الفهرس 
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Abstract
Summary
Diabetes mellitus is a metabolic disorder characterized by hyperglycemia and insufficiency of secretion or action of endogenous insulin. Maternal diabetes mellitus is associated with a five fold increase in risk of cardiovascular malformations in infants of diabetic mothers..
Echocardiography has become the primary imaging tool in the diagnosis and assessment of congenital and acquired heart disease in infants, children, and adolescents. Transthoracic echocardiography (TTE) is an ideal tool for cardiac assessment, as it is non invasive, portable, and efficacious in providing detailed anatomic, hemodynamic, and physiologic information about the pediatric heart.
This cross-sectional study case study was conducted on 60 infant of diabetic mothers admitted in NICU of Al-Azhar university hospitals and Banha university hospitals in the period from Feburauary2011 to November2011.
• Each of the newly born infants included in this study was subjected to the following: Family history of previous affected siblings:detailed family history to detect any previous affected sibling suffered from congenital heart disease .
• Thorough history taking specially maternal DM history ,duration,control& its treatment. 16 of the mothers had pregestational DM and 44 had gestational DM .32 of the mothers had glycosylated hemoglobin (HbA1c) just at or shortly before delivery. Normal range: 4.2-6.2% Diabetic Good control: 5.5-6.8%
Fair control:6.8-7.6%
Poor control: Above 7.6%
28 of them were uncontrolled (Above 7.6%),4 of them were controlled(5.5-6.8%).the rest of the mothers (28) were known to be controlled by history of their general condition and their serial random glucose level.It is important to mention that all the pregestational mothers (16) had HbA1c 9 of them were uncontrolled and 7 of them were controlled.0nly 16 of the gestational DM mothers had HbA1c the rest of them admitted that they did not need to have HbA1c because their general condition and their serial random blood glucose were accepted.the 60 infants included in this study were subgrouped according to the type of maternal DM(gestational and pregestational), the state of control of maternal DM(controlled and uncontrolled),sex(male and female)and weight (≥ 4 kg and< 4 kg).
• Full clinical assessment including general and local examination to detect any other associated condition or congenital anomalies .
• blood glucose measures using Hemo-Glucotest, 20-800 (Boehringer Manheim) 1 hour after delivery.
• ECG,chest x ray.to detect any abnormalities and malformation.
- Neonatal echocardiography was performed in the first three days of life and cardiac measurements were determined by 2D, cross sectional M mode & color Doppler study echocardiography. Echocardiographic measurements were: interventricular septum diameter (IVS), posterior wall thickness, left ventricular end-systolic (LVES), left ventricular end-diastolic (LVED), left atrium (LA) and aorta diameters. Two-D echocardiograms were performed, including subcostal, parasternal apical and suprasternal views. M-mode measurements in the short axis parasternal view of LVED, LVES diameters and IVS, PW thickness were used for the calculation of the ejection fraction(EF%) and IVS,PW respectively.
The neonates under study were subdivided according to their initial presentations after delivery into the following groups:
Group 1(Pregestational IDM):It comprised sixteen (26.7%) infants of diabetic mothers .
Group 2(Gestational IDM): It included forty-four (73.3%) infants of diabetic mother.
The results of the current study are:
As regards birth weight of the sixty infants included in this study the mean birth weight was 3.65± 0.76 and the weight ranged between 1.75-5.25 (table 1).22 infants were ≥ 4kg (36.6%),macrosomia was defined as birth weight above 90th percentile or ≥ 4kg. Potter and Kicklighter, (2009) declared that fetal macrosomia occurs in 15-45% of diabetic pregnancies, but this was discordant with results of Arteaga et al. (2008) who found 18% macrosomia in infants of diabetic mothers compared to controls. Kernaghan et al. (2007) found birth weights of the infants of diabetic mothers higher than those of a reference population. Catalone et al. (2007) declared that not all infants of women with diabetes mellitus are macrosomic and, under certain circumstances, because of the interaction of genes and environment, can present as small for gestational age at birth.
