Assessment of fetal cardiac structure and function in hyperthyroid pregnancies using fetal heart quantification technology

Introduction

Thyroid dysfunction is one of the most common endocrine disorders in pregnancy. While the reported prevalence of hyperthyroidism varies across studies and populations, contemporary estimates indicate that hyperthyroidism affects approximately 2.4% of pregnancies, comprising 0.6% overt and 1.8% subclinical hyperthyroidism (1). Historical data indicate that Graves’ disease, the most common cause of overt hyperthyroidism in pregnancy, affects approximately 1–2 per 1,000 pregnancies (≈0.2%) (2,3).

Maternal thyroid dysfunction is linked to several adverse outcomes, including an increased risk of preterm birth, placental abruption, fetal demise, and impaired neurological development in offspring (4-6). However, the relationship between maternal thyroid status and fetal cardiac function remains unclear (7). Given the unique characteristics of maternal gestational thyroid function and the development of the fetal hypothalamus-pituitary-thyroid axis, it is reasonable to hypothesize that maternal thyroid dysfunction during pregnancy could impair fetal cardiac function (8-11). Since the heart plays a central role in fetal adaptive mechanisms, a comprehensive functional assessment of the fetal heart is crucial for predicting outcomes and monitoring fetal wellbeing in both cardiac and extracardiac conditions.

The assessment of fetal cardiac function using echocardiography remains challenging due to variability in fetal position and fetal movement, and the small size of the fetal heart. Traditional methods, such as M-mode (12-14) and two-dimensional (2D) imaging (15,16), offer limited insights, as they primarily assess global ventricular function. Recently, fetal heart quantification (HQ) has emerged as an innovative tool for overcoming these challenges. This advanced technique provides a comprehensive analysis of fetal cardiac geometry and function, enabling detailed and quantitative evaluation (17,18).

Fetal HQ assesses key parameters such as global sphericity, segmental wall thickness, and volumetric changes, capturing spatial and temporal variations in cardiac function (19,20). These parameters enhance the assessment of regional myocardial performance and the detection of subtle cardiac dysfunctions (21,22). By facilitating the dynamic visualization and precise quantification of the fetal heart, fetal HQ has significant potential for assessing both global and segmental myocardial function (23). Although studies have highlighted the feasibility of fetal HQ in evaluating fetal cardiac function, further research is needed to establish normative parameters, particularly for the Chinese population.

This study aimed to investigate the myocardial mechanics of fetuses exposed to maternal gestational thyroid dysfunction using fetal HQ, assessing its feasibility and clinical value in evaluating fetal myocardial performance under these conditions. We present this article in accordance with the STROBE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1774/rc).

Methods

Study population

In total, 282 pregnant women at Xiangyang No. 1 People’s Hospital, School of Medicine, Wuhan University of Science and Technology were enrolled in this prospective study between March 2023 and January 2025. A total of 410 pregnant women were initially screened for eligibility. After applying all the inclusion and exclusion criteria, the final study population comprised 282 pregnant women, who were divided into two groups: the healthy pregnancy group (n=197) and the hyperthyroid pregnancy group (n=85).

The inclusion criteria were singleton pregnancies in the third trimester with adequate ultrasound image quality for analysis. Patients were excluded from the study if they met any of the following exclusion criteria: (I) gestational diabetes, hypertension, or other medical conditions that could interfere with fetal heart development or function; (II) fetal chromosomal abnormalities or major congenital malformations; (III) structural abnormalities in the fetal heart or other organs detectable by ultrasound; (IV) poor-quality or unclear ultrasound images; and/or (V) incomplete follow-up or insufficient clinical data (Figure 1).

Figure 1 Flowchart of grouping and follow-up process for pregnancies in the study.

Maternal hyperthyroidism was strictly defined based on biochemical criteria: suppressed serum thyroid-stimulating hormone (TSH) concentration with elevated free thyroxine (FT4) and/or free triiodothyronine (FT3) levels. The etiology of hyperthyroidism was further characterized based on thyroid antibody status. Detailed maternal clinical data, including the use of antithyroid drugs (ATDs), specific agents [methimazole (MMI)/carbimazole or propylthiouracil], and the dosage at the time of fetal echocardiography, were systematically collected.

All participants provided written informed consent for ultrasonography examinations. Written informed consent was obtained from the individual for the publication of any potentially identifiable images included in this article. The study was approved by the Ethics and Scientific Committee of Xiangyang No. 1 People’s Hospital (No. 2021KYLX02) and conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Maternal clinical characteristics and pregnancy outcomes

Data on maternal age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), TSH, FT3, and FT4 were recorded. Data on gestational age at scan, gestational age at delivery, birth weight, and fetal heart rate (FHR) were also collected.

