Reference Ranges and Clinical Significance of Key Fetal Cardiac Parameters Measured by Color Doppler Ultrasound at 11+0 to 16+0 Weeks of Gestation

Reference Ranges and Clinical Significance of Key Fetal Cardiac Parameters Measured by Color Doppler Ultrasound at 11+0 to 16+0 Weeks of Gestation | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Reference Ranges and Clinical Significance of Key Fetal Cardiac Parameters Measured by Color Doppler Ultrasound at 11 +0 to 16 +0 Weeks of Gestation Zheng Shuai, Gu Xiaoyan, Wang Jingyi, Ling Wen, Hao Xiaoyan, Ruan Yanping, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7003626/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective: This study aims to investigate the application value of four parameters, namely, V-angle (VSA), cardiothoracic ratio (CTR), global sphericity index (GSI), and cardiac axis (CAx), in the early detection of congenital heart disease (CHD) during the first trimester by using color Doppler ultrasound and increase the accuracy of CHD prediction in early pregnancy. Methods : A prospective study was conducted from January 2022 to March 2024 across two centers: Haidian District Maternal and Child Health Hospital in Beijing and Fujian Maternal and Child Health Hospital. A total of 2,529 normal fetuses and 50 fetuses with CHD underwent color Doppler fetal echocardiography between 11 +0 and 16 +0 weeks of gestation. The correlation between each parameter and gestational age (GA) during early pregnancy was analyzed. Normative reference ranges and diagnostic models were established and validated. The diagnostic efficacy of the four parameters for CHD was quantitatively assessed based on the established models, and their clinical application value was explored. Results: In normal fetuses during early pregnancy, GA showed negative correlation with VSA, positive correlation while CTR and GSI, and no correlation with CAx. Z-score models and reference ranges for the four parameters were established across five different GA groups. The polynomial linear regression model significantly improved the detection rate of CHD compared with univariate regression models. The four parameters demonstrated statistical significance in different CHD subtypes, especially in severe forms of CHD, confirming their value as effective parameters for early CHD screening in fetuses. Conclusion: CAx, CTR, VSA, and CSI were identified as effective parameters for the early diagnosis of CHD in fetuses during the first trimester. This research has, for the first time, established normal reference value ranges for the four parameters in early pregnancy and developed a multiparameter joint prediction model. The findings provide quantifiable indicators for CHD screening and further enhance the accuracy of CHD prediction in early pregnancy. Early pregnancy Fetus V-sign angle Cardiothoracic ratio Global sphericity index Cardiac axis Congenital heart disease Color Doppler ultrasound Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Congenital heart disease (CHD) is the most common type of congenital malformation and has rapidly become a global pediatric health concern because of its high morbidity and mortality and severe effects on survival and quality of life [1,2] . Early prenatal screening and diagnosis of CHD are vital to prevent and reduce neonatal mortality. According to 2013 Practice Guidelines on Fetal Cardiac Screening formulated by the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), standard fetal cardiac screening is typically performed between 18 and 22 weeks of gestation [3] . With continuous advancements in ultrasound technology and growing clinical expertise, the ability to diagnose certain types of CHD in early pregnancy has improved, resulting in high diagnostic rates and timely and appropriate assessment and clinical management of severe cases. Cardiac axis (CAx) and cardiothoracic ratio (CTR) are important indicators in mid-to-late gestation and have established reference ranges internationally and domestically [4] . V-sign angle (VSA) and global sphericity index (GSI) are new parameters used to evaluate fetal CHD, and their normal reference ranges for mid-to-late pregnancy have been documented [5–7] . Scholars at home and abroad have attempted to measure and study some parameters of early pregnancy fetuses with small samples and proposed that they have a certain value for the detection of certain types of CHD in early pregnancy fetuses. However, comprehensive large-sample studies involving VSA, CTR, GSI, and CAx for CHD screening are still lacking. The present study aims to measure and analyze four key parameters (VSA, CTR, GSI, and CAx) of normal fetuses with a large sample size during early pregnancy, explore their normal reference values, and build regression models for validation. Findings will provide a quantitative reference for the diagnosis of fetal CHD in early pregnancy, prognosis assessment, and perinatal management strategies. Additionally, the study will explore the clinical value of the four parameters in the screening of CHD in early pregnancy. Color Doppler ultrasound was used as the primary diagnostic tool to supplement the imaging of the fetal heart because 2D grayscale imaging quality in early pregnancy is often suboptimal. Materials and METHODS 1. Research object This study prospectively collected data from January 2022 to March 2024 at two centers: Haidian District Maternal and Child Health Hospital in Beijing and Fujian Maternal and Child Health Hospital. A total of 2,529 normal fetuses underwent heart color Doppler ultrasound examination and 50 fetuses diagnosed with CHD were included. The inclusion criteria were as follows: (1) gestational age (GA) between 11 +0 and 16 +0 weeks; (2) clear and complete color Doppler ultrasound images; and (3) informed consent provided by the participant. The exclusion criteria included the following: (1) incomplete follow-up data; and (2) inability or refusal to cooperate during the ultrasound examination. The study complied with the principles of the Declaration of Helsinki (2013 revision) and was approved by the Ethics Committee of Haidian District Maternal and Child Health Hospital (Ethics Approval No. 2021-23). All participating pregnant women were fully informed about the content of the ultrasound measurements before joining the study and provided written informed consent. 2. Instruments and Methods 2.1 Instruments Fetal cardiac ultrasound examinations were conducted using the GE Voluson E8 and E10 color Doppler ultrasound systems equipped with a 2D abdominal convex probe with a frequency range of 4–8 MHz. 2.2 Methods This study analyzed cross-sectional data from the two centers and established normal reference value ranges and models for the four key fetal cardiac parameters (VSA, CTR, GSI, and CAx) in normal fetuses during early pregnancy. The models were then applied and validated in both centers to differentiate between normal fetal hearts and those affected by CHD. The study also assessed the diagnostic efficacy and clinical application value of VSA, CTR, GSI, and CAx in the screening of CHD based on the established models. This study included 2529 fetuses with complete data who underwent CAx, CTR, VSA, and GSI examination. The GA was between 11 +0 and 16 +0 weeks. The age of pregnant women ranged from 19 to 52 years, with an average of 31.7 ± 3.8 years. The 2,529 normal cases were divided into a training set (2,049 cases) and a validation set (480 cases). The training set was further categorized into five groups based on GA: 11 +0 to 11 +6 weeks (91 cases), 12 +0 to 12 +6 weeks (1,297 cases), 13 +0 to 13 +6 weeks (544 cases), 14 +0 to 14 +6 weeks (70 cases), and 15 +0 to 16 +0 weeks (47 cases). The distribution of the measurements for VSA, CTR, GSI, and CAx in the training set, which included 2049 normal fetal hearts, was tested for normality by using a normal Q-Q plot (quartile-quartile plot) to assess whether the data follow a normal distribution. If the data conform to a normal distribution, then Spearman’s correlation coefficients were calculated to assess the relationship between the four parameters and GA. Univariate regression models were then established to calculate the reference ranges of VSA, CTR, GSI, and CAx across the five GA groups. A binary logistic regression model (backward stepwise method) was used to construct a polynomial linear regression model. The model’s fit and generalizability were evaluated using the Hosmer–Lemeshow test. The model was refined to optimize its performance in CHD detection. The validation set, comprising 480 normal fetal hearts and 50 CHD-affected fetal hearts, was used to validate the predictive performance of the regression models based on the four parameters (VSA, CTR, GSI, and CAx). These models included the univariate regression models (normalized by GA) and the polynomial linear regression models. Receiver Operating Characteristic (ROC) curves were constructed, and the diagnostic performance of each model was recorded. The validation population for CHD included 50 fetuses with prenatal diagnosis of CHD from the two centers, from January 2022 to March 2024. The cases included 3 cases of single ventricle, 3 cases of hypoplastic left heart syndrome, 7 cases of endocardial cushion defects, 11 cases of tetralogy of Fallot, 2 cases of persistent arterial trunk, 6 cases of double outlet right ventricle, 2 cases of transposition of the great arteries, 5 cases of aortic atresia or stenosis, 4 cases of pulmonary atresia or stenosis, 6 cases of right-sided aortic arch, and 1 case of ventricular septal defect. The application value of the four parameters for screening various types of CHD was analyzed. Examination after birth or autopsy result after termination of pregnancy of fetuses enrolled from the two centers was regarded as the gold standard. In cases where the examination after birth or autopsy confirmation was not available, the diagnosis was validated by consensus between two physicians with over 10 years of experience in fetal cardiac ultrasound diagnosis to ensure accuracy. 