Cord insulin and C-peptide--distribution in an unselected population.

OBJECTIVE: To assess the distribution of cord blood insulin in an unselected population, and examine its relation to birthweight centiles. SETTING: District General Hospital in Nottinghamshire. SUBJECTS: 209 unselected singleton births. MEAN OUTCOME MEASURE: Cord blood insulin; cord blood C-peptide; birthweight centiles. RESULTS: Hyperinsulinaemic babies (greater than 97th centile for cord insulin) were found at all birthweight centiles. 15% of high birthweight babies were hyperinsulinaemic. For low birthweight babies, the distribution of cord insulin/C-peptide was skewed indicating a high number of low values. Hypoinsulinaemic babies were present up to the 50th centile for birthweight. CONCLUSIONS: Abnormalities of fetal insulinisation may be found in babies of all birthweights.     

Cord blood insulin level in relation to metabolic control of maternal diabetes, duration of pregnancy and neonatal birth weight

The aim of the study was to examine whether an association between cord blood insulin level (Ic) and maternal glycemic control, duration of pregnancy as well as neonatal birthweight exists. The study was performed in diabetic group consisted of 149 diabetic mothers (91 with GDM and 58 with IDDM) and 149 their babies as well as in the control group consisted of 100 healthy mothers and 100 their babies. Maternal glycemic control was indirectly assessment by using HbA1c and fructosamine levels estimated on the day of delivery. That was found a significant positive correlation between Ic and maternal HbA1c and fructosamine levels as well as between Ic and neonatal birthweight in the diabetic group. That was also found the significant negative correlation between Ic and duration of pregnancy in the diabetic group. We conclude that fetal hyperinsulinemia is a result of poor glycemic control during the last weeks of diabetic pregnancy. Furthermore the significant association exists between cord blood hyperinsulinemia and preterm delivery as well as higher birthweight of newborns born to diabetic mothers.     

GDM孕中、晚期及子代胰岛素抵抗与正常妊娠的对照研究

目的探讨妊娠期糖尿病(GMD)与正常妊娠孕中、晚期及子代胰岛素抵抗、胰岛β细胞功能及胎儿脐血流的差异。方法选择上海交通大学医学院附属国际和平妇幼保健院产检、分娩的70例GDM产妇及其子代为GDM组,同期产检、分娩的70例健康母子配对样本为对照组。两组孕妇孕24~28周OGTT筛查时行胰岛素释放试验、孕33~34周、孕37~38周检测空腹血糖、胰岛素及C肽;比较两组稳态模型评估的胰岛素抵抗指数(HOMA-IR);B超测定孕晚期胎儿脐血流;分娩时检测脐血血糖、胰岛素及C肽值并获取胎儿出生体重、胎龄等资料;比较两组母子配对样本间各项指标的差异。结果 GDM组OGTT时胰岛素峰值较对照组延迟1h;GDM组孕33~34周母血空腹胰岛素、C肽高于对照组,差异有统计学意义(P<0.05);孕37~38周母血空腹胰岛素、C肽虽仍高于对照组,但差异无统计学意义(P>0.05);GDM组孕中、晚期HOMA-IR高于对照组,差异有统计学意义(P<0.05);GDM组新生儿脐血胰岛素、C肽高于对照组,差异有统计学意义(P<0.05);两组间孕晚期胎儿脐动脉S/D值、搏动指数(PI)、阻力指数(RI)比较差异无统计学意义(P>0.05)。结论 GDM患者孕中、晚期胰岛素抵抗较正常孕妇增加,并出现胰岛β细胞功能下降,其胎儿在宫内已发生糖代谢异常,但脐血流未受到显著影响。     

Leptin concentrations in maternal serum and cord blood in diabetic and nondiabetic pregnancy