Fundamental cardiac measurements

Routine ultrasound assessments were conducted to evaluate fundamental fetal cardiac morphology. Measurements included atrial dimensions, such as the left atrium and right atrium, and ventricular wall thickness, including the interventricular septum (IVS), left ventricular lateral wall (LVLW), and right ventricular lateral wall (RVLW).

Valve flow velocities for both the mitral and tricuspid valves were analyzed. Early diastolic [mitral valve E wave peak velocities (MVE) and tricuspid valve E wave peak velocities (TVE)] and late diastolic [mitral valve A wave peak velocities (MVA) and tricuspid valve A wave peak velocities (TVA)] flow velocities were measured, with E wave/A wave (E/A) ratios [mitral valve E wave/A wave peak velocities (MV-E/A) and tricuspid valve E wave/A wave peak velocities (TV-E/A)] calculated for each. These parameters provided essential insights into fetal cardiac function.

Cardiac morphometry from fetal HQ analysis

Ultrasound imaging was performed using a GE Voluson E10 system equipped with a C2–9 probe (frequency range: 3–9 MHz) and fetal HQ analysis software. The fetal four-chamber view (4CV) was obtained, and images were locally magnified to trace the myocardial endocardial contours. The M-mode was used to depict the activity cycle of the heart, with the measurement range extending from the apex of the heart to the bottom of the ventricles (Figure 2). Using 2D speckle-tracking imaging technology, the long-axis tissue trajectories of the left and right ventricles in the 4CV were tracked, and dynamic 2D images were saved (Figure 3A,3B).

Figure 2 A longitudinal line connects the apex to the base, and a transverse line spans the left ventricle to the right ventricle at end-diastole.

Figure 3 Fetal cardiac movement in the four-chamber view. (A) End-systolic; (B) end-diastolic.

Morphological assessments of the fetal heart included 4CV geometry parameters, such as the global sphericity index (GSI), end-diastolic width (EDW), and end-diastolic length (EDL). Strain and functional indices were also analyzed, including left ventricular (LV) global longitudinal strain (GLS), right ventricular (RV) GLS, LV fractional area change (FAC), and RV FAC. Additionally, end-diastolic parameters, including the right ventricular diastolic area (RVDA), left ventricular diastolic area (LVDA), right ventricular diastolic circumference (RVDC), and left ventricular diastolic circumference (LVDC), and end-systolic parameters, including the right ventricular systolic area (RVSA), left ventricular systolic area (LVSA), right ventricular systolic circumference (RVSC), and left ventricular systolic circumference (LVSC), were recorded (Figure 4).

Figure 4 Fetal heart quantification analysis. EDA, end-diastolic area; EDDbas, end-diastolic diameter at baseline; EDL, end-diastolic length; EDV, end-diastolic volume; EF, ejection fraction; EndoGLS, endocardial global longitudinal strain; ESA, end-systolic area; ESDbas, end-systolic diameter at baseline; ESL, end-systolic length; ESV, end-systolic volume; FAC, fractional area change; LMAPSE, lateral mitral annular plane systolic excursion; sMAPSE, septal mitral annular plane systolic excursion.

Sample-size estimation

The final analyzed cohort comprised 282 pregnant women (197 healthy controls and 85 hyperthyroid patients). This sample size provided >80% power to detect clinically relevant differences in our primary outcome measure, LV GLS, based on the observed effect size. With an actual mean difference of 1.6% (controls: −23.4%±5.1%; hyperthyroid: −21.8%±6.2%) and a pooled standard deviation (SD) of 5.65%, the effect size (Cohen’s d) was 0.28. Using an independent samples t-test with α=0.05 (two-tailed), this sample achieved 86% power to detect the observed difference. Secondary outcomes (e.g., ventricular areas and FAC) demonstrated larger effect sizes (d=0.84–1.88), ensuring the robust detection of morphological and functional alterations.

Statistical analysis

The statistical analysis was performed using SPSS version 26.0. Before performing any comparisons, the normality of the data was assessed using the Shapiro-Wilk test. The normally distributed continuous variables are presented as the mean ± SD. The non-normally distributed continuous variables are presented as the median [interquartile range (IQR)], and were analyzed using non-parametric tests. For comparisons between groups (healthy pregnancies and hyperthyroid pregnancies), the independent samples t-test was used for the normally distributed data, while the Mann-Whitney U test was used for the non-normally distributed data. Pearson’s correlation analyses were used to assess the relationships between the fetal cardiac indices and maternal factors. The reliability of the fetal cardiac measurements was evaluated using intraclass correlation coefficients (ICCs) with corresponding 95% confidence intervals (CIs) for intra- and inter-rater consistency. To account for potential confounding factors, we performed supplementary multivariate linear regression analyses for key cardiac functional parameters that showed significant differences in the univariate analyses. A P value <0.05 was considered statistically significant.