2.3 Measurement Parameters and Standards According to practice guidelines of fetal ultrasound scanning in the early pregnancy [8] issued by the International Society of Ultrasound in Obstetrics and Gynecology(ISUOG) fetal biological parameters, such as crown-rump length, were shown and GA was corrected. The measurement of VSA, CTR, GSI, and CAx also followed the ISUOG practice guidelines [3] , the statement on safe Doppler use in early pregnancy ultrasound [9] , and the fetal echocardiography guidelines [10] . The ultrasound mode specifically for fetal heart examination was used with mechanical index and thermal index set to less than 0.8. Color Doppler ultrasound was employed by physicians who are qualified in prenatal screening to obtain four-chamber view (4CV) and three-vessel view (3VV) cross-sections of the fetal heart. The parameters measured were CAx, CTR, VSA, and GSI for fetal heart screening. (1) VSA: in the 3VV, the angle between the first line connecting the left outer boundary of the ductal arch and the second line connecting the right outer boundary of the aortic arch was measured on the color Doppler ultrasound image; (2) CTR: in the 4CV, the heart diameter (HD) at the level of the atrioventricular valves in diastole (when all four chambers are visible in color Doppler) was measured; thoracic diameter (TD) was measured at the widest part of the chest cavity, and CTR was calculated as HD/TD; (3) GSI: in the 4CV, the maximum horizontal diameter of the heart (HD) and the maximum longitudinal distance from the apex to the base of the heart (heart length, HLE) were measured at the level of the atrioventricular valves or slightly lower in diastole (when all four chambers are visible in color Doppler); GSI was calculated as HLE/H; and (4) CAx: in the 4CV, the anatomy displayed should include at least one complete rib, and atria and ventricles should be visible; color Doppler was used to determine the position of the atrioventricular septum. In systole (when only the two ventricles are visible in color Doppler), CAx angle was measured. This angle was determined by drawing a line from the midline of the sternum to the midline of the spine, dividing the fetal chest into left and right symmetrical portions, and then drawing another line along the atrioventricular septum’s position. The angle between the two lines was defined as CAx, as shown in Figure 1. Each fetus had three measurements of VSA, CTR, GSI, and CAx, and the average value was taken. The echocardiographic images from the Haidian District Maternal and Child Health Hospital were measured by two physicians (Zheng S and Zhao H) after removing individual information, and the average value was taken. The echocardiographic images from the Fujian Provincial Maternal and Child Health Hospital were also measured by two physicians (Ruan Y and Wang J) from the Fetal Heart and Maternal–Fetal Medicine Center of Beijing Anzhen Hospital, Capital Medical University, after removing individual information, and the average value was taken. All research participants were trained in the aforementioned measurement standards, and only magnified echocardiographic images were used for data measurement. 3 Statistical analysis Statistical analysis was performed using SPSS 29.0 software. The fetal VSA, CTR, GSI, and CAx values were treated as continuous variables. The normality of data was checked using the Kolmogorov–Smirnov test. Spearman correlation coefficients were used to analyze the relationship between gestational week and VSA, CTR, GSI, and CAx, with P < 0.05 considered statistically significant. Descriptive statistics were used to report continuous variables that followed a normal distribution as mean (standard error), and 95% confidence intervals were used as normal reference ranges. Categorical data were expressed as n (%). The ROC curve was used to calculate the area under the curve (AUC) of individual VSA, CTR, GSI, CAx, and their combinations and assess its application value in screening for CHD. The diagnostic efficiency of the standard to be tested such as sensitivity, specificity, accuracy, false-positive rate, positive predictive value, and negative predictive value was analyzed based on diagnostic 2x2 tables. The χ2 test was used for comparison of independent samples, with P < 0.05 considered statistically significant. Results 1 Relationship of Normal Fetal VSA, CTR, GSI, and CAx with GA and Construction of Single-Parameter Models The measured data of VSA, CTR, GSI, and CAx in 2049 normal fetuses were normally distributed (Figure 2). The Pearson’s product–moment correlation coefficient analysis revealed that GA was negatively correlated with VSA but positively correlated with CTR and GSI in 2049 fetuses ( P 0.05). Linear regression models were used to construct growth models for VSA, CTR, and GSI, while CAx was modeled using mean ± standard deviation (` x±s ). A Z-score model for the four parameters was established in Table 1. The normal reference ranges for VSA, CTR, GSI, and CAx in fetuses at 11 +0 to 16 +0 weeks were expressed as (` x±s ) and 95% confidence intervals (Supplementary Table S1). Table 1: Correlation analysis of VSA, CTR, GSI, and CAx with GA. Parameters Correlation with GA r-value P-Value Regression Equation / Mean ± SD Z-value Model VSA Negative Correlation -0.102 ＜0.05 Y =71.216-1.591GA Z =（VSA-（71.216-1.591GA））/（51.5567） CTR Positive Correlation 0.100 ＜0.05 Y =0.225+0.004GA Z =（CTR-（0.225+0.004GA））/（0.2768） GSI Positive Correlation 0.051 ＜0.05 Y =1.167+0.009GA Z =（GSI-（1.167+0.009GA））/（0.0062） CAx No correlation 0.062 44.91±8.57 Z =（CAx-44.91）/（8.57） 2. Evaluation of Models for Normal Fetal VSA, CTR, GSI, and CAx A total of 530 fetuses at 11 +0 to 16 +0 weeks were included as a validation set, which consisted of 480 normal fetuses and 50 fetuses with CHD. ROC curves were constructed using the Z-score model and the established reference ranges for the four parameters. The diagnostic performance of VSA, CTR, GSI, and CAx was evaluated (Table 2 and Figure 3). Table 2: Diagnostic performance of Z-score Models for Normal Fetal VSA, CTR, GSI, and CAx. Parameters Fetal Heart Gold Standard Z-score model established based on xx Accuracy (%) Sensitivity (%) Specificity (%) Positive Predictive Value (%) Negative Predictive Value (%) AUC 95% Confidence Interval Normal Fetal Hearts (480 cases) CHD Fetuses (50 cases) VSA Normal 471 18 94.91 98.13 64 78.05 96.32 0.811 0.728–0.893 CHD 9 32 CTR Normal 436 35 85.09 30 90.83 25.42 92.57 0.604 0.513–0.695 CHD 44 15 GSI Normal 470 41 90.38 18 97.92 47.37 91.98 0.580 0.488–0.671 CHD 10 9 CAx Normal 454 26 90.19 48 94.58 48 94.58 0.713 0.623–0.803 CHD 26 24 3. Establishment of Polynomial Logistic Regression Model Using Binary Logistic Regression and Parameter Optimization A polynomial logistic regression model was constructed using the forward selection method in binary logistic regression (LR): Y = –4.443 + 4.574 X 1 + 1.944 X 2 + 2.080 X 3 + 3.099 X 4 . The model fit was evaluated using the Hosmer–Lemeshow goodness-of-fit test (P = 0.610). The Hosmer–Lemeshow statistic follows a chi-square distribution, with P > 0.2, which confirmed that the model provided a good fit to the original data (Table 3). The results indicated that all the four parameters (VSA, CTR, GSI, and CAx) at 11 +0 to 16 +0 weeks are valuable for CHD screening, and their combination had the highest diagnostic performance. The AUC for the combined parameters was 0.871 (Figure 4). Table 3: Independent variables and coefficients of the binary logistic regression model. Parameters B S.E. Wald P value OR EXP(B) 95% Confidence Interval Lower limit Upper limit VSA 4.574 0.565 65.487 ＜ 0.001 96.915 32.010 293.420 CTR 1.944 0.576 11.388 ＜ 0.001 6.985 2.259 21.598 GSI 2.080 0.829 6.295 0.012 8.002 1.576 40.623 CAx 3.099 0.544 32.500 ＜ 0.001 22.179 7.642 64.367 Constant -4.443 0.415 114.797 ＜ 0.001 0.012 4. Application Value of VSA, CTR, GSI, and CAx for Different CHD Types at 11 +0 to 16 +0 Weeks All the four parameters were statistically significant when categorized by the abnormal location of fetal CHD and can be used as effective parameters for CHD screening in early pregnancy. When categorized by the severity of CHD (mild vs. severe), VSA, CTR, and CAx were statistically significant for mild CHD and could serve as effective screening parameters. In severe CHD, all the four parameters were statistically significant and could be used as effective screening parameters (Table 4). Table 4: Application value of VSA, CTR, GSI, and CAx for different CHD types at 11 +0 to 16 +0 weeks Fetal Heart Gold Standard Number of cases VSA CTR GSI CAx Number of cases χ2 P Number of cases χ2 P Number of cases χ2 P Number of cases χ2 P Normal 480 9 44 10 26 CHD Type 1 Cardiac Chamber Abnormalities (Size, Position) 11 8 ＜0.001 4 6.198 0.013 3 0.002 9 ＜0.001 Major Artery Abnormalities 40 30 274.152 ＜0.001 12 14.579 ＜0.001 7 23.089 ＜0.001 20 85.570 ＜0.001 Valve Abnormalities 18 12 ＜0.001 7 13.597 ＜0.001 5 ＜0.001 10 57.774 ＜0.001 Atrioventricular Septal Abnormalities 32 16 139.418 ＜0.001 11 17.340 ＜0.001 7 30.702 ＜0.001 14 56.002 ＜0.001 Type 2 Mild CHD 13 7 ＜0.001 4 4.488 0.034 1 0.257 4 0.005 Severe CHD 37 25 230.716 ＜0.001 11 13.193 ＜0.001 8 33.426 ＜0.001 20 94.342 ＜0.001 Discussion 1. Introduction to the Clinical Problem, Research Background, and Contribution of the Study Fetal CHD is the most severe and prevalent congenital anomaly globally, ranking first among all birth defects and accounting for more than 40% of congenital abnormalities [ 1 ] . 4CV and 3VV are the fundamental planes for mid-trimester screening of CHD. The detection rate of CHD by using the 4CV alone is 60.3% [ 11 ] , while that of the 3VV alone is 71.43% [ 12 ] . The combination of both views increases the diagnostic accuracy up to 90.9% [ 13 ] . Previous studies reported a first-trimester CHD detection rate of 74%, with a sensitivity of 85% and a specificity of 99% [ 14 , 15 ] . Therefore, fetal cardiac ultrasound screening in the first trimester is important and feasible. The parameters CAx, HD, HL, and TD were measured on the 4CV, while VSA was measured on the 3VT. Once standard 4CV and 3VT images are acquired, sonographers can intuitively assess fetal CAx, HD, HL, TD, and VSA. The measurement methods are simple and practical. However, the quality of grayscale 2D images of the fetal heart in the first trimester is often suboptimal because of factors, such as fetal movement, position, rapid heart rate, small cardiac size, unclear visualization of the atrioventricular septum and internal cardiac structures, and shadowing from ribs and placenta. Color Doppler ultrasound can better delineate vascular and cardiac chamber morphology and can be used to assess structural details. It allows for the determination of cardiac position, size, orientation, margins, and course and caliber of the great arteries during the first trimester. Thus, color Doppler imaging offers significant advantages in fetal cardiac imaging during early pregnancy and could serve as an excellent complement to grayscale imaging [ 16 ] . It can also be used as the primary tool for first-trimester fetal cardiac screening. 2. Diagnostic Advantages and Analytical Findings of VSA, CTR, GSI, and CAx VSA is a relatively new parameter used to assess fetal CHD and detect abnormalities of the conotruncal region, such as aortic coarctation, right aortic arch, double aortic arch, and vascular rings [3]. The present study shows a CHD detection rate of 94.91% and an accuracy of 98.13% by using VSA, confirming its effectiveness as a diagnostic parameter in first-trimester CHD screening; this finding is consistent with the report of Wiechec et al. [ 17 ] . A negative correlation was found between VSA and GA, which differs from previous studies [ 5 ] . The discrepancy may be attributed to the large sample size in the present study and the division of the 11 + 0 to 16 + 0 weeks gestational period into five subgroups for intergroup statistical comparison, which optimizes study design and enhances efficiency and accuracy. The concept of CTR was first introduced by Garrett et al. [ 18 ] in 1970. In early pregnancy, CTR may reflect cardiac enlargement, reduction, or dysfunction, and its abnormality may suggest internal cardiac anomalies. The CHD detection rate for CTR is 85.09%, with a specificity of 90.83%, supporting its role as a valuable early screening parameter. However, variability exists in the reported normal CTR reference ranges and diagnostic thresholds. Tongsong et al. [ 19 ] proposed a CTR < 0.5 as normal during early pregnancy, consistent with that in mid-later trimesters, and this criterion is still widely used. In the present work, CTR shows a positive correlation with GA, aligning with the findings of previous study [ 20 ] . However, the reference range for normal CTR in this study was lower than that reported by Tongsong. This discrepancy may be due to the use of color Doppler imaging for distinguishing the epicardium of four chambers and obtaining numerical values of cardiac transverse diameter, which