Volume 154, Issue 1 , Pages 24-26, January 2011
Fetal myocardial morphological and functional changes associated with well-controlled gestational diabetes
Article Outline
- Abstract
- 1. Introduction
- 2. Materials and methods
- 3. Results
- 4. Comment
- Conflict of interest
- References
- Copyright
Abstract
Objective
To make a global evaluation of the fetal myocardial changes in a well-controlled gestational diabetic population.
Study design
Twenty-four pregnant well-controlled diabetic patients were selected. Sixteen normal pregnancies were randomly collected as a control group. Measurements of morphological and functional myocardial parameters were performed. Data from the left ventricular outflow tract and peripheral Doppler data were obtained.
Result
The thickness of the interventricular septum was increased in diabetic pregnancies (p
<0.001). Tricuspid E/A index was the only functional parameter showing a significant variation, with lower values in diabetic pregnancies. Doppler parameters from the left ventricular outflow tract and peripheral Doppler waveforms were similar between groups.
Conclusion
A tendency towards interventricular septum hypertrophy was observed even in well-controlled diabetic pregnancies. Mild hypertrophic cardiac changes were not associated with abnormal cardiac function or signs of left ventricular outflow obstruction, although minor changes in right ventricular diastolic function were recorded.
Keywords: Diabetes, Hypertrophic congenital cardiomyopathy, Doppler, Fetal echocardiography
1. Introduction
Fetuses of diabetic mothers are at risk of myocardial hypertrophic changes due to fetal hyperglycemia and hyperinsulinism despite good capillary glycemic control. These apparently transient changes mainly affect the interventricular septum, and even a variable degree of left ventricular outflow obstruction has been described in severe cases. There are discordant results from diverse studies, as major changes seem to be related to poor maternal glycemic control (glycosylated hemoglobin (HbA1c)>6.5%) [1], [2], [3], [4], [5].
The objective of the present study was to perform a systematic morphological and functional evaluation of the fetal myocardial changes in well-controlled diabetic pregnancies and compare these findings with normal pregnancies from the same population.
2. Materials and methods
A prospective case-control study was performed to identify morphological and functional features of fetal hypertrophic cardiomyopathy in our population. A total of 24 pregnant women with gestational diabetes according to WHO criteria were selected from the Diabetes and Pregnancy Unit, La Paz University Hospital (Madrid). In addition, another group of 16 normal pregnancies were randomly collected from the same center.
The following criteria were used for exclusion: maternal hypertension, renal disease, multiple pregnancy, ultrasonographic evidence of congenital morphological anomalies and intrauterine growth restriction. HbA1c levels were obtained during pregnancy in diabetic women in order to follow up glycemic control and persistent values above 6.5% were excluded. All the patients in the control group underwent a normal 50g glucose challenge test, which was performed between 24 and 27 weeks. Pregestational body mass index (BMI) was recorded in all patients.
The project was approved by the Ethics Committee and informed consent was obtained from all the participants. All the patients underwent fetal echocardiographic examination between 31 and 35 weeks by specialized personnel. GE/Kretz Voluson 730 system (GE Healthcare, Milwaukee, WI) equipment with 7–2 or 6–4MHz curved linear arrays was used to perform ultrasound and Doppler examinations. All Doppler data were obtained with the patient in a slightly left lateral position and in the absence of maternal and fetal movements as well as of fetal breathing movements; fetal heart rate was within the range of 120–160 beats/min. For the Doppler measurements, the angle of insonation was maintained below 30° and corrected manually when necessary. Each patient underwent a single examination and only one measurement from each participant was included for the statistical analysis. The ultrasound operator was not informed as to whether the patient being examined was diabetic or not.
The interventricular septum (IVS) thickness was measured at end-diastole at a point in the mid-septal region perpendicular to the endocardial surface of the ventricular walls. Cardiothoracic index (CTI) and aortic, pulmonary, mitral and tricuspid valvular diameters were also obtained. Left ventricle myocardial performance index (MPI) and other indices of systolic (left ventricular fractional shortening) and diastolic (E/A index) cardiac function were collected. To obtain the MPI, the Doppler sample volume was positioned on the mitral and aortic valve in an apical 5-chamber view. The isovolumetric contraction, isovolumetric relaxation, and ejection times were determined using the valve click method [6]. The MPI was calculated as: (isovolumetric relaxation time)/(ejection time). Assessment of left ventricular fractional shortening using the M-mode cursor perpendicular to the interventricular septum was performed. The mitral and tricuspid flow waveforms were obtained by positioning the Doppler sample volume at the tip of the atrioventricular valve leaflets in an apical 4-chamber view. E/A diastolic index was calculated dividing the E wave (passive filling phase) velocity by the A wave velocity (atrial systolic contraction). The presence of atrioventricular regurgitation was assessed using color and pulsed Doppler and classified as present (holosystolic regurgitation) or absent.