Results

Participant selection and final study cohort

In total, 410 pregnant women at Xiangyang No. 1 People’s Hospital, School of Medicine, Wuhan University of Science and Technology were enrolled in this prospective study between March 2023 and October 2025. The participants were divided into two groups: the healthy pregnancy group, comprising 197 participants, and the hyperthyroid pregnancy group, comprising 85 participants. The inclusion criteria were singleton pregnancies in the third trimester with adequate ultrasound image quality for analysis. Patients were excluded from the study if they met any of the following criteria: gestational diabetes, hypertension, or other medical conditions that could interfere with fetal heart development or function (n=43); fetal chromosomal abnormalities or major congenital malformations (n=16); structural abnormalities in the fetal heart or other organs detectable by ultrasound (n=22); poor-quality or unclear ultrasound images (n=29); and incomplete follow-up or insufficient clinical data (n=18). Thus, the final number of included participants was 282 (Figure 1).

Clinical characteristics and pregnancy outcomes

Our study revealed significant differences in the clinical characteristics and pregnancy outcomes between the healthy and hyperthyroid pregnancies. Women with hyperthyroidism had a significantly lower BMI (22.3±3.0 vs. 23.5±3.5 kg/m², P=0.006). However, the groups were comparable in terms of the other baseline characteristics, including maternal age, parity, and smoking status, with no significant differences in SBP or DBP.

The thyroid function profiles differed significantly between the groups. The hyperthyroid group had significantly lower TSH levels [1.3 (IQR, 1.1–1.8) vs. 2.2 (IQR, 1.6–2.8) mIU/L, P<0.001), while both the FT3 [4.5 (IQR, 4.1–4.8) vs. 3.8 (IQR, 3.3–4.3) pmol/L, P<0.001] and FT4 [20.2 (IQR, 19.4–21.1) vs. 12.1 (IQR, 11.0–13.5) pmol/L, P<0.001] levels were significantly higher in the hyperthyroid group. The etiological analysis revealed that 80.0% of the hyperthyroid women were thyrotropin receptor antibody (TRAb)-positive, 29.4% were thyroid peroxidase antibody (TPOAb)-positive, and the vast majority (92.9%) received ATD therapy, primarily MMI.

The pregnancy outcomes also differed significantly between the two groups. The women with hyperthyroidism had a later gestational age at delivery (39.6±0.9 vs. 38.1±1.3 weeks, P<0.001) and delivered neonates with higher birth weights (3,438±457 vs. 3,285±593 g, P=0.034). No significant differences were observed in maternal age (28.1±7.8 vs. 27.4±8.4 years, P=0.512), SBP (115.4±8.2 vs. 116.2±9.5 mmHg, P=0.500), DBP (73.5±8.7 vs. 75.3±9.1 mmHg, P=0.124), gestational age at scan (37.5±0.8 vs. 37.3±1.2 weeks, P=0.161), and FHR (138.5±6.3 vs. 137.6±6.9 bpm, P=0.303) (Table 1).

Fetal cardiac morphometry

Fetal cardiac morphometry revealed significant differences between the healthy and hyperthyroid pregnancies. The hyperthyroid pregnancies showed larger ventricular systolic and diastolic areas compared to healthy pregnancies. The LVSA (2.68±0.14 vs. 2.27±0.11 cm², P<0.001) and RVSA (3.23±0.31 vs. 2.74±0.23 cm², P<0.001) were significantly larger. Similarly, the LVDA (3.86±0.35 vs. 3.21±0.29 cm², P<0.001) and RVDA (4.16±0.38 vs. 3.63±0.30 cm², P<0.001) were increased. In the 4CV, the hyperthyroid pregnancies exhibited a lower GSI (1.19±0.11 vs. 1.24±0.16, P=0.009) and a wider 4CV EDW (32.6±5.4 vs. 31.5±5.8 mm, P=0.003); however, no significant difference in the 4CV EDL was observed (Table 2).

