantly higher (p<0.05) in umbilical venous samples of diabetic group compared to that of control. Significant differences in Cu:Zn ratio of maternal venous and umbilical samples and fetal-maternal ratios of some elements were noted between control and study group as well. We speculate that altered status of some essential trace elements and altered antioxidant mineral ratio observed in insulin dependent diabetic patients could have deleterious influences on the health of the mother as well as the fetus and newborn.

Circulating biomarkers of oxidative stress in complicated pregnancies.

Increased lipid peroxidation (LPO) and reduced antioxidant activity may contribute to the development of complications in pregnancy. The present study discusses the possibility of LPO and antioxidant activity in both maternal and umbilical cord blood as an indicator of oxygen radical activity. For this aim, pregnancies with hypertension and pre-eclampsia, diabetes mellitus (insulin dependent diabetes mellitus and gestational diabetes mellitus), oligohydramnios and abruptio placentae, as well as a healthy control group, were subjected in the present study. Simultaneous determination of glutathione S-transferase (GST), selenium dependent glutathione peroxidase (Se-GPx), catalase (CAT) activities and thiobarbituric acid reactive-substances (TBARs) levels were carried out in maternal erythrocyte and plasma in the antenatal period (in the third trimester) and immediately after the delivery. The same oxidative stress-related parameters were determined in umbilical cord blood as well. Erythrocyte GST activity was significantly increased in insulin-dependent diabetic pregnancy (IDDP) when compared to the control (P<0.05). Erythrocyte Se-GPx activity was found to be significantly increased in hypertensive preeclamptic pregnancy (HPP) (P<0.05) and in IDDP (P<0.05). Alterations in enzyme activities were accompanied by a simultaneous significant increase in the levels of TBARs in plasma samples of HPP (P<0.05), and IDDP (P<0.05). Enzyme activities were found to be significantly lower in cord blood samples than the maternal values, except GST. This enzyme represents about two- to threefold higher activity than those of the maternal activity in uncomplicated and complicated groups. Cord blood erythrocyte and plasma Se-GPx and CAT activities were decreased significantly in the HPP group when compared to the maternal value (P<0.05). Cord blood erythrocyte CAT activity was significantly decreased in the HPP group compared to the control (P<0.05). Cord blood TBARs levels were significantly lower than the before deliveries maternal value in the HPP group (P<0.05). No difference was detected between umbilical cord blood and maternal blood TBARs levels after delivery. The results of the present study suggest that oxidative stress and subsequent lipid peroxidation accompany the complications of hypertension, preeclampsia and diabetes mellitus in pregnancy. Maternal erythrocyte GST activity seems to be a sensitive indicator of oxidative stress in IDDP before delivery. The same enzyme can be used in cord blood as a biomarker of oxidative stress upon a sudden increase in oxygenation during delivery. These multiparameter biomarkers can also be used in monitoring the efficiency of antioxidant supplementation in complicated pregnant women, as has recently been suggested for diabetic and preeclamptic pregnancies.

Kinetics of palmitic acid transport in insulin-dependent diabetic pregnancies: In vitro study

The paucity of data relating to transport kinetics of free fatty acids (FFA) in pregnant diabetic women prompted the undertaking of the present study. Transport kinetics of a model FFA, palmitic acid, have been investigated in Type I diabetic pregnancies, using in vitro perfusion of isolated placental lobules. National Cancer Tissue Culture medium diluted with Earle's buffered salt solution was used as the perfusate and control placental lobules were perfused for comparison. In five Type I diabetic women, the palmitic acid transport fraction (TF) averaged 5.6 +/- 0.42% of injected maternal bolus dose, representing 11.8 +/- 2.1% that of tritiated water used as reference. In control perfusions (n = 5), the palmitic acid TF represented 10.2 +/- 1.3% of tritiated water TF. Differential transport rates of palmitic acid for 10, 25, 50, 75 and 90% of efflux in fetal veins differed significantly from the corresponding values for tritiated water in both study and control series. However, palmitic acid transport rates for the various efflux fractions in the two series were not significantly different. For kinetic parameters, such as area under the curve, clearance, elimination constant, time for maximum response, absorption rate and elimination rate, the values for palmitic acid in the diabetic and control series also did not differ significantly. Transport kinetics of palmitic acid in Type I human diabetic pregnancies in in vitro conditions do not differ significantly from those observed in normal pregnancies.

