Evaluation of fetal heart size, morphology and function with fetal growth restriction using fetal HQ (2024)

Background

Fetal growth restriction (FGR) is associated with various perinatal complications. Limited research has focused on the fetal heart in the context of FGR. This study aimed to investigate the application value of fetal heart quantification (HQ) technology in evaluating the size, morphology, and function of the heart in FGR.

Methods

A total of 31 fetuses diagnosed with FGR in our hospital from April 2022 to May 2024 were included, alongside another 31 normal fetuses matched for gestational age as the control group. Ultrasound Doppler parameters of the middle cerebral artery (MCA), umbilical artery (UA), venous catheter, and fetal HQ parameters were collected for comparative analysis, and perinatal data were followed up.

Results

Fetuses with FGR exhibited significant differences in various parameters of the MCA and UA compared to the control group (P < 0.05). The four-chamber view end-diastolic transverse width, end-diastolic area, left ventricular (LV) end-diastolic area, end-systolic area, end-systolic length, end-diastolic volume, end-systolic volume, and right ventricular (RV) end-systolic area in the FGR group were significantly lower than those in the control group (P < 0.05). In the 24-segment analysis, the LV fractional shortening in the FGR group was greater than in the control group at segments 12 to 14, while the end-diastolic diameter (ED) at segments 5 to 13 of the LV and segments 1 to 14 of the RV were smaller than those in the control group, with statistical significance (P < 0.05). Analysis of each subgroup indicated that fractional shortening (FS) in the early-onset group was significantly greater than in the late-onset group at RV segments 2 to 8. LV-ED at segments 1 to 15 and RV-ED at segments 1 to 16 were significantly smaller in the early-onset group than in the control group, and LV ED segments 20 to 21 were significantly smaller in the early-onset group compared to the late-onset group (P < 0.05). FS in the mild group was significantly larger than in the normal group at LV segments 10 to 16. The severe group exhibited significantly smaller LV segment 2 to 11 ED and the mild group showed smaller RV segments 1 to 13 compared to the control group (P < 0.05).

Conclusions

Fetal HQ is a promising technique for evaluating the cardiac function, size, and morphology in cases of FGR.

FGR refers to pathological factors affecting the fetus, placenta, and other elements that prevent the fetus from reaching its inherent genetic potential, leading to various complications during pregnancy and adverse maternal and fetal outcomes. In severe cases, FGR can endanger the life of the fetus. The incidence of FGR is approximately 3–9%, with a mortality rate ranging from 5 to 20% [1,2,3,4,5]. The etiology of FGR remains unclear, as it results from a combination of maternal, fetal, and placental factors. The clinical management of FGR primarily involves monitoring fetal growth rates and Doppler blood flow, predicting fetal metabolic acidosis, and ensuring timely delivery before irreversible organ damage and mortality occur [6].

The small size and rapid heart rate of the fetal heart render many methods employed for assessing adult cardiac function unsuitable for fetuses, such as magnetic resonance imaging. Currently, the assessment of fetal cardiac function predominantly relies on echocardiography. However, many traditional methods have notable drawbacks and limitations, preventing effective evaluation of fetal cardiac function [7, 8]. The fetal heart quantitative technique (fetal HQ) is a new technology specifically designed for fetal cardiac quantitative assessment, utilizing speckle tracking imaging technology [9,10,11]. The fetal HQ technique is based on the four-chamber view and uses the endocardium as a reference point for conducting 24-segment deformation analysis of both the left and right ventricles, thus providing a rapid and comprehensive quantitative evaluation of cardiac chamber dimensions, morphology, and functionality. Currently, fetal HQ technology has received recognition from researchers as a reliable method for assessing fetal cardiac status [12,13,14]. However, there are still relatively few studies employing fetal HQ technology to assess fetal heart conditions. This study aims to investigate the clinical utility of fetal HQ technology in assessing fetal heart dimensions, morphology, and functionality in cases of FGR.

Study population

A total of 31 pregnant women diagnosed with FGR at Shanghai First Maternity and Infant Hospital between April 2022 and May 2024 were selected for the experimental group. This group comprised 11 cases of mild FGR, 20 cases of severe FGR, 25 cases of early-onset FGR, and 6 cases of late-onset FGR. The diagnostic criteria for FGR included an estimated fetal weight or abdominal circumference below the 10th percentile corresponding to gestational age as determined by ultrasound examination [15]. Severe FGR was diagnosed when the estimated fetal weight or circumference on ultrasound fell below the third percentile for the corresponding gestational age. Early-onset and late-onset FGR were defined based on gestational age at 32 weeks [6, 16].Inclusion criteria: (1) Pregnant women aged 18 years or older; (2) enrolled in our hospital’s prenatal care program; (3) singleton pregnancy; (4) absence of fetal malformations or chromosomal abnormalities confirmed through noninvasive prenatal testing or amniocentesis; (5) diagnosed with FGR; and (6) no family history of genetic disorders.