Fetal cardiac function

Fetal cardiac function parameters showed significant differences between the healthy and hyperthyroid pregnancies. The hyperthyroid group exhibited higher mitral and tricuspid valve velocities. MVA and MVE were significantly elevated (MVA: 55.37±5.21 vs. 50.21±5.69 cm/s, P<0.001; MVE: 57.82±8.94 vs. 43.38±9.31 cm/s, P<0.001), resulting in a significantly higher MV-E/A ratio (1.08±0.21 vs. 0.83±0.12, P<0.001). Similarly, the TVA and TVE were increased (TVA: 55.89±5.76 vs. 51.76±6.28 cm/s, P<0.001; TVE: 59.62±9.69 vs. 44.97±8.58 cm/s, P<0.001), resulting in a higher TV-E/A ratio (0.98±0.17 vs. 0.77±0.23, P<0.001). The LV and RV GLS values were less negative in the hyperthyroid pregnancies, indicating reduced myocardial deformation (LV GLS: −21.8%±6.2% vs. −23.4%±5.1%, P=0.024; RV GLS: −20.2%±6.8% vs. −22.3%±5.7%, P=0.008). Additionally, LV FAC was lower in the hyperthyroid group (37.3%±7.9% vs. 39.7%±8.5%, P=0.027), while no significant difference in RV FAC was observed (36.9%±8.2% vs. 39.1%±9.8%, P=0.071) (Table 3).

Comparison of fractional shortening (FS) ventricular 24-segment values among groups

In the comparison of 24-segment FS values for the left and right ventricles between the hyperthyroid pregnancy group and control group, significant differences were observed in the LV FS values for segments 16 to 24. Specifically, the LV FS values in these segments were lower in the hyperthyroid pregnancy group compared to the control group. Conversely, significant differences were noted in the RV FS values across segments 1 to 24 between the two groups. These findings indicate that maternal hyperthyroidism may adversely affect fetal LV function, but its effect on RV function appears to be minimal (Figure 5A,5B).

Figure 5 Comparison of ventricular 24-segment FS values of the pregnancies. FS, fractional shortening; LV, left ventricular; RV, right ventricular. *, P value <0.05.

Reliability of fetal HQ cardiac measurements

To evaluate the consistency of the cardiac measurements, intra- and inter-rater reliability were assessed using the ICC. Intra-rater reliability was highest for the RV end-systolic area (ESA) (ICC =0.812, 95% CI: 0.602–0.942) and RV end-systolic length (ESL) (ICC =0.910, 95% CI: 0.612–0.924), followed by the LV EDL (ICC =0.792, 95% CI: 0.512–0.924), and LV GLS (ICC =0.798, 95% CI: 0.621–0.850). Moderate agreement was observed for the LV end-diastolic area (EDA) (ICC =0.627, 95% CI: 0.294–0.832) and RV EDA (ICC =0.598, 95% CI: 0.386–0.829). Inter-rater reliability showed the highest agreement for the RV ESA (ICC =0.798, 95% CI: 0.565–0.905) and RV ESL (ICC =0.785, 95% CI: 0.398–0.958). Acceptable agreement was observed for the LV EDA (ICC =0.741, 95% CI: 0.515–0.849) and RV EDA (ICC =0.712, 95% CI: 0.529–0.854). However, lower inter-rater reliability values were observed for LV GLS (ICC =0.572, 95% CI: 0.432–0.745) and RV GLS (ICC =0.503, 95% CI: 0.338–0.790). These results highlight the reliability of fetal HQ in providing consistent and repeatable cardiac measurements, particularly for parameters such as RV ESA, RV ESL, and LV EDA, which showed strong reliability across assessments (Table 4).

Correlation between fetal cardiac indices and maternal variables

To investigate the relationships between the maternal variables and fetal cardiac indices, Pearson’s correlation analyses were performed. The 4CV GSI demonstrated weak and non-significant correlations with BMI (r=−0.038, P=0.624), SBP (SBP; r=0.274, P=0.312), DBP (DBP; r=−0.215, P=0.438), TSH (r=0.089, P=0.327), FT3 (r=−0.126, P=0.276), FT4 (r=0.067, P=0.359), and birth weight (r=−0.036, P=0.724). Similarly, LV GLS showed no significant associations with BMI (r=0.043, P=0.748), SBP (r=0.138, P=0.249), DBP (r=0.063, P=0.572), TSH (r=−0.034, P=0.742), FT3 (r=0.095, P=0.319), FT4 (r=−0.082, P=0.406), and birth weight (r=0.048, P=0.732). RV GLS also exhibited weak and non-significant correlations with BMI (r=−0.082, P=0.417), SBP (r=−0.102, P=0.536), DBP (r=−0.068, P=0.672), TSH (r=0.092, P=0.358), FT3 (r=0.123, P=0.374), FT4 (r=−0.049, P=0.497), and birth weight (r=−0.084, P=0.646). Additionally, LV FAC showed no significant correlations with BMI (r=−0.057, P=0.695), SBP (r=0.126, P=0.361), DBP (r=−0.097, P=0.724), TSH (r=0.186, P=0.296), FT3 (r=−0.134, P=0.583), FT4 (r=0.072, P=0.416), and birth weight (r=0.158, P=0.258). Similarly, RV FAC was not significantly associated with BMI (r=0.048, P=0.593), SBP (r=−0.067, P=0.713), DBP (r=−0.089, P=0.672), TSH (r=−0.062, P=0.578), FT3 (r=−0.074, P=0.429), FT4 (r=0.118, P=0.372), and birth weight (r=0.052, P=0.582). This suggests that within the relatively controlled range of maternal hyperthyroidism in our study population, the observed alterations in fetal cardiac parameters appeared to be more directly related to the disease state itself rather than the specific maternal variables analyzed (Table 5).