defines the outer myocardial boundary more precisely than grayscale imaging, resulting in smaller measured values and a narrower normal range. GSI, which was first introduced by DeVore et al., is a reproducible parameter for quantifying cardiac remodeling and assessing geometric characteristics of the ventricles, atria, and the entire heart. GSI reference ranges for the second and third trimesters have been established, and previous studies found no significant correlation between GSI and GA in mid-to-late pregnancy [ 6 – 7 ] . Most existing studies focus on cardiac remodeling due to fetal ischemia or hypoxia, such as in α-thalassemia major or late-onset intrauterine growth restriction, but studies during early pregnancy are lacking. In the present work, a large dataset was used to establish reference ranges for normal GSI values in the first trimester. The GSI detection rate for CHD is 90.38%, with an accuracy of 97.92%, confirming its diagnostic value in early CHD screening and its positive correlation with GA. Ultrasound was first used to measure fetal CAx during the second trimester by Comstock [ 21 ] in 1987 to establish corresponding reference values. Abnormal CAx may indicate intracardiac structural anomalies. Fetuses with abnormal CAx have a nearly 45-fold increased risk of CHD compared with those with normal CAx [ 22 ] , and CAx has been identified as an independent predictor of chromosome 22q11.2 microdeletion syndrome [ 23 ] . In the present study, CAx has a CHD detection rate of 90.19% and an accuracy of 94.58%, demonstrating its effectiveness in first-trimester screening. The lack of correlation between CAx and GA is consistent with the findings of Sinkovskaya et al. [ 24 ] . The univariate polynomial regression models established for CAx, CTR, VSA, and GSI in yield superior detection rates compared with other studies that used single-parameter regression models [ 20 , 25 – 27 ] . The polynomial linear regression model significantly improves CHD detection performance over univariate models (AUC = 0.871). 3. Validity and Innovation of Data and Methodology Currently, first-trimester fetal cardiac assessment has no expert consensus domestically and internationally. Fetal cardiac ultrasound remains highly operator-dependent, and existing literature on early gestational fetal heart studies is scarce, which is often limited to small sample sizes and single-parameter diagnostics. In the present study, a dual-center, large-sample design incorporating four parameters were adopted to calculate reference ranges and establish models for normal fetal cardiac values in the first trimester. The predictive model demonstrates high efficacy, and the ROC curves clearly illustrate that polynomial linear regression modeling substantially improves CHD detection over univariate models. The GA is divided into five groups for intergroup comparison, and correlations between parameters and GA are analyzed to optimize experimental design and enhance the efficiency and accuracy of the experiment. The validation dataset includes CHD cases and approximately 500 normal first-trimester fetuses for prediction modeling. It encompasses 14 types of mild to severe CHD to analyze the clinical application of the four parameters across different CHD subtypes during early gestation. This study comprehensively and efficiently bridges normal and abnormal fetal cardiac data in the first trimester, thereby effectively advancing the diagnostic window. 4. Limitations of the Study This study has some limitations. ① The distribution of case numbers across the five GA groups was uneven because of scheduling constraints among pregnant participants, which may introduce statistical bias.② The number of CHD validation cases was relatively small, and the predictive performance of the model requires further validation. Conclusion This study is the first to establish reference ranges and a multi-parameter predictive model for CAx, CTR, VSA, and GSI during the first trimester, providing quantitative indicators for CHD screening. It further explores the correlation between each parameter and GA in the first trimester to enhance the precision of early CHD prediction. Fetuses with parameters outside the established normal ranges should be closely monitored. Repeated measurements from different maternal positions are recommended to confirm the presence or absence of cardiac anomalies and to minimize the risk of missed or incorrect diagnoses. Abbreviations CHD : Congenital Heart Disease CAx : Cardiac Axis CTR : Cardiothoracic Ratio VSA : V Sign Angle GSI : Global Sphericity Index Q-Q plot : Quartile-Quartile Plot GA : Gestational Age HL : Hosmer-Lemeshow ISUOG : The International Society of Ultrasound in Obstetrics and Gynecology 4CV : Four-Chamber View 3VV : Three-Vessel View HD : Heart Diameter TD : Thorax Diameter HLE : Heart Length ROC : Receiver Operating Characteristics AUC : Area Under the Curve Declarations Ethics approval and consent to participate This study was approved by the Ethics Committee of the Haidian District Maternal and Child Health Hospital, Beijing (Ethical approval number: 2021-23). Prior to inclusion, the specific content of the ultrasound measurements required for the study was explained to the participants. Consent for publication The manuscript is approved by all authors for publication. Availability of data and material All the data are true and valid. Competing interests The authors declare no competing interests. Funding Beijing Natural Science Foundation (7244325) Authors' contributions Z.S.: Conceptualization, Writing–Original Draft, Writing–Review & Editing, Study Design, Investigation, Image Analysis, Image Processing, Data Analysis. G.X.Y.:Writing–Review & Editing. W.J.Y.: Literature Review, Investigation, Funding Acquisition, Study Design. L.W.:Image collection. H.X.Y.:Study Design, Data Analysis. R.Y.P.:Study Design, Data Analysis. Z.H.W.:Image collection, Image Analysis. H.Y.H.: Supervision, Writing–Review & Editing, Final Approval. W.Z.J.: Image collection, Final Approval. Acknowledgements We want to thank all pregnant women who participated in the study. Authors' information Zheng Shuai 1,2, † , Gu Xiaoyan 1, † , Wang Jingyi 1 , Ling Wen 3 , Hao Xiaoyan 1 , Ruan Yanping 1 , Zhao Huawei 2 , He Yihua 1,* , Weng Zongjie 3,* *Corresponding authors: He Yihua (E-mail: [email protected] );Weng Zongjie (E-mail: [email protected] ) † These authors contributed equally to this work. ¹Fetal Cardiology and Maternal–Fetal Medicine Center, and Cardiac Ultrasound Center, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China; ²Department of Ultrasound, Haidian District Maternal and Child Health Hospital, Beijing 100080, China; ³Department of Ultrasound, Fujian Maternal and Child Health Hospital, Fuzhou 350001, China References He YH, Jiang YX. Guidelines for Prenatal Ultrasound Diagnosis and Perinatal Management of Fetal Heart Disease (1st ed.). Beijing: People’s Medical Publishing House.2015;7-20. https://doi.org/10.3760/cma.j.issn.1007-9408.2016.03.005 GBD 2017 Congenital Heart Disease Collaborators. 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J Ultrasound Med. 2015 Apr;34(4):585-94. Li, X. W. (2018). Application of the four-chamber view combined with the three-vessel view in the mid-to-late pregnancy ultrasound screening of fetal heart disease. China Medical Herald, 16(17), 134–135. VAYNA ANA MARIA, VEDUTA ALINA, DUTA SIMONA, et al. Diagnosis of Fetal Structural Anomalies at 11 to 14 Weeks[J]. Journal of Ultrasound in Medicine: Official Journal of the American Institute of Ultrasound in Medicine,2018,37(8):2063-2073. Zheng, M. M., Tang, H. R., Zhang, Y., Ru, T., Li, J., Xu, B. Y., Xu, Y., & Hu, Y. L. (2019). Contribution of the Fetal Cardiac Axis and V-Sign Angle in First-Trimester Screening for Major Cardiac Defects. Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine, 38(5), 1179–1187. Alfred A, Rabin C. Practical Guide to Fetal Echocardiography: Normal and Abnormal Hearts (3rd ed.). Beijing: Beijing Science and Technology Press. 2017: 461-465. Wiechec M, Knafel A, Nocun A. Prenatal detection of congenital heart defects at the 11- to 13-week scan using a simple color Doppler protocol including the 4-chamber and 3-vessel and trachea views. J Ultrasound Med 2015; 34:585–594. Garrett WJ，Robinson DE． Fetal heart size measured in vivo by ultrasound［J］.Pediatrics，1970，46( 1) : 25—27． Tongsong T, Wanapirak C, Sirichotiyakul S,Piyamongkol W, Chanprapaph P.. Fetal sonographic cardiothoracic ratio at midpregnancy as a predictor of Hb Bart disease. J Ultrasound Med. 1999;18(12): 807–811. https://doi.org/10.7863/jum.1999.18.12.807 Pang, C. Y., Li, X. Y., Huang, H., et al. (2021). Construction of a Z-score model for normal fetal cardiothoracic ratio. Chinese Journal of Medical Imaging Technology, 37(9), 1363–1367. Comstock CH. Normal fetal heart axis and position. Obstet Gynecol, 1987, 70:255-259． Su, F. F., Wang, J. J., Yin, C. H., Yue, W. T., & Wu, Q. Q. (2019). Relationship between fetal cardiac axis angle and congenital heart disease in mid-pregnancy. Journal of Capital Medical University, 40(6), 838–841. Vigneswaran T V,Kametas N A,Zinevich Y et al. Assessment of cardiac angle in fetuses with congenital heart disease at risk of 22q11.2 deletion. [J] .Ultrasound Obstet Gynecol, 2015, 46: 695-9. Sinkovskaya ES, Chaoui R, Karl K, et al. Fetal cardiac axis and congenital heart defects in early gestation [J]. Ultrasound Obstet Gynecol, 2015, 125(2): 453-460. Zheng MM, Tang HR, Zhang Y, Ru T, Li J, Xu BY, Xu Y, Hu YL. Contribution of the Fetal Cardiac Axis and V-Sign Angle in First-Trimester Screening for Major Cardiac Defects. J Ultrasound Med. 2019 May;38(5):1179-1187. Pang, C. Y., Li, X. Y., Huang, H., et al. (2021). Reference range study of fetal global sphericity index Z-score. Chinese Journal of Ultrasound in Medicine, 37(4), 446–449. Lin, W. Z., Deng, X. D., Yin, L. L., et al. (2019). Reference values and clinical significance of fetal cardiac axis in early pregnancy. Chinese Journal of Medical Ultrasound (Electronic Edition), 16(4), 270–274. Additional Declarations No competing interests reported. Supplementary Files AppendixS1.