Neonatal macrosomia and hypoglycaemia in children of mothers with insulin-treated gestational diabetes mellitus.

All newborn children to mothers with gestational diabetes mellitus (GDM) in the county of Orebro were investigated during a one year prospective study. Neonatal macrosomia (birthweight greater than 3 SD) was observed in 27% of children of mothers with GDM and was significantly correlated to the cord C-peptide concentration. Hypoglycaemia (B-glucose less than 1.5 mmol/l) was observed in 38% of the children, most frequently two hours after delivery. Hypoglycaemia was not more common in macrosomic children and could not be predicted by the blood glucose concentration of the mother at delivery or by the cord C-peptide level. It is concluded that mothers with GDM must be intensively treated in order to avoid the occurrence of macrosomia in their infants and that the newborn child must be carefully observed and treated in order to avoid neonatal hypoglycaemia.     

Asymmetric septal hypertrophy in infants of diabetic mothers. Fetal echocardiography and the impact of maternal diabetic control.

Maternal hyperglycemia may result in fetal hyperinsulinemia and asymmetric septal hypertrophy, macrosomia, and hypoglycemia in infants of diabetic mothers. We monitored glycosylated hemoglobin levels in 61 pregnant diabetic women each trimester as an index of maternal glycemic control and did serial fetal echocardiograms starting at 18 weeks of gestation. At delivery, cord blood C-peptide levels were obtained as an index of fetal hyperinsulinemia. Infants were assessed for hypoglycemia, macrosomia and septal thickening by echocardiography. Nineteen of the 61 infants (31%) had septal hypertrophy, were heavier, and had higher cord blood C-peptide levels and lower serum glucose levels than unaffected infants. Maternal glycosylated hemoglobin levels were higher during the third trimester in mothers of affected infants. Our data support a possible relationship between third-trimester maternal hyperglycemia and neonatal asymmetric septal hypertrophy, macrosomia, and hypoglycemia.     

Macrosomia,top of the iceberg: The charm of underlying factors

Background: Macrosomia is associated with childhood obesity. Gestational diabetes mellitus (GDM) is a risk factor for macrosomia. The aim of this large‐scale investigation was to determine the incidence, risk factors, characteristic features, and perinatal outcome of macrosomic infants. Methods: This prospective study was carried out on 6385 newborns. Demographic data included maternal age, paternal age, type of delivery, sex, parity and gestational age at delivery. Anthropometric measurements were recorded. ABO/Rh typing was performed and GDM was diagnosed. Results: Out of 6385 term deliveries, 477 infants (7.47%) were macrosomic. Incidence of GDM was 0.6% and 4.8% in the control group and in macrosomic births, respectively. Incidence of GDM(+) cases was 4% among macrosomic infants weighing 4000–4500 g. GDM(+) cases were densely populated (11%) in macrosomic infants weighing ≥ 4500 g (P≤ 0.05). Male/female ratio was significantly higher in macrosomic infants weighing ≥ 4500 g than those weighing 4000–4500 g (P≤ 0.05). High parental age was the risk factor for GDM. Blood group A was the most frequently observed type among mothers with macrosomic infants, however, blood group O was dominant in cases with GDM. In multivariate logistic regression analysis, the male infant was the most striking infant characteristic and GDM was the most striking maternal characteristic that were significantly associated with increased odds of macrosomic birth. Conclusions: This research reports the association between blood group system and macrosomia as well as parental age and GDM simultaneously. Our study reports a prevalence of GDM in both infants with normal birth weight and macrosomic newborns at the same time.     

妊娠糖尿病母亲儿激素水平的变化

妊娠期糖尿病(gestational diabetes mellitus,GDM)的发病率逐年上升,既往认为糖尿病母亲儿的异常主要由宫内高血糖引起,越来越多的研究发现即使GDM孕妇血糖控制较好,仍易分娩巨大儿及出现围生期并发症,目前普遍认为与某些激素的异常分泌有关.大量研究表明妊娠期糖尿病母亲儿的多种激素水平均发生了改...     