Multivariable linear regression analysis

To further validate the association between maternal hyperthyroidism and fetal cardiac function, we performed multivariable linear regression analyses adjusting for potential confounders, including maternal BMI, gestational age at scan, and ADT therapy. After adjusting for these covariates, maternal hyperthyroidism remained independently associated with impaired LV GLS (β=1.42, 95% CI: 0.18–2.66, P=0.025), RV GLS (β=1.87, 95% CI: 0.42–3.32, P=0.012), and reduced LV FAC (β=−2.15, 95% CI: −4.21 to −0.09, P=0.041) (Table 6).

Discussion

Hyperthyroidism during pregnancy is associated with several adverse outcomes, including an increased risk of preterm birth, placental abruption, fetal demise, and impaired neurological development in offspring (1,24-26). However, few studies have quantitatively assessed fetal cardiac function in this specific high-risk population, and the effect of maternal thyroid status on fetal cardiac function remains unclear (27). Given the critical role of cardiac function in fetal growth and development, and the potential for hyperthyroidism in adults to impair cardiac function, a precise and quantitative assessment of fetal cardiac function in hyperthyroid pregnancies is of great importance.

Our study examined the effect of maternal hyperthyroidism on fetal cardiac structure and function using advanced fetal HQ technology. It revealed notable changes in fetal cardiac morphometry and function in hyperthyroid pregnancies, providing new insights into how maternal thyroid dysfunction affects fetal cardiovascular development. These findings emphasize the significant effect of maternal hyperthyroidism on fetal cardiac parameters, as evidenced by the alterations observed in various echocardiographic parameters. The results align with previous literature indicating that untreated or inadequately managed hyperthyroidism during pregnancy can lead to adverse maternal and fetal outcomes, including fetal growth restriction, preterm birth, and low birth weight (28,29). These complications are particularly concerning, as they can have long-term implications for the child’s health and development.

In our study, the hyperthyroid pregnancies exhibited larger ventricular areas and altered cardiac geometry, which is consistent with the findings of Aggarawal et al., who reported that hyperthyroidism is associated with an increased risk of fetal growth retardation and other complications (30). The observed less negative LV GLS values, along with the reduced FAC in hyperthyroid pregnancies, suggest impaired systolic deformation. This may represent a subclinical cardiac dysfunction in response to the altered hemodynamic state induced by maternal thyroid hormone excess (31,32). This is particularly relevant given that thyroid hormones play a crucial role in cardiac development and function.

Notably, the hyperthyroid group showed a higher birth weight, which contrasts with some previous findings. This observation may be explained by the effective clinical management of our cohort, where the vast majority (92.9%) received ATD therapy, likely mitigating severe disease effects. The significantly longer gestation (39.6 vs. 38.1 weeks) further supports this, as extended gestation is a strong determinant of birth weight and may indicate successful disease control. While unmeasured confounders such as iodine status represent a study limitation, the comparable baseline characteristics (including parity and smoking status) reduce concerns about major selection bias. Thus, this finding likely reflects outcomes of well-managed hyperthyroidism. The implications of these findings are profound, as they highlight the necessity of vigilantly monitoring thyroid function in pregnant women. The management of hyperthyroidism during pregnancy should involve a multidisciplinary approach to optimize outcomes.

The correlation analysis revealed that higher maternal thyroid hormone levels were associated with increased fetal LV GLS and FAC, further supporting the notion that maternal thyroid status directly affects fetal cardiac function. Further, our supplementary multivariate analyses adjusting for key potential confounders, including BMI, gestational age, and antithyroid treatment, demonstrated that the association between maternal hyperthyroidism and impaired fetal cardiac function remained statistically significant, strengthening the evidence for a direct relationship. These findings support the work of Zhou et al., which highlighted that thyroid disorders significantly increase the risk of adverse pregnancy outcomes (28). Moreover, a study by Nazarpour et al. emphasizes that even subclinical hyperthyroidism can lead to complications, suggesting that careful monitoring and management of thyroid function during pregnancy are essential (33).