Aortic arterial Doppler waveforms were obtained from the aorta in the long axis of the 5-chamber view of the heart. The peak or maximum velocity was obtained by measuring the highest velocity of the time velocity Doppler signal. The time-to-peak velocity was measured from the beginning of the waveform to the point of peak velocity. Left cardiac output in the aorta was calculated using the following equation:
Pulsed Doppler examination of the umbilical artery pulsatility index was performed in a free loop of the umbilical cord, that of the ductus venosus in a transverse or, alternatively, in a sagittal view of the fetal abdomen at its emergence from the portal vein, and examination of the middle cerebral artery in a transverse view of the fetal head immediately after its origin from the circle of Willis. The umbilical vein was sampled at the level of its intra-abdominal course and its Doppler pattern was classified as normal (no pulsations) or abnormal (venous pulsations).
Results were expressed as mean±standard deviation. Student's t-test was used for statistical analysis. Statistical significance was reached at p<0.05. Statistical analyses were carried out using the SPSS 13.0 software.
3. Results
Both groups were similar with regard to gestational age at the time of the ultrasound examination [32.58 weeks (SD 1.17) in the diabetic group and 32.12 weeks (SD 0.88) in the control group; p=0.17] and BMI [28.33 (SD 4.01) in the diabetic group and 25.65 (SD 2.95) in the control group; p=0.08]. The mean level for HbA1c in diabetic patients was 5.51% (SD 0.63).
On echocardiography, the thickness of the IVS was increased in diabetic pregnancies compared with the control group (p<0.001). There were no significant differences between the two groups in valvular diameters or CTI (Table 1). It was found that 66.6% (16/24) of the diabetic pregnancies were above the 95th percentile for the IVS thickness in the control group, which was estimated at 3.51mm.
Table 1. Morphological cardiac parameters.
| Parameter | Diabetes (N=24) | Control (N=16) | p |
|---|---|---|---|
| Interventricular septum thickness (mm) | 3.93 (SD 0.57) | 3.05 (SD 0.23) | <0.001 |
| Cardiothoracic index | 0.51 (SD 0.29) | 0.50 (SD 0.32) | 0.90 |
| Mitral valve diameter (mm) | 11.02 (SD 1.15) | 11.28 (SD 1.12) | 0.52 |
| Tricuspid valve diameter (mm) | 12.02 (SD 1.25) | 11.94 (SD 1.24) | 0.86 |
| Aortic valve diameter (mm) | 6.26 (SD 0.78) | 5.95 (SD 0.71) | 0.19 |
| Pulmonary valve diameter (mm) | 7.66 (SD 1.16) | 7.21 (SD 0.70) | 0.13 |
Tricuspid E/A index was the only myocardial function parameter which showed a significant variation. We found lower values for E/A diastolic index in the tricuspid valve in diabetic pregnancies. Mitral E/A index, left ventricular MPI and left ventricular fractional shortening did not show any significant differences between groups (Table 2). Color Doppler mapping did not identify any case of atrioventricular regurgitation.
Table 2. Myocardial function parameters.
| Parameter | Diabetes (N=24) | Control (N=16) | p |
|---|---|---|---|
| Mitral E/A index | 0.73 (SD 0.76) | 0.69 (SD 0.85) | 0.12 |
| Tricuspid E/A index | 0.72 (SD 0.64) | 0.78 (SD 0.84) | 0.03 |
| Left ventricular MPI | 0.32 (SD 0.77) | 0.31 (SD 0.92) | 0.70 |
| Left ventricular fractional shortening | 36.64 (SD 9.47) | 37.53 (SD 10.45) | 0.81 |
Doppler waveform parameters from the left ventricular outflow tract were similar between both groups (Table 3). There were no differences for umbilical artery Doppler, medium cerebral artery Doppler or ductus venosus Doppler (Table 4). We did not find any case of venous pulsations in the umbilical vein or reverse A wave in the ductus venosus.