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7003626","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":488135901,"identity":"4fa40d3a-f4ba-46a5-81f8-e9f3d784c3ff","order_by":0,"name":"Zheng Shuai","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA80lEQVRIiWNgGAWjYDACCTB5gIGBGUglVEjIyZOm5cEZC2PDBqK1AAHjw7aKRCgbN5Cf3Xzs4Zc/dxL725mPfUicJ5HA2MD88NENPFoY5xxLN5Zte5Y44zBb8ozEbRJ57AxsxsY5eLQwS+SYSUs2HE5sOMxjzADUUszYwMMmjU8Lm0T+N2mJP4cT5x/m/8yQOEciseEAAS08Ejlskh/YDiduOMzDzJDYQIQWCYk0M2nGtsPGGw+zGTMkHJMwNmwm4Bf5GcnPJH/8OSw77/zhx4w/aurk5NmbHz7GpwUEmHlQuQSUgwDjDyIUjYJRMApGwQgGAB7uTJdzEAQbAAAAAElFTkSuQmCC","orcid":"","institution":"¹Fetal Cardiology and Maternal–Fetal Medicine Center, and Cardiac Ultrasound Center, Capital Medical University","correspondingAuthor":true,"prefix":"","firstName":"Zheng","middleName":"","lastName":"Shuai","suffix":""},{"id":488135902,"identity":"10b2f212-3b34-435c-b3c7-44bba9081f4e","order_by":1,"name":"Gu Xiaoyan","email":"","orcid":"","institution":"¹Fetal Cardiology and Maternal–Fetal Medicine Center, and Cardiac Ultrasound Center, Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Gu","middleName":"","lastName":"Xiaoyan","suffix":""},{"id":488135903,"identity":"712ac403-2745-485f-bed6-97f9bc38314f","order_by":2,"name":"Wang Jingyi","email":"","orcid":"","institution":"¹Fetal Cardiology and Maternal–Fetal Medicine Center, and Cardiac Ultrasound Center, Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wang","middleName":"","lastName":"Jingyi","suffix":""},{"id":488135904,"identity":"20ee0490-8272-469c-becc-9e554c861ca4","order_by":3,"name":"Ling Wen","email":"","orcid":"","institution":"¹Fetal Cardiology and Maternal–Fetal Medicine Center, and Cardiac Ultrasound Center, Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Ling","middleName":"","lastName":"Wen","suffix":""},{"id":488135905,"identity":"33071fd0-4ad2-43fa-b604-af679f2a8ea6","order_by":4,"name":"Hao Xiaoyan","email":"","orcid":"","institution":"¹Fetal Cardiology and Maternal–Fetal Medicine Center, and Cardiac Ultrasound Center, Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Hao","middleName":"","lastName":"Xiaoyan","suffix":""},{"id":488135906,"identity":"e37f6e35-e8d6-4958-8c93-6b29f4d98146","order_by":5,"name":"Ruan Yanping","email":"","orcid":"","institution":"¹Fetal Cardiology and Maternal–Fetal Medicine Center, and Cardiac Ultrasound Center, Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Ruan","middleName":"","lastName":"Yanping","suffix":""},{"id":488135907,"identity":"91f0b591-35b8-4818-8b24-acc864063897","order_by":6,"name":"Zhao Huawei","email":"","orcid":"","institution":"¹Fetal Cardiology and Maternal–Fetal Medicine Center, and Cardiac Ultrasound Center, Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zhao","middleName":"","lastName":"Huawei","suffix":""},{"id":488135908,"identity":"cf0f08ae-6f95-4888-a975-b2d23de2281e","order_by":7,"name":"He Yihua","email":"","orcid":"","institution":"¹Fetal Cardiology and Maternal–Fetal Medicine Center, and Cardiac Ultrasound Center, Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"He","middleName":"","lastName":"Yihua","suffix":""},{"id":488135909,"identity":"6331a375-0763-4986-adbd-13221e0819df","order_by":8,"name":"Weng Zongjie","email":"","orcid":"","institution":"¹Fetal Cardiology and Maternal–Fetal Medicine Center, and Cardiac Ultrasound Center, Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Weng","middleName":"","lastName":"Zongjie","suffix":""}],"badges":[],"createdAt":"2025-06-29 15:38:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7003626/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7003626/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":87372766,"identity":"e3978bcb-1431-4155-8a8d-35943c1b3b39","added_by":"auto","created_at":"2025-07-23 07:24:48","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":485591,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eUltrasound images of VSA, CTR, GSI, and CAx measurements in normal early pregnancy fetal heart.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNote: a. VSA measurement is taken by identifying the left outer boundary of the ductal arch and the right outer boundary of the aortic arch; b. CTR measurement is taken by identifying the heart's outer horizontal diameter and the chest cavity's outer horizontal diameter; c. GSI measurement is taken by identifying the maximum horizontal diameter of the heart and the maximum longitudinal diameter from the apex to the base; d. CAx measurement is taken by identifying the midline of the sternum to the midline of the spine and the line through the atrioventricular septum. 3VV: three-vessel view; 4CH: four-chamber view; VSA: cardiac V angle; CAx: cardiac axis\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7003626/v1/8dd4aea487199bf90b56a61a.png"},{"id":87372763,"identity":"966c2a12-4e23-4532-86ff-88f047b4631c","added_by":"auto","created_at":"2025-07-23 07:24:48","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":95131,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eNormal Q-Q plots of VSA, CTR, GSI, and CAx parameters for fetuses at 11\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e+0\u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003e to 16\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e+0\u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003e weeks.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNote: a. Normal Q-Q plot of VSA with respect to GA in normal fetuses. b. Normal Q-Q plot of CTR with respect to GA in normal fetuses. c. Normal Q-Q plot of GSI with respect to GA in normal fetuses. d. Normal Q-Q plot of CAx with respect to GA in normal fetuses.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7003626/v1/86715a26eeda6ef02bb48bec.png"},{"id":87372765,"identity":"8ee18497-bb52-41f7-bc93-7b2e147af74d","added_by":"auto","created_at":"2025-07-23 07:24:48","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":112188,"visible":true,"origin":"","legend":"\u003cp\u003eROC curves for screening CHD using VSA, CTR, GSI, and CAx in fetuses at 11\u003csup\u003e+0\u003c/sup\u003e to 16\u003csup\u003e+0\u003c/sup\u003e weeks.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNote: VSA:AUC=0.811 (0.728–0.893); CTR: AUC=0.604 (0.513–0.695); GSI: AUC=0.580 (0.488–0.671); CAx: AUC=0.713 (0.623–0.803)\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7003626/v1/12e140637217bc487ba6a269.png"},{"id":87373640,"identity":"e23d7ed5-bd68-4db5-8395-ef03544aa711","added_by":"auto","created_at":"2025-07-23 07:32:48","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":94156,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eROC curve for combined VSA, CTR, GSI, and CAx parameters in CHD screening.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNote: ① VSA; ② CTR; ③ GSI; ④CAx; ①+②+③+④: AUC=0.871 (0.823–0.920); ①+②+③: AUC=0.838 (0.771–0.904); ②+③+④: AUC=0.790 (0.717–0.863); ①+③: AUC=0.831 (0.754–0.909); ②+④: AUC=0.768 (0.690–0.846); ①: AUC=0.811 (0.728–0.893)\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7003626/v1/f6af72134f1816c6765a950c.png"},{"id":87375272,"identity":"23cfd738-1fc6-4c40-9aaf-7e485780db72","added_by":"auto","created_at":"2025-07-23 07:48:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2908092,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7003626/v1/37668695-3db8-47bd-b261-5bdec6aa818a.pdf"},{"id":87372762,"identity":"38e8e200-64cb-4ae1-bda6-dc5b91ed5450","added_by":"auto","created_at":"2025-07-23 07:24:48","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":16149,"visible":true,"origin":"","legend":"","description":"","filename":"AppendixS1.docx","url":"https://assets-eu.researchsquare.com/files/rs-7003626/v1/f833a74fbded2bb8aff7362a.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eReference Ranges and Clinical Significance of Key Fetal Cardiac Parameters Measured by Color Doppler Ultrasound at 11\u003csup\u003e+0\u003c/sup\u003e to 16\u003csup\u003e+0\u003c/sup\u003e Weeks of Gestation\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCongenital heart disease (CHD) is the most common type of congenital malformation and has rapidly become a global pediatric health concern because of its high morbidity and mortality and severe effects on survival and quality of life\u003csup\u003e\u0026nbsp;[1,2]\u003c/sup\u003e. Early prenatal screening and diagnosis of CHD are vital to prevent and reduce neonatal mortality. According to 2013 Practice Guidelines on Fetal Cardiac Screening formulated by the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), standard fetal cardiac screening is typically performed between 18 and 22 weeks of gestation\u003csup\u003e\u0026nbsp;[3]\u003c/sup\u003e. With continuous advancements in ultrasound technology and growing clinical expertise, the ability to diagnose certain types of CHD in early pregnancy has improved, resulting in high diagnostic rates and timely and appropriate assessment and clinical management of severe cases. Cardiac axis (CAx) and cardiothoracic ratio (CTR) are important indicators in mid-to-late gestation and have established reference ranges internationally and domestically\u003csup\u003e\u0026nbsp;[4]\u003c/sup\u003e. \u0026nbsp;V-sign angle (VSA) and global sphericity index (GSI) are new parameters used to evaluate fetal CHD, and their normal reference ranges for mid-to-late pregnancy have been documented \u003csup\u003e[5\u0026ndash;7]\u003c/sup\u003e. Scholars at home and abroad have attempted to measure and study some parameters of early pregnancy fetuses with small samples and proposed that they have a certain value for the detection of certain types of CHD in early pregnancy fetuses. However, comprehensive large-sample studies involving VSA, CTR, GSI, and CAx for CHD screening are still lacking. The present study aims to measure and analyze four key parameters (VSA, CTR, GSI, and CAx) of normal fetuses with a large sample size during early pregnancy, explore their normal reference values, and build regression models for validation. Findings will provide a quantitative reference for the diagnosis of fetal CHD in early pregnancy, prognosis assessment, and perinatal management strategies. Additionally, the study will explore the clinical value of the four parameters in the screening of CHD in early pregnancy. Color Doppler ultrasound was used as the primary diagnostic tool to supplement the imaging of the fetal heart because 2D grayscale imaging quality in early pregnancy is often suboptimal.\u003c/p\u003e"},{"header":"Materials and METHODS","content":"\u003cp\u003e\u003cstrong\u003e1. Research object\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study prospectively collected data from January 2022 to March 2024 at two centers: Haidian District Maternal and Child Health Hospital in Beijing and Fujian Maternal and Child Health Hospital. A total of 2,529 normal fetuses underwent heart color Doppler ultrasound examination and 50 fetuses diagnosed with CHD were included. The inclusion criteria were as follows: (1) gestational age (GA) between 11\u003csup\u003e+0\u003c/sup\u003e and 16\u003csup\u003e+0\u003c/sup\u003e weeks; (2) clear and complete color Doppler ultrasound images; and (3) informed consent provided by the participant. The exclusion criteria included the following: (1) incomplete follow-up data; and (2) inability or refusal to cooperate during the ultrasound examination. The study complied with the principles of the Declaration of Helsinki (2013 revision) and was approved by the Ethics Committee of Haidian District Maternal and Child Health Hospital (Ethics Approval No. 2021-23). All participating pregnant women were fully informed about the content of the ultrasound measurements before joining the study and provided written informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2. Instruments and Methods \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.1 Instruments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFetal cardiac ultrasound examinations were conducted using the GE Voluson E8 and E10 color Doppler ultrasound systems equipped with a 2D abdominal convex probe with a frequency range of 4\u0026ndash;8 MHz.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2 Methods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study analyzed cross-sectional data from the two centers and established normal reference value ranges and models for the four key fetal cardiac parameters (VSA, CTR, GSI, and CAx) in normal fetuses during early pregnancy. The models were then applied and validated in both centers to differentiate between normal fetal hearts and those affected by CHD. The study also assessed the diagnostic efficacy and clinical application value of VSA, CTR, GSI, and CAx in the screening of CHD based on the established models.