Glucose tolerance of 2- to 5-yr-old offspring of diabetic mothers

The aim of this study was to determine the prevalence of and some risk factors for impaired glucose tolerance (IGT) in 2- to 5-yr-old offspring of diabetic mothers (ODM). The glucose tolerance of 51 offspring born to women with pregnancies complicated by diabetes (type 1) and of 109 children of the control group was analyzed. Our results showed that the fasting glycemia of ODM was similar, when compared to the controls, but 2 h after the glucose loading the glycemia of ODM was significantly higher than that in the control group (5.47 +/- 1.79 mmol/L vs. 4.86 +/- 1.13 mmol/L). Normal glucose tolerance was found in 68.6% of ODM and 86.2% of controls; IGT was found in 17.6% of ODM and 4.6% of controls. Children with macrosomia at birth or overweight at 2-5 yr had IGT at 2-5 yr more often than children with normal weight at birth or normal weight at 2-5 yr. A significant, though relatively low, positive correlation was found between the duration of breastfeeding and fasting glycemia (r=0.241, p <0.01), and positive correlation was found between the duration of breastfeeding and glycemia 2 h after glucose loading (r=0.458, p=0.002) in the offspring of diabetic mothers. In conclusion, the average glycemia of ODM after glucose loading was higher than that in the control group. Macrosomia after birth, overweight, and obesity in childhood had a significant influence on the glucose tolerance of the ODM. The results of the oral glucose tolerance test correlated with the length of breastfeeding.     

Follow-up of Children of Insulin-dependent and Gestational Diabetic Mothers: Neuropsychological Outcome

ABSTRACT. Ninety-four infants of 28 weeks gestation or more were born to 85 women, 64 type I and 21 gestational diabetics, between 1969–1972 at Sabbatsberg's Hospital, Stockholm. Perinatal mortality rate was 6.3%. The follow-up study was conducted when the children were approximately 5 years of age and included a physical and a neurological evaluation, IQ determination of mother and child, and an interview of mother by a psychologist. Fifty-three infants of insulin-dependent (IDM) and 20 infants of gestational diabetic mothers (IGDM) (83 %) participated, 3 families could not be traced and 12 were unwilling. The group lost to follow-up (13 IDM, 2 IGDM) had more perinatal complications induding congential malformations than the follow-up group. All children had normal physical and neurological development. IQ was normal, the majority were above 100, the average in IDM was 115 (range 89–144) and 112 in IGDM (range 95–133). No obvious relationship was found between maternal acetonuria during pregnancy, infant birthweight, blood glucose during first hours after birth or neonatal complications and IQ of the children. A correlation (r= 0.364, p<0.01) was found between maternal and child IQ. Mothers exhibiting emotional disorders (anxiety, depression) had significantly higher life stress scores based on 29 stress variables and reported more frequently about conduct and behavioural disorders in their children than mothers without emotional disturbances.     

Follow-up of Children of Insulin-dependent and Gestational Diabetic Mothers: Neuropsychological Outcome

ABSTRACT. Ninety-four infants of 28 weeks gestation or more were born to 85 women, 64 type I and 21 gestational diabetics, between 1969–1972 at Sabbatsberg's Hospital, Stockholm. Perinatal mortality rate was 6.3%. The follow-up study was conducted when the children were approximately 5 years of age and included a physical and a neurological evaluation, IQ determination of mother and child, and an interview of mother by a psychologist. Fifty-three infants of insulin-dependent (IDM) and 20 infants of gestational diabetic mothers (IGDM) (83 %) participated, 3 families could not be traced and 12 were unwilling. The group lost to follow-up (13 IDM, 2 IGDM) had more perinatal complications induding congential malformations than the follow-up group. All children had normal physical and neurological development. IQ was normal, the majority were above 100, the average in IDM was 115 (range 89–144) and 112 in IGDM (range 95–133). No obvious relationship was found between maternal acetonuria during pregnancy, infant birthweight, blood glucose during first hours after birth or neonatal complications and IQ of the children. A correlation (r= 0.364, p<0.01) was found between maternal and child IQ. Mothers exhibiting emotional disorders (anxiety, depression) had significantly higher life stress scores based on 29 stress variables and reported more frequently about conduct and behavioural disorders in their children than mothers without emotional disturbances.     