There were 38 males (63.3%) and 22 females (36.7%) (table 1). Male gender had high percentage in our 60 IDMS ,also male gender was significantly higher in pregestational group than in gestational group(table 3) . But, on the contrary Potter and Kicklighter (2006) reported that frequency of involvement in boy and girl IDMs is equal and Kozak-Barany et al. (2004) found that males are more involved as infants of diabetic mothers than females.
In the current study there was 16 infants among 60 showed respiratory distress symptoms (26.7%)(table1) with insignificant difference between the pregestational group and the gestational group(table 4) . Barnes-Powell et al. (2007) declared that infants of diabetic mothers are more likely to have respiratory symptoms in the newborn period from either RDS (surfactant deficiency) or retained fetal lung fluid (transient tachypnea of the newborn) after operative delivery. Hermensen and Lorah, (2007) found the incidence of respiratory disorders approximately six times higher in infants whose mothers have diabetes, because of delayed pulmonary maturity despite macrosomia.
In our present study the mean neonatal random blood sugar was 35.95 ± 10.87mg/dl(table 5). Maayan-Metzger et al. (2009) found the main risk factors for developing glucose concentrations below ’normoglycemia’ in the first day of life were large size for gestational age and maternal insulin-dependent diabetes mellitus. In addition, according to their opinion, infants who were large for gestational age tended to have more ’moderate hypoglycemia’ when born to diabetic mothers compared to small and appropriate-for-gestational-age infants. Iafusco et al. (2008) declared that in the diabetic pregnant the stress during the labour usually induces a further increase of women blood glucose levels with a consequent rise of the fetal production of insulin and increased risk of hypoglycemia. On comparing neonatal random blood sugar done initially within the first hour after delivery in the present study between the two groups(pregestational and gestational) , there was insignificantly difference between the two groups,the mean blood sugar in the pregestational group was (39.94±9.75) while it was (34.50±10.99)in the gestational group(table 7).
In our study the echocardiographic studying of the frequency distribution of congenital heart diseases and hypertrophic cardiomyopathy among the 60 IDM under study, it was found that it was 35 IDM with congenital heart affection (58.3%),21 infants had PDA(35%),4 infants had VSD(6.7%),6 infants had PFO(10%) and 16 infants had hypertrophic cardiomyopathy(26.7%) (table 6) . Wren et al. ( 2003) found that maternal diabetes mellitus is associated with a five fold increase in risk of cardiovascular malformations in infants of diabetic mothers .These malformations include endocardial cushion defects, persistent truncus arteriosus and ventricular septal defects which appear to result from aberrant cardiac neural crest development. A recent study reported that the exposure of cardiac neural crest cells to elevated glucose leads to congenital heart defects (Roest et al., 2007). Morgan et al. (2008) found that in diabetic pregnancy, oxidative stress, which inhibits expression of genes required for CNC(Cardiac Nueral Crest) viability, causes subsequent CNC depletion by apoptosis during migration, which leads to outflow tract defects.
