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.     

Insulin and Leptin Levels in Appropriate-for-Gestational-Age Infants of Diabetic Mother

Objective

Intensified management of gestational diabetes mellitus can normalize birth weight. However, it is still unknown whether intrauterine exposure to maternal diabetes is a risk factor for changing hormone levels involved in the development of insulin resistance in these infants. We compared insulin and leptin levels in appropriate for gestational age (AGA) infants of diabetic and non diabetic mothers.

Methods

We performed a cross-sectional study in the department of Neonatology of the Hospital of Gynecology-Pediatrics, in Leon, Mexico. We evaluated 182 full term AGA newborns (86 infants of diabetic and 96 of non-diabetic mothers). A venous blood sample was taken from cord blood immediately after the separation of the placenta and glucose, insulin and leptin levels were measured. In all diabetic mothers HbA1c was also evaluated immediately post-partum.

Findings

Leptin, insulin and insulin resistance index were significantly higher in infants of diabetic mothers. Leptin levels were positive correlated with insulin, parents‘ body mass index and age in the entire group. In infants of diabetic mothers only insulin levels showed a significantly correlation, whereas in those of non-diabetic mothers only mothers‘ age was significantly correlated with leptin levels.

Conclusion

AGA infants of diabetic mothers showed higher leptin, insulin levels and insulin resistance index than those of non-diabetic mothers.     

Glucose disappearance in infants of diabetic mothers I. Relationship to maternal glucose tolerance and insulin production

Glucose disappearance and insulin response were determined in mother--infant pairs of normal, gestational diabetic and diabetic pregnancies following an intravenous glucose load. Mothers were studied in the third trimester of pregnancy and at least 6 wk postpartum. Significant differences were present in glucose disappearance and insulin response in both gestational diabetic and diabetic mothers during pregnancy compared with the control group. Infants were studied within 4 h of birth while fasting, and glucose and insulin levels followed through the first 3 days of life. Neonatal hypoglycemia did not occur and glucose disappearance (KT) was not different among the three groups. There was no correlation between maternal glucose tolerance or insulin production and that of their infants. The only distinguishing factor among the infants was higher insulin production in infants of diabetic mothers during the 60-min intravenous glucose tolerance test which persisted up to 4 h following the infusion. It is concluded that factors other than the degree of maternal glucose tolerance are responsible for the development of neonatal hypoglycemia in infants of diabetic mothers, most notably control of maternal diabetes, the amount of glucose infused immediately before delivery and neonatal glucose production.     

PLACENTAL TRANSFUSION IN INFANTS OF DIABETIC MOTHERS ELUCIDATED BY PLACENTAL RESIDUAL BLOOD VOLUME

The influence of the method of delivery and the clamping technique on the placental transfusion is investigated by measurement of the placental residual blood volume in 58 infants of diabetic mothers and in 65 infants of nondiabetic mothers. It is shown that infants of diabetic mothers delivered vaginally compared with infants of diabetic mothers delivered by caesarean section, have a larger placental residual blood volume, if early clamping is employed. This relation suggests that also in infants of diabetic mothers, a temporary deposition of the distribution of the foeto-placental blood volume between the infant and the placenta occurs during vaginal delivery, because of the impaired venous backflow to the infant. The difference in the placental residual blood volume is more pronounced for infants of diabetic mothers than for infants of non-diabetic mothers. Further, it is shown that the placental residual blood volume is significant larger in infants of diabetic mothers but only after vaginal delivery with early clamping, compared with the same group of infants of non-diabetic mothers.     

Ponderal index of large-for-gestational age infants: comparison between infants of diabetic and non-diabetic mothers

Ponderal index (PI) is a weight-height related parameter that is mainly used to assess the pattern of fetal growth in small-for-gestational age infants. We aimed to use PI for large-for-gestational age (LGA) infants who were born to diabetic or non-diabetic mothers, in order to predict the fetal growth pattern. One hundred sixty-six LGA infants born at the Department of Obstetrics, Hacettepe University Hospital, Ankara, Turkey were included in the study. The PI was calculated by using the following formula: PI = weight (g) x 100/(height, cm)3. Sixty-seven (40%) of these infants were born to diabetic mothers. Maternal age, maternal weight and maternal weight gain during pregnancy were similar in the diabetic and non-diabetic groups. Mean birthweight, height and head circumference were similar in both groups, but median PI of infants of diabetic mothers was significantly higher than of infants of non-diabetic mothers (3.02 and 2.89, respectively, p < 0.05). Fetal growth was different between LGA infants of diabetic and non-diabetic mothers, and PI provided useful information on the proportionality of fetal growth in LGA infants.     