Additionally, 31 pregnant women with normal prenatal examinations and without complications were randomly selected and matched for gestational age with the FGR group (with a maximum difference of one week) as the control group. This study was approved by the Ethics Committee of Shanghai First Maternity and Infant Hospital (KS22311).

Instruments

A GE Voluson E8/E10 color Doppler ultrasound system (GE Healthcare, Chicago, IL, USA), equipped with C1-6/C2-9 transducers and the fetal HQ software package (GE Healthcare), was used in this study.

Steps

General information of the pregnant women was collected, including age, last menstrual period, early ultrasound results (to verify gestational age), and past medical history. After instructing the pregnant women to assume a supine or lateral position, two-dimensional ultrasound imaging was employed to assess fetal biparietal diameter, head circumference, abdominal circumference, and femoral length to determine gestational age. Subsequently, Doppler ultrasound was used to acquire hemodynamic parameters of the fetal middle cerebral artery (MCA), umbilical artery (UA), and ductus venosus (DV). For blood flow parameter detection, ultrasound measurements were optimized by selecting periods of calm fetal breathing and ensuring that the angle between the ultrasound beam and the vessel remained below 30°. Once 5–6 consistent and stable waveforms were observed on the interface, the measurement was frozen. The instrument automatically calculated values such as peak systolic velocity (PSV) and pulsatility index (PI).

The fetal echocardiography examination was conducted to comprehensively assess the fetal heart according to established guidelines, ruling out cardiac malformations [17,18,19,20].The thickness of the fetal ventricular wall was also recorded (no ventricular wall thickening was found on examination). Next, a four-chamber dynamic cardiac map was obtained while avoiding rib shadowing. The ventricular septum was positioned at either the 3 o’clock or 9 o’clock position, maintaining an angle with the horizontal within ± 45°. Instrument settings were adjusted to achieve an image frame rate exceeding 80 frames per second, minimizing the impact of maternal breathing and fetal movement. This approach allowed for stable acquisition of dynamic four-chamber images, encompassing approximately 3 to 5 cardiac cycles. The images were optimized to enhance the boundaries between the blood pool and the endocardium. In the fetal HQ operation interface, the end-diastolic basal-apical length and the end-diastolic transverse width were measured in the longest dimension according to the prompts. The global sphericity index (GSI) was calculated by dividing the end-diastolic basal-apical length by the end-diastolic transverse width. A cardiac cycle was selected, and M-mode echocardiography was used to draw an M-mode sampling line from the apex of the heart through the base of the right ventricular wall (at the location where the tricuspid valve attaches). The diastolic end was identified at the lowest point on the M-wave tracing at the mitral valve annulus, while the systolic end was determined at the highest point on the M-wave tracing, between two diastolic end markers. By manually adjusting and automatically enveloping, the endocardial contour curves for the left ventricular systolic and diastolic ends were determined, as well as for the right ventricular systolic and diastolic ends. Finally, the fetal HQ automatically calculated parameters including left ventricular (LV) and right ventricular (RV) diastolic end-systolic length, width, area, 24-segment sphericity index (SI), fractional shortening (FS), end-diastolic diameter (ED), and additional metrics such as changes in ventricular area, ejection fraction, stroke volume, and cardiac output.

Statistical analysis

Statistical analysis was conducted using SPSS 26.0. Normality tests were performed for all cardiac parameters. Quantitative data were presented as means ± standard deviations. For normally distributed qualitative data, t-tests were employed to compare two groups, while one-way ANOVA was utilized for comparisons among three groups. Non-parametric tests were applied for qualitative or quantitative data that did not meet the assumption of normal distribution. The chi-square test was used to compare the abnormal rates of Z scores. A p-value < 0.05 was considered statistically significant.

Baseline characteristics of the study subjects

Clinical data of pregnant women and newborns were compared between the FGR group and the normal group. The FGR group exhibited a lower gestational week at delivery, birth weight, and Apgar score at 5min compared to the control group, with statistically significant differences. Additionally, the cesarean section rate, the proportion of newborns with complications, and the proportion of newborns admitted to the neonatal intensive care unit were significantly higher in the FGR group than in the control group. In the FGR group, 12 neonatal complications occurred, primarily consisting of neonatal respiratory distress syndrome (6 cases) and transient tachypnea (4 cases). Please refer to Table1 for further details.