Oral supplementation of vitamin K for pregnant women and effects on levels of plasma vitamin K and PIVKA-II in the neonate

Levels of plasma vitamin K1 (VK1) and vitamin K2 (VK2) and protein-induced vitamin K absence-II (PIVKA-II) were measured in Japanese mothers and their newborn (N = 33). Twenty milligrams of VK1 (N = 11) or VK2 (N = 12) were given orally to randomly selected mothers 7 to 10 days prior to delivery. Means of plasma VK1 and VK2 concentrations were significantly higher in VK1 (p less than 0.01) and VK2 (p less than 0.01) treated mothers than in the controls at delivery, respectively. Similarly, these levels were significantly elevated in cord plasma in VK1 (p less than 0.05) and VK2 (p less than 0.05) treated groups, compared with findings in the control group, although there was a large concentration gradient between maternal and cord plasma (mostly less than one-tenth). A significant positive correlation was found in VK1 concentration between maternal and cord plasma (N = 33, p less than 0.01), and the proportion of PIVKA-II-positive infants was significantly lower in the VK treated groups than in the control group at birth (p less than 0.05). On the fifth postnatal day, mean levels of VK1 (p less than 0.01) and VK2 (p less than 0.01) in breast milk were significantly higher in the VK1 and VK2 treated mothers than in the control mothers, respectively. In the control group, 9 of 10 infants had a positive PIVKA-II, but no one in the treated groups was positive, thereby indicating significant differences between control and treated groups (p less than 0.01 and p less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

SELENIUM AND VITAMIN E IN CORD BLOOD FROM PRETERM AND FULL TERM INFANTS

ABSTRACT. Selenium was determined in erythrocytes and serum, and vitamin E and β-lipoprotein in serum from cord blood samples of 31 full term and 20 preterm infants. Venous samples from 21 mothers at birth and 15 normal adult women were also analyzed. No difference for either selenium or vitamin E was found between the preterm and full term infants. The selenium concentration in red blood cells was the same for newborn, mothers at birth, and normal adult women. The serum concentration of selenium was, however, significantly lower in the newborn, the mean level in the children being 64% of that in the mothers. The level in the mothers did not differ from that in non-pregnant women. The vitamin E concentration was found to correlate very well with the β-lipoprotein concentration. This indicates that differences in the transport capacity account for the large difference in the serum tocopherol levels of mothers at birth and newborn.     

母亲妊娠期糖尿病对新生儿左心功能的影响

目的：评估妊娠期糖尿病（GDM）母亲的新生儿左心功能状况。方法：GDM母亲娩出的新生儿40例（GDM组）及正常新生儿40例（对照组）作为研究对象,应用超声二维斑点追踪成像技术检测室间隔厚度、左室后壁厚度、射血分数,并计算左室旋转和扭转参数。结果：GDM组新生儿室间隔舒张厚度（0.45±0.06 mm）较对照组（0.34±0.05 mm）增大;GDM组左室后壁舒张厚度（0.45±0.17 mm）亦较对照组（0.31±0.02 mm）增大,差异均有统计学意义（P0.05）。GDM组新生儿内膜旋转峰值、外膜旋转峰值、平面旋转峰值、跨壁扭转峰值均较对照组升高,差异有统计学意义（P<0.05）。结论：GDM母亲的新生儿左心室的形态和旋转及扭转运动发生变化,心功能虽受到损害,但处于代偿状态,能维持正常的射血功能。超声二维斑点追踪成像技术可作为早期检测新生儿左心功能的良好手段。     

Effect of spontaneous gestational diabetes on fetal and postnatal hepatic insulin resistance in Lepr(db/+) mice

Infant macrosomia is a classic feature of a gestational diabetes mellitus (GDM) pregnancy and is associated with increased risk of adult obesity and type II diabetes mellitus, however mechanisms linking GDM and later disease remain poorly understood. The heterozygous leptin receptor-deficient (Lepr(db/+)) mouse develops spontaneous GDM and the fetuses display characteristics similar to infants of GDM mothers. We examined the effects of GDM on maternal insulin resistance, fetal growth, and postnatal development of hepatic insulin resistance. Fetal body weight on d 18 of gestation was 6.5% greater (p < 0.05) in pups from ad libitum-fed db/+ mothers compared with wild-type (WT) controls. Pair-feeding db/+ mothers to the intake of WT mothers normalized fetal weight despite less than normal maternal insulin sensitivity. More stringent caloric restriction reduced insulin and glucose levels below WT controls and resulted in fetal intrauterine growth restriction. The level of hepatic insulin receptor protein was decreased by 28% to 31% in both intrauterine growth restriction and fetuses from ad libitum-fed GDM mothers compared with offspring from WT mothers. In 24-wk-old adult offspring from GDM mothers, body weight was similar to WT offspring, however, the females from GDM mothers were fatter and hyperinsulinemic compared with offspring from WT mothers. Insulin-stimulated phosphorylation of Akt, a key intermediate in insulin signaling, was severely decreased in the livers of adult GDM offspring. Hepatic glucose-6-phosphatase activity was also inappropriately increased in the adult offspring from GDM mothers. These results suggest that spontaneous GDM in the pregnant Lepr(db/+) mouse is triggered by overfeeding, and this effect results in obesity and insulin resistance in the livers of the adult offspring. The specific decrease in Akt phosphorylation in livers of adult offspring suggests that this may be a mechanism for reduced insulin-dependent physiologic events, such as suppression of hepatic glucose production, a defect associated with susceptibility to type II diabetes mellitus.     