OBJECTIVE: The purpose of this study was to examine the relationships between maternal and cord leptin concentrations, maternal and neonatal outcomes, and measures of glycemic control in diabetic and nondiabetic pregnancy. STUDY DESIGN: This was a prospective study of 60 type 1 diabetic and 50 nondiabetic pregnancies in a university teaching hospital. Serum leptin and hemoglobin A(1c) were measured serially throughout pregnancy; leptin, insulin, insulin-like growth factor-1, and C-peptide in venous cord blood were measured at delivery. Leptin was measured with the use of enzyme-linked immunosorbent assay. Data were analyzed with specific computer software. RESULTS: Maternal leptin levels correlated with cord leptin levels in the nondiabetic group only. Cord leptin levels correlated with cord C-peptide, cord insulin-like growth factor-1, birth weight, birth weight corrected for gestational age, and neonatal anthropometry in both groups and with hemoglobin A(1c) in the diabetic group only. Cord leptin levels increased significantly with increasing birth weight corrected for gestational age but remained significantly higher at all birth weights in the diabetic group. CONCLUSION: There are strong associations between cord leptin levels and other measures of fetal growth in both groups and with glycemic control in the diabetic group.     

Relationship of maternal glycosylated hemoglobin and fetal beta-cell activity with birth weight

A population of 40 mother-newborn pairs with a wide range of birth weight has been studied. Seventeen of the mothers were diabetic, while the other 23 were normal pregnant women. The chronic blood glucose levels were assessed in the mothers through the percentage of glycosylated hemoglobin (HbA1) at delivery. The functional activity of the pancreatic beta-cells in the newborns was estimated through the concentration of insulin and C-peptide in the cord blood. Maternal HbA1 was not quantitatively related to the birth weight ratio. In contrast, both insulin and C-peptide correlated significantly with it. Is is concluded that in populations with a good metabolic control, blood glucose levels, as measured by HbA1, are not the major determinant of fetal growth.     

Amniotic fluid C-peptide and cortisol in normal and diabetic pregnancies and pregnancies accompanied by fetal growth retardation

The interrelationship between amniotic fluid (AF) concentration and content (AF X conc) of C-peptide and cortisol was studied in four groups of women comprising 10 gestational and 16 type-I diabetics, 11 women with intrauterine growth retarded fetuses (IUGR), and 17 healthy control women. Mean AF volume was significantly greater (P less than 0.05) in the type-I diabetic group than in the control group. Both concentration and content of AF C-peptide was significantly higher in the type-I diabetic group than in the control group (P less than 0.05 and P less than 0.01, respectively). The corresponding values were significantly lower in mothers with IUGR fetuses compared to controls (P less than 0.05). AF cortisol content was significantly higher (P less than 0.05) in the gestational diabetic group compared to the control group; there were no other significant differences between the groups regarding the cortisol concentration or content. Both cortisol and C-peptide contents were significantly interrelated in both control women (r = 0.68, P less than 0.01) and women with gestational (r = 0.68, P less than 0.05) and type-I diabetes (r = 0.63, P less than 0.01). The C-peptide/cortisol ratio was lowest in the IUGR group and highest in the type-I diabetic group. The same ratio was intermediate and almost equal in the control and gestational diabetic group. Both C-peptide and cortisol concentrations were unrelated to AF volume as well as infant birthweight. C-peptide content was significantly correlated to birthweight percentile in type-I diabetic women (r = 0.61, P less than 0.05). No such correlation was found in the three other groups.     

A study of fetal macrosomia

We describe the maternal characteristics in pregnancy with fetal macrosomia, fetal and maternal complications related to macrosomia, and the risk of impaired glucose tolerance. The study is based on a comparison of maternal and neonatal data in 956 cases of fetal macrosomia (birthweight > or =4000 g) in non-diabetic pregnancy with data in a control group of 6407 mothers with non-macrosomic infants (birthweight 3000-3999 g). The main factors investigated were maternal age, weight, parity, gestosis rate, maternal and fetal birth injuries, maternal oral glucose tolerance test results and umbilical blood insulin levels. Macrosomic infants occurred in 9.1% of all deliveries. Mothers delivering macrosomic infants were significantly older, of higher parity and of greater weight than mothers of the control group. Fetal macrosomia was associated with a higher frequency of gestosis, operative deliveries, birth injuries and postpartum haemorrhages. 26.2% of the mothers had abnormal of oGTT results. The macrosomic infants were more often male and had a significantly higher risk of shoulder dystocia and birth injuries. No essential differences could be observed in the Apgar-scores and umbilical artery pH values. 34% of macrosomic infants had higher insulin levels in umbilical blood.     