Aortic intima-media thickness and lipid profile in macrosomic newborns

Macrosomia is associated with alterations in lipoprotein composition and concentration at birth. Exposure to diabetes in utero has been established as a significant risk factor for some of the components of metabolic syndrome. The aim of this study was to investigate the effect of macrosomia on lipid metabolism, aortic intima-media thickness (aIMT) and subsequent atherogenic risk in newborn infants. Aortic intima-media thickness was measured in 40 macrosomic neonates of diabetic mothers (group A), 30 macrosomic neonates of healthy mothers (group B) and 30 healthy neonates (group C). Lipid profile was determined in all infants and their mothers. Mean aIMT was significantly higher in macrosomic neonates of diabetic and healthy mothers (0.56±0.06 and 0.49±0.03 mm respectively) than in controls (0.39±0.03 mm). Weight-adjusted aIMT in macrosomic neonates of diabetic mothers (0.129±0.013 mm/kg) was significantly higher than in groups B and C (0.114±0.008 and 0.113±0.011 mm/kg respectively). There were significant alterations of total serum, high-density lipoprotein (HDL), very low-density lipoprotein (VLDL) cholesterols and triglyceride levels in the macrosomic neonates of diabetic mothers compared with controls. Macrosomia was associated with increased lipid concentrations. Macrosomic neonates of diabetic mothers have significantly higher aIMT with lipid alterations. This may play a role in the pathogenesis of atherosclerosis in adult life.     

Beta glucuronidase and hyperbilirubinaemia in breast fed infants of diabetic mothers.

A prospective study was performed comparing bilirubin concentrations in 10 breast fed term infants of diabetic mothers (IDM) to those of 10 breast fed normal term infants. The beta-glucuronidase concentrations in serum and breast milk were assayed in the respective mothers. Significantly higher bilirubin concentrations were noted in the IDM group. Serum and breast milk beta-glucuronidase concentrations were significantly higher in diabetic mothers as compared with those of non-diabetic mothers. We suggest that the high concentration of beta-glucuronidase in breast milk of diabetic mothers is an additional important cause leading to hyperbilirubinaemia in their breast fed infants.     

High incidence of Down's syndrome in infants of diabetic mothers

The incidence of Down''s syndrome was studied in 1870 infants of diabetic mothers out of 22 300 neonates born between January 1987 and April 1994 in our institution. All pregnancies were screened for diabetes and all cases of Down''s syndrome were confirmed by chromosome analysis.
Down''s syndrome (all trisomy 21) was diagnosed in 35 infants: seven were born to mothers with gestational diabetes and 28to non-diabetic mothers. The incidence of Down''s syndrome was higher in infants of diabetic mothers (3.75 per 1000 v 1.36 per 1000) (p= 0.02) with a relative risk of 2.75. No significant difference was found in maternal age between both groups (p= 0.67) and the rate of Down''s syndrome was higher in infants of diabetic mothers when compared with infants of non-diabetic mothers of similar age.
Down''s syndrome should be added to the congenital malformations already known to occur more frequently in infants of diabetic mothers.

     

Cerebral blood flow velocity and cardiac output in infants of insulin-dependent diabetic mothers.

Cardiac output and cerebral blood flow velocity in the anterior cerebral and internal carotid arteries were investigated in eight large-for-date infants of insulin-dependent diabetic mothers and 12 healthy term infants during the first four days of life using two-dimensional/pulsed Doppler ultrasound. Temporal mean flow velocity was used as an indicator of changes in cerebral blood flow. Six of the eight infants of diabetic mothers had ventricular septal hypertrophy with reduced cardiac outputs and stroke volumes. Mean flow velocity in both cerebral vessels showed a comparable pattern in both groups throughout the study period and was independent of mean arterial pressure, suggesting unaltered cerebral hemodynamics in the infants of diabetic mothers.     