Blood sugar,free fatty acids and triglycerides in infants of diabetic mothers

Blood sugar (BS), free fatty acids (FFA) and triglycerides (TG) were estimated in eighteen neonates of diabetic mothers (IDM) and 36 appropriate for gestational age (AGA) term newborns of non-diabetic mothers, delivered normally and having normal blood sugar levels (30 mg/dl and above) were taken as controls. Even though blood sugar levels in the cord blood were higher in IDM group, mean levels were much lower than controls in first few hours of birth and nearly 45 per cent them developed hypoglycemia. A rise in FFA from cord levels in first few hours of birth was seen in all the cases, but levels were lower in IDM as compared to controls. TG levels showed a steady and mild rise from birth onwards. Changes in BS and FFA in IDM can be explained on the basis of hyperinsulinemic state in them in utero and in immediate postnatal period.     

Normal auditory brain stem evoked responses in infants of diabetic mothers

Auditory brain stem responses potentials were recorded from 71 newborns within the first 2 weeks after birth; conceptional age ranged from 37 to 41 weeks. Thirty-nine newborns were infants of diabetic mothers (IDMs) (17 White A, 22 White B-D) and 32 healthy term newborns served as control group. IDMs with additional high risk for cochlear or brain stem integrity were excluded. Birthweight for gestational age was significantly higher for IDMs. No differences in auditory brain stem responses wave latencies or amplitudes were observed between healthy infants of the control group and IDMs.     

Glucose disappearance in infants of diabetic mothers. III. Relationship of spontaneous glucose disappearance to glucose tolerance,neonatal hypoglycemia and lowest blood glucose

Spontaneous glucose disappearance in the first 90 min of life and glucose disappearance following an intravenous injection of 1 g/kg dextrose were measured in 23 infants of insulin-dependent diabetic mothers. Spontaneous disappearance was log-linear in 12/23 infants, providing for calculation of an endogenous K_t which correlated significantly (P < 0.01) with the exogenous Kt determined after the dextrose injection, r = 0.74.Hypoglycemia <20 mg/dl occurred in 4/23 infants, and was identified during the spontaneous glucose disappearance (3 infants) and/or predicted by an endogenous K_t > 3.0%/min (2 infants). There was also a significant inverse correlation (P < 0.01) of the lowest blood glucose obtained within the first 24 h of life with the endogenous K_t, r = 0.61. There was no correlation of the endogenous or exogenous Kt, lowest blood glucose or hypoglycemia with White's classification of the maternal diabetes, diabetic control during pregnancy, the maternal blood glucose at delivery or the cord blood glucose.These data indicate that determination of spontaneous glucose disappearance within the first 90 min of life is useful in identifying infants of diabetic mothers with hypoglycemia or those who will subsequently develop hypoglycemia.     

Cardiopulmonary adaptation in large for gestational age infants of diabetic and nondiabetic mothers

AIM: To compare cardiopulmonary adaptation in large for gestational age infants of diabetic and nondiabetic mothers. METHODS: Color Doppler echocardiography was performed in 113 (22 large for gestational age infants of diabetic mothers, 21 of nondiabetic mothers and 70 adequate for gestational age newborns) full-term infants. RESULTS: Pulmonary arterial pressure was significantly higher in infants of diabetic mothers than in those of nondiabetic mothers and normal infants at 24 h (38.5 vs. 32.5, and 35.5 mmHg, respectively). However, slow fall in this parameter was shown in all large for gestational age infants. Open ductus arteriosus was frequent in all large for gestational age infants, but its closure was significantly delayed in infants of diabetic mothers. Septal hypertrophy was higher in infants of diabetic mothers than in large for gestational age infants of nondiabetic mothers. CONCLUSION: Large for gestational age infants born from nondiabetic mothers showed delayed fall in pulmonary arterial pressure similar to those born from diabetic mothers but showed lower proportion of septal hypertrophy. Patent ductus arteriosus persisted for longer period of time in all large for gestational age infants than in normal infants, but its closure was significantly delayed in infants of diabetic mothers.     

