Beta-Cell Hyperplasia in Macrosomic Infants and Fetuses of Nondiabetic Mothers

The objective of this study was to test the hypothesis that macrosomic infants of nondiabetic mothers have beta-cell hyperplasia in their pancreases. Pancreatic tissues were examined from 10 macrosomic fetuses and liveborn infants and from 10 comparison cases matched for gestational age and gender. None of the mothers had a history of diabetes and all had normal glucose screening during pregnancy. Tissues were stained with hematoxylin and eosin and a monoclonal antibody against beta cells and were analyzed using an image analysis program to evaluate the size and surface area of beta-cell clusters. Brain/liver weight ratios were calculated and compared. The total surface area and cluster size of beta cells in the pancreases of macrosomic subjects were significantly larger than in the comparison pancreases. The study subjects lacked macroscopic and histopathologic findings expected in infants of diabetic mothers. We conclude that some macrosomic fetuses and infants of nondiabetic mothers manifest beta-cell hyperplasia. This corresponds to the higher insulin levels in macrosomic infants of nondiabetic mothers described in previous clinical studies. In macrosomic fetuses the stimulus for beta-cell hyperplasia may not involve aberrant maternal glucose levels.     

Cardiac Malformations in Fetuses of Gestational and Pre Gestational Diabetic Mothers

Objective

In this study we aimed to determine the prevalence of cardiac malformations in fetuses of Iranian diabetic mothers with pre-gestational and gestational diabetes mellitus (GDM) and to find the patterns of different cardiac malformations.

Methods

One-hundred and seventy diabetic pregnant women (68 preGDM and 102 GDM) (mean age: 32.17±4.8 years) and 85 healthy controls (mean age: 31.35±4.55 years) were recruited from September 2008 to July 2012. Fetal echocardiography was performed to assess cardiac malformation. In order to study major factors that may affect the results, a complete history was obtained.

Findings

Fetal echocardiography was performed at mean gestational age of 24.7±5.4 and 20.27±3.9 weeks in diabetic patients and control group, respectively. Fifteen (8.8%) fetuses of diabetic mothers were detected to have cardiac malformations compared with 1 (1.17%) fetus in control group (OR: 8.13, 95%CI: 1.1-62.61, P-value=0.02). Hypertrophic cardiomyopathy noted as the most common cardiac malformation occurred in 6 out of 15 (40%) fetuses, and was found significantly more common in pre-GDM compared to GDM group (7.4% vs 1%, P-value =0.04). Despite the higher incidence of cardiac malformation in pre-GDM compared to GDM group, the difference was not significant. Further, no significant association was observed between the variables including; parity, diabetic regimen, parents’ consanguinity, maternal history of hypertension or hypothyroidism and occurring cardiac malformations (P-value>0.05).

Conclusion

In this study we detected cardiac malformations in 8.8% of our diabetic referrals. The result of the present study shows that screening diabetic mothers for fetal cardiac malformations could be beneficial.     

Neonatal Jaundice in Infants of Diabetic Mothers

Jährig, D., Jährig, K., Stiete, S., Beyersdorff, E., Poser, H. and Hopp, H. (Department of Paediatrics, the Data Centre of the Ernst Moritz Arndt University of Greifswald, Greifswald, and the'Gerhard Katsch'Central Research Institute for Diabetes, Karlsburg, G.D.R.). Neonatal jaundice in infants of diabetic mothers. Acta Paediatr Scand Suppl 360: 101, 1989.
357 IDMs and 20 healthy newborns of non-diabetic mothers were examined at term for body measurements, red blood cell count, serum bilirubin, cord blood insulin and blood glucose during the first postnatal week. The stage of maternal diabetes did not influence the course of neonatal bilirubin levels, but the IDMs had prolonged and higher bilirubinaemia compared with the controls. Hyperbilirubinaemia was found to be most prominent in newborns with an increased birthweightllength ratio and was not simply related to macrosomia (LGA). These infants had significantly lower blood glucose concentrations immediately after birth, whereas cord blood insulin was found to be identical between the IDM sub-groups. Bilirubinaemia in heavy for length infants was slightly correlated to haematocrit. For the pathogenesis of hyperbilirubinaemia in IDMs induction of heme oxygenase (due to a lack of energy provision following a phosphory lation disorder) is discussed. Nutritional support (early feeding, glucose infusions) does not affect the course of bilirubinaemia.     