Comparison of Doppler parameters of middle cerebral artery, umbilical artery, and vein duct in FGR group and normal group

After excluding patients with incomplete data, a total of 16 cases were included in the FGR group, with an equal number of 16 matched cases selected for the control group. The analysis revealed a significantly higher end-diastolic velocity (EDV) of the middle cerebral artery (MCA) in the FGR group compared to the normal group, while the peak systolic velocity/end-diastolic velocity ratio (S/D), pulsatility index (PI), and resistance index (RI) were all lower in the FGR group than in the control group. Additionally, a significant decrease in umbilical artery peak systolic velocity (UA-PSV) was observed in the FGR group compared to the control group (P < 0.05). Please refer to Table2 for further details.

Comparison of overall cardiac parameters between the FGR group and the control group

The four-chamber view end-diastolic transverse width (4CV Trv. Width ED), four-chamber view end-diastolic area (4CV Area), left ventricular end-diastolic area (LV_ED Area), end-systolic area (LV_ES Area), end-systolic length (LV_ES Length), end-diastolic volume (LV_EDV), end-systolic volume (LV_ESV), and right ventricular end-systolic area (RV_ES Area) were significantly lower in the FGR group than in the control group (P < 0.05). The right ventricular fractional area change (RV_Frac Area change) was significantly larger in the FGR group than in the control group (P < 0.05). No statistically significant differences were found in the other parameters. Please refer to Table3 for further details. When the thickness of the left ventricular lateral wall(2.49 ± 0.208mm vs. 2.58 ± 0.220mm), right ventricular lateral wall(2.47 ± 0.211mm vs. 2.55 ± 0.127mm), and septum(2.79 ± 0.152mm vs. 2.90 ± 0.236mm) of FGR group were compared with control group, no significant difference was found(P>0.05).

Comparison of the FS, ED, SI for 24 segments in the left and right ventricle between the FGR group and the normal group

Pairwise comparisons of the FS values in the 24 segments of the LV between fetuses in the FGR group and the normal group are shown in Fig.1. The FS in left ventricular segments 12 to 14 was significantly higher in the FGR group compared to the control group, indicating a statistically significant difference. Pairwise comparisons of the FS in the 24 segments of the RV between fetuses in the FGR group and the normal group are shown in Fig.2. The FS of the right ventricular segments did not exhibit any significant differences between the two groups. Pairwise comparisons of the SI in the 24 segments of the left and right ventricles between fetuses in the FGR and normal groups are shown in Figs.3 and 4. There was no statistical difference in the SI between the left and right ventricular segments in either group. Pairwise comparisons of the ED in the 24 segments of the left and right ventricles between fetuses in the FGR and normal groups are shown in Figs.5 and 6. The ED of the left ventricular segments 5 to 13 and the right ventricular segments 1 to 14 in the FGR group exhibited statistically significant reductions compared to those in the control group, indicating a pronounced disparity.

Comparison of Fetal HQ parameters in early-onset FGR group, late-onset FGR group, and control group

The 4CV Trv. Width ED, 4CV Length ED, 4CV Area, LV-ED Area, LV-ES Area, LV_ESV, LV_EDV, RV-ED Area, RV-ES Area, RV_ES Length, and LV CO in the early-onset group were all significantly smaller than those in the normal group. The RV Fractional Area Change [%] in the early-onset group was significantly larger than in the normal group. The LV Fractional Area Change [%] in the late-onset group was significantly larger than in the normal group. The LV CO in the early-onset group was significantly smaller than in the late-onset group. Variations in the data can be observed in Table4. Additionally, analysis of each subgroup indicated that FS in the early-onset group was significantly larger than in the late-onset group at RV segments 2 to 8. LV-ED at segments 1 to 15 and RV-ED at segments 1 to 16 were significantly smaller in the early-onset group than in the control group, and LV ED segments 20 to 21 were significantly smaller in the early-onset group than in the late-onset group (P < 0.05).

Comparison of Fetal HQ parameters in mild FGR group, severe FGR group, and control group

RV_ES Area, 4CV Length, LV_ES Area, LV_ESV, and RV Global Strain [%] in the mild group were all significantly smaller than those in the normal group. RV Frac. Area change [%] in the mild group was significantly larger than in the normal group. Variations in the data can be observed in Table5.