Glycemic Control Throughout Pregnancy and Fetal Growth in Insulin-Dependent Diabetes

In Brief Objective To determine the time of growth acceleration in fetuses of insulin-dependent diabetic women who are large for gestational age (LGA) at birth and the relationship between growth acceleration and diabetic control throughout pregnancy. Methods We studied a consecutive sample of 76 women with insulin-dependent diabetes divided by those who delivered LGA or normally grown infants. Fetal abdominal circumference (AC) was measured ultrasonically at regular intervals between 20 and 34 weeks' gestation. Diabetic control was assessed by regular measurement of glycosylated hemoglobin and capillary blood glucose levels. Results A significant difference in fetal AC between groups developed between 20 and 24 weeks' gestation, and the LGA group continued to have accelerated fetal growth. Between 18 and 24 weeks glycosylated hemoglobin and capillary blood glucose concentrations were significantly higher in women who delivered LGA infants. After 28 weeks, blood glucose concentrations and glycosylated hemoglobin did not differ significantly between groups. There was a nonsignificant trend toward more vaginal deliveries in the normal group (45% versus 32%). Conclusion In insulin-dependent diabetic pregnancy, although actual growth acceleration occurred from about 20 weeks' gestation, growth potential of fetuses appeared to be determined by prevailing maternal glucose concentrations before then. Excessive growth continued despite subsequent satisfactory glucose control. If strict blood glucose control is maintained during first and second trimesters, it might reduce the incidence of LGA infants. Poor glycemic control during the second trimester in women with insulin-dependent diabetes was associated with subsequent fetal growth acceleration.

Glycemic control throughout pregnancy and fetal growth in insulin-dependent diabetes

Objective: To determine the time of growth acceleration in fetuses of insulin-dependent diabetic women who are large for gestational age (LGA) at birth and the relationship between growth acceleration and diabetic control throughout pregnancy. Methods: We studied a consecutive sample of 76 women with insulin-dependent diabetes divided by those who delivered LGA or normally grown infants. Fetal abdominal circumference (AC) was measured ultrasonically at regular intervals between 20 and 34 weeks’ gestation. Diabetic control was assessed by regular measurement of glycosylated hemoglobin and capillary blood glucose levels. Results: A significant difference in fetal AC between groups developed between 20 and 24 weeks’ gestation, and the LGA group continued to have accelerated fetal growth. Between 18 and 24 weeks glycosylated hemoglobin and capillary blood glucose concentrations were significantly higher in women who delivered LGA infants. After 28 weeks, blood glucose concentrations and glycosylated hemoglobin did not differ significantly between groups. There was a nonsignificant trend toward more vaginal deliveries in the normal group (45% versus 32%). Conclusion: In insulin-dependent diabetic pregnancy, although actual growth acceleration occurred from about 20 weeks’ gestation, growth potential of fetuses appeared to be determined by prevailing maternal glucose concentrations before then. Excessive growth continued despite subsequent satisfactory glucose control. If strict blood glucose control is maintained during first and second trimesters, it might reduce the incidence of LGA infants.

Oral Calcium Loading in Normal and Insulin Dependent Diabetic (IDD) Pregnancy

Oral Calcium Loading in Normal and Insulin Dependent Diabetic (IDD) Pregnancy

Normalization of Blood Glucose in Insulin-Dependent Diabetic Pregnancies and the Risks of Hypoglycemia

Intensive insulin therapy delays the onset and progression of microvascular complications in insulin-dependent diabetes mellitus (IDDM). Such therapy, however, is associated with an increased risk of potentially life-threatening hypoglycemia due to the loss of normal counterregulatory hormonal responses to hypoglycemia and to the syndrome of hypoglycemia unawareness. Current standards for glycemic control during pregnancy in IDDM women require intensive insulin therapy to optimize pregnancy outcome. Therefore, obstetricians and gynecologists providing prenatal care for women with IDDM should be aware that intensive insulin therapy predisposes these patients to the significant risks of severe hypoglycemia. It often becomes necessary to individualize the optimal balance between glycemic control during pregnancy and the risks of hypoglycemia.

Deformations in infants of diabetic and control pregnancies.