Infants of diabetic mothers: echocardiographic measurements and cord blood IGF-I and IGFBP-1

El‐Ganzoury MM, El‐Masry SA, El‐Farrash RA, Anwar M, Abd Ellatife RZ. Infants of diabetic mothers: echocardiographic measurements and cord blood IGF‐I and IGFBP‐1. Background: Cardiac malformations in infants of diabetic mothers (IDMs) are five times higher than in normal pregnancies. Insulin‐like growth factor‐I (IGF‐I) is the most important growth factor in utero and is predominantly bound by IGF binding protein‐1 (IGFBP‐1). Objective: To examine the echocardiographic findings of neonates of diabetic mothers and the relationship with cord blood IGF‐I and IGBP‐1. Subjects and methods: This study was conducted on 69 neonates born to diabetic mothers who were admitted to the neonatal intensive care unit, Ain Shams University Hospitals between August 2007 and February 2008. They were classified into three groups: 20 small for gestational age, 25 appropriate for gestational age, and 24 large for gestational age. Neonates were subjected to thorough clinical examination and echocardiographic evaluation. Maternal hemoglobin A1c (HbA1c) and cord blood IGF‐I and IGBP‐1 were assessed. Results: Thirty neonates (43.5%) had hypertrophic cardiomyopathy (HCM); all of them were infants of suboptimally controlled diabetic mothers (HbA1c ≥ 7) with positive correlation between HbA1c and interventricular septal (IVS) thickness. Impaired left ventricular contractility was recorded in 52 IDMs (75.4%). The echocardiographic and laboratory measurements showed significant difference between the three studied groups. Cardiac morphological data were negatively correlated to IGFBP‐1 and positively correlated to IGF‐I and birth weight. Conclusions: The opposing relationships between cord blood IGF‐I and IGFBP‐1 on the cardiac morphological measurements supporting their putative opposing roles in HCM seen in IDMs. Birth weight is the best predictor of hypertrophied IVS especially in infants born to suboptimally controlled diabetic mothers.     

Cyclopic malformation in infants of diabetic mothers

Two cases of cyclopic malformations are described among 450 infants of diabetic mothers during a period of four years. Both died within 30 min. of birth. Both belonged to unrelated Libyan families with absent consanguinity and family history. No chromosomal defect was found in either. A possible etiological association with uncontrolled maternal diabetes is discussed.     

HAEMOGLOBIN Atc: A PREDICTOR FOR THE DURATION OF THE REMISSION PHASE IN JUVENILE INSULIN-DEPENDENT DIABETIC PATIENTS

Abstract. Vetter, U., Heinze, E., Beischer, W., Kohne, E., Kleihauer, E. and Teller, W. M. (Centers of Paediatrics and Internal Medicine, University of Ulm, FRG). Haemoglobin A_1c: a predictor for the duration of the remission phase in juvenile insulin dependent diabetic patients. Acta Paediatr Scand, 69:481, 1980.—Increased HbA_1cconcentrations in diabetic patients indicate retrospectively a poor metabolic control during the preceding 2–3 months. In the present study attempts have been made to use the HbA_1c concentration at the time of diagnosis as an indicator of the duration of the remission phase in 23 juvenile diabetic children. The regression analysis revealed a significant negative correlation between the initial HbA_1c concentrations and the duration of the remission phase defined as no glucose excretion, an insulin requirement of less than 0.5 U/kg/day and detectable serum C-peptide concentration ( r = -0.84, p < 0.001). The results suggest that the initial HbA_1c concentration may serve as a useful indicator to predict the duration of the remission phase in juvenile-onset diabetic patients     