\u003c/p\u003e\n\u003cp\u003eThis study included 2529 fetuses with complete data who underwent CAx, CTR, VSA, and GSI examination. The GA was between 11\u003csup\u003e+0\u003c/sup\u003e and 16\u003csup\u003e+0\u003c/sup\u003e weeks. The age of pregnant women ranged from 19 to 52 years, with an average of 31.7 \u0026plusmn; 3.8 years. The 2,529 normal cases were divided into a training set (2,049 cases) and a validation set (480 cases). The training set was further categorized into five groups based on GA: 11\u003csup\u003e+0\u003c/sup\u003e to 11\u003csup\u003e+6\u003c/sup\u003e weeks (91 cases), 12\u003csup\u003e+0\u003c/sup\u003e to 12\u003csup\u003e+6\u003c/sup\u003e weeks (1,297 cases), 13\u003csup\u003e+0\u003c/sup\u003e to 13\u003csup\u003e+6\u003c/sup\u003e weeks (544 cases), 14\u003csup\u003e+0\u003c/sup\u003e to 14\u003csup\u003e+6\u003c/sup\u003e weeks (70 cases), and 15\u003csup\u003e+0\u003c/sup\u003e to 16\u003csup\u003e+0\u003c/sup\u003e weeks (47 cases). The distribution of the measurements for VSA, CTR, GSI, and CAx in the training set, which included 2049 normal fetal hearts, was tested for normality by using a normal Q-Q plot (quartile-quartile plot) to assess whether the data follow a normal distribution. If the data conform to a normal distribution, then Spearman\u0026rsquo;s correlation coefficients were calculated to assess the relationship between the four parameters and GA. Univariate regression models were then established to calculate the reference ranges of VSA, CTR, GSI, and CAx across the five GA groups. A binary logistic regression model (backward stepwise method) was used to construct a polynomial linear regression model. The model\u0026rsquo;s fit and generalizability were evaluated using the Hosmer\u0026ndash;Lemeshow test. The model was refined to optimize its performance in CHD detection. The validation set, comprising 480 normal fetal hearts and 50 CHD-affected fetal hearts, was used to validate the predictive performance of the regression models based on the four parameters (VSA, CTR, GSI, and CAx). These models included the univariate regression models (normalized by GA) and the polynomial linear regression models. Receiver Operating Characteristic (ROC) curves were constructed, and the diagnostic performance of each model was recorded. The validation population for CHD included 50 fetuses with prenatal diagnosis of CHD from the two centers, from January 2022 to March 2024. The cases included 3 cases of single ventricle, 3 cases of hypoplastic left heart syndrome, 7 cases of endocardial cushion defects, 11 cases of tetralogy of Fallot, 2 cases of persistent arterial trunk, 6 cases of double outlet right ventricle, 2 cases of transposition of the great arteries, 5 cases of aortic atresia or stenosis, 4 cases of pulmonary atresia or stenosis, 6 cases of right-sided aortic arch, and 1 case of ventricular septal defect. The application value of the four parameters for screening various types of CHD was analyzed. Examination after birth or autopsy result after termination of pregnancy of fetuses enrolled from the two centers was regarded as the gold standard. In cases where the examination after birth or autopsy confirmation was not available, the diagnosis was validated by consensus between two physicians with over 10 years of experience in fetal cardiac ultrasound diagnosis to ensure accuracy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3 Measurement Parameters and Standards\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAccording to practice guidelines of fetal ultrasound scanning in the early pregnancy\u003csup\u003e\u0026nbsp;[8]\u003c/sup\u003e issued by the International Society of Ultrasound in Obstetrics and Gynecology(ISUOG) fetal biological parameters, such as crown-rump length, were shown and GA was corrected. The measurement of VSA, CTR, GSI, and CAx also followed the ISUOG practice guidelines \u003csup\u003e[3]\u003c/sup\u003e, the statement on safe Doppler use in early pregnancy ultrasound \u003csup\u003e[9]\u003c/sup\u003e, and the fetal echocardiography guidelines \u003csup\u003e[10]\u003c/sup\u003e. The ultrasound mode specifically for fetal heart examination was used with mechanical index and thermal index set to less than 0.8. Color Doppler ultrasound was employed by physicians who are qualified in prenatal screening to obtain four-chamber view (4CV) and three-vessel view (3VV) cross-sections of the fetal heart. The parameters measured were CAx, CTR, VSA, and GSI for fetal heart screening. (1) VSA: in the 3VV, the angle between the first line connecting the left outer boundary of the ductal arch and the second line connecting the right outer boundary of the aortic arch was measured on the color Doppler ultrasound image; (2) CTR: in the 4CV, the heart diameter (HD) at the level of the atrioventricular valves in diastole (when all four chambers are visible in color Doppler) was measured; thoracic diameter (TD) was measured at the widest part of the chest cavity, and CTR was calculated as HD/TD; (3) GSI: in the 4CV, the maximum horizontal diameter of the heart (HD) and the maximum longitudinal distance from the apex to the base of the heart (heart length, HLE) were measured at the level of the atrioventricular valves or slightly lower in diastole (when all four chambers are visible in color Doppler); GSI was calculated as HLE/H; and (4) CAx: in the 4CV, the anatomy displayed should include at least one complete rib, and atria and ventricles should be visible; color Doppler was used to determine the position of the atrioventricular septum. In systole (when only the two ventricles are visible in color Doppler), CAx angle was measured. This angle was determined by drawing a line from the midline of the sternum to the midline of the spine, dividing the fetal chest into left and right symmetrical portions, and then drawing another line along the atrioventricular septum\u0026rsquo;s position. The angle between the two lines was defined as CAx, as shown in Figure 1. Each fetus had three measurements of VSA, CTR, GSI, and CAx, and the average value was taken. The echocardiographic images from the Haidian District Maternal and Child Health Hospital were measured by two physicians (Zheng S and Zhao H) after removing individual information, and the average value was taken. The echocardiographic images from the Fujian Provincial Maternal and Child Health Hospital were also measured by two physicians (Ruan Y and Wang J) from the Fetal Heart and Maternal\u0026ndash;Fetal Medicine Center of Beijing Anzhen Hospital, Capital Medical University, after removing individual information, and the average value was taken. All research participants were trained in the aforementioned measurement standards, and only magnified echocardiographic images were used for data measurement.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3 Statistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistical analysis was performed using SPSS 29.0 software. The fetal VSA, CTR, GSI, and CAx values were treated as continuous variables. The normality of data was checked using the Kolmogorov\u0026ndash;Smirnov test. Spearman correlation coefficients were used to analyze the relationship between gestational week and VSA, CTR, GSI, and CAx, with \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05 considered statistically significant. Descriptive statistics were used to report continuous variables that followed a normal distribution as mean (standard error), and 95% confidence intervals were used as normal reference ranges. Categorical data were expressed as \u003cem\u003en\u003c/em\u003e (%). The ROC curve was used to calculate the area under the curve (AUC) of individual VSA, CTR, GSI, CAx, and their combinations and assess its application value in screening for CHD. The diagnostic efficiency of the standard to be tested such as sensitivity, specificity, accuracy, false-positive rate, positive predictive value, and negative predictive value was analyzed based on diagnostic 2x2 tables. The \u003cem\u003e\u0026chi;2\u003c/em\u003e test was used for comparison of independent samples, with \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05 considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003e1 Relationship of Normal Fetal VSA, CTR, GSI, and CAx with GA and Construction of Single-Parameter Models\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe measured data of VSA, CTR, GSI, and CAx in 2049 normal fetuses were normally distributed (Figure 2). The Pearson\u0026rsquo;s product\u0026ndash;moment correlation coefficient analysis revealed that GA was negatively correlated with VSA but positively correlated with CTR and GSI in 2049 fetuses (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05). CAx showed no correlation with GA (\u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05). Linear regression models were used to construct growth models for VSA, CTR, and GSI, while CAx was modeled using mean \u0026plusmn; standard deviation (`\u003cem\u003ex\u0026plusmn;s\u003c/em\u003e). A Z-score model for the four parameters was established in Table 1. The normal reference ranges for VSA, CTR, GSI, and CAx in fetuses at 11\u003csup\u003e+0\u003c/sup\u003e to 16\u003csup\u003e+0\u003c/sup\u003e weeks were expressed as (`\u003cem\u003ex\u0026plusmn;s\u003c/em\u003e) and 95% confidence intervals (Supplementary Table S1).\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1: Correlation analysis of VSA, CTR, GSI, and CAx with GA.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"654\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 7.65697%;\"\u003e\n \u003cp\u003eParameters\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.7106%;\"\u003e\n \u003cp\u003eCorrelation with GA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.72894%;\"\u003e\n \u003cp\u003er-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.26953%;\"\u003e\n \u003cp\u003eP-Value\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.7366%;\"\u003e\n \u003cp\u003eRegression Equation / Mean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38.8974%;\"\u003e\n \u003cp\u003eZ-value Model\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 7.65697%;\"\u003e\n \u003cp\u003eVSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.7106%;\"\u003e\n \u003cp\u003eNegative Correlation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.72894%;\"\u003e\n \u003cp\u003e-0.102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.26953%;\"\u003e\n \u003cp\u003e＜0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.7366%;\"\u003e\n \u003cp\u003e\u003cem\u003eY\u003c/em\u003e=71.216-1.591GA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38.8974%;\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e=（VSA-（71.216-1.591GA））/（51.5567）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 7.65697%;\"\u003e\n \u003cp\u003eCTR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.7106%;\"\u003e\n \u003cp\u003ePositive Correlation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.72894%;\"\u003e\n \u003cp\u003e0.100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.26953%;\"\u003e\n \u003cp\u003e＜0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.7366%;\"\u003e\n \u003cp\u003e\u003cem\u003eY\u003c/em\u003e=0.225+0.004GA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38.8974%;\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e=（CTR-（0.225+0.004GA））/（0.2768）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 7.65697%;\"\u003e\n \u003cp\u003eGSI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.7106%;\"\u003e\n \u003cp\u003ePositive Correlation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.72894%;\"\u003e\n \u003cp\u003e0.051\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.26953%;\"\u003e\n \u003cp\u003e＜0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.7366%;\"\u003e\n \u003cp\u003e\u003cem\u003eY\u003c/em\u003e=1.167+0.009GA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38.8974%;\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e=（GSI-（1.167+0.009GA））/（0.0062）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 7.65697%;\"\u003e\n \u003cp\u003eCAx\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.7106%;\"\u003e\n \u003cp\u003eNo correlation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.72894%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.26953%;\"\u003e\n \u003cp\u003e0.062\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.7366%;\"\u003e\n \u003cp\u003e44.91\u0026plusmn;8.