Antenatal biochemical screening to predict low birthweight infants

Summary. Urine and plasma oestriol, plasma progesterone, human placental lactogen, α-glycoprotein and serum cystyl aminopeptidase were measured at intervals during 608 pregnancies. The predictive accuracy of low values for identification of pregnancies with low birthweight outcomes was assessed for each test at various gestations. Data were analysed to obtain 10th–90th centile values for each test from 28 weeks to delivery.
Groups with values under different centile levels were compared: those under the lower centiles had higher proportions but smaller absolute numbers of low birthweight infants than those under higher centiles. No test was superior to the others at all centiles and gestations. Biochemical screening of pregnant populations to identify high-risk groups for intensive fetal monitoring has limited potential. If screening is used, the definition of high-risk groups is best achieved by practical rather than statistical criteria. If monitoring facilities are available and well accepted by patients then higher centile'cut-offs'to define fetal risk may be used than when they are not. Combining any pair of tests with values below the 10th centile did not reduce false positive and negative predictions any more than could be achieved by movement of centiles up or down for a single test.     

Antenatal biochemical screening to predict low birthweight infants

Urine and plasma oestriol, plasma progesterone, human placental lactogen, beta 1-glycoprotein and serum cystyl aminopeptidase were measured at intervals during 608 pregnancies. The predictive accuracy of low values for identification of pregnancies with low birthweight outcomes was assessed for each test at various gestations. Data were analysed to obtain 10th-90th centile values for each test from 28 weeks to delivery. Groups with values under different centile levels were compared: those under the lower centiles had higher proportions but smaller absolute numbers of low birthweight infants than those under higher centiles. No test was superior to the others at all centiles and gestations. Biochemical screening of pregnant populations to identify high-risk groups for intensive fetal monitoring has limited potential. If screening is used, the definition of high-risk groups is best achieved by practical rather than statistical criteria. If monitoring facilities are available and well accepted by patients then higher centile 'cut-offs' to define fetal risk may be used than when they are not. Combining any pair of tests with values below the 10th centile did not reduce false positive and negative predictions any more than could be achieved by movement of centiles up or down for a single test.     

妊娠肝内胆汁淤积症孕妇胎儿总胆酸水平对胎儿胰腺内分泌功能及胎儿生长发育的影响

目的 探讨妊娠肝内胆汁淤积症(ICP)孕妇的胎儿总胆酸水平与胎儿胰腺内分泌功能变化的关系及其对胎儿生长发育的影响.方法 选择2007年3月至2008年2月在中南大学湘雅二医院妇产科行剖宫产分娩的30例单胎ICP孕妇为ICP组,同期行剖宫产分娩的30例正常单胎孕妇为对照组.采用放射免疫法测定两组新生儿脐动脉血中胰岛素、胰高糖素水平;循环酶法测定总胆酸水平;氧化酶-过氧化物法测定血糖水平.并测量两组新生儿出生体重、身长,计算肥胖指数(PI).结果 (1)ICP组新生儿脐动脉血中胰岛素水平为(9.0±3.3)mU/L、胰岛素/胰高糖素比值为0.048±0.028,分别低于对照组的(10.1±3.7)mU/L及0.050±0.020,差异有统计学意义(P<0.05);ICP组新生儿脐动脉血中总胆酸水平为(10.3±3.8)μmol/L、胰高糖素水平为(235±57)ns/L,分别高于对照组的(4.1±1.3)μmol/L及(205±34)ng/L,差异有统计学意义(P<0.05);ICP组新生儿脐动脉血中血糖水平为(3.4±1.1)mmol/L,对照组为(3.6±1.2)mmol/L,两组比较,差异无统计学意义(P>0.05).(2)ICP组新生儿出生体重及身长分别为(3163±478)g及(46.5±2.3)cm,对照组分别为(3498±393)g及(49.3±1.9)cm,两组分别比较,差异均有统计学意义(P<0.01);ICP组新生儿PI(3.13±0.23)明显高于对照组(2.92±0.29),差异有统计学意义(P<0.01).(3)ICP组新生儿总胆酸水平分别与胰岛素、胰高糖素水平及胰岛素/胰高糖素比值呈直线关系,且随着总胆酸水平的升高,胰岛素水平及胰岛素/胰高糖素比值均降低,胰高糖素水平升高(P<0.01);ICP组新生儿脐动脉血中胰岛素水平及胰岛素/胰高糖素比值分别与出生体重、身长呈正相关,与PI呈负相关(P均<0.01);而胰高糖素水平与出生体重、身长呈负相关,与PI呈正相关(P均<0.01).结论 ICP孕妇的胎儿存在胰岛素分泌不足,胰高糖素分泌增多,胰岛素/胰高糖素比值下降的情况,其变化与脐动脉血总胆酸水平密切相关;胎儿胰腺内分泌功能变化可能影响胎儿的生长发育.     

