Discussion:
In this prospective case-control study, we demonstrated that the fetal EFT value was higher in the group with GDM compared to the control group. Higher BMI and amniotic fluid values were found in the GDM group than in the control group. The optimal fetal EFT cut-off value for predicting GDM disease was determined as 1.55 mm with a specificity of 74.4% and sensitivity of 75.0%. Spearman’s correlation tests revealed statistically significant but weak positive correlations among fetal EFT value, 1-hour 100 gr OGTT, BMI, and birth weight. To the best of our knowledge, this is the first study to demonstrate the association between fetal EFT and perinatal outcomes of GDM disease and to identify an optimal cut-off value for fetal EFT for GDM in the 3rd trimester.
Epicardial fat, the visceral fat deposit of the heart, has endocrine, paracrine, and metabolic activities [13-16]. It secretes various inflammatory and proinflammatory factors and adipokines such as interleukin 6, omentin, tumor necrosis factor alpha, and adiponectin, which may be associated with metabolic syndrome, obesity, and heart disease [13-16]. It also serves as an important source of energy for the heart muscle by releasing free fatty acids, having a high storage capacity, and stimulating lipogenesis by insulin [13]. Recent studies have demonstrated that higher EFT levels may be associated with cardiometabolic events, particularly diabetes mellitus and coronary heart disease [17,20-22,27]. Therefore, it is proposed as a metabolic marker in adults.
It is well known that hyperinsulinemia and hyperglycemia resulting from disorders of glucose metabolism can lead to conditions such as polyhydramnios, macrosomia, fetal cardiac septal hypertrophy, changes in fetal cardiac morphology, and in subcutaneous adipose tissue distribution [1,6,7,28]. The altered fetal environment caused by diabetes results in greater and earlier fat deposition in epicardial fat than in other fat stores. Given the prolonged exposure to changes in the intrauterine fetal environment, it is expected that these conditions may occur more frequently in the third trimester. Studies have shown that long-term sequelae such as diabetes mellitus, metabolic syndrome, obesity, and heart disease may occur in children born to mothers with GDM [7-9]. It has been suggested that this situation may be caused by numerous metabolic processes triggered by high glucose and insulin levels, i.e., it may be the late reflection of diabetic fetopathy. Given this information, we examined fetal EFT in GDM in the third trimester and investigated the relationship between fetal EFT value and clinical parameters of the disease and perinatal outcomes.
The review of the literature regarding fetal EFT in diabetic pregnancies demonstrated that the significance of fetal EFT in diabetic pregnancies was first revealed in the study by Jackson et al. [22]. In this retrospective study, which included a small number of participants including 28 pregnant women diagnosed with type 1 and type 2 DM, and 28 healthy pregnant women, it was found that the mean fetal EFT value was higher in the fetuses of diabetic mothers compared with the control group. In this study, which included pregnant women in the 2nd trimester, it was shown that there was a statistically significant positive relationship between fetal EFT value and TFA, but no significant relationship was found between BMI and fetal EFT. In another retrospective study by Akkurt et al. involving 106 pregnant women diagnosed with pregestational DM and GDM, diabetic pregnancies had a higher fetal EFT value than the control group [23]. The first prospective case-control study of fetal EFT in GDM was conducted by Yavuz et al. In this study, 40 pregnant women diagnosed with GDM and 40 healthy pregnant women in the second trimester were enrolled [24]. It was found that fetal EFT values were higher in the women with GDM than in the control group. This study also found a positive and moderate correlation between 2-hour glucose level and fetal EFT. In the other study by Aydın et al. fetal EFT measurements were performed at 18-22 weeks of gestation [25]. They showed that the fetal EFT values of GDM patients were significantly higher than those of the control group. Moreover, correlation analysis showed that a strong positive correlation was observed between fetal EFT and Hba1c values and EFW.
Our study was designed as a prospective case-control study and included cases in the 3rd trimester with prolonged exposure to hyperinsulinemia and hyperglycemia. Consistent with previous studies, we found that the fetal EFT value was increased in GDM compared with the control group. Moreover, in contrast to other studies, we proposed a cut-off value of 1.55 mm with a specificity of 74.4% and a sensitivity of 75.0% that can predict GDM disease in 3rd trimester. Another strength of our study is that we also investigated the relationship between the EFT value, clinical parameters, and perinatal outcomes. In the study by Yavuz et.al, a positive and moderate correlation was shown between the 2-hour glucose level and fetal EFT, but we found a positive correlation between the 1-hour glucose level and fetal EFT. Although Aydın et.al. found positive correlations between Hba1c and fetal EFT at 18-22 weeks of gestation, we did not find any relationship between these parameters in the 3rd trimester. In agreement with the results of the study by Jackson et al and Aydın et.al, correlation tests in our study revealed a statistically significant but weak positive correlation between the EFT value and birth weight. Although higher NICU admission, higher C/S rate, and nonreassuring fetal heart rate recording patterns and lower Apgar scores at 1 minute and 5 minutes were found in the GDM group compared with the control group. There was no association between fetal EFT levels and these parameters.
The EFT measurement technique was first described by Iacobellis et al. [26]. The original description of the technique recommended that the measurement be performed during end systole to avoid possible changes, such as underestimation of EFT due to compression of epicardial adipose tissue during diastole. Because measurement at different sites and with different scan schedules results in different EFT values, standardization of the measured area increases the accuracy and value of the study. In contrast to other studies, the fact that our study is a prospective study allowed us to measure EFT during end systole. Another advantage of our study is that we performed the measurements based on a single reference point in a single plan, i.e., we standardized the measurement technique in each case.
This current study has some drawbacks. First, the groups in our study were not matched for BMI. However, in recent studies, similar to our study, no statistically significant association was found between BMI and EFT. Subgrouping by BMI values in GDM will contribute to our understanding of whether obesity, which plays a role in the development of diabetes, or diabetes itself is associated with high EFT. Second, our study did not examine the association with neonatal metabolic profile and fetal EFT. A prospective study with more participants and an examination of neonatal metabolic parameters will more clearly demonstrate the importance of fetal EFT and its impact on neonatal outcomes.
In conclusion, despite these drawbacks. This prospective case-control study has shown that one of the fetal effects of changes in glucose metabolism in pregnant women diagnosed with GDM may be an increase in fetal EFT value. In addition, we found a cut-off value that can predict GDM disease. This study, in which we examined the relationship between perinatal outcomes and fetal EFT in GDM, will shed light on other studies in the future adding larger randomized controlled, neonatal metabolic markers. With the contribution of future studies, the practicality of measuring EFT, which is accepted as a cardiometabolic marker in adults, in determining the impact of changes in the intrauterine environment in GDM on fetal metabolic status will become apparent.