In this study, it was found that the frequency of congenital heart defects in pregestational and gestational IDM was patent ductus arteriosus which was much more encountered in pregeatational group, while 9/16 infants had PDA (56.2%) and it was significantly higher than gestational group,P value<0.05, where PDA was only 12/44 (27.3%)(table 9). Patent foramen ovale was present in 4/16 IDMs ( 25%)in pregestational group and it was significantly higher than gestational group ,P value<0.05, where it was only in 2 /44 IDM(4.5%)(table 9), and ventricular septum defect was present in 3 /16 pregestational IDM (18.8%) while it was only in 1/44 gestational IDM(2.3%) with no significant difference(table 9). Corrigan et al. (2009) declared that maternal diabetes mellitus is associated with increased teratogenesis, which can occur in pregestational type 1 and type 2 diabetes. Cardiac defects and with neural tube defects are the most common malformations observed in fetuses of pregestational diabetic mothers. The sequelae of maternal pregestational diabetes, such as modulating insulin levels, altered fat levels, and increased reactive oxygen species, may play a role in fetal damage during diabetic pregnancy, hyperglycemia is thought to be the primary teratogen, causing particularly adverse effects on cardiovascular development. Abu-Sulaiman & Subaih, (2004) found the most common congenital heart defects in IDMs were patent ductus arteriosus (70%), patent foramen ovale (68%), atrial septal defect (5%), small muscular ventricular septal defect (4%), mitral valve prolapse (2%), and pulmonary stenosis (1%). Narchi & Kulaylat, (2000) found that the most frequent cardiac anomalies in IDMs include ventricular septal defect, transposition of great arteries and aortic stenosis. Defects involving the great arteries, including truncus arteriosus and double outlet right ventricle, are also more prevalent in IDMs
There was significant difference(p value<0.05) in frequency of HCM(hypertrophic cardiomyopathy) between pregestational and gestational diabetes ,it was present in 9/16 IDM(56.2%) in pregestational group while it was in 7/44 IDM(9.76%)(table 9).(Ulmo et al 2007) also found that HCM was much encountered in pregestational diabetes (type 1and type 2)than in gestational diabetes .
On comparing echocardiographic measurements of infants of pre-gestational and gestational diabetes enrolled in this study it was found that there was statistical significant difference in LA measurement between pregestational IDM (1.23± 0.19cm) while it was (1.04± 0.19cm) in gestational IDM (table 8). Similarly, there was significant statistical difference in FS and AO respectively between pregestational group FS(45.41±15.18),AO(1.02±0.13) and gestational group FS(38.45±9.41),AO(0.93±0.16)(table 8).High significant statistical difference(p value <0.001) in LVPW(left ventricle posterior wall) was found between pregestational group mean ,LVPW was(0.52±0.14)and gestational group, LVPW was (0.37±0.11)(table 8) . Similarly Ullmo et al. (2007) found that gestational diabetes showed lowest percentage of pathological ventricular hypertrophy when compared to pre-gestational diabetes.On the contrary Demiroren et al. (2005) compared infants of pre-gestational and gestational diabetes they found no significant difference between the two groups as regard echocardiographic measurements of both systolic and diastolic dimensions. Kozac-Barney et al, (2004) also didn’t find significant difference in systolic and diastolic dimensions between pre-gestational and gestational diabetic mothers when they were studying impaired left ventricular diastolic functions in newborn infants of mothers with pregestational or gestational diabetes. Ullmo et al. (2007) found that gestational diabetes showed lowest percentage of pathological ventricular hypertrophy when compared to pre-gestational diabetes.
In the current study there was significant statistical difference (p value <0.05)regarding PDA between uncontrolled and controlled diabetes(table 12). Corrigan et al. (2009) declared that fetal cardiac defects are associated with raised maternal glycosylated hemoglobin levels and are up to five times more likely in infants of mothers with pregestational diabetes compared with those without diabetes.
Fetal macrosomia has been defined in several different ways, including two standard deviations above the mean (Lee, 2008), birth weight of 4000-4500 g or greater than 90% for gestational age after correcting for neonatal sex and ethnicity (Jazayeri &Contreras, 2005). In the current study there was significant statistical difference (p value<0.05)regarding LVPW(left ventricle posterior wall)between newborn≥4kg and newborn <4kg(table 20).A high statistical difference (p value<0.001)was noted regarding FS(fractional shortening)between newborn≥4kg and newborn <4kg(table 20).
. In support to our results Kampmann et al. (2000) who studied 200 healthy neonates in central Europe stated that the strongest correlation was obtained between M-mode echocardiographic measures and birth weight. In addition, Ibrahim, (2005) who studied normal echocardiographic patterns of Egyptian neonates found significant correlation between echocardiographic measurements and neonatal body weight. Moreover, Czeszyńska et al. (2004) found significant positive correlation between IVS, LVDd, Ao& LV dimensions and birth weight of infants of diabetic mothers.