Neonatal hypoglycaemia in infants of diabetic mothers

OBJECTIVE: To determine whether umbilical cord blood glucose correlates with subsequent hypoglycaemia after birth in infants of well-controlled diabetic mothers. METHODOLOGY: Thirty-eight term infants of well-controlled diabetic mothers were enrolled. Five mothers had pre-existing diabetes. Of the 33 gestational diabetic mothers, 16 were managed on insulin and 17 on diet. Maternal blood glucose was maintained between 4 and 8 mmol/L during labour and delivery. Infants' plasma glucose levels were measured from venous cord blood and serially, at less than 30 min, 1 h and 2 h of life by glucose hexokinase method. Blood glucose levels were further monitored by bedside Dextrostix for 24 h. RESULTS: Eighteen (47%) infants developed hypoglycaemia (blood glucose level less than 2 mmol/L) during the first 2 h of life. There was no difference in the cord blood glucose levels between infants with or without hypoglycaemia (3.7 +/- 1.1 vs 4.5 +/- 1.1 mmol/L, respectively). Infants of mothers with diabetes diagnosed prior to 28 weeks gestation were at a higher risk of developing hypoglycaemia (8 of 10 vs 10 of 28, OR 7.2, 95%CI 1.3-40.7). Hypoglycaemic infants were of significantly higher birthweight, and were more likely to be born to Caucasian mothers and by Caesarean section. Raised maternal fructosamine blood level, the need for insulin treatment or the infant's haematocrit were not different between infants with or without hypoglycaemia. CONCLUSIONS: In well-controlled diabetic mothers, the incidence of early hypoglycaemia in infants is still high, particularly in those mothers who had a longer duration of diabetes. Cord blood glucose level did not identify the infants with hypoglycaemia.     

Prediction of neonatal hypoglycemia in infants of diabetic mothers by glucose disappearance in the first hour of life

Whole blood glucose determinations were obtained in the first hour of life in 44 infants of diabetic mothers in order to predict the occurrence of subsequent hypoglycemia by means of the calculated glucose disappearance rate. Hypoglycemia (whole blood glucose < 20 mg/dl) occurred in 10 infants with linear glucose disappearance of whom 9 had a glucose disappearance rate ? 3.0% per min (90% sensitivity). Nine of 11 infants with glucose disappearance rates ? 3.0% per min had hypoglycemia (82% specificity). This relatively simple procedure offers an accurate method for prediction of neonatal hypoglycemia due to reactive hyperinsulinemia in infants of diabetic mothers.     

Transient right sided hypertrophic cardiomyopathy in an infant born to a diabetic mother

Hypertrophie cardiomyopathy (HCM) is a rare primary myocardial disease, characterized by hypertrophy of the left and/or right ventricle. Infants of diabetic mothers (IDM) are at risk for development of HCM, respiratory distress and persistent pulmonary hypertension. A case of severe right sided HCM in an infant born to a diabetic mother is presented. The patient’s findings were complementary to the previous observations reporting HCM in IDM. The presence of disproportionate septal hypertrophy in the echocardiography of an infant born to a diabetic mother is highly suggestive of HCM in IDM. In our opinion, further cardiac evaluation is not indicated unless other cardiac abnormalities are suspected.     

Maternal environment affects endogenous virus induction in the offspring of type 1 diabetes model non-obese diabetic mice

Type 1 diabetes results from the destruction of pancreatic b-cells (insulitis). It is a multifactorial disease involving genetic and environmental factors, including the maternal environment. Viruses have also been implicated in the pathogenesis of human type 1 diabetes as well as in its model non-obese diabetic (NOD) mice during the perinatal period, as endogenous viruses and/or as infectious agents vertically transmitted from mothers. However, the role of virus as genetic or environmental factor and its interaction with other maternal factors remain unclear. In a series of experiments, we transplanted preimplantation-stage NOD embryos into the uterus of recipient Institute of Cancer Research (ICR) mice, which are without diabetic genetic predisposition, and NOD mice, which did not exhibit overt diabetes during the experiment, and designated offspring as NOD/ICR and NOD/NOD, respectively. We previously observed that NOD/ICR offspring developed insulitis significantly earlier than NOD/NOD offspring. To assess the role of viruses in the development of insulitis, we examined the appearance of viral particles and expression of retroviruses between NOD/ICR and NOD/NOD. NOD/ICR showed earlier expression of env region of the xenotropic type C retrovirus by polymerase chain reaction analysis than NOD/NOD, while the retrovirus-like particles were observed in the islet b-cells similarly in both groups by electron microscopy. Serum corticosterone level, which is suggested to enhance retroviral induction, was significantly higher in the ICR than in the NOD surrogate mothers. These findings suggest that the observed virus is endogenous and that maternal environmental factors, including hormone levels, affect the induction of endogenous viruses and cause the earlier onset of insulitis.     