Troponin T and NT ProBNP Levels in Gestational,Type 1 and Type 2 Diabetic Mothers and Macrosomic Infants

This study compares NT proBNP and troponin T levels in umbilical cord arterial blood and postnatal echocardiographic findings for infants of gestational and pregestational diabetic mothers and macrosomic infants. Twenty-seven infants of pregestational diabetic mothers, 61 infants of gestational diabetic mothers and 37 macrosomic infants of nondiabetic mothers were prospectively enrolled in this study along with a control group of 58 healthy infants of mothers without any pregestational or gestational disorders as the control group. All enrollees were born after 34 weeks of gestation. For this study, umbilical cord blood was drawn during delivery to determine NT proBNP and troponin T levels. Echocardiography was performed 24–72 h after the delivery. Umbilical cord troponin T and NT proBNP levels were found to be higher in the diabetic and macrosomic groups than in the control group (all of them p < 0.001). NT proBNP levels were positively correlated with interventricular septum thickness in the pregestational and gestational infants of diabetic mothers groups (r = 0.564 and r = 0.560, respectively, p < 0.01). Both pregestational and gestational diabetic mothers were divided into two groups according to HbA1c levels in the third trimester as good (<6.1 %) and suboptimal (>6.1 %) metabolic control. In the good and suboptimal metabolic control diabetic groups, NT proBNP levels were also positively correlated with interventricular septum thickness (r = 0.536 and r = 0.576, respectively, p < 0.01). In the suboptimal metabolic control diabetic group, NT proBNP was only found to be positively correlated with the left ventricular mass index (r = 0.586, p < 0.01). While there was no correlation in the myocardial performance index between infants of diabetic mothers and the control group, the myocardial performance index of macrosomic infants was lower than that of the control group (p = 0.017). Cardiac biomarkers (NT proBNP and troponin T) were elevated in infants of diabetic mothers and macrosomic infants. While there was a positive correlation between NT proBNP levels and cardiac structure in infants of pregestational and gestational diabetic mothers, there was no relationship between NT proBNP levels and cardiac function.     

Growth hormone levels during the first week of life in full-term normal infants, infants of diabetic mothers and in premature infants

Growth hormone levels during insulin- and glucose load have been studied, in normal infants, infants of diabetic mothers and in premature infants during the first week of life.
Base levels of HGH were elevated in all patients when compared to older infants. The highest levels were present on the first day of life. Lower levels were found in infants of diabetic mothers than in the other patients studied.
Insulin-induced hypoglycaemia increased HGH levels in all patients. The increase was more pronounced at the age of one day as compared, to 5—6 days if the absolute levels were compared. The increase was more moderate in infants of diabetic mothers. If the response to hypoglycaemia is expressed as the per cent maximal increment from basic levels no difference in response can be shown between the first day of life and the age of 5—6 days or between normal infants and infants of diabetic mothers. For premature infants the response in per cent increment was more pronounced at the end of the first week and of much higher degree than for other infants studied.
Hyperglycaemia induced an increase in HGH levels comparable to that found during hypoglycaemia. The differences between the groups studied are the same as for hypoglycaemia.     

Blood glucose and plasma amino acid concentrations in infants of diabetic mothers.

Postnatal blood glucose and individual plasma free amino acid levels were measured in 14 newborn infants of diabetic mothers. All infants had a significantly lower blood glucose concentration than normal controls but no significant correlation was observed between the blood glucose values and any of the amino acids determined. As regards the quantitative and qualitative changes of the plasma aminogram, the total concentration of amino acids and the level of a few individual amino acids (glycine, alanine, taurine, and valine) were significantly elevated in full-term babies. However, no significant difference was found in the total plasma concentration of amino acids between premature infants of diabetic mothers and premature control infants, but the plasma alanine level was higher in the former. It is of interest that total plasma amino acid, alanine, and glycine levels were elevated in the asphyxiated babies. This suggests that the postnatal hyperaminoacidemia observed in infants of diabetic mothers was due to birth asphyxia rather than to impaired gluconeogenesis. The possible role of a defective gluconeogenesis in the etiology of postnatal hypoglycemia in infants of diabetic mothers is not supported by these data.     

