Echocardiographic Evaluation of Cardiac Function in Infants of Mothers with Diabetes

Maryam Fatima; Shaad Abqari; Syed Manazir Ali; Seema Hakim

doi:10.4103/jiae.jiae_26_23

ORIGINAL RESEARCH

Year : 2023 | Volume : 7 | Issue : 2 | Page : 85-92

Echocardiographic Evaluation of Cardiac Function in Infants of Mothers with Diabetes

Maryam Fatima¹, Shaad Abqari¹, Syed Manazir Ali¹, Seema Hakim²
¹ Department of Pediatrics, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
² Department of Obstetrics and Gynaecology, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India

Date of Submission	09-May-2023
Date of Decision	09-Jun-2023
Date of Acceptance	11-Jun-2023
Date of Web Publication	30-Aug-2023

Correspondence Address:
Shaad Abqari
Department of Pediatrics, Jawaharlal Nehru Medical College, AMU, Aligarh, Uttar Pradesh
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jiae.jiae_26_23

Abstract

Introduction: A large number of pregnancies are complicated by diabetes mellitus in the mother which is associated with the risk of various cardiac structural and functional complications in the neonates. A diagnostic tool is needed to detect these dysfunctions early. In contrast to conventional pulsed-wave Doppler, which is influenced by heart rate and the impact of volume changes on transmitral flow, tissue Doppler imaging is the mode of echocardiography that is relatively independent of the loading state. Two-dimensional (2D) speckle-tracking echocardiography-derived strain imaging is a new technology increasingly being used to estimate cardiac systolic and diastolic dysfunction and has superior prognostic value for predicting major adverse cardiac events. Objective: The objective of this study was to evaluate cardiac function in neonates of mothers with diabetes on echocardiography and differences in the extent of cardiac dysfunction between neonates of well-controlled and poorly controlled mothers with diabetes. Methods: This is a cross-sectional observational study which was done on 152 neonates born to mothers with diabetes (22 overt vs. 130 gestational and 23 well-controlled vs. 129 poorly controlled) and 96 born to nondiabetic mothers. Three modes of echocardiography, i.e. M-mode, Doppler (pulsed wave and tissue), and 2D speckle-tracking echocardiography, were done and cardiac functions were compared among different groups. Results: Infants of diabetic mothers (IDMs) had lower ejection fraction on M-mode echocardiography and lower values of global longitudinal strain on 2D speckle-tracking echocardiography along with significantly lower values of mitral and tricuspid E velocity and E/A ratio with higher values of A velocity on pulsed-wave Doppler. Tissue Doppler showed higher left ventricle E/E' in IDM implying more systolic as well as diastolic dysfunction in IDM as compared to non-IDM. In neonates born to mothers with poorly controlled diabetes, Doppler showed lower values of mitral and tricuspid E/A ratio and left ventricle E'/A' ratio signifying more diastolic dysfunction as compared to neonates born to mothers having good glycemic control. Similarly, neonates born to mothers with pregestational diabetes had significantly deranged systolic and diastolic functions. Conclusions: IDMs have significant cardiac dysfunction on echocardiography which is also related to the degree of glycemic control and onset of diabetes.

Keywords: Cardiac dysfunction, echocardiography, infants of diabetic mother, two-dimensional speckle tracking

How to cite this article:
Fatima M, Abqari S, Ali SM, Hakim S. Echocardiographic Evaluation of Cardiac Function in Infants of Mothers with Diabetes. J Indian Acad Echocardiogr Cardiovasc Imaging 2023;7:85-92

How to cite this URL:
Fatima M, Abqari S, Ali SM, Hakim S. Echocardiographic Evaluation of Cardiac Function in Infants of Mothers with Diabetes. J Indian Acad Echocardiogr Cardiovasc Imaging [serial online] 2023 [cited 2023 Oct 3];7:85-92. Available from: https://jiaecho.org/text.asp?2023/7/2/85/384771

Introduction

Diabetes is the most common medical complication seen during pregnancy.^[1] It may be pregestational (overt) diabetes mellitus or gestational diabetes mellitus (GDM) depending on the time of onset of diabetes in relation to pregnancy. GDM is defined as any degree of glucose intolerance having its onset or first recognized during pregnancy.^[2]

Diabetes in pregnancy has adverse outcomes for the mother, fetus, and newborn. There is a risk of various congenital anomalies in newborns including cardiac diseases. Cardiovascular abnormality in infants of diabetic mothers (IDM) occurs either as congenital heart disease or cardiomyopathy. Cardiomyopathy is mainly due to poor glycemic control of maternal diabetes. Asymmetrical septal hypertrophy resulting in cardiac dysfunction is the most prevalent cardiac pathology seen in newborns of mothers with diabetes.^[3] Hypertrophic cardiomyopathy usually regresses spontaneously in the 1^st few months of life but asymptomatic neonates without cardiac hypertrophy develop subclinical decrease in systolic and diastolic myocardial function.^[4] There is an association between glycemic control and cardiac dysfunctions. Good maternal glycemic control during pregnancy assures normal fetal cardiac growth.^[5] Adverse perinatal outcomes could be reduced if hyperglycemia in mothers with diabetes is effectively treated.