In segmental analysis, FS in the mild group was significantly larger than in the normal group at left ventricular segments 10 to 16. The severe group exhibited a significantly smaller left ventricular end-diastolic diameter in segments 2 to 11 compared to the control group, while the mild group showed a significantly smaller right ventricular end-diastolic diameter in segments 1 to 13 compared to the control group (P < 0.05).

FGR is associated with various perinatal complications, including stillbirth, prematurity, neonatal morbi-mortality, endocrine and metabolic alterations, increased cardiovascular risk, and long-term neurological sequelae [6]. The onset of FGR is multifactorial, and currently, no effective therapeutic interventions are available. Therefore, our approach primarily focuses on enhancing supervision and providing symptomatic treatment. Early identification of abnormalities in fetuses with FGR is crucial for improving the prognosis of this condition. Studies indicate that poor placental perfusion is a significant cause of intrauterine growth restriction in fetuses, leading to oxygen deprivation [21]. The fetal endocardium is highly sensitive to hypoxia, and initial studies suggest that changes in heart size, shape, and contraction occur before alterations in Doppler or other parameters. The hearts of fetuses with FGR exhibit three morphological changes: (a) elongation of the atria and ventricular walls, (b) a round or spherical shape of the ventricular cavity, and (c) thickening of the ventricular walls. These alterations result in a reduction in the sphericity index and an increase in the surface area of the fetal heart [22]. Some studies have demonstrated that cardiac function parameters in FGR fetuses significantly differ from those in normal fetuses. The likelihood of ventricular contraction abnormalities in FGR fetuses is high, and there is a notable difference in the cardiac work index. Moreover, abnormal cardiac function parameters manifest earlier than changes in various Doppler parameters in the fetus [23, 24]. These studies indicate that FGR fetuses have abnormalities in heart size, shape, and function compared to normal fetuses, potentially accompanied by compensatory effects. However, the findings of these studies are not consistent and clear. Hobbins JC et al. compared the overall heart size, sphericity index, length diameter, and left and right ventricular areas of FGR fetuses and found a significant increase in the proportion of larger, rounder, and wider hearts among FGR fetuses, but they did not conduct a detailed 24-segment analysis of the heart [25]. DeVore GR et al. analyzed FGR fetal hearts less than 34 weeks and similarly found that FGR fetal hearts were larger, wider, and closer to spherical; however, they targeted only fetuses less than 34 weeks, and the control group fetuses were not matched for gestational age [26].This study utilizes the latest Fetal HQ technology to evaluate the fetal heart in utero for FGR and combines ultrasound Doppler blood flow parameters to assess the fetal condition from multiple angles.

Fetal HQ is a new technology specifically designed for fetal cardiac quantitative assessment based on speckle tracking imaging (STI) technology. STI is a non-invasive technique that tracks the movement and displacement trajectories of cardiac tissue, quantifying local and global strain to evaluate cardiac function. The value of STI in assessing cardiac function in both adults and children has been widely recognized by clinicians and is included in guidelines [27,28,29]. However, the faster and more active fetal heart rate, along with the non-fixed position of the fetus, complicates the widespread application of STI technology in fetal cardiac function assessment. Professor Devore utilized TomTec’s 2D cardiac quantitative analysis software as a foundation, incorporating his own data algorithms to develop a novel system exclusively designed for evaluating fetal cardiac function. This innovative system has been seamlessly integrated into the latest version of the GE Voluson E10 ultrasound diagnostic device, known as Fetal HQ. Fetal HQ is primarily intended for fetuses between 20 and 40 weeks of gestation. This technology divides the left and right ventricles into 24 segments, providing more precise data on the segmentation of the heart chambers [10]. The present study revealed that the overall dimensions of the fetal heart in FGR cases were comparatively smaller than those observed in normal fetuses, including both width and area measurements. Additionally, reduced diameters and areas of the left and right ventricles were evident within the FGR group. RV Frac. Area change was significantly larger in the FGR group than in the control group, indicating that the right ventricle in the FGR group may require more work to maintain systemic blood supply, as the right heart is dominant in fetal circulation.

However, no statistically significant differences were detected between the two groups concerning the global sphericity index (GSI), global strain, and ejection fraction (EF) of the heart. This conclusion contrasts with the findings of some researchers, who reported that the hearts of FGR fetuses tend to be more circular [22, 30].

Additionally, this study revealed a significantly higher FS of the LV segments 12 to 14 in the FGR group compared to the control group. These findings suggest that FGR fetuses may exhibit compensatory mechanisms, such as enhanced placental nutrient circulation and alterations in fetal LV contraction, to counteract oxygen deprivation. However, the ED measurements of the LV segments 5 to 13 and the RV segments 1 to 14 in the FGR group were significantly smaller than those in the control group. Nevertheless, no statistically significant difference was observed in the sphericity index between the two groups. A more detailed analysis revealed that the overall diameter of the heart was primarily reduced in the basal and middle segments of both ventricles, indicating a predominant decrease in diameter without significant alterations in shape.