Follow-up of Children of Insulin Dependent (Type I) and Gestational Diabetic Mothers

ABSTRACT. Fifty-three children of insulin dependent (IDM) and 20 children of gestational diabetic mothers (IGDM) representing 80 and 91 %, respectively, of all surviving infants of diabetic mothers born between 1969 and 1972 at Sabbatsberg's hospital, Stockholm, participated in the follow-up study. The first follow-up examination was performed when the children had reached approximately 5 years of age and included measurement of height and weight, insulin response to intravenous glucose, and HLA typing. When the children were approximately 11 years old, a search was performed in the national register for type I diabetes in children in order to ascertain the frequency of type I diabetes mellitus in the total series ( n =88). The majority of children had a normal height for age and desirable weight for height. At the first follow-up all children had normal glucose disappearance rates ( k _t) and the insulin response including the early insulin response to glucose were not different between IDM and IGDM groups. The frequency distribution of HLA antigens (A, B, C) was not different from normal and there was no association between HLA B 8 and/or B 15 and early insulin respone or k _t values. At the second follow-up, two children of type I diabetic mothers had acquired type I diabetes, both were HLA B 15 positive, had normal k _t values at the first follow-up, one with low, one with a high early insulin response. The frequency of type I diabetes in offspring of insulin dependent diabetic mothers was 3%.     

Prolonged QT Dispersion in the Infants of Diabetic Mothers

Myocardial hypertrophy and cardiac dysfunction frequently occur in newborns of diabetic mothers. The authors hypothesized that wall hypertrophy or disproportionate left ventricular wall thickness in newborns of diabetic mothers may affect both QT and QTc dispersion. This study aimed to assess whether left ventricular hypertrophy affects the QT variables of infants born to diabetic mothers. This prospective cross-sectional study was conducted with 47 consecutively selected neonates of gestational diabetic mothers and 30 healthy neonates born to healthy mothers. All the subjects were evaluated during the neonatal period. Electrocardiography with echocardiography was performed for the patients and the control subjects. The newborns of the diabetic mothers were classified according to septal thickness as group 1 (16 newborns with septal hypertrophy) or group 2 (31 newborns without septal hypertrophy). The study group consisted of three cohorts: groups 1, 2, and 3 (control group). Both QT and QTc dispersion were computed from a randomly selected beat as well as from an average beat derived from 12 beats included in a 10-s electrocardiography. A total of 16 infants (34 %) had a septal thickness of 6 mm or greater. The left ventricular end-systolic diameter in group 1 was smaller (p = 0.0029) than in groups 2 and 3 (p = 0.003). The interventricular septal thickness at end diastole (IVSTd) and the left ventricular posterior wall thickness at end diastole in group 1 were higher than in of groups 2 and 3. The QT and QTc dispersion intervals were longer in group 1 than in groups 2 and 3 (p < 0.001), and a highly significant positive correlation was detected between IVSTd and QT dispersion (r = 0.514, p = 0.042). Elevated QT and QTc dispersions may be risk factors for the development of arrhythmias in newborns of diabetic mothers. These patients may critically need systematic cardiac screening.     

Assessment of Cardiac Functions in Fetuses of Gestational Diabetic Mothers

We investigated cardiac function in 67 fetuses of gestational diabetic mothers (FGDMs) and 122 fetuses of healthy mothers between 24 and 36 weeks of gestation. Cardiac functions were evaluated by M-mode, pulsed-wave, and tissue Doppler echocardiography. Fetal echocardiograms were performed at 24, 28, 32, and 36 weeks of gestation. Glycated hemoglobin (HbA1c) levels were obtained from all pregnant women at 24 weeks of gestation. The mean age of diabetic pregnant women was significantly greater than that of controls. Serum HbA1c values of both groups were within normal limits, but they were significantly greater in the diabetic group (p = 0.003). The increase in peak aortic and pulmonary artery velocities were greater in FGDM (p < 0.001). No pathological interventricular septal (IVS) hypertrophy was observed. There was a significant increase in IVS thickness in FGDM compared with controls, which was more prominent at the end of the third trimester (p < 0.001). During the course of pregnancy, mitral E-wave (p < 0.001), A-wave (p = 0.007), tricuspid E-wave (p < 0.001) and A-wave (p = 0.002) velocities were greater in FGDM. The increases in mitral E/A and tricuspid E/A ratios were lower in FGDM with advancing gestation. The E _a-wave (p = 0.02), A _a-wave (p = 0.04), and S _a-wave (p < 0.001) velocities of the right-ventricular (RV) free wall and the E _a (p = 0.02) and A _a (p = 0.01) velocities of the left-ventricle (LV) posterior wall were greater in FGDM during the course of pregnancy. The E _a/A _a ratio of the RV posterior wall was greater in FGDM with advancing gestation (p < 0.03). LV and RV E/E _a ratios were similar in both groups. The LV myocardial performance index measured by pulsed-wave Doppler was greater in FGDM (p < 0.001). We detected diastolic dysfunction in FGDM. The data suggest that gestational diabetes mellitus may impair ventricular diastolic functions without causing pathological fetal myocardial hypertrophy. We detected subclinical diastolic dysfunction using both pulsed-wave and tissue Doppler imaging in FGDM.     