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38.8974%;\"\u003e\n \u003cp\u003e\u003cem\u003eZ\u003c/em\u003e=（CAx-44.91）/（8.57）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e2. Evaluation of Models for Normal Fetal VSA, CTR, GSI, and CAx\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 530 fetuses at 11\u003csup\u003e+0\u003c/sup\u003e to 16\u003csup\u003e+0\u003c/sup\u003e weeks were included as a validation set, which consisted of 480 normal fetuses and 50 fetuses with CHD. ROC curves were constructed using the Z-score model and the established reference ranges for the four parameters. The diagnostic performance of VSA, CTR, GSI, and CAx was evaluated (Table 2 and Figure 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2: Diagnostic performance of Z-score Models for Normal Fetal VSA, CTR, GSI, and CAx.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"750\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eParameters\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFetal Heart Gold Standard\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eZ-score model established based on \u003cem\u003exx\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eAccuracy (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eSensitivity (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eSpecificity (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePositive Predictive Value (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNegative Predictive Value (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eAUC\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e95% Confidence Interval\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNormal Fetal Hearts\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(480 cases)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCHD Fetuses\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(50 cases)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVSA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNormal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e471\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e18\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e94.91\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e98.13\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e64\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e78.05\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e96.32\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.811\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.728\u0026ndash;0.893\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCHD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e32\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCTR\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNormal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e436\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e35\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e85.09\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e30\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e90.83\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e25.42\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e92.57\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.604\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.513\u0026ndash;0.695\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCHD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e44\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e15\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGSI\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNormal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e470\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e41\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e90.38\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e18\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e97.92\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e47.37\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e91.98\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.580\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.488\u0026ndash;0.671\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCHD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e10\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCAx\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNormal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e454\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e26\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e90.19\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e48\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e94.58\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e48\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e94.58\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.713\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.623\u0026ndash;0.803\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCHD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e26\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e24\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e3. Establishment of Polynomial Logistic Regression Model Using Binary Logistic Regression and Parameter Optimization\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA polynomial logistic regression model was constructed using the forward selection method in binary logistic regression (LR): \u003cem\u003eY\u003c/em\u003e = \u0026ndash;4.443 + 4.574\u003cem\u003eX\u003c/em\u003e\u003csub\u003e1\u003c/sub\u003e + 1.944\u003cem\u003eX\u003c/em\u003e\u003csub\u003e2\u003c/sub\u003e + 2.080\u003cem\u003eX\u003c/em\u003e\u003csub\u003e3\u003c/sub\u003e + 3.099\u003cem\u003eX\u003c/em\u003e\u003csub\u003e4\u003c/sub\u003e. The model fit was evaluated using the Hosmer\u0026ndash;Lemeshow goodness-of-fit test (P = 0.610). The Hosmer\u0026ndash;Lemeshow statistic follows a chi-square distribution, with P \u0026gt; 0.2, which confirmed that the model provided a good fit to the original data (Table 3).\u0026nbsp;The results indicated that all the four parameters (VSA, CTR, GSI, and CAx) at 11\u003csup\u003e+0\u003c/sup\u003e to 16\u003csup\u003e+0\u003c/sup\u003e weeks are valuable for CHD screening, and their combination had the highest diagnostic performance. The AUC for the combined parameters was 0.871 (Figure 4).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3: Independent variables and coefficients of the binary logistic regression model.\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eB\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eS.E.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWald\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEXP(B) \u0026nbsp;95% Confidence Interval\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLower limit\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUpper limit\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVSA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e4.574\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.565\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e65.487\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e96.915\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e32.010\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e293.420\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCTR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.944\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.576\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e11.388\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e6.985\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.259\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e21.598\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGSI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.080\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.829\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e6.295\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.012\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e8.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.576\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e40.623\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCAx\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3.099\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.544\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e32.500\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e22.179\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e7.642\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e64.367\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eConstant\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-4.443\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.415\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e114.797\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.012\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003e4. Application Value of VSA, CTR, GSI, and CAx for Different CHD Types at 11\u003csup\u003e+0\u003c/sup\u003e to 16\u003csup\u003e+0\u003c/sup\u003e Weeks\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the four parameters were statistically significant when categorized by the abnormal location of fetal CHD and can be used as effective parameters for CHD screening in early pregnancy. When categorized by the severity of CHD (mild vs. severe), VSA, CTR, and CAx were statistically significant for mild CHD and could serve as effective screening parameters. In severe CHD, all the four parameters were statistically significant and could be used as effective screening parameters (Table 4).