Table 3. Left ventricular outflow tract Doppler parameters.
| Parameter | Diabetes (N=24) | Control (N=16) | p |
|---|---|---|---|
| Aortic peak velocity (cm/s) | 79.04 (SD 14.63) | 80.56 (SD 14.99) | 0.75 |
| Aortic time-to-peak velocity (ms) | 54.36 (SD 7.43) | 54.75 (SD 6.95) | 0.87 |
| Left cardiac output (mL/min) | 442.28 (SD 102.26) | 432.55 (SD 133.63) | 0.81 |
Table 4. Peripheral Doppler parameters.
| Parameter | Diabetes (N=24) | Control (N=16) | p |
|---|---|---|---|
| Umbilical artery PI | 0.97 (SD 0.14) | 0.93 (SD 0.14) | 0.50 |
| Middle cerebral artery PI | 2.24 (SD 0.42) | 2.19 (SD 0.49) | 0.74 |
| Ductus venosus PI | 0.57 (SD 0.12) | 0.63 (SD 0.13) | 0.25 |
4. Comment
All morphological and functional parameters were within normal ranges in both groups [7], although there were statistically significant differences between them. We found an enlargement of the interventricular septum thickness in fetuses of diabetic mothers compared to the control group. The rest of the morphological measurements showed no differences between groups.
Although there have been some published cases of severe intrauterine myocardial hypertrophic changes associated with signs of myocardial insufficiency [8], [9], there is still a controversy about the real effect of myocardial hypertrophy on global cardiac function. The population of this study, with well-controlled diabetic pregnancies and mild morphological changes, did not display any case of abnormal cardiac function or signs of left ventricular outflow obstruction [10].
There was a significant difference in tricuspid valve diastolic function, i.e., an early change in right ventricular filling probably due to altered cardiac compliance because of the increased hypertrophy of the free ventricular wall, as published in prior studies [4], [11]. This finding is consistent with the infiltrative nature of the fetal diabetic cardiomyopathy, which would mainly affect diastolic cardiac function, although none of the cases in this study showed a pathological diastolic E/A index or tricuspid regurgitation [12].
As concluded by other published studies, there were no changes in arterial peripheral Doppler values in the diabetic population [13], [14], [15], [16], [17].
There is still no agreement about the criteria for selecting the diabetic population at risk of fetal diabetic cardiomyopathy. There are also few analytical studies on functional myocardial changes in the presence of moderate and severe hypertrophic changes [4], [5]. This is difficult to achieve because these cases mainly correspond to poorly controlled diabetic pregnancies, which are not frequently found in specialized units.
The present study uses HbA1c as a glycemic control parameter and a random cut-off point in 6.5% for ‘well-controlled’ diabetic patients, similar to prior studies. It is well known, however, that HbA1c is not always an accurate predictor for diabetic complications. Further research should be done focusing on the value of other parameters of glycemic control (e.g., capillary glycemic determinations) for the prediction of diabetic-related fetal changes.
There are few publications dealing with the neonatal outcome of diabetic hypertrophic cardiomyopathy [8]. Left ventricular obstructive symptoms tend to be associated with severe interventricular septum growth with signs of cardiac insufficiency. Most frequently there is a mild or asymptomatic transitory clinical presentation. Further studies should include a systematic investigation relating ultrasound antenatal changes to neonatal outcome data.
In conclusion, this study upholds that any justification of routine late gestation fetal echocardiography in uncomplicated and well-controlled diabetic pregnancies is questionable due to the small chance of pathological findings. IVS thickness is the most valuable measurement to determine the effect of glycemic control on the fetal heart. Therefore, the finding of a hypertrophic IVS should be followed by a systematic systolic and diastolic functional study, as well as a detailed study of the left ventricular outflow tract. The absence of any abnormal function in a hypertrophic IVS does not exclude fetal risk, as it may be associated with higher perinatal mortality as part of a diabetic fetopathy, and may be the sign of an unknown poor maternal glycemic control.
Conflict of interest
The authors state no conflict of interest.
References
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PII: S0301-2115(10)00406-9
doi:10.1016/j.ejogrb.2010.08.002
© 2010 Elsevier Ireland Ltd. All rights reserved.
Volume 154, Issue 1 , Pages 24-26, January 2011
