Fetal heart biventricular diameter/foot length index as a diagnostic marker of fetal macrosomia in the second and third trimester of pregnancy

Abstract Purpose Fetal macrosomia may have serious effects on both mother and newborn, so it is important to correctly evaluate the fetal weight before delivery. Fetal routine biometry, height of the fundus of uterus, interventricular septal thickness seems to be very good but still not perfect. In our study the relation between fetal biventricular (AP) diameter and fetal foot length was elaborated in the 2nd and 3rd trimester of pregnancy. Material and methods The analyzed group (n = 423 fetuses) was divided into 2 subgroups: a control group (n = 109 fetuses) with normal biometry, normal heart anatomy and normal cardiac function, no extracardiac malformation, no extracardiac anomalies, gestational age ranged from 17.5 to 37.1 weeks of gestation, born at term with birth weight 3000–3600 g, and a study group (n = 314 fetuses) with gestational age 17.5–39.5 weeks. Among the study group there were 20 patients (n = 20 fetuses) with macrosomia defined as a neonatal birth weight of greater than or equal to 4000 g. The control group was used to generate normograms on fetal AP, foot length and AP/Foot Index. The Statistica 13.3 and Excel 365 software were used to calculate the sensitivity, specificity, positive predictive value and negative predictive values. Results In control group, the mean biventricular fetal heart (AP) measurement was 23 mm (12.9 mm–38 mm), the mean foot length was 43 mm (24 mm–71 mm), and the mean AP/Foot Index was 0.52 (0.40–0.65). The value of the AP/Foot Index in the second trimester of the control group was 0.53, whereas the AP/Foot Index in the third trimester of pregnancy was 0.51. The use of standard fetal biometry resulted in the prediction of macrosomia in 20%, whereas the AP/Foot index in addition to standard fetal biometry enabled the detection of 65% of macrosomia. Conclusions The AP/Foot Index higher than 0.52 has greater sensitivity and negative predictive value to detect macrosomia compared to standard ultrasound fetal biometry.


Introduction
Ultrasound examination is a noninvasive tool used for advanced evaluation of the anatomy and function of fetuses [1]. By definition, macrosomia is a fetal or newborn body weight greater than or equal to 4000 g [2]. Nevertheless, some authors argue that macrosomia occurs when the fetal weight assessed by ultrasound or the birth weight of a newborn is 4500 g [3]. A standard ultrasound assessment of the fetal body weight includes the measurement of the abdominal circumference, femur length and fetal head (biparietal diameter and head circumference) [4].
Factors such as previous episodes of fetal macrosomia, maternal obesity, maternal age and height, and maternal diseases, mainly diabetes, excessive weight gain and prolonged duration of pregnancy may lead to fetal macrosomia [5]. The diagnosis of fetal macrosomia is important to arrange further procedures, including cesarean section to reduce the risk of shoulder dystocia and plexus paralysis [6].
The already used markers for the prediction of fetal weight such as fetal biometry, height of the fundus of uterus and interventricular septal thickness seem to be good but not perfect [7]. There are still fetuses whose weight is underestimated in the 3rd trimester.
Can fetal foot be a good potential diagnostic marker of fetal macrosomia? The size of the heart is considered to be equal to the size of the fist [8], however it is very difficult to find and measure fetal hand. According to Leonardo Da Vinci, the foot should be two times bigger than the size of the heart [9]. Therefore, the analysis of the AP/Foot Index in healthy fetuses and in cases of macrosomia seems to be reasonable.