Intellectual development and nutrition

One newborn child was selected from 14 families in which kwashiorkor had occurred. Undernutrition in this test group was prevented for the first two years of life by the provision of supplementary feeding. Controls who were the siblings directly preceding each of the 14 test children received no supplementary feeding, but received medical attention and management. In each family an older child who previously had kwashiorkor (kwashiorkor group), and the nearest sibling who had received neither extra feeding nor medical management (kwasiorkor control group) were also available for comparison. A battery of psychologic tests was administered when the mean age of the test group was 8.9 years. The mean full-scale IQ of the supplementary feeding group at an average age of 8.9 years was significantly higher than that of any of the other three groups. There was no significant difference between test and control groups on nonverbal IQ. Measures of "brain damage" did not discriminate between any of the four groups. The results suggest that nutritional factors contribute especially to the elevation of verbal intelligence. Environmental stimulation (daily contact with a more alert child) apparently contributed to the elevation of the nonverbal scores of the controls.     

高龄妊娠对子鼠海马神经干细胞发育的影响

目的 探讨高龄妊娠对子鼠海马神经干细胞发育的影响。方法 将3月龄（n=10）与12月龄（n=10）的雌性大鼠分别与3月龄雄性大鼠（n=20）合笼,以其子鼠为研究对象,分为适龄子代组和高龄子代组,每组40只。分别采用免疫荧光及Western blot法定位及定量检测生后第7天两组海马组织巢蛋白（Nestin）、双皮质素（DCX）及生后第28天成熟神经元标志物NeuN、胶质纤维酸性蛋白（GFAP）表达水平;采用免疫荧光法定位检测生后第14天两组海马组织多聚唾液酸神经细胞黏附分子（PSA-NCAM）表达情况;每组各检测指标随机取8只大鼠。结果 Western blot检测结果发现高龄子代组海马DCX蛋白的表达明显低于适龄子代组（P < 0.05）,Nestin、NeuN及GFAP蛋白表达在两组间比较差异均无统计学意义（P > 0.05）。免疫荧光检测结果显示,高龄子代组海马齿状回（DG）区Nestin、DCX及PSA-NCAM的表达均明显低于适龄子代组（P < 0.05）,而上述指标分别在两组海马CA1区、CA3区的表达比较差异均无统计学意义（P > 0.05）。高龄子代组海马CA1区NeuN的表达高于适龄子代组（P < 0.01）,两组CA3区和DG区NeuN的表达比较差异无统计学意义（P > 0.05）。高龄子代组海马CA1区、CA3区、DG区GFAP的表达均低于适龄子代组（P < 0.05）。结论 高龄妊娠可能引起子鼠海马神经干细胞的增殖、存活及迁移受到抑制,并影响其向神经元和星形胶质细胞的分化,最终导致子鼠海马神经干细胞发育障碍。     

Cardiac output in infants of insulin-dependent diabetic mothers

The purpose of our study was to quantitate left ventricular outflow obstruction in the infant of the diabetic mother (IDM) through estimation of cardiac output by pulsed Doppler ultrasound. We evaluated 42 IDMs (White class B, C, or D) and compared them with two control groups, one similar in birth weight and the other similar in gestational age. Ventricular septal hypertrophy was found in 18 (43%) of 42 of the IDMs, but in none of the control infants. Morbidity increased with advancing septal thickness. None had hyaline membrane disease. Twenty-nine IDMs were asymptomatic, 11 of whom had septal hypertrophy. Thirteen IDMs developed congestive heart failure, seven of whom had septal hypertrophy. Cardiac output per kilogram diminished linearly with increasing septal thickness (r = -0.78, P less than 0.001) secondary to reduced stroke volumes at comparable heart rates. The IDMs had higher left atrial/aortic ratios and greater right ventricular systolic time intervals than the control infants. We conclude that cardiac output is significantly reduced in IDMs with septal hypertrophy. This reduction is secondary to reduced stroke volume and is directly related to the degree of septal hypertrophy.