\u003c/p\u003e\n\u003cp\u003eTable 4: Application value of VSA, CTR, GSI, and CAx for different CHD types at 11\u003csup\u003e+0\u003c/sup\u003e to 16\u003csup\u003e+0\u003c/sup\u003e weeks\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"775\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" rowspan=\"2\" valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003eFetal Heart Gold Standard\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003eNumber of cases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 149px;\"\u003e\n \u003cp\u003eVSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 145px;\"\u003e\n \u003cp\u003eCTR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003eGSI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 152px;\"\u003e\n \u003cp\u003eCAx\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003eNumber of cases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026chi;2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003eNumber of cases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026chi;2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003eNumber of cases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026chi;2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003eNumber of cases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.8065%;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026chi;2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.1612%;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 152px;\"\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e480\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 51px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.8065%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.1612%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"6\" valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eCHD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eType 1\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003eCardiac Chamber Abnormalities (Size, Position)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003e6.198\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 51px;\"\u003e\n \u003cp\u003e0.013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.8065%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.1612%;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003eMajor Artery Abnormalities\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e274.152\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003e14.579\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 51px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e23.089\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.8065%;\"\u003e\n \u003cp\u003e85.570\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.1612%;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003eValve Abnormalities\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003e13.597\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 51px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.8065%;\"\u003e\n \u003cp\u003e57.774\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.1612%;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003eAtrioventricular Septal Abnormalities\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e139.418\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003e17.340\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 51px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e30.702\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.8065%;\"\u003e\n \u003cp\u003e56.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.1612%;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eType 2\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003eMild CHD\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003e4.488\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 51px;\"\u003e\n \u003cp\u003e0.034\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e0.257\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.8065%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.1612%;\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003eSevere CHD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e230.716\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 50px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003e13.193\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 51px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e33.426\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.8065%;\"\u003e\n \u003cp\u003e94.342\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 5.1612%;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\n\u003ch3\u003e1. Introduction to the Clinical Problem, Research Background, and Contribution of the Study\u003c/h3\u003e\n\u003cp\u003eFetal CHD is the most severe and prevalent congenital anomaly globally, ranking first among all birth defects and accounting for more than 40% of congenital abnormalities \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. 4CV and 3VV are the fundamental planes for mid-trimester screening of CHD. The detection rate of CHD by using the 4CV alone is 60.3% \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e, while that of the 3VV alone is 71.43% \u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. The combination of both views increases the diagnostic accuracy up to 90.9% \u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. Previous studies reported a first-trimester CHD detection rate of 74%, with a sensitivity of 85% and a specificity of 99% \u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. Therefore, fetal cardiac ultrasound screening in the first trimester is important and feasible. The parameters CAx, HD, HL, and TD were measured on the 4CV, while VSA was measured on the 3VT. Once standard 4CV and 3VT images are acquired, sonographers can intuitively assess fetal CAx, HD, HL, TD, and VSA. The measurement methods are simple and practical. However, the quality of grayscale 2D images of the fetal heart in the first trimester is often suboptimal because of factors, such as fetal movement, position, rapid heart rate, small cardiac size, unclear visualization of the atrioventricular septum and internal cardiac structures, and shadowing from ribs and placenta. Color Doppler ultrasound can better delineate vascular and cardiac chamber morphology and can be used to assess structural details. It allows for the determination of cardiac position, size, orientation, margins, and course and caliber of the great arteries during the first trimester. Thus, color Doppler imaging offers significant advantages in fetal cardiac imaging during early pregnancy and could serve as an excellent complement to grayscale imaging \u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. It can also be used as the primary tool for first-trimester fetal cardiac screening.\u003c/p\u003e\n\u003ch3\u003e2. Diagnostic Advantages and Analytical Findings of VSA, CTR, GSI, and CAx\u003c/h3\u003e\n\u003cp\u003eVSA is a relatively new parameter used to assess fetal CHD and detect abnormalities of the conotruncal region, such as aortic coarctation, right aortic arch, double aortic arch, and vascular rings [3]. The present study shows a CHD detection rate of 94.91% and an accuracy of 98.13% by using VSA, confirming its effectiveness as a diagnostic parameter in first-trimester CHD screening; this finding is consistent with the report of Wiechec et al. \u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. A negative correlation was found between VSA and GA, which differs from previous studies \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. The discrepancy may be attributed to the large sample size in the present study and the division of the 11\u003csup\u003e+\u0026thinsp;0\u003c/sup\u003e to 16\u003csup\u003e+\u0026thinsp;0\u003c/sup\u003e weeks gestational period into five subgroups for intergroup statistical comparison, which optimizes study design and enhances efficiency and accuracy.\u003c/p\u003e\u003cp\u003eThe concept of CTR was first introduced by Garrett et al. \u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e in 1970. In early pregnancy, CTR may reflect cardiac enlargement, reduction, or dysfunction, and its abnormality may suggest internal cardiac anomalies. The CHD detection rate for CTR is 85.09%, with a specificity of 90.83%, supporting its role as a valuable early screening parameter. However, variability exists in the reported normal CTR reference ranges and diagnostic thresholds. Tongsong et al. \u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e proposed a CTR\u0026thinsp;\u0026lt;\u0026thinsp;0.5 as normal during early pregnancy, consistent with that in mid-later trimesters, and this criterion is still widely used. In the present work, CTR shows a positive correlation with GA, aligning with the findings of previous study \u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. However, the reference range for normal CTR in this study was lower than that reported by Tongsong. This discrepancy may be due to the use of color Doppler imaging for distinguishing the epicardium of four chambers and obtaining numerical values of cardiac transverse diameter, which defines the outer myocardial boundary more precisely than grayscale imaging, resulting in smaller measured values and a narrower normal range.\u003c/p\u003e\u003cp\u003eGSI, which was first introduced by DeVore et al., is a reproducible parameter for quantifying cardiac remodeling and assessing geometric characteristics of the ventricles, atria, and the entire heart. GSI reference ranges for the second and third trimesters have been established, and previous studies found no significant correlation between GSI and GA in mid-to-late pregnancy \u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. Most existing studies focus on cardiac remodeling due to fetal ischemia or hypoxia, such as in α-thalassemia major or late-onset intrauterine growth restriction, but studies during early pregnancy are lacking. In the present work, a large dataset was used to establish reference ranges for normal GSI values in the first trimester. The GSI detection rate for CHD is 90.38%, with an accuracy of 97.92%, confirming its diagnostic value in early CHD screening and its positive correlation with GA.\u003c/p\u003e\u003cp\u003eUltrasound was first used to measure fetal CAx during the second trimester by Comstock \u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e in 1987 to establish corresponding reference values. Abnormal CAx may indicate intracardiac structural anomalies. Fetuses with abnormal CAx have a nearly 45-fold increased risk of CHD compared with those with normal CAx \u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e, and CAx has been identified as an independent predictor of chromosome 22q11.2 microdeletion syndrome \u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. In the present study, CAx has a CHD detection rate of 90.19% and an accuracy of 94.58%, demonstrating its effectiveness in first-trimester screening. The lack of correlation between CAx and GA is consistent with the findings of Sinkovskaya et al. \u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe univariate polynomial regression models established for CAx, CTR, VSA, and GSI in yield superior detection rates compared with other studies that used single-parameter regression models \u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. The polynomial linear regression model significantly improves CHD detection performance over univariate models (AUC\u0026thinsp;=\u0026thinsp;0.871).\u003c/p\u003e\n\u003ch3\u003e3. Validity and Innovation of Data and Methodology\u003c/h3\u003e\n\u003cp\u003eCurrently, first-trimester fetal cardiac assessment has no expert consensus domestically and internationally. Fetal cardiac ultrasound remains highly operator-dependent, and existing literature on early gestational fetal heart studies is scarce, which is often limited to small sample sizes and single-parameter diagnostics. In the present study, a dual-center, large-sample design incorporating four parameters were adopted to calculate reference ranges and establish models for normal fetal cardiac values in the first trimester. The predictive model demonstrates high efficacy, and the ROC curves clearly illustrate that polynomial linear regression modeling substantially improves CHD detection over univariate models. The GA is divided into five groups for intergroup comparison, and correlations between parameters and GA are analyzed to optimize experimental design and enhance the efficiency and accuracy of the experiment. The validation dataset includes CHD cases and approximately 500 normal first-trimester fetuses for prediction modeling. It encompasses 14 types of mild to severe CHD to analyze the clinical application of the four parameters across different CHD subtypes during early gestation. This study comprehensively and efficiently bridges normal and abnormal fetal cardiac data in the first trimester, thereby effectively advancing the diagnostic window.