Materials and methods
This study focused on the elaboration of a new marker for better prediction of the fetal macrosomia and was performed based on the data retrieved from 2016 to 2020 from our unit computer database (Fetal Pathology of the Medical University of Lodz). The total number of 423 fetuses was divided into 2 groups: a control group (n ¼ 109) fetuses who presented normal biometry, normal cardiac anatomy (NHA), normal heart study, normal cardiac function (NHS), no extracardiac malformation (ECM) and no extracardiac anomalies (ECA) and their gestational age ranged from 17.5 weeks to 37.1 weeks of gestation and were born at term with a birth weight of 3000-3600 g. The fetuses were used to generate normal ranges of the fetal AP, foot length and AP/Foot Index. The study group (n ¼ 314) had gestational age ranged from 17.5 weeks to 39.5 weeks of gestation and presented normal biometry, normal cardiac anatomy (NHA), normal heart study, normal cardiac function (NHS), no extracardiac malformation (ECM) and no extracardiac anomalies (ECA). Among the study group there were 20 fetuses (20/314 ¼ 6.4%) with macrosomia defined as neonatal birth weight more than or equal to 4000 g. In this study, the definition of macrosomia as weight greater than or equal to 4000 g was applied.
The ultrasound examinations were performed with the use of the Voluson E10, Philips and Voluson Expert ultrasound machines with convex transabdominal transducers.
The transverse diameter of the heart (AP) was measured in short axis of the fetal chest in the 4chamber view at end-diastole with the calipers placed on the outer wall of the heart. The results of the AP measurements are presented in Figure 1. The measurements of both AP and fetal foot were performed two times by one ultrasound specialist. This provided a uniform measurement data.
Interobserver and intraobserver variations were not analyzed. The first author (W.S.) performed an analysis of the collected data.
The fetal foot was measured from the most posterior tip of the foot to the end of the first or second toe in the longitudinal plane and the results of the measurements were presented in Figure 2. Heart biventricular diameter (AP in mm) and fetal foot length (foot in mm) were retrieved from the last prenatal ultrasound examination before the delivery in cases having more than one visit. AP to foot index was calculated and presented in Figure 3. The gestational age used to generate all the figures were referred to gestational age evaluated based on fetal biometry.
The data on standard ultrasound biometry included the analysis of the estimated fetal weight, which was obtained by the measurement of the fetal BPD, HC, AC, and FL. The EFW values were automatically calculated by the built-in modules in the ultrasound machine software.
Linear regression analysis was based on Microsoft Statistical analysis. The Statistica 13.3 and Excel 365 software were used to calculate the sensitivity, specificity, positive predictive value and negative predictive value.

Results
Fetal heart biventricular diameter (AP) in mm from 17.5 week of gestation to 37.1 week of gestation in the control group of healthy fetuses is presented in Figure 1.
The results presented in Figure 1 demonstrate an upward trend in fetal heart biventricular diameter (AP) with the gestational age (in terms of weeks of gestation). The heart diameter (AP) in healthy fetuses (with normal biometry, normal cardiac anatomy and function, without extracardiac malformation and extracardiac anomalies observed) during pregnancy from the 17.5 week of gestation to the 37.1 week of gestation demonstrated the minimum value of 12.9 mm at 17th week of gestation, maximum value of 38 mm at term and the median value was 23 mm.
Measurement of the fetal foot in mm from 17.5 week of gestation to 37.1 week of gestation in the control group of healthy fetuses is presented in Figure 2.
The results presented in Figure 2 demonstrate an upward trend in fetal foot size with the gestational age (in terms of weeks of gestation). The size of the foot in healthy fetuses (with normal biometry, cardiac structure and function, without extracardiac malformation and extracardiac anomalies observed) during pregnancy from the 17.5 week of gestation to the 37.1 week of gestation was on average 43 mm, with the minimum value of 24 mm at 17th week of gestation, maximum value of 71 mm at term and the median value of 43 mm.
Measurement of the fetal AP to foot index (AP/F index) in mm from 17.5 week of gestation to 37.1 week of gestation in the study group is presented in Figure 3.
The results presented in Figure 3 demonstrate a virtually constant value of the fetal AP to foot index in relation to the gestational age (in terms of weeks of gestation). This index in healthy fetuses (with normal biometry, cardiac structure and function, without extracardiac malformation and extracardiac anomalies observed) during pregnancy from the 17.5 week of gestation to the 37.1 week of gestation demonstrated minimum value of 0.40, maximum value of 0.65 and median and average value of 0.52.
The value of the AP/Foot Index in the second trimester of the control group was 0.53, whereas the AP/Foot Index in the third trimester of pregnancy was 0.51. The value for both the second and third trimester was 0.52.
This value was accepted as a reference value for the analysis of 20 fetuses with macrosomia (Table 1). Based on routine fetal ultrasound biometry only 4 fetuses (20%) were predicted to be macrosomic. Based on the AP/Foot Index, 13 (65%) of fetuses could be predicted as fetal macrosomia.
The fetal AP/Foot Index used for the detection of fetal macrosomia showed 65% of sensitivity and 97.62% of specificity compared to standard biometry, which demonstrated 20% of sensitivity and 94.56% of specificity ( Table 2).
The fetuses with a neonatal birth weight of more than or equal to 4000 g are presented in Table 1 below.

Discussion
In prenatal ultrasound, it is important to correctly evaluate the fetal weight, and especially to detect fetal  macrosomia as it may have serious effects on both mother and newborn [1]. Proper diagnosis helps to take appropriate prevention. The already used ultrasound markers for prediction of fetal weight such as fetal biometry, height of the fundus of uterus, amniotic fluid index and interventricular septal thickness seem to be good however insufficient predictors [2][3][4][5]7].
Fetal macrosomia may have an effect on the child's obesity in the postnatal life. Fetuses with a weight of 3400-3499 g show a statistically significant increase in the risk of obesity in childhood [10]. According to Oc¸er et al. when fetal weight in the fetal biometry assessed by ultrasound during prenatal examinations exceeds 3400 g, this value should be considered a cutoff line for suspected fetal macrosomia in patients without diabetes [11]. In patients with diabetes, blood glucose control and the use of targeted treatment may reduce the risk of macrosomia [10][11][12][13]. The other very important maternal factors which may lead to the development of macrosomia in fetus include maternal age, BMI, blood pressure, PAPP-A, BhCG and PlGF levels, fetal CRL and uterine artery PI [14]. Recently, some studies have suggested that the analysis of the umbilical vein flow may constitute a useful marker for the prediction of fetal macrosomia [15].
Another very important risk factor for macrosomia is maternal obesity. There is a relationship between maternal BMI and the birth of LGA (large for gestational age) newborn [12]. If the fetus weight is more than 4000 g, there is an increased risk of complications related to delivery. Birth weight of more than 4500 g increases the risk factors for newborns health complications, whereas birth weight of more than 5000 g increases the risk of neonatal death [16].
The measurement of fetal biventricular diameter (AP) is very easy and is clinically important due to the fact that it can help in the assessment of fetal condition [17,18]. The obtained results are generally correlated to gestational age [19]. The minimum value of the fetal heart anterior-posterior (AP) measurement in our research was 12.9 mm and maximum value of AP was 38 mm at term. These values reflect the summary data presented in other studies [20,21].
The size of the heart is considered to be equal to the size of the fist of an adult [8]. According to Leonardo Da Vinci first observation, the foot is much longer than the hand [9], therefore the foot is larger than the heart and probably twice as big as the heart. This paper was aimed at verifying this hypothesis based on our own data.
The measurement of fetal foot length during daily ultrasound examinations is relatively easy and can be an additional useful marker for the evaluation of many conditions related to pregnancy [5,[22][23][24]. It may constitute an additional marker for the assessment of fetal gestational age and thus the weight [6,23,25,26]. The produced tables of measurements of fetal foot and fetal heart AP can constitute reference tables for daily ultrasound practice [11,27,28].
In our study, we presented a new biometric marker that could be used in addition to standard ones to focus on fetuses who might be out of normal weight range [29]. We analyzed the AP/Foot Index in relation to macrosomia in a period from the 15.6 week of gestation because the studied anatomical structures are developed quite well and can be easily observed during ultrasound examination.
The fetal foot was measured from the most posterior tip of the foot to the end of the first or second toe [30,31]. The choice of the toe depended on the length of the toewe decided to choose the longest one. It was important to provide an appropriate projection and make sure that the foot is not bent or somehow deformed due to the fact that it could affect the results of our index [30,32]. The results obtained in this study confirmed that the measurement of the fetal heart AP and foot and then the calculation of the AP/Foot Index in the second and third trimester of pregnancy seems to have a higher sensitivity and specificity compared to standard ultrasound biometry (ultrasound measurement of fetal BPD, HC, AC, FL). According to the majority of recommendations, including ISUOG, the measurement of fetal length, so far, is not recommended. It is only recommended to visualize fetal upper and lower limbs to make sure that they are present [29]. However, our index, which is relatively simple and easy to obtain, could be used in daily practice. The main limitation of this study is a small group of patients, which is due to the fact that measurement of the fetal foot is not easy. Our promising results still require further validation by conducting prospective studies on a larger group of fetuses, probably only in the 3rd trimester to be able to answer the question of how early enough we could detect fetal macrosomia using the Heart/Foot index. As an additional marker to the already existing ones, this index may be a very useful and promising marker for better prediction of fetal macrosomia.

Conclusions
The range of the fetal heart to foot index (AP/Foot Index) was 0.40 (min.)-0.65 (max.) with a median value of 0.52. The inclusion of the fetal heart to foot index, in addition to standard fetal biometry, enabled the detection of 65% of cases of macrosomia.

Disclosure statement
No potential conflict of interest was reported by the author(s).

Funding
The author(s) reported there is no funding associated with the work featured in this article.