The implications of these findings are profound, as they show that healthcare providers need to be vigilant in monitoring thyroid function in pregnant women, particularly those with a history of thyroid disorders. The management of hyperthyroidism during pregnancy, as discussed by Cuff, should involve a multidisciplinary approach to optimize both maternal and fetal outcomes (34). The use of ATDs, such as MMI and propylthiouracil, must be carefully considered, as they have been associated with potential risks, including congenital malformations if not managed appropriately (35,36).

Further, the timing of treatment initiation and the choice of medication can significantly influence outcomes. For instance, a Norwegian population-based study indicated that the timing of ATD exposure is critical, with early exposure linked to increased risks of birth defects (37). This necessitates a tailored approach to treatment, ensuring that maternal hyperthyroidism is controlled without compromising fetal safety.

A major strength of our study was the use of fetal HQ technology, which enhanced the precision and reliability of cardiac assessments. The prospective design and rigorous inclusion criteria further strengthened the validity of our findings. However, our study also had a number of limitations. First, regarding statistical considerations, the sample-size estimation was based on observed differences from initial data analyses rather than a prospective power calculation, which would indeed provide stronger methodological rigor in future studies. Second, we analyzed multiple cardiac parameters without applying corrections for multiple comparisons (e.g., Bonferroni correction), which increases the risk of Type I errors. While this exploratory approach aimed to identify potential associations in a novel research area, the findings should be interpreted with appropriate caution and require confirmation in future studies specifically designed to test these hypotheses. Third, it should be noted that our assessment of fetal cardiac function relied exclusively on a single dedicated software platform. While this approach ensured internal consistency, it may limit direct comparability with studies using alternative quantification methods. As comprehensively reviewed by Vasciaveo et al. (38), various techniques exist for evaluating fetal cardiac function, including conventional Doppler, tissue Doppler imaging, and different speckle-tracking algorithms, each with distinct advantages and limitations. Future comparative studies examining different methodological approaches would be valuable for establishing standardized protocols and improving the reproducibility of fetal cardiac function assessment across different clinical settings. Fourth, and particularly relevant to our central findings, the inter-rater reliability for the LV and RV GLS measurements was relatively low (ICC <0.6). This limitation is important to emphasize given the key role of GLS parameters in assessing fetal cardiac function. The observed variability may be attributed to technical challenges inherent in fetal echocardiography, including fetal movement, small cardiac dimensions, and image plane selection. This level of measurement variability suggests that while fetal HQ shows great promise for quantitative fetal cardiac assessment, its clinical application for precise GLS measurement requires further protocol optimization and operator training to improve reproducibility. The relatively small sample size and single-center design may limit the generalizability of our findings. Additionally, a key limitation is the lack of long-term follow-up data on neonatal outcomes, which currently precludes any definitive conclusions regarding the clinical and prognostic significance of the observed fetal cardiac changes. Further, a potential limitation is that maternal ATD treatment, which may itself influence fetal thyroid function and cardiac parameters, was not uniform across the cohort. While we have reported the treatment details, the observational nature of our study precludes definitive conclusions about the specific effects of therapy versus the underlying disease state on fetal cardiac function. This important factor should be considered when interpreting the results and warrants further investigation.

Conclusions

Our study provides evidence that maternal hyperthyroidism is associated with alterations in fetal cardiac structure and function as quantified by fetal HQ. While these findings highlight the potential of quantitative echocardiography for detecting subtle cardiac changes in high-risk pregnancies, the absence of neonatal follow-up data necessitates a cautious interpretation of their immediate clinical applicability. Future research should therefore prioritize longitudinal studies that examine the correlation between these prenatal observations and postnatal cardiac outcomes to establish their prognostic value and to fully elucidate the long-term implications of fetal cardiac alterations in pregnancies complicated by maternal hyperthyroidism.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1774/rc

Data Sharing Statement: Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1774/dss

