The role of Umbilical Cord thickness, Interventricular Septum thickness and HbA1c levels in the prediction of Fetal Macrosomia in patients with Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) is defi ned as any degree of glucose intolerance with onset or fi rst recognition during pregnancy [1]. Maternal hyperglycemia leads to fetal hyperglycemia, which stimulates pancreatic islet cells and consequently fetal hyperinsulinemia. This state results in excessive fat tissue and total body size and the major reason for poor perinatal outcome is accelerated fetal growth and macrosomia [2,3]. Fetal macrosomia complicates 20–30 % of pregnancies with gestational diabetes mellitus (GDM) [4]. The presence of hyperglycemia infl uences biochemical transformation processes in the fetus [5]. The birth of a macrosomic fetus has been associated with adverse outcomes for both mother and fetus. Shoulder dystocia during delivery and related permanent brachial plexus injury may be seen. Both neonatal mortality and morbidity are higher in macrosomic fetuses compared with normal weight fetuses [6]. Maternal complications such as postpartum hemorrhage, infections, as well as third or fourth-degree vaginal lacerations may occur because of operative delivery. Today, cesarean sections performed for fetal macrosomia are not rare at all. Birth weight of the fetus is an important factor in determining the mode of delivery, but pelvic assessment should not be ignored [7]. Ultrasound-based birth weight prediction is still insuffi cient. Investigators have attempted to improve ultrasound-based prediction of fetal macrosomia by various methods, such as the assessment of fat deposition at different locations. None of these methods have gained wide popularity because of the inability to accurately estimate fetal weight against conventional biometric formulas [8,9]. The umbilical cord is responsible for materno-fetal blood fl ow. Normally, it is composed of two arteries permeated with venous blood and a vein that transports arterial blood, cushioned by a special type Rehab Mohamed Abdelrahman* and Mostafa Mostafa Salama


Introduction
Gestational diabetes mellitus (GDM) is defi ned as any degree of glucose intolerance with onset or fi rst recognition during pregnancy [1]. Maternal hyperglycemia leads to fetal hyperglycemia, which stimulates pancreatic islet cells and consequently fetal hyperinsulinemia. This state results in excessive fat tissue and total body size and the major reason for poor perinatal outcome is accelerated fetal growth and macrosomia [2,3]. Fetal macrosomia complicates 20-30 % of pregnancies with gestational diabetes mellitus (GDM) [4]. The presence of hyperglycemia infl uences biochemical transformation processes in the fetus [5]. The birth of a macrosomic fetus has been associated with adverse outcomes for both mother and fetus. Shoulder dystocia during delivery and related permanent brachial plexus injury may be seen. Both neonatal mortality and morbidity are higher in macrosomic fetuses compared with normal weight fetuses [6]. Maternal complications such as postpartum hemorrhage, infections, as well as third or fourth-degree vaginal lacerations may occur because of operative delivery. Today, cesarean sections performed for fetal macrosomia are not rare at all. Birth weight of the fetus is an important factor in determining the mode of delivery, but pelvic assessment should not be ignored [7].
Ultrasound-based birth weight prediction is still insuffi cient.
Investigators have attempted to improve ultrasound-based prediction of fetal macrosomia by various methods, such as the assessment of fat deposition at different locations.
None of these methods have gained wide popularity because of the inability to accurately estimate fetal weight against conventional biometric formulas [8,9]. The umbilical cord is responsible for materno-fetal blood fl ow. Normally, it is composed of two arteries permeated with venous blood and a vein that transports arterial blood, cushioned by a special type of mucous connective tissue known as Wharton's jelly and by remnants of the allantois [10]. Ultrasonographic examination of umbilical cord is usually limited to Doppler blood fl ow and assessment of the number of vessels. Also, the effect of umbilical cord morphology on the fetus and neonates has not been adequately shown [11][12][13]. Studies that have assessed umbilical cord components to predict fetal weight have shown that there is a correlation between umbilical cord diameter, area and fetal biometric parameters [14]. In addition, some observers have suggested that combination of these two methods should give more reliable results for estimating macrosomic fetuses.