Ten-year Experience of Insulin Treatment in Gestational Diabetes

ABSTRACT. Between 1975–1984, 119 women with gestational diabetes (GDM) were treated with insulin in Uppsala, representing a mean yearly incidence of 4.5/1000 pregnancies. Women with GDM were older and more obese than the general pregnant population. Insulin treatment was instituted during a 5–7 day stay in hospital. The mean total daily dose of insulin prepartum, when fasting blood glucose had been normalized, was 53 (SD ± 25) units (34 ± 15 units of rapid-acting and 20 ± 11 units of medium-acting insulin), divided into two doses daily. Mean duration of treatment was 6.4 weeks. The perinatal mortality was 0.8%, compared with 7.4 % in previous pregnancies in the same women. The perinatal morbidity was generally mild and included hypoglycaemia (10.9 %), hyperbilirubinaemia requiring treatment (2.5 %), shoulder dystocia (2.5 %) and one case of mild respiratory distress syndrome. The rate of macrosomia was reduced in the present pregnancies compared with previous ones in the women with GDM, but not abolished completely, probably because of too short a duration of improved metabolic control. Spontaneous delivery was favoured and the rate of Caesarean section was 13.596. Thus, treatment with high doses of insulin in an unselected group of women with GDM is feasible. Normal perinatal mortality, reduced macrosomia, and no gross perinatal morbidity was found in the infants. Though the extent to which insulin treatment per se contributed to the favourable outcome is difficult to assess, it is suggested that the case for a high level of ambition for metabolic normalization in GDM should be a subject of further study.     

Selenium and vitamin E in cord blood from preterm and full term infants.

Selenium was determined in erythrocytes and serum, and vitamin E and beta-lipoprotein in serum from cord blood samples of 31 full term and 20 preterm infants. Venous samples from 21 mothers at birth and 15 normal adult women were also analyzed. No difference for either selenium or vitamin E was found between the preterm and full term infants. The selenium concentration in red blood cells was the same for newborn, mothers at birth, and normal adult women. The serum concentration of selenium was, however, significantly lower in the newborn, the mean level in the children being 64% of that in the mothers. The level in the mothers did not differ from that in non-pregnant women. The vitamin E concentration was found to correlate very well with the beta-lipoprotein concentration. This indicates that differences in the transport capacity account for the large difference in the serum tocopherol levels of mothers at birth and newborn.     

Sympatho-adrenal activity and metabolic adjustment during the first 12 hours after birth in infants of diabetic mothers

Plasma adrenaline and noradrenaline concentrations at birth were the same in infants of diabetic mothers and controls after both vaginal and abdominal delivery. The infants delivered vaginally had significantly higher noradrenaline concentrations than those delivered by caesarean section. During the first 12 postnatal hours, the concentration of noradrenaline decreased to levels similar to those found in newborn infants with minor respiratory problems. No hypoglycemic values were recorded in infants of diabetic mothers at birth nor during the first twelve hours after birth. The C-peptide concentrations at birth were significantly lower in infants of diabetic mothers delivered vaginally as compared to those delivered by caesarean section. The FFA concentrations increased after birth possibly as a result of the lipolytic action of catecholamines released during labour and delivery. We have not been able to confirm the increased sympatho-adrenal activity previously reported in infants of diabetic mothers. We suggest that the difference is due to better metabolic control in the diabetic mothers during pregnancy and delivery in this study.     

Cord blood diazepam: Clinical effects in neonates of eclamptic mothers

Diazepam used in the treatment of eclampsia crosses the placental barrier readily, and may cause various clinical effects in the neonates. Twenty-five (25) live born babies of eclamptic mothers receiving diazepam were studied and cord blood diazepam concentration was estimated. Effect of low dose of diazepam is minimal apart from lowering of rectal temperature and the effects lasted for a period of 12 hours. But high dose (>30mg) of diazepam and prolonged duration of diazepam therapy in mothers causes significant depression of the newborn and the effects lasted for a period of 36–48 hours. As the clinical condition of the newborn is not related to the diazepam concentration in cord blood, the cord blood estimation is not helpful in the assessment of clinical effects of the drug in newborn. The tissue storage of the drug in newborn appears to be responsible for the clinical effects.     