There is a need to have a diagnostic tool which can detect these dysfunctions early. Tissue Doppler echocardiography can detect cardiac dysfunction early in IDMs.^[6] Tissue Doppler imaging is a noninvasive technique relatively independent of loading conditions in contrast to conventional pulsed wave Doppler which is affected by heart rate and the influence of volume changes on transmitral flow.

Two-dimensional (2D) speckle-tracking echocardiography-derived strain imaging is a recent technology to estimate cardiac systolic and diastolic function. It provides non-Doppler, angle-independent, and objective quantification of myocardial deformation and left ventricular (LV) systolic and diastolic dynamics by analyzing the motion of speckles identified on routine 2D echocardiographic images. Strain and strain rate can be measured by tracking the displacement of speckles during the cardiac cycle.^[7]

Methods

This cross-sectional study was conducted in the Neonatal unit and Pediatric cardiac unit of the Department of Pediatrics in collaboration with the Department of Obstetrics and Gynecology at Jawaharlal Nehru Medical College and Hospital, AMU Aligarh.

Approval of Institutional Ethical Committee of the hospital was taken before the commencement of the study.

The study population was classified into two groups as 152 neonates born to mothers with diabetes and 96 born to nondiabetic mothers and were evaluated between 24 and 72 h of life. Informed written consent was obtained from parents of neonates satisfying the inclusion and exclusion criteria and eligible for participation in the study [Figure 1].

Figure 1: Flowchart of the study. 2D: Two dimensional

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Neonates were excluded if they were born <37 weeks, small for gestational age (birth weight <10^th centile), or had intrauterine growth retardation, perinatal asphyxia or APGAR score <7 at 5 min, required mechanical ventilation, or had in utero infections, metabolic disorders, some major congenital malformations, congenital heart disease, or apparent chromosomal anomaly. Furthermore, neonates born to mothers with some chronic illness such as hypertension, preeclampsia, or heart disease were excluded.

Cardiovascular function was assessed echocardiographically using GE Vivid E95 3D/4D echocardiography machine. Three modes of echocardiography were used, i.e. M-Mode, tissue Doppler, and 2D speckle-tracking echocardiography.

M-mode parameters studied were LV diameter during systole [LVDs] and diastole (LVDd), interventricular septum thickness during systole (IVSs) and diastole, LV posterior wall thickness during systole and diastole, and LV ejection fraction.

Pulsed-wave Doppler measures included peak early (E) and late (A) diastolic velocities and E/A ratio across mitral and tricuspid valves.

On tissue Doppler imaging, the velocity of the longitudinal motion of the mitral annulus, tricuspid annulus, and the basal part of interventricular septum was measured in the form of systolic myocardial velocities (S') at the basal segments of the lateral LV wall, septal wall, and right ventricular free wall, as well as early and late diastolic myocardial velocities and their ratio (E', A', and E'/A', respectively) of the same basal segments.

2D speckle-tracking echocardiography was done to measure LV global longitudinal strain (GLS).

Comparison between cardiac functions in neonates of diabetic mothers with a neonate born to nondiabetic mother was done, and further subgroup analysis was done between (1) well-controlled (n = 129) versus poorly controlled diabetes (n = 23) on the basis of glycemic control (defined as glycated hemoglobin level <7 g/dL or fasting blood glucose <95 mg/dL and postprandial blood glucose <140 mg/dL at 1 h and <120 mg/dL at 2 h (60) and (2) overt diabetes (n = 22) versus GDM (n = 130).

Data analysis

All statistical calculations were performed using SPSS 25 (Statistical package for Social Sciences, Armonk, NY, USA). Continuous variables were expressed as means, standard deviation and confidence interval (95%), and categorical variables as frequency and percentage. A probability value (P value) <0.05 was considered statistically significant. All comparisons between the two groups for continuous variables were done using Student's “t” test. To define associations between nonparametric categorical variables, Chi-square test was used.

Results

All of the 248 studied subjects were evaluated between 24 and 72 h of life and there were 129 males and 119 females. Majority of neonates born to nondiabetic mothers had birth weights between 2.5 and 3 kg, while among IDM, a large proportion of them had birth weights in 2.5–3 kg and 3–3.5 kg range. A significant number of IDM also had birth weights more than 3.5 kg [Table 1]. Among 152 mothers with diabetes, 22 were having pregestational (overt) diabetes and 130 were having GDM. Maternal hyperglycemia was well controlled in 129 (84.9%) mothers but 23 (15.1%) had poorly controlled diabetes.

Table 1: Baseline characteristics

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Cardiac function in infants of diabetic mothers versus infants of nondiabetic mothers

As shown in [Table 2], on M-mode, IDM showed a significant reduction in mean LVDs (P = 0.016) and LVDd (P < 0.001). Posterior wall thickness during diastole and systole was significantly raised in IDM (P < 0.001). Interventricular septal thickness during diastole was significantly increased in IDM (P = 0.001). LV ejection fraction was also significantly reduced (P < 0.001). This decrease in ejection fraction signifies some degree of systolic dysfunction in neonates born to mothers with diabetes. On comparing pulsed-wave Doppler parameters, there was a significant reduction in mitral and tricuspid E velocities in IDM versus non-IDM while the corresponding A velocities were significantly more in IDM (P < 0.001). As a result, the E/A ratios in IDM were significantly lower (P < 0.001) than in non-IDM. Tissue Doppler echocardiography showed significantly lower E' velocity (P < 0.001) and E'/A' ratios (P < 0.001) of interventricular septum and right and left ventricles. LV E/E' ratio was significantly more in IDM (<0.001). This indicated evidence of diastolic dysfunction in IDM. However, there was no significant difference in the S' velocity of the interventricular septum and left and right ventricles. On 2D speckle tracking echocardiography among IDM, the mean value of GLS was − 13.99 ± 4.12% and it was significantly impaired as compared to non-IDMs (−18.83 ± 1.05) with P < 0.001.

Table 2: Comparison between echocardiographic parameters of infants of diabetic mothers versus noninfants of diabetic mothers

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Effect of type of maternal diabetes on cardiac functions

On comparing cardiac functions in those born to overt (pregestational) versus gestational diabetic mothers, M-mode echocardiography and pulsed-wave Doppler did not show any significant difference in various parameters [Table 3]. Tissue Doppler echocardiography showed that interventricular septum velocities and ratio were not significantly different among the two groups. LV E'/A' was increased but not statistically significant. LV A' was significantly higher (P < 0.003) in IDM born to the pregestational group as compared to the gestational group. Furthermore, LV E/E' ratio was significantly more (P = 0.012) in the pregestational group than the gestational group. All this signifies more diastolic dysfunction in neonates born to mothers having pregestational diabetes. Right ventricular (RV) E', A', S', and E'/A' showed no significant difference between pregestational and gestational groups. On 2D speckle tracking echocardiography, LV GLS was significantly deranged (P = 0.001) in the pregestational group than gestational.

Table 3: Comparison between echocardiographic parameters of infants born to overt versus gestational diabetic mother

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Effect of maternal glycemic control on cardiac functions of infants of diabetic mother

Comparison was also made between the echocardiographic parameters of those born to mothers with poorly controlled diabetes (23) and those to well-controlled maternal diabetes (129) [Table 4]. No significant difference was seen in M-mode parameters of the two groups. On pulsed-wave Doppler, no significant difference in mitral E, A velocity, tricuspid E, and A velocity was seen. Mitral E/A ratio was lower in neonates of poorly controlled diabetic mothers but it was not significantly different. However, tricuspid E/A ratio was significantly lower (P = 0.011) in the poorly controlled group than the value seen in the well-controlled group. Tissue Doppler parameters showed that IVS S' and left ventricle E'/A' were significantly lower (P = 0.016 and P = 0.036, respectively) in the poorly controlled group as compared to the well-controlled group. Rest other parameters including LV E/E', LV E', A', and RV velocities showed no significant difference. 2D speckle tracking echocardiography showed no significant difference in GLS between the two groups.

Table 4: Comparison between echocardiographic parameters of neonates born to poorly controlled versus well-controlled diabetic mother

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Discussion

Large numbers of pregnancies are complicated by diabetes mellitus which can impact neonatal outcomes. Women with diabetes in pregnancy whether pregestational or gestational are at risk for many fetal complications including congenital heart disease as well as cardiac dysfunctions, some specific to pregnancy, and while others due to diabetes. Most of the problems that occur in the infant of a diabetic mother are the result of fetal hyperglycemia and hyperinsulinism. A study by Kozák-Bárány et al.^[8] showed that infants of mothers with well-controlled pregestational or gestational diabetes had impaired LV relaxation. They related this finding to the effects of maternal hyperglycemia during the third trimester and subsequent fetal hyperinsulinemia leading to neonatal cardiac hypertrophy.

Cardiac performance in infants of diabetic mothers versus infants of nondiabetic mothers

In our study, IDM showed evidence of systolic dysfunction in the form of reduced ejection fraction on echocardiography. Demiroren et al.^[9] in their study found that LVD during systole and diastole were significantly lower and IVS thickness and LV posterior wall were more in cases as compared to controls but LV ejection fraction was increased in IDMs. Iwashima et al.^[10] and Ghandi et al.^[11] found that median interventricular septal thickness during diastole was more in infants of GDM mothers when compared to controls.

The study conducted by Sobeih et al.^[6] had results similar to our study in the form of lower values of mitral and tricuspid E velocity and E/A ratio in IDM on pulsed-wave Doppler but no significant difference in A velocity of mitral and tricuspid inflow. On tissue Doppler, IDM showed lower values of septal, LV, and RV E' and lower E'/A' of septum and left ventricle. Septal, LV, and RV A' were significantly higher in IDM as compared to controls. Mehta et al.^[12] observed an altered diastolic filling pattern in the form of shifting of ventricular filling from early to late filling phase and lower E/A ratio in infants of mothers with GDM. Results of study by Zablah et al.^[4] showed significantly lower values of LV, RV, and IVS E' with high value of LV E/E'. In a study by Ghandi et al.,^[11] the left ventricle had significantly lower values of E velocity and E/A ratio on pulsed-wave Doppler and E' and E'/A' ratio on tissue Doppler. Arslan et al.^[13] showed statistically significant differences in E, A, E/A, and E'/A' between cases and controls signifying abnormal diastolic function in neonates born to mothers with diabetes. Çimen and Karaaslan.^[14] observed a significant reduction in left and right ventricle myocardial velocities and the E/A ratio was <1 in infants of mothers with diabetes.

2D speckle tracking echocardiography showed significantly deranged values of GLS which signifies systolic dysfunction in IDM and this was in congruence with the results observed by Al-Biltagi et al.^[15] and Iwashima et al.^[10]

Cardiac performance in infants of diabetic mothers born to pregestational versus gestational diabetes

M-mode and pulsed-wave Doppler showed no significant difference between the two groups. This was similar to the results in a study by Al-Biltagi et al.^[15] On tissue Doppler, they found that statistically significant difference (lower) was present only in RV E'/A' between pregestational and gestational diabetic newborns. In a study conducted by Kozák-Bárány et al.,^[8] no significant difference was found in LV diastolic function parameters on Doppler echocardiography between neonates born to pregestational and gestational diabetes.

Cardiac performance in infants of diabetic mothers born to mothers with well-controlled versus poorly controlled diabetes

Our study showed that in those born to mothers with poorly controlled diabetes, Doppler showed lower values of mitral and tricuspid E/A ratio and left ventricle E'/A' ratio signifying more diastolic dysfunction than in those born to mothers having good glycemic control.

Sobeih et al.^[6] found similar results in the form of statistically lower values of mitral E/A ratio, tricuspid E velocity, and E/A ratio with higher mitral A velocity in the poorly controlled group. Furthermore, they observed significantly lower values of septal E', E'/A', and LV E' with higher LV A' velocity in neonates born to mothers with poor glycemic control. Their study showed more LV diastolic dysfunction in the poorly controlled group on both pulsed-wave Doppler and tissue Doppler echocardiography as compared to the well-controlled group.

[Table 5] summarizes the studies done on IDMs involving various echocardiographic parameters suggestive of significant cardiac involvement among these neonates. We have tried to incorporate all the available parameters to look into the extent of involvement among IDM.

Table 5: Summary of studies done on IDMs involving various echocardiographic parameters

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The present study was undertaken to study the change in echocardiographic parameters in neonates with mothers with diabetes and to see the impact of long-standing diabetes which was not adequately controlled on these parameters. The attempt was to detect cardiac dysfunction early even when the child was not clinically symptomatic. The results are relevant for further research to study the impact of subclinical cardiac dysfunction on the outcomes, especially of sick newborns.

Limitations

Our study had few limitations such as relatively small sample size and unavailability of follow-up data of infants with cardiac dysfunction.

Conclusions

IDMs have more cardiac dysfunctions as seen on M-mode, Doppler, and 2D speckle-tracking echocardiography. On comparing parameters of cardiac function between neonates born to pregestational and gestational diabetic mothers, there was evidence of more diastolic as well as systolic dysfunction in the pregestational group. Furthermore, those in the poorly controlled group had more diastolic dysfunction than those born to mothers having good glycemic control.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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