Severe and mild deformations in newborn infants of insulin dependent diabetic mothers (IDDMs) and control mothers were evaluated with respect to the types of anomalies and previously hypothesized constraint factors. Factors evaluated were gestational length, birth weight, corrected birth weight for gestation (weight ratio), maternal height and parity, and severe deformations. Newborn infants from 81 control and 133 insulin dependent diabetic pregnancies were recruited periconceptually as part of a larger study of diabetes in early pregnancy. Examinations were done at 48 to 72 hours of life by one examiner blinded to maternal status using a checklist of major and minor deformations and malformations. Mild deformations were found to be common and were present in 84% of newborn infants. Severe deformations occurred in three (1.4%) IDMs, with two of three newborn infants having major malformations involving the CNS and/or musculoskeletal system which affected fetal movement. There was no significant difference between IDMs and control newborn infants with respect to the number with deformations; however, fetal macrosomia was not present in study participants. Using the entire cohort, a significantly greater number of deformations were present in newborn infants with a gestation > 36 weeks (P < 0.001), birth weight > 3,000 g (P < 0.001), and weight ratio > or = 1.2 (P = 0.05). There was no significant association with primiparous mothers or women with a height < 165 cm and the presence of deformations. For gestational age and birth weight, mild deformations were apparent only after 33 weeks gestation (P << 0.001) and/or birth weights of 2.0 kg or more (P << 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Fetal biophysical activities in third-trimester pregnancies complicated by diabetes mellitus

Our purpose was to compare third-trimester fetal biophysical activities in normal and well-controlled insulin-dependent diabetic pregnancies. We performed serial bimonthly fetal biophysical studies from 30 to 38 weeks in 18 normal and 18 well-controlled insulin-dependent diabetic pregnancies (White classes B through D). Each study contained 60 minutes of simultaneous ultrasonographic recordings of fetal breathing movements and rates, baseline heart rate, and body movements. Mean daily blood glucose levels of diabetic patients were determined from home monitors; HbA1c was determined every 6 weeks and ultrasonographic fetal growth rates every 3 weeks. Data were compared with t tests, analysis of variance with repeated measures, and chi 2 tests. Women in the diabetic group maintained good glycemic control and were delivered of normal infants of weights similar to those of nondiabetic gravidas. Their fetuses had higher mean incidences of fetal breathing movement, fetal heart rates, and fetal breathing rates but lower fetal movements and fetal heart rate acceleration counts than did controls throughout the study. Neither short- nor long-term maternal glycemic levels correlated well with fetal biophysical performance. In spite of good maternal glycemic control fetuses of diabetic women behaved differently from those of nondiabetic women. Modulation of their biophysical activities may be affected by maternal glycemic status before the last trimester. Different standards might need to be applied to interpret their tests.

Outcome of Pregnancies Complicated by Type 1 Insulin-Dependent Diabetes in Sweden: Acute Pregnancy Complications, Neonatal Mortality and Morbidity

This prospective nationwide study conducted during 1982-1985 examined the rates of hypertensive disorders, perinatal mortality and morbidity in 491 insulin-dependent diabetic pregnancies (White's classes: B, 164; C, 129; D, 172; F, 26) and in the total population of 279,000. The rates of pregnancy-induced hypertension (PIH) or pre-eclampsia (20.6%), premature delivery (24.6%), and cesarean section (45.2%) in the diabetic group were more than four times higher than normal. PIH or preeclampsia occurred significantly (p < 0.01) more frequently in patients with diabetic microangiopathy. Mean birthweight was similar in the two populations but gestational age was significantly (p < 0.001) shorter (38 weeks) in the diabetic group. The rate of large for gestational age infants (20%) in the diabetic group was considerably above normal (3.5%). Although perinatal mortality rate in the diabetic group was only 3.1%, it was 4.4 times higher than normal; five of ten fetal deaths were associated with poor glycemic control and thus may not really be unexplained. Neonatal morbidity was significantly more frequent in the diabetic group; still, the incidence of idiopathic respiratory distress syndrome was only 1.6% compared with 0.6% in the general population. Discriminant analysis revealed that gestational age at birth and elevated maternal HbA1c values in early pregnancy independently of each other had a significant impact on the occurrence of neonatal morbidity.

LONGITUDINAL EVALUATION OF FETAL CARDIAC GROWTH AND VENTRICULAR COMPLIANCE IN WELL CONTROLLED DIABETIC MOTHERS

Hypertrophic cardiomyopathy & abnormal ventricular compliance (VC) in the infant of the diabetic mother is related to poor maternal glycemic control. We prospectively evaluated cardiac growth, VC, & somatic growth in 11 normal (N) & 8 nongestational insulin dependent diabetic (D) pregnancies using tetal echo from mid gestation to term. Studies were performed at gestational age (GA) P1) 20-26 wks; P2) 27-33 wks; P3) 34-40 wks & P4) 48-72 hrs postnatally. Septal (S) wall thickness (mm) in diastole was obtained using M-mode echo (4 chamber view). Indices of right & left VC were obtained from diastolic tricuspid & mitral E & A wave time velocity integral ratios (TViE/A, MViE/A). Weight (W) in grams was estimated from biparietal diameter & abdominal circumference. Glycemic control was measured from % glycosylated hemoglobin (A1C). Placental resistance was evaluated by the Pulsatility Index (PI) from umbilical artery flow. Values are expressed as the mean ± 1 SD.