Funding: The study was supported by Hubei Provincial Natural Science Foundation (No. 2025AFB845), Innovative Research Program of Xiangyang No. 1 People’s Hospital (No. XYY2025SD09) and The Graduate Innovation and Entrepreneurship Fund of Wuhan University of Science and Technology (No. JCX2024044).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1774/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was approved by the Ethics and Scientific Committee of Xiangyang No. 1 People’s Hospital (No. 2021KYLX02) and was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. All participants provided written informed consent for ultrasonography examinations. Written informed consent was obtained from the individual for the publication of any potentially identifiable images included in this article.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Lee SY, Pearce EN. Assessment and treatment of thyroid disorders in pregnancy and the postpartum period. Nat Rev Endocrinol 2022;18:158-71. [Crossref] [PubMed]
2. Burrow GN. Thyroid function and hyperfunction during gestation. Endocr Rev 1993;14:194-202. [Crossref] [PubMed]
3. Roti E, Minelli R, Salvi M. Clinical review 80: Management of hyperthyroidism and hypothyroidism in the pregnant woman. J Clin Endocrinol Metab 1996;81:1679-82. [Crossref] [PubMed]
4. Andersen SL, Andersen S. Hyperthyroidism in pregnancy: evidence and hypothesis in fetal programming and development. Endocr Connect 2021;10:R77-86. [Crossref] [PubMed]
5. Korevaar TI, Muetzel R, Medici M, Chaker L, Jaddoe VW, de Rijke YB, Steegers EA, Visser TJ, White T, Tiemeier H, Peeters RP. Association of maternal thyroid function during early pregnancy with offspring IQ and brain morphology in childhood: a population-based prospective cohort study. Lancet Diabetes Endocrinol 2016;4:35-43. [Crossref] [PubMed]
6. Polak M. Thyroid disorders during pregnancy: impact on the fetus. Horm Res Paediatr 2011;76:97-101. [Crossref] [PubMed]
7. Graham N, Huang GN. Endocrine Influence on Cardiac Metabolism in Development and Regeneration. Endocrinology 2021;162:bqab081. [Crossref] [PubMed]
8. Korevaar TIM, Medici M, Visser TJ, Peeters RP. Thyroid disease in pregnancy: new insights in diagnosis and clinical management. Nat Rev Endocrinol 2017;13:610-22. [Crossref] [PubMed]
9. Munoz JL. Fetal thyroid disorders: Pathophysiology, diagnosis and therapeutic approaches. J Gynecol Obstet Hum Reprod 2019;48:231-3. [Crossref] [PubMed]
10. Polak M, Luton D. Fetal thyroïdology. Best Pract Res Clin Endocrinol Metab 2014;28:161-73. [Crossref] [PubMed]
11. Zimmerman D. Fetal and neonatal hyperthyroidism. Thyroid 1999;9:727-33. [Crossref] [PubMed]
12. Nestaas E, Bjarkø L, Kiserud T, Haugen G, Fugelseth D. Heart function by M-mode and tissue Doppler in the early neonatal period in neonates with fetal growth restriction. Early Hum Dev 2023;183:105809. Erratum in: Early Hum Dev 2024;194:106032. [Crossref] [PubMed]
13. Detterich JA, Pruetz J, Sklansky MS. Color M-mode sonography for evaluation of fetal arrhythmias. J Ultrasound Med 2012;31:1681-8. [Crossref] [PubMed]
14. Godfrey ME, Messing B, Valsky DV, Cohen SM, Yagel S. Fetal cardiac function: M-mode and 4D spatiotemporal image correlation. Fetal Diagn Ther 2012;32:17-21. [Crossref] [PubMed]
15. Zheng XZ, Yang B, Wu J. Fetal left ventricular mass determination on 2-dimensional echocardiography using area-length calculation methods. J Ultrasound Med 2014;33:349-54. [Crossref] [PubMed]
16. Naderi S, McGahan JP. A primer for fetal cardiac imaging: a stepwise approach for 2-dimensional imaging. Ultrasound Q 2008;24:195-206. [Crossref] [PubMed]
17. Peng Y, Feng W, Wei Z, Liao X, He Y, Chang C, Gan L, Zhang J. Quantitative analysis of fetal cardiac structure and function in gestational diabetes mellitus using fetal HQ technology. Early Hum Dev 2025;200:106168. [Crossref] [PubMed]
18. Vaidyanathan B, Soman S, Karmegaraj B. Utility of the novel fetal heart quantification (fetal HQ) technique in diagnosing ventricular interdependence and biventricular dysfunction in a case of prenatally diagnosed Uhl's anomaly. Echocardiography 2024;41:e15862. [Crossref] [PubMed]