Sympatho-Adrenal Activity and Metabolic Adjustment during the First 12 Hours after Birth in Infants of Diabetic Mothers

Plasma adrenaline and noradrenaline concentrations at birth were the same in infants of diabetic mothers and controls after both vaginal and abdominal delivery. The infants delivered vaginally had significantly higher noradrenaline concentrations than those delivered by caesarean section. During the first 12 postnatal hours, the concentration of noradrenaline decreased to levels similar to those found in newborn infants with minor respiratory problems. No hypoglycemic values were recorded in infants of diabetic mothers at birth nor during the first twelve hours after birth. The C-peptide concentrations at birth were significantly lower in infants of diabetic mothers delivered vaginally as compared to those delivered by caesarean section. The FFA concentrations increased after birth possibly as a result of the lipolytic action of catecholamines released during labour and delivery. We have not been able to confirm the increased sympatho-adrenal activity previously reported in infants of diabetic mothers. We suggest that the difference is due to better metabolic control in the diabetic mothers during pregnancy and delivery in this study.     

Prenatal diagnosis of familial neonatal hyperinsulinemia

A kindred with familial neonatal hyperinsulinemia is described. Infant A was macrosomatic and stillborn. Infant B was macrosomatic at birth following a pregnancy uncomplicated by maternal diabetes. Following diagnosis of hyperinsulinemic hypoglycemia, this patient was treated with oral diazoxide. Therapy continued until hyperinsulinemia resolved by two years of age. Based on this history, the pregnancy with infant C was intensively monitored using ultrasonography and amniocentesis. Insulin and C-peptide concentrations in amniotic fluid were markedly increased compared to control pregnancies. Based on these results, infant C was delivered immediately upon obtaining evidence of lung maturation. Neonatal hyperinsulinemia was confirmed by a markedly increased cord plasma insulin concentration. Based on our experience, we recommend that insulin concentrations in amniotic fluid be used as an indicator of fetal hyperinsulinemia in kindreds with prior newborn hyperinsulincmic hypoglycemia. This information may be used to direct timing of delivery and therapy in the immediate postnatal period.     

Prenatal diagnosis of familial neonatal hyperinsulinemia

A kindred with familial neonatal hyperinsulinemia is described. Infant A was macrosomatic and stillborn. Infant B was macrosomatic at birth following a pregnancy uncomplicated by maternal diabetes. Following diagnosis of hyperinsulinemic hypoglycemia, this patient was treated with oral diazoxide. Therapy continued until hyperinsulinemia resolved by two years of age. Based on this history, the pregnancy with infant C was intensively monitored using ultrasonography and amniocentesis. Insulin and C-peptide concentrations in amniotic fluid were markedly increased compared to control pregnancies. Based on these results, infant C was delivered immediately upon obtaining evidence of lung maturation. Neonatal hyperinsulinemia was confirmed by a markedly increased cord plasma insulin concentration. Based on our experience, we recommend that insulin concentrations in amniotic fluid be used as an indicator of fetal hyperinsulinemia in kindreds with prior newborn hyperinsulincmic hypoglycemia. This information may be used to direct timing of delivery and therapy in the immediate postnatal period.     

Thyroglobulin in cord blood

The cord thyroglobulin (Tg) concentration was estimated in 160 full-term newborns of whom 103 were delivered normally, 26 by elective Ceasarean section and 31 by vacuum extraction. There was no correlation between the median cord Tg concentration and gestational age at delivery (37–43 weeks), birth weight or sex of the child or the median cord TSH concentration. The median cord Tg concentration was significantly higher in the children born by Ceasarean section than in those delivered by vacuum extraction (P<0.001). The same tendency was found when smokers and non-smokers were compared separately. Mechanical force on the thyroid gland during labour and delivery therefore does not seem to increase the cord Tg concentration.The influence of maternal cigarette smoking on the cord Tg concentration was studied also. Forty-five mothers were smokers. The median cord Tg concentration in the children of these women was significantly higher than in the children of non-smoking mothers (130 g/l vs 100 g/l,P<0.001), whereas the median cord TSH concentration did not differ between these groups. It therefore seems possible that components of cigarette smoke, e.g. thiocyanate, may have a direct effect on the thyroid gland of the fetus.Abbreviations Tg thyroglobulin - VE vacuum extraction - Tg-ab Tg antibodies - S-Tg serum thyroglobulin     

Levels of lipid peroxides and of some antioxidants in placenta and cord blood of newborns whose mothers smoked during pregnancy