Cardiac Troponin T and Cardiac Dysfunction in Extremely Low-Birth-Weight Infants

Extremely low-birth-weight (ELBW) infants frequently manifest signs of cardiac dysfunction requiring inotropic support. It is not clear if this is due to cardiac injury, which can be monitored by measuring cardiac troponin T (cTnT). We performed a nested prospective cohort study at a university level III neonatal intensive care unit. The study included 27 infants weighing between 500 and 999 g. Exclusion criteria included evidence of sepsis, use of postnatal steroids, and cardiac anomalies. Measurements included serum cTnT and echocardiogram in the first 48 hours of life. The mean serum cTnT level of the study population was 0.52 ± 0.38 ng/ml. It was higher in those with lower Apgar scores (0.89 ± 0.37 if 5-minute Apgar < 4 vs 0.36 ± 0.26 ng/ml, p < 0.001) and correlated to initial base deficit (r = −0.37, p < 0.05). Infants who required inotropic support had higher cTnT levels than those who did not (0.73 ± 0.43 vs 0.39 ± 0.29 ng/ml, p < 0.03). cTnT concentrations did not relate to simultaneous echocardiographic measures of cardiac function. In ELBW infants, serum cTnT levels are higher than normally seen in term infants and adults, and they are higher in infants with greater perinatal stress as well as those who show evidence of cardiac dysfunction requiring pressor support.     

Congenital Heart Disease in Infants of Diabetic Mothers: Echocardiographic Study

Our objective was to study neonates born to insulin-dependent diabetes mellitus (IDDM) mothers to detect the spectrum of congenital heart disease (CHD). Between July 2000 and June 2001, a prospective study of 100 consecutive infants of diabetic mothers (IDMs) at King Khalid University Hospital in Riyadh was undertaken. Family and maternal history, physical examination with special attention to the cardiovascular system, and echocardiography were performed. A total of 100 consecutive IDMs examined. The most common echocardiographic findings were patent ductus arteriosus (PDA; 70%), patent foramen ovale (68%), atrial septal defect (5%), small muscular ventricular septal defect (4%), mitral valve prolapse (2%), and pulmonary stenosis (1%). Hypertrophic cardiomyopathy (HCMP) was observed in 38% of cases, mainly hypertrophy of the interventricular septum. Severe forms of CHD encountered were D-transposition of great arteries, tetralogy of Fallot, and hypoplastic left heart syndrome (1% each). Isolated aortic stenosis and coarctation of aorta were not encountered in this series. Overall incidence of congenital heart disease was 15% after excluding PDA and HCMP. Maternal IDDM is a significant risk factor for CHD. Careful evaluation and early diagnosis of CHD in this high-risk group are highly indicated. There is a need for development of prenatal screening programs for CHD in our population.     

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.     

小于胎龄足月新生儿和适于胎龄足月新生儿血清瘦素及胰岛素水平的变化

目的 探讨不同类型足月新生儿血清瘦素及胰岛素水平及其与胎儿宫内生长发育的关系.方法 收集2009年9月-2010年5月在山西省儿童医院新生儿科住院的无严重疾病的88例足月新生儿的临床资料,其中44例小于胎龄儿(SGA),44例适于胎龄儿(AGA),用酶联免疫吸附测定法(ELISA)检测其出生24 h内血清瘦素及胰岛素水平,并分析血清瘦素和胰岛素水平与出生体质量的关系.采用SPSS 17.0软件进行统计学分析.结果 AGA组血清瘦素水平及血清胰岛素水平均高于SGA组(t=-73.624、-11.729,Pa<0.01);血清瘦素水平及血清胰岛素水平与出生体质量均呈正相关(r=0.96、0.91,Pa<0.01);血清瘦素与胰岛素之间也存在正相关(r=0.85,P<0.01).结论 瘦素及胰岛素在一定程度上反映了胎儿宫内生长发育的情况,在调节足月儿的生长代谢中发挥了重要作用.