Glucose, insulin, HGH and IGF-I levels in maternal serum, amniotic fluid and umbilical venous serum: a comparison between late normal pregnancy and pregnancies complicated with diabetes and fetal growth retardation.

Fetal growth and development is dependent upon various growth factors such as glucose, insulin, HGH and IGF-I. These growth factors were measured in maternal serum (MS), amniotic fluid (AF) and umbilical venous serum (UV) in late gestation in normal, insulin dependent diabetic pregnancies (IDDM) and in pregnancies complicated with intrauterine growth retardation (IUGR). The UV glucose values of 1.9 +/- 0.9 mmol/L and UV insulin values of 8.0 +/- 1.8 mU/L were the lowest in IUGR pregnancies, and the highest were in UV serum from IDDM pregnancies, and the difference was statistically significant for this two groups. IGF-I values in UV indicated that there was significant difference in IGF-I concentrations when both, IUGR and IDDM groups were compared to the controls. There was a parallel shift in AF and MS glucose and insulin concentration as birthweight increased. The highest IGF-I values of 7.2 +/- 9.6 mumol/L in AF and MS were found in pregnancies with infants whose birthweight was 3500 grams and greater. Infants from pregnancies complicated with IUGR and IGF-I low values of 0.6 +/- 1.2 mumol/L in AF. HGH concentrations of 15.6 +/- 9.4 micrograms/L in UV were observed in IDDM pregnancies and significantly lower than the values in IUGR and normal pregnancies. HGH umbilical venous values decreased with duration of pregnancy and with increase in fetal size. The high HGH concentrations in the fetus and its dramatic fall after parturition, and the obtained negative correlation between HGH and IGF-I in umbilical vein may exhibit the maturation of the hypothalamic-growth hormone-IGF-I axis. It seems likely that changes in maternal serum, umbilical venous and amniotic fluid insulin-like growth factor I influence birthweight in normal and IUGR infants and in those of diabetic mothers.

Maternal serum unconjugated oestriol and human chorionic gonadotrophin levels in pregnancies with insulin-dependent diabetes: implications for screening for Down's syndrome.

To investigate maternal serum unconjugated oestriol (uE3) and human chorionic gonadotrophin (hCG) levels in pregnant women with insulin-dependent diabetes mellitus and to consider the implications of the results for antenatal screening for Down's syndrome. Descriptive study using stored antenatal serum samples. Stored serum samples collected from women receiving routine antenatal care in Oxford. 126 singleton pregnancies in 92 women with insulin-dependent diabetes mellitus and for each pregnancy, two pregnancies without diabetes matched for gestational age and duration of storage of the serum sample. None of the pregnancies was associated with fetal neural tube defect or Down's syndrome. Maternal serum uE3 and hCG levels at 15-22 weeks gestation. Alpha-fetoprotein (AFP) levels were also measured for comparison. The median uE3 level in the diabetic pregnancies was 0.92 multiples of the median (MoM) for pregnancies without diabetes at the same gestational age (P less than 0.05); and the hCG level was 0.95 MoM (P = 0.48). The median AFP level was also reduced to 0.77 MoM (P less than 0.001). The reduction in uE3 and AFP levels in insulin-dependent diabetic pregnancies is sufficiently great to be taken into account in maternal serum screening programmes for Down's syndrome. Dividing the uE3 and AFP levels in such pregnancies by the corresponding median for insulin-dependent diabetic pregnancies will yield a similar false-positive rate in pregnancies with and without insulin-dependent diabetes mellitus.

127 Prenatal Complications in Insulin-Dependent Diabetic Pregnancies

127 Prenatal Complications in Insulin-Dependent Diabetic Pregnancies

96 Accelerated Fetal Growth Following Early Growth Delay in Insulin-Dependent Diabetic Pregnancies

96 Accelerated Fetal Growth Following Early Growth Delay in Insulin-Dependent Diabetic Pregnancies

141 Risk profile for spontaneous abortion in insulin-dependent diabetic pregnancies

141 Risk profile for spontaneous abortion in insulin-dependent diabetic pregnancies