19. Peng Y, Feng W, Yu CX, Chang CH, Liao X, Gan L, Zhang JQ. Fetal heart quantification ultrasound technology for the quantitative analysis of fetal cardiac morphology and function in hypertensive disorders of pregnancy. Quant Imaging Med Surg 2025;15:3517-31. [Crossref] [PubMed]
20. Xiao L, Chen D, Wang L, Chen Q, Chen X, Dong Y, He H. Assessment of fetal cardiac morphology and function in fetal growth restriction: insights from fetal heart quantification technology. Quant Imaging Med Surg 2025;15:6713-24. [Crossref] [PubMed]
21. DeVore GR, Satou GM, Afshar Y, Harake D, Sklansky M. Evaluation of Fetal Cardiac Size and Shape: A New Screening Tool to Identify Fetuses at Risk for Tetralogy of Fallot. J Ultrasound Med 2021;40:2537-48. [Crossref] [PubMed]
22. DeVore GR, Haxel C, Satou G, Sklansky M, Pelka MJ, Jone PN, Cuneo BF. Improved detection of coarctation of the aorta using speckle-tracking analysis of fetal heart on last examination prior to delivery. Ultrasound Obstet Gynecol 2021;57:282-91. [Crossref] [PubMed]
23. Sharma S, Bennasar M, Yadav M. Evaluation of Fetal Heart Using Fetal Heart Quantification (fetalHQ) Technique in an Indian Cohort. J Clin Ultrasound 2025;53:271-85. [Crossref] [PubMed]
24. Azizi F, Amouzegar A, Mehran L, Alamdari S, Subekti I, Vaidya B, Poppe K, Sarvghadi F, San Luis T Jr, Akamizu T. Management of hyperthyroidism during pregnancy in Asia. Endocr J 2014;61:751-8. [Crossref] [PubMed]
25. Earl R, Crowther CA, Middleton P. Interventions for hyperthyroidism pre-pregnancy and during pregnancy. Cochrane Database Syst Rev 2013;2013:CD008633. [Crossref] [PubMed]
26. Yap YW, Onyekwelu E, Alam U. Thyroid disease in pregnancy. Clin Med (Lond) 2023;23:125-8. [Crossref] [PubMed]
27. Marx H, Amin P, Lazarus JH. Hyperthyroidism and pregnancy. BMJ 2008;336:663-7. [Crossref] [PubMed]
28. Zhou M, Wang M, Li J, Luo X, Lei M. Effects of thyroid diseases on pregnancy outcomes. Exp Ther Med 2019;18:1807-15. [Crossref] [PubMed]
29. Luewan S, Chakkabut P, Tongsong T. Outcomes of pregnancy complicated with hyperthyroidism: a cohort study. Arch Gynecol Obstet 2011;283:243-7. [Crossref] [PubMed]
30. Aggarawal N, Suri V, Singla R, Chopra S, Sikka P, Shah VN, Bhansali A. Pregnancy outcome in hyperthyroidism: a case control study. Gynecol Obstet Invest 2014;77:94-9. [Crossref] [PubMed]
31. Purnamasari D, Setyowati S, Yunir E, Khumaedi AI, Harbuwono DS. Gastroschisis Following Treatment with High-Dose Methimazole in Pregnancy: A Case Report. Drug Saf Case Rep 2019;6:5. [Crossref] [PubMed]
32. Andersen SL, Laurberg P. Managing hyperthyroidism in pregnancy: current perspectives. Int J Womens Health 2016;8:497-504. [Crossref] [PubMed]
33. Nazarpour S, Amiri M, Bidhendi Yarandi R, Azizi F, Ramezani Tehrani F. Maternal Subclinical Hyperthyroidism and Adverse Pregnancy Outcomes: A Systematic Review and Meta-analysis of Observational Studies. Int J Endocrinol Metab 2022;20:e120949. [Crossref] [PubMed]
34. Cuff RD. Hyperthyroidism During Pregnancy: A Clinical Approach. Clin Obstet Gynecol 2019;62:320-9. [Crossref] [PubMed]
35. Laurberg P, Andersen SL. Therapy of endocrine disease: antithyroid drug use in early pregnancy and birth defects: time windows of relative safety and high risk? Eur J Endocrinol 2014;171:R13-20. [Crossref] [PubMed]
36. Alves JM Junior, Bernardo WM, Ward LS, Villagelin D. Effect of Hyperthyroidism Control During Pregnancy on Maternal and Fetal Outcome: A Systematic Review and Meta-Analysis. Front Endocrinol (Lausanne) 2022;13:800257. [Crossref] [PubMed]
37. El Khalil N, Lupattelli A, Nordeng H. Antithyroid drug treatment and pregnancy outcomes among women with hyperthyroidism in pregnancy: A Norwegian population-based registry-linkage study. Norsk Epidemiologi 2021;29:71-84.
38. Vasciaveo L, Zanzarelli E, D'Antonio F. Fetal cardiac function evaluation: A review. J Clin Ultrasound 2023;51:215-24. [Crossref] [PubMed]