Materials and Methods
This prospective case-control study was carried out at Ain shams University maternity hospital between April 2015 and October 2015 on 80 pregnant women.
They were divided into two groups: 40 pregnant women as case group with gestational diabetes mellitus and 40 non-diabetic pregnant women as control group after being approved by the local hospital ethics and research committee.
A verbal consent was taken from each patient.
Inclusion criteria were singleton gestation, gestational age over 27 weeks, intact membranes, normal umbilical morphology (two arteries and one vein) and Diagnosis of gestational diabetes.
Exclusion criteria were congenital anomalies, Multifetal pregnancy, maternal chronic diseases (hypertension, renal disease, cardiac and pulmonary disease, etc.) and Patients with a diagnosis such as oligohydramnios, preeclampsia and intrauterine growth retardation.
Ultrasound examination was performed at 36-37 weeks of gestation with Voluson E6 equipped with a 3.5 Hz transabdominal probe.
Ultrasound examination included fetal biometry (biparietal diameter, abdominal circumference, femur length) and estimated fetal weight were calculated automatically according to hadlock's formula additionally.
The sonographic cross sectional area of umbilical cord, the umbilical arteries and the umbilical vein were measured in a free loop of the umbilical cord using the software of the ultrasound device.
The cross-sectional area of Wharton's jelly was computed by subtracting the cross-sectional area of the vessels from that of the umbilical cord.
The interventricular septum thickness was measured. HbA1c levels was measured for diabetic patients.
These patients were followed up till delivery.
The neonates were weighed and fetal macrsomia was diagnosed if fetal weight is 4 kg or more.

Sample size justifi cation
A sample size of 40 diabetic and 40 non-diabetic pregnant women is enough to predict if there is a correlation between umbilical cord thicknesses, inter ventricular septum thickness, the HbA1c level and fetal macrosomia.

Statistical analysis
Statistical analysis will be performed using Microsoft Differences between variables of two groups will be analyzed by using student's T-Test (for quantitative parametric measures). Mann-Whitney's test V-test (for quantitative non-parametric measures). Person's correlation coeffi cient (for parametric values) and Spearmann's correlation coeffi cient (for rank variables). A receiver-operating characteristic (ROC) curve "cutoff" between two variables will be estimated in terms of sensitivity, specifi city, positive and negative predictive values and accuracy as well as likelihood ratios.

Statistical methods
Data were analyzed using IBM© SPSS© Statistics version 23 (IBM© Corp., Armonk, NY, USA). Normality of numerical data distribution was examined with the Shapiro-Wilk.
Continuous numerical variables were presented as mean ± SD and inter-group differences were compared using the unpaired Student t test. Discrete numerical variables were presented as median and interquartile range and betweengroup differences were compared using the Mann-Whitney U test. Categorical variables were presented as number (%) and inter-group differences were compared using Fisher's exact test. Receiver-operating characteristic (ROC) curve analysis was used to examine the value of umbilical cord dimensions, IVS thickness, or HbA1c level for discrimination between cases with gestational DM and normal controls, and for discrimination between women with or without macrosomic babies. The DeLong method was used to compare the area under different ROC curves. A two-sided p-value <0.05 was considered statistically signifi cant.

Discussion
Fetal macrosomia affects 20-30% of gestational diabetes pregnancies 4 . Delivery of a macrosomic fetus is correlated to unfavorable clinical outcomes at maternal and fetal levels.
Brachial plexus injuries and shoulder dystocia issues could be experienced in gestations affected by fetal macrosomia particularly when causative gestational DM exists. Macrosomic fetuses have higher incidence of morbidity and mortality      [17], concluded and revealed that fetuses of diabetic gestations are at risk of developing hypertrophic myocardial changes due to fetal hyperglycemia and hyper insulinism in spite of good capillary glycemic control. These apparently temporary changes chiefl y impact the fetal cardiac interventricular septum. In that research study mean+/-SD IVS value = 0.86±0.33 within fetuses with macrosomia and 0.65±0.24 within non macrosomic fetuses. IVS had a calculated sensitivity, specifi city, positive predictive value and negative predictive value 64.7%, 73%, 39.3%, 88.5% consecutively. That research study displayed that prenatal interventricular septal thickness is considered a reliable parameter in predictability of macrosomic fetus pathological development with cut off value > 0.71. This is in harmony with Gracia-Flores et al. research group [17]. as they mentioned and concluded that IVS thickness is the most sonographically important parameter to reveal the impact of glycemic control on the fetal heart development, the observation of a hypertrophic IVS requires evaluation and assessment of systemic, systolic and diastolic functional fl ow and parameters. Nonexistence of functional abnormalities in fetuses with hypertrophic IVS could not exclude fetal risk, since it could be correlated with greater perinatal mortality due to pathological development of diabetic fetopathy, and could denote a hidden and unknown poor maternal glycemic control.