Endocrine pancreatic function in growth-retarded fetuses

Maternal-fetal glucose gradient and fetal plasma glucose, insulin, and glucagon were measured in 63 fetuses: 34 controls and 29 with growth retardation (nine with and 20 without end-diastolic frequencies in the umbilical artery). Maternal-fetal glucose gradient and fetal glucagon levels were higher in the growth-retarded group than in controls (P less than .001), whereas fetal insulin and glucose concentrations were lower (P less than .001). Although maternal-fetal glucose gradient, fetal glucose, and insulin concentrations were similar among the growth-retarded fetuses, fetuses without end-diastolic frequencies in the umbilical artery had higher fetal glucagon levels (P = .01) than those with end-diastolic frequencies. In growth-retarded fetuses, the increase in fetal glucagon might reflect a compensatory response to hypoglycemia and appears to be a better index of fetal compromise than is glucose or insulin.     

Smoking and low birth weight: absence of influence by carbon monoxide?

Fetal outcome in 77 uneventful pregnancies was examined and related to venous cord carboxyhaemoglobin (HbCO) levels. 30 women were smokers, 47 were non-smokers. Birth weight and birth weight centiles were found to be substantially reduced in children of mothers who smoked. HbCO levels were significantly elevated in venous cord blood of children of smokers compared with non-smokers. The role of fetal HbCO as a causal factor in reducing birth weight centiles of children of smoking mothers is discussed. It is concluded that carboxyhaemoglobin concentration in fetal venous cord blood did not account for fetal growth retardation in pregnant women who smoked.     

Umbilical cord androgens in infants of diabetic mothers

The aim was to measure umbilical cord testosterone and androstenedione and to explore possible relationships with fetal weight and insulin levels. Testosterone, androstenedione and insulin were measured at birth in venous umbilical blood in 12 infants of gestational diabetic mothers and in 12 control subjects. The mean concentrations of umbilical testosterone and androstenedione were not significantly different between the infants of the diabetic and control mothers. No significant correlation was found between maternal weight, fetal weight or insulin concentrations and androgen levels. Received: 15 October 1996 / Accepted: 31 October 1996     

Fetal beta cell function in diabetic pregnancy. Amniotic fluid concentrations of proinsulin, insulin, and C-peptide during the last trimester of pregnancy

Proinsulin, insulin C-peptide, insulin-binding antibody, and glucose concentrations were measured in amniotic fluid samples from 43 insulin-treated diabetic patients and 17 nondiabetic control patients between the thirty-six and thirty-ninth weeks of gestation. Insulin-binding antibodies in amniotic fluid were present in only three diabetic patients, although antibodies in maternal serum were found in 22 of the diabetic subjects. In the diabetic group, maternal serum insulin-binding antibodies were statistically unrelated to levels of C-peptide in amniotic fluid. The mean amniotic fluid concentrations of proinsulin (0.07 nmole/L), insulin (0.08 nmole/L), C-peptide (1.17 nmoles/L), and glucose (2.09 mmoles/L) were markedly elevated (p less than 0.001) in diabetic patients, as compared to nondiabetic control patients, thus suggesting exaggerated fetal beta cell function. C-peptide was correlated to both insulin (r = 0.69) and proinsulin (r = 0.35) in the diabetic group only. Infant birth weight and amniotic fluid C-peptide was significantly correlated in both the control group (r = 0.54) and the diabetic group (r = 0.38). Diabetic pregnancies associated with neonatal morbidity (n = 25) had significantly higher mean amniotic fluid concentrations of both insulin and C-peptide than did pregnancies without neonatal morbidity (n = 18). The amniotic fluid values of C-peptide and insulin in these latter two subgroups were overlapping and, therefore, could not serve to predict neonatal outcome in the individual case.     