\u003c/p\u003e\n\u003ch3\u003e4. Limitations of the Study\u003c/h3\u003e\n\u003cp\u003eThis study has some limitations. ① The distribution of case numbers across the five GA groups was uneven because of scheduling constraints among pregnant participants, which may introduce statistical bias.② The number of CHD validation cases was relatively small, and the predictive performance of the model requires further validation.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study is the first to establish reference ranges and a multi-parameter predictive model for CAx, CTR, VSA, and GSI during the first trimester, providing quantitative indicators for CHD screening. It further explores the correlation between each parameter and GA in the first trimester to enhance the precision of early CHD prediction. Fetuses with parameters outside the established normal ranges should be closely monitored. Repeated measurements from different maternal positions are recommended to confirm the presence or absence of cardiac anomalies and to minimize the risk of missed or incorrect diagnoses.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCHD\u003c/em\u003e\u003c/strong\u003e: Congenital Heart Disease\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCAx\u003c/em\u003e\u003c/strong\u003e: Cardiac Axis\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCTR\u003c/em\u003e\u003c/strong\u003e: Cardiothoracic Ratio\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eVSA\u003c/em\u003e\u003c/strong\u003e: V Sign Angle\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eGSI\u003c/em\u003e\u003c/strong\u003e: Global Sphericity Index\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eQ-Q plot\u003c/em\u003e\u003c/strong\u003e: Quartile-Quartile Plot\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eGA\u003c/em\u003e\u003c/strong\u003e: Gestational Age\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eHL\u003c/em\u003e\u003c/strong\u003e: Hosmer-Lemeshow\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eISUOG\u003c/em\u003e\u003c/strong\u003e: The International Society of Ultrasound in Obstetrics and Gynecology\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e4CV\u003c/em\u003e\u003c/strong\u003e: Four-Chamber View\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e3VV\u003c/em\u003e\u003c/strong\u003e: Three-Vessel View\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eHD\u003c/em\u003e\u003c/strong\u003e: Heart\u0026nbsp;Diameter\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eTD\u003c/em\u003e\u003c/strong\u003e: Thorax Diameter\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eHLE\u003c/em\u003e\u003c/strong\u003e: Heart Length\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eROC\u003c/em\u003e\u003c/strong\u003e: Receiver Operating Characteristics\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAUC\u003c/em\u003e\u003c/strong\u003e: Area Under the Curve\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of the Haidian District Maternal and Child Health Hospital, Beijing (Ethical approval number: 2021-23). Prior to inclusion, the specific content of the ultrasound measurements required for the study was explained to the participants.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe manuscript is approved by all authors for publication.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the data are true and valid.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBeijing Natural Science Foundation (7244325)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZ.S.: Conceptualization, Writing\u0026ndash;Original Draft, Writing\u0026ndash;Review \u0026amp; Editing, Study Design, Investigation, Image Analysis, Image Processing, Data Analysis.\u003c/p\u003e\n\u003cp\u003eG.X.Y.:Writing\u0026ndash;Review \u0026amp; Editing.\u003c/p\u003e\n\u003cp\u003eW.J.Y.: Literature Review, Investigation, Funding Acquisition, Study Design.\u003c/p\u003e\n\u003cp\u003eL.W.:Image collection.\u003c/p\u003e\n\u003cp\u003eH.X.Y.:Study Design, Data Analysis.\u003c/p\u003e\n\u003cp\u003eR.Y.P.:Study Design, Data Analysis.\u003c/p\u003e\n\u003cp\u003eZ.H.W.:Image collection, Image Analysis.\u003c/p\u003e\n\u003cp\u003eH.Y.H.: Supervision, Writing\u0026ndash;Review \u0026amp; Editing, Final Approval.\u003c/p\u003e\n\u003cp\u003eW.Z.J.: Image collection, Final Approval.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe want to thank all pregnant women who participated in the study.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; information\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZheng Shuai\u003csup\u003e1,2,\u003c/sup\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003e, Gu Xiaoyan\u003csup\u003e1,\u003c/sup\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003e, Wang Jingyi\u003csup\u003e1\u003c/sup\u003e, Ling Wen\u003csup\u003e3\u003c/sup\u003e, Hao Xiaoyan\u003csup\u003e1\u003c/sup\u003e, Ruan Yanping\u003csup\u003e1\u003c/sup\u003e, Zhao Huawei\u003csup\u003e2\u003c/sup\u003e, He Yihua\u003csup\u003e1,*\u003c/sup\u003e, Weng Zongjie\u003csup\u003e3,*\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e*Corresponding authors: He Yihua (E-mail: [email protected]);Weng Zongjie (E-mail: [email protected])\u003c/p\u003e\n\u003cp\u003e\u0026dagger;\u0026nbsp;These authors contributed equally to this work.\u003c/p\u003e\n\u003cp\u003e\u0026sup1;Fetal Cardiology and Maternal\u0026ndash;Fetal Medicine Center, and Cardiac Ultrasound Center, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China; \u0026sup2;Department of Ultrasound, Haidian District Maternal and Child Health Hospital, Beijing 100080, China; \u0026sup3;Department of Ultrasound, Fujian Maternal and Child Health Hospital, Fuzhou 350001, China\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHe YH, Jiang YX. Guidelines for Prenatal Ultrasound Diagnosis and Perinatal Management of Fetal Heart Disease (1st ed.). Beijing: People\u0026rsquo;s Medical Publishing House.2015;7-20. https://doi.org/10.3760/cma.j.issn.1007-9408.2016.03.005\u003c/li\u003e\n\u003cli\u003eGBD 2017 Congenital Heart Disease Collaborators. Global, regional, and national burden of congenital heart disease, 1990-2017:a systematic analysis for the Global Burden of Disease Study 2017. Lancet Child Adolesc Health.2020;4(3):185-200. \u003c/li\u003e\n\u003cli\u003eInternational Society of Ultrasound in Obstetrics and Gynecology, Carvalho, J. S., Allan, L. D., Chaoui, R., Copel, J. A., DeVore, G. R., Hecher, K., Lee, W., Munoz, H., Paladini, D., Tutschek, B., \u0026amp; Yagel, S. (2013). ISUOG Practice Guidelines (updated): sonographic screening examination of the fetal heart. Ultrasound in obstetrics \u0026amp; gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology, 41(3), 348\u0026ndash;359.\u003c/li\u003e\n\u003cli\u003eUltrasound Obstet Gynecol. 2023 Jun;61(6):788-803.ISUOG Practice Guidelines (updated): fetal cardiac screening J S Carvalho 1, R Axt-Fliedner 2, R Chaoui 3, \u003c/li\u003e\n\u003cli\u003eDu, Z. S., Zhang, Y., \u0026amp; Zhu, L. F. (2019). Comparative analysis of normal fetal cardiac axis and aortic-pulmonary angle in early and mid-pregnancy [Conference presentation]. Proceedings of the 2019 Zhejiang Medical Ultrasound Academic Conference, Zhejiang Medical Association, Ningbo Second Hospital, 2019:1.\u003c/li\u003e\n\u003cli\u003eDEVOREG R , KLAS B , SATOU G , et al. 24-segment sphe- ricity index: A new technique to evaluate fetal cardiac diastolic shape [J] . Ultrasound Obstet Gynecol , 2018 , 51 (5) : 650- 658.\u003c/li\u003e\n\u003cli\u003eDEVORE G R , SATOU G , SKLANSKY M , et al. Abnormal fetalfindings associatedwith a global sphericity indexofthe 4- chamberview below the 5\u003csup\u003eth\u003c/sup\u003e centile [J] . J Ultrasound Med , 2017 , 36 (11) : 2309-2318.\u003c/li\u003e\n\u003cli\u003eSalomon LJ, Alfirevic Z, Bilardo CM, Chalouhi GE, Ghi T, Kagan KO, Lau TK, Papageorghiou AT, Raine-Fenning NJ, Stirnemann J, Suresh S, Tabor A, Timor-Tritsch IE, Toi A, Yeo G. ISUOG practice guidelines: performance of first-trimester fetal ultrasound scan. Ultrasound Obstet Gynecol. 2013 Jan;41(1):102-13. \u003c/li\u003e\n\u003cli\u003eSalvesen K, Abramowicz J, Ter HG,Miloro P, Sinkovskaya E, Dall\u0026apos;Asta A, Mar\u0026scaron;\u0026aacute;l K, Lees C. ISUOG statement on the safe use of Doppler for fetal ultrasound examination in the first 13\u0026thinsp;+\u0026thinsp;6\u0026thinsp;weeks of pregnancy (updated). Ultrasound Obstet Gynecol, 2021;57(6):1020. https://doi.org/10.1002/uog.23610\u003c/li\u003e\n\u003cli\u003eInternational Society of Ultrasound in Obstetrics and Gynecology, Carvalho JS, Allan LD, et al. ISUOG Practice Guidelines (updated): sonographic screening examination of the fetal heart [J]. Ultrasound Obstet Gynecol, 2013, 41(3): 348-359.\u003c/li\u003e\n\u003cli\u003eOgg\u0026egrave;, G., Gaglioti, P., Maccanti, S., Faggiano, F., \u0026amp; Todros, T. (2006). Prenatal screening for congenital heart disease with four-chamber and outflow-tract views: a multicenter study. Ultrasound in obstetrics \u0026amp; gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology, 28(6), 779-784.\u003c/li\u003e\n\u003cli\u003eWiechec M, Knafel A, Nocun A. Prenatal detection of congenital heart defects at the 11- to 13-week scan using a simple color Doppler protocol including the 4-chamber and 3-vessel and trachea views. J Ultrasound Med. 2015 Apr;34(4):585-94.\u003c/li\u003e\n\u003cli\u003eLi, X. W. (2018). Application of the four-chamber view combined with the three-vessel view in the mid-to-late pregnancy ultrasound screening of fetal heart disease. China Medical Herald, 16(17), 134\u0026ndash;135.\u003c/li\u003e\n\u003cli\u003eVAYNA ANA MARIA, VEDUTA ALINA, DUTA SIMONA, et al. Diagnosis of Fetal Structural Anomalies at 11 to 14 Weeks[J]. Journal of Ultrasound in Medicine: Official Journal of the American Institute of Ultrasound in Medicine,2018,37(8):2063-2073. \u003c/li\u003e\n\u003cli\u003eZheng, M. M., Tang, H. R., Zhang, Y., Ru, T., Li, J., Xu, B. Y., Xu, Y., \u0026amp; Hu, Y. L. (2019). Contribution of the Fetal Cardiac Axis and V-Sign Angle in First-Trimester Screening for Major Cardiac Defects. Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine, 38(5), 1179\u0026ndash;1187. \u003c/li\u003e\n\u003cli\u003eAlfred A, Rabin C. Practical Guide to Fetal Echocardiography: Normal and Abnormal Hearts (3rd ed.). Beijing: Beijing Science and Technology Press. 2017: 461-465. \u003c/li\u003e\n\u003cli\u003eWiechec M, Knafel A, Nocun A. Prenatal detection of congenital heart defects at the 11- to 13-week scan using a simple color Doppler protocol including the 4-chamber and 3-vessel and trachea views. J Ultrasound Med 2015; 34:585\u0026ndash;594.\u003c/li\u003e\n\u003cli\u003eGarrett WJ，Robinson DE． Fetal heart size measured in vivo by ultrasound［J］.Pediatrics，1970，46( 1) : 25\u0026mdash;27．\u003c/li\u003e\n\u003cli\u003eTongsong T, Wanapirak C, Sirichotiyakul S,Piyamongkol W, Chanprapaph P.. Fetal sonographic cardiothoracic ratio at midpregnancy as a predictor of Hb Bart disease. J Ultrasound Med. 1999;18(12): 807\u0026ndash;811. https://doi.org/10.7863/jum.1999.18.12.807\u003c/li\u003e\n\u003cli\u003ePang, C. Y., Li, X. Y., Huang, H., et al. (2021). Construction of a Z-score model for normal fetal cardