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.