Prediction of size of infants at birth by measurement of symphysis fundus height

Symphysis fundus heights (SF) were measured approximately 15 times during pregnancy in a consecutive series of 2941 women with regular menstrual cycles and known last menstrual period. A reference SF chart from 17 to 40 weeks of pregnancy was derived from measurements in 1350 of these women who were healthy, and heights and pre-pregnancy weights within the 10th and 90th centiles and were delivered vaginally of healthy infants with a birthweight/length ratio within +/- 2 SD. The reference chart was used to predict fetal growth deviations in the unselected series of pregnancies. The effectiveness of SF measures to detect fetuses with an infant birthweight/length ratio below -2 SD or a birthweight below the 10th centile was low; the sensitivity was only 16.7 and 26.6% and the predictive value of positive screening result was 1.8 and 18.0%, respectively. Corresponding values for fetuses with an infant birthweight/length ratio above + 2 SD or a birthweight above the 90th centile were 31.8 and 37.5% and 3.3 and 24.5%, respectively. Symphysis fundus (SF) measurement has thus been found to be of limited value as a screening method to detect abnormal size at birth.     

Determination of reference ranges and effect of maternal and fetal factors on insulin and C-peptide level in umbilical cord blood

OBJECTIVE: The risks of pregnancy caused by maternal diabetes are well known. Patients with unrecognized gestational diabetes mellitus (GDM) represent a special problem. The aim of our study was to find out, whether the determination of insulin and C-peptide in cord blood serum offers a valuable tool for retrospective analysis. MATERIAL AND METHODS: In 600 paired serum samples from maternal venous blood and neonatal cord blood insulin and C-peptide were determined radioimmunologically. A reference group consisting of 338 mothers and their newborns was established by exclusion of all patients with known pregnancy complications. RESULTS: Positive correlations could be identified between fetal insulin and fetal C-peptide, as well as correlations of these parameters with birth weight and body length, with maternal values of insulin, C-peptide, body-mass index, weight, and weight gain during pregnancy respectively. Increased levels of cord serum insulin were found in complicated pregnancies as well as in patients with previous pregnancy losses, preterm deliveries or stillbirths. CONCLUSIONS: Cord serum insulin and C-peptide were found to be useful parameters for immediate postnatal identification of impaired glucose tolerance during the course of pregnancy.     

Prediction of size of infants at birth by measurement of symphysis fundus height

Summary. Symphysis fundus heights (SF) were measured approximately 15 times during pregnancy in a consecutive series of 2941 women with regular menstrual cycles and known last menstrual period. A reference SF chart from 17 to 40 weeks of pregnancy was derived from measurements in 1350 of these women who were healthy, and heights and pre-pregnancy weights within the 10th and 90th centiles and were delivered vaginally of healthy infants with a birthweight/length ratio within ±2SD. The reference chart was used to predict fetal growth deviations in the unselected series of pregnancies. The effectiveness of SF measures to detect fetuses with an infant birthweight/length ratio below −2SD or a birthweight below the 10th centile was low; the sensitivity was only 16·7 and 26·6% and the predictive value of positive screening result was 1·8 and 18·0%, respectively. Corresponding values for fetuses with an infant birthweight/length ratio above +2 SD or a birthweight above the 90th centile were 31·8 and 37·5% and 3·3 and 24·5%, respectively. Symphysis fundus (SF) measurement has thus been found to be of limited value as a screening method to detect abnormal size at birth.     