Cigarette smoking during pregnancy increases the risk of oxidative damage and induces not only intrauterine foetal growth retardation, but also causes disturbances in postnatal growth and development. In the presented studies oxidative damage was estimated through the measurement of lipid peroxides concentration and the level of some antioxidants in placenta and in cord blood of newborns whose mothers smoked during pregnancy. We observed that the concentration of lipid peroxides was higher in cord blood and in placenta tissue (8%) than in the newborns of non-smoking mothers, but the activity of superoxide dismutase and glutathione peroxidase were lower by 20% and 16% respectively. Plasma level of vitamin A (p<0.005), vitamin E (p<0.05), fS-carotene (p< 0.0001) and total plasma antioxidant capacity (p<0.05) were significantly lower in the newborn of smoking than the non-smoking mother group. It is suggested that placental tissue protected the foetus against oxidative stress, but not sufficiently. Antioxidant activities of cord blood may also be insufficient in dismutation of free radicals and their detoxication in order to protect newborns against smoking dependent metabolic disturbances.     

Hypoglycaemia in Childhood Diabetes I.

ABSTRACT. Hypoglycaemia (blood glucose 1.3–2.5 mmol/l) was induced in twenty-eight diabetic children by reduction of their morning meal. Fatigue and pallor were the most common signs of hypoglycaemia. Compared to findings during normoglycaemia, plasma concentrations of adrenalin, noradrenalin and Cortisol were significantly higher at glucose nadir. Plasma glucagon concentration at glucose nadir was correlated to the fasting C-peptide concentration and inversely to the duration of diabetes. Children who lacked C-peptide also lacked glucagon response to hypoglycaemia. The parents' opinion of the need to give carbohydrates corresponded to the blood glucose level. The presence of adrenergic signs correlated to the plasma adrenalin and the neuroglucopenic signs to blood glucose. The lowest glucose level correlated inversely to the concentration of free insulin. When facilities for glucose infusion are lacking, a rational step in treating the unconscious hypoglycaemic child seems to be the injection of glucagon, considering the blunted or absent glucagon secretion.     

Fetal macrosomia--a continuing obstetric challenge

BACKGROUND: Macrosomic fetuses represent a continuing challenge in obstetrics. OBJECTIVES: We studied maternal risk factors of fetal macrosomia and maternal and infant outcome in such cases. METHODS: A retrospective cohort study was carried out with a total of 26,961 singleton pregnancies between 1989 and 2001. Records of 886 mothers who gave birth to live born infants weighing > or =4,500 g were compared to those of 26,075 mothers with normal weight (<4,500 g) infants. Multiple regression analysis was used to identify independent reproductive risk factors. Perinatal complications were also assessed. RESULTS: The incidence of fetal macrosomia was 3.4%. Diabetes, previous macrosomic birth, postdatism (>42 weeks of gestation), obesity (BMI > 25 before pregnancy), male infant, gestational diabetes mellitus, and non-smoking were independent risk factors of fetal macrosomia, with adjusted risks of 4.6, 3.1, 3.1, 2.0, 1.9, 1.6, 1.4, respectively. In the macrosomic group, birth and maternal traumas occurred significantly more often than in the control group. However, records of subsequent pregnancies (n = 250) after the study period showed that a previous uncomplicated birth appeared to decrease complication risks. CONCLUSIONS: Most cases of fetal macrosomia occur in low-risk pregnancies and evaluation of maternal risks cannot accurately predict which women will eventually give birth to an overweight newborn. After an uncomplicated birth of a macrosomic infant, vaginal delivery may be a safe option for the infant and mother.     

Gestational diabetes mellitus--implications of different treatment protocols

OBJECTIVE: To assess the impact of different management approaches to gestational diabetes mellitus (GDM) on perinatal outcome. PATIENTS AND METHODS: The study group consisted of 2,060 patients with GDM treated in our center from January 1980 through December 1999. Four time periods were defined on the basis of changes in treatment protocols. Perinatal complications were compared between the periods and with normal pregnancy controls. RESULTS: The last two periods (1993-1999) were characterized by lower mean glucose level, lower mean gestational age at delivery, and a decline in macrosomia, shoulder dystocia and perinatal mortality rates, but also by high rates of labor induction and Cesarean delivery. A significant difference was found between the GDM and normal control groups in rates of labor induction (38.6% vs 10.8%, p < 0.001) and Cesarean delivery (34% vs 20%, p < 0.001) for the last period. CONCLUSIONS: Perinatal complications are preventable with good glycemic control and early induction of labor, but at a cost of a higher Cesarean section rate.