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.     

Cerebral Blood Flow Velocity and Cardiac Output in Infants of Insulin-Dependent Diabetic Mothers

ABSTRACT. Cardiac output and cerebral blood flow velocity in the anterior cerebral and internal carotid arteries were investigated in eight large-for-date infants of insulin-dependent diabetic mothers and 12 healthy term infants during the first four days of life using two-dimensional/pulsed Doppler ultrasound. Temporal mean flow velocity was used as an indicator of changes in cerebral blood flow. Six of the eight infants of diabetic mothers had ventricular septal hypertrophy with reduced cardiac outputs and stroke volumes. Mean flow velocity in both cerebral vessels showed a comparable pattern in both groups throughout the study period and was independent of mean arterial pressure, suggesting unaltered cerebral hemodynamics in the 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.     

Are the neonatal outcomes similar in large-for-gestational age infants delivered by women with or without gestational diabetes mellitus?

Background

Infants are considered large for gestational age (LGA) if their birth weight is greater than the 90th percentile for gestational age and they have an increased risk for adverse perinatal outcomes. Maternal diabetes is one of the factors affecting birthweight. However there are limited data on the perinatal outcomes of infants of gestational diabetic mothers. The aim of the present study was to compare the neonatal outcomes of LGA infants delivered by women with and without gestational diabetes mellitus.

Methods

This was a retrospective study of LGA infants of ??36 weeks of gestation born at the Gazi University Medical School Hospital during the period of 2006?C2009. Neonatal outcomes included hypoglycemia and polycythemia in the early neonatal period and hospital admissions. The Chi-square and Student??s t test were used for comparing variables.

Results

Seven hundred eligible infant-mother pairs were enrolled in the study. Eighty-seven of them (12.4%) were infants of gestational diabetic mothers and 613 (87.6%) were infants of non-diabetic mothers. The incidence of hypoglycemia at the first hour was higher in infants of diabetic mothers (12.8%) than in infants of non-diabetic mothers (5.3%) (P=0.014). Polycythemia was also more frequently observed in infants of the gestational diabetic mothers (9.3%) than in infants of the non-diabetic mothers (3.0%) (P=0.010). Although overall hospital admission rates were not different between the two groups, infants of diabetic mothers were more likely to be admitted because of resistant hypoglycemia (P=0.045).

Conclusions

The results of this study suggested that LGA infants of mothers with gestational diabetes mellitus were at a greater risk for hypoglycemia and polycythemia in the early neonatal period than LGA infants of nondiabetic mothers.     

A simple method for the assessment of infants of diabetic mothers at birth.

Twenty-five infants of diabetic mothers were analysed over a 6-month period from three hospitals to determine the value of arm/head ratio in the identification of infants of diabetic mothers at birth. The infants were grouped according to control of maternal disease and quality of intra-uterine growth. The sensitivity and specificity of arm/head ratio in the identification of infants based on maternal control were 82 and 93 per cent, respectively. The ratio is a simple method and is suggested for routine evaluation of infants of diabetic mothers especially in developing countries.     

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.     

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.     

Non-Enzymatic Glycation of Fetal Tissue in Diabetic Pregnancy

ABSTRACT. Non-enzymatic glycation of fetal tissue was studied by determining the glucitollysine content of umbilical cord extracts from twelve infants of diabetic mothers and fourteen infants of healthy, non-diabetic women (controls). The single, glycated amino-acid glycitollysine, which reflects the extent of glycation processes in biological samples, was measured by a standard amino acid ion exchange chromatography followed by reverse phase high pressure liquid chromatography. Infants of diabetic mothers had significantly higher cord glucitollysine levels than infants of control mothers (14.3+4.6 vs. 5.5+2.1 ng/mg dry tissue; M+SD, p <0.001). Moreover, five infants of diabetic mothers with congenital anomalies had strikingly high glucitollysine levels, higher than the mean +4 SD of the controls. We conclude, that non-enzymatic glycation of fetal tissue does occur as a result of an in utero exposure to cumulative glycemia. Major congenital anomalies in diabetic pregnancies are associated with a greater extent of non-enzymatic glycation of umbilical cord tissue.