Fetal alpha-melanocyte-stimulating hormone levels: no correlation with late fetal growth but increased with diabetes mellitus

The pars intermedia of the fetal pituitary produces alpha-melanocyte-stimulating hormone. Previous reports suggest that alpha-melanocyte-stimulating hormone may be a determinant of early fetal growth in animal models. Based on anencephalic fetuses, a similar role was suggested in humans. To examine its relationship to late human fetal growth, alpha-melanocyte-stimulating hormone levels were measured by radioimmunoassay in 185 umbilical cord blood samples from anatomically normal fetuses of 28 to 42 weeks' gestation. With use of stepwise multiple regression analysis, no significant relationship was demonstrated between alpha-melanocyte-stimulating hormone levels and fetal growth. However, significantly higher levels were found in infants of diabetic mothers (p less than 0.05) independent of birth weight, gestational age, or both. No significant relationship with other maternal factors related to fetal growth, labor, and delivery was demonstrated. We conclude that fetal plasma alpha-melanocyte-stimulating hormone levels do not correlate with late human fetal growth. It is speculated that increased alpha-melanocyte-stimulating hormone levels among infants of diabetic mothers might be related to altered neurological maturation.     

Studies on developmental changes in rat pancreatic endocrine system during perinatal period

During the perinatal development of rats, pancreatic endocrine cells (B, A and D cells) were quantitated morphometrically and plasma insulin, glucagon and somatostatin were measured. Moreover, intrauterine growth retardation (IUGR) rat fetuses were induced by uterine artery ligation and at the 21st day of gestation their volume density of pancreatic endocrine cells and plasma hormone levels were compared with that of normal fetuses. At the 16th day A cells were more numerous than B cells. But after then, the volume density of B cells increased rapidly. Plasma insulin also increased in the fetal period and was very high at the late fetal day. Just after birth plasma insulin decreased immediately and plasma glucagon increased and reached a very high peak. The volume density of D cells was much lower than that of the other cell types, and plasma somatostatin did not change remarkably throughout the perinatal period. In the IUGR rat fetuses the volume density of B cells was significantly lower than that of controls. In addition, plasma insulin was lower in the IUGR group, whereas plasma glucagon was higher. These results suggest that the pancreatic endocrine system, especially insulin and glucagon play some important roles in fetal development and postnatal metabolic changes.     

Oversized infant of diabetic mother: its cause and prevention

In this study the birth weights of 431 infants of diabetic mothers of the Milan series have been compared with the birth weights of infants of a control group. The averages and the centile distributions of weights of infants of gestational diabetic mothers (Class A) and of diabetic mothers without vascular complications (Classes B and C) did not differ substantially from those of control newborns (table I, figure 1). This confirms the clinical indication, based on the hyperglycemia-hyperinsulinism theory that fetal macrosomia can be prevented provided maternal metabolism is strictly controlled. In this series insulin was administered at the maximal tolerated dose (MTD), a therapeutic regimen that provides excellent metabolic control of the mother. In multiparae, the birth weights of the infants of the latest pregnancy were drastically lower than the birth weights of the infants in their previous pregnancies (without MTD insulin) (table II). Our results do not confirm the recent hypothesis that pregnant diabetics with strict metabolic control during pregnancy generally give birth to growth retarded infants. The MTD of insulin has also been administered to gestational diabetic mothers, and fetal macrosomia was prevented (table I, figure 1). This confirms the opinion of those who believe that a diet-regimen must be accompanied by insulin administration to correct the slight metabolic abnormality of these patients. As would be expected because of placental insufficiency, infants of patients with vascular complications, including those who have only calcifications of the pelvic vessels (White' Class E), were growth retarded (table I, figure 1). The risk of fetal growth retardation in Class E has not been remarked upon in the literature, since pathology of pelvic vessels is usually disregarded and the patients remain undifferentiated among Classes A-C. The possibility to prevent fetal macrosomia with a strict control of maternal diabetes has been questioned because of the lack of correlation between fetal macrosomia and the degree of maternal hyperglycemia and of fetal hyperinsulinism. We postulate that, if fetal hyperinsulinism causes hypoxia, as it does in experimental animals, the lack of correlation may be due to the fetal hyperinsulinism itself.