A comparative analysis of each FGR subgroup and the control group revealed that 4CV Trv. Width ED, 4CV Length ED, 4CV Area, LV-ED Area, LV-ES Area, LV ESV, LV EDV, RV-ED Area, RV-ES Area, RV ES Length, and LV CO in the early-onset group were all significantly smaller than those in the normal group. Additionally, RV Frac. Area change [%] in the early-onset group was significantly larger than in the normal group. This study aligns with the findings of DeVore GR et al., which showed that FGR fetuses less than 34 weeks and neonatal survivors had smaller RV areas, smaller LV transverse widths, and smaller LV areas [26]. In the late-onset group, a significant difference was observed only in LV Frac. Area change [%] compared to the control group. This result indicates that the changes in heart size and function in the early-onset group are more severe than those in the late-onset group. This discrepancy may be attributed to the longer duration of disease in the early-onset group, resulting in prolonged effects on the heart and providing a theoretical basis for the differences in the pathogenesis of early-onset and late-onset FGR. From a more detailed 24-segment analysis, the RV segment 2 to 8 FS value in the early-onset group was significantly larger than that in the late-onset group, while the LV ED segments 1 to 15 and RV ED segments 1 to 16 in the early-onset group were significantly smaller than those in the control group. The LV ED segments 20 to 21 in the early-onset group were also significantly smaller than those in the late-onset group. This suggests that changes in cardiac contractility in the early-onset group were primarily evident in the RV segments 2 to 8, which may relate to the right-sided dominance of the fetal heart. Additionally, this analysis provides a clearer view of which segments are undergoing changes.

In comparing the mild group, FS was significantly larger than that in the normal group at LV segments 10 to 16. In the severe group, the LV segment 2 to 11 ED was significantly smaller than in the control group, while the mild group exhibited significantly smaller RV segment 1 to 13 measurements compared to the control group. This may suggest that changes in the heart of the severe group have already affected the left ventricle, whereas the mild group remains in the stage of right ventricular compensation.

The present study has certain limitations, with the small sample size being one of the most prominent deficiencies. Therefore, future investigations with a larger sample size are imperative.

The Fetal HQ software was utilized in this study to comprehensively analyze the fetal heart in cases of FGR, assessing it from a holistic perspective down to detailed measurements, in conjunction with ultrasound Doppler parameters. It was observed that the size, shape, and function of the hearts of FGR fetuses exhibited significant alterations. These findings underscore the effectiveness of the Fetal HQ software in analyzing fetal cardiac conditions associated with FGR, providing valuable clinical insights for healthcare professionals involved in diagnosing and treating this condition.

FGR:

Fetal growth restriction

HQ:

Heart quantification

MCA:

Middle cerebral artery

UA:

Umbilical artery

DV:

Ductus venosus

PSV:

Peak systolic velocity

PI:

Pulsatility index

RI:

Resistance Index

S/D:

Peak systolic velocity / end-diastolic velocity

4CV Trv.:

Width ED four chamber view end-diastolic transverse width

4CV Area:

Four chamber view end-diastolic area

LV:

Left ventricular

ED:

End-diastolic

ES:

End-systolic

EDV:

End-diastolic volume

ESV:

End-systolic volume

Frac:

Fractional

FS:

Fractional shortening

ED:

End-diastolic diameter

GSI:

Global sphericity index

Authors and Affiliations

1. Ultrasound Department, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, No.2699 West Gaoke Road, Shanghai, 200092, China

   Yunqi Chen,Xiaoli Lv,Lijuan Yang,Dan Hu&Min Ren

Contributions

Min Ren and Yunqi Chen designed the study. Yunqi Chen wrote the manuscript. Min Ren, Xiaoli Lv, Dan Hu and Lijuan Yang collected, analyzed, and interpreted the data. Min Ren and Dan Hu critically reviewed, edited, and approved the manuscript. All author read and approved the final manuscript.

Corresponding authors

Correspondence to Dan Hu or Min Ren.

Ethics approval and consent to participate

The study protocol was approved by the Ethics Committee of Shanghai First Maternity and Infant Hospital (No. KS22311). All the women recruited agreed to participate in the study and provided written informed consent. All methods were performed in accordance with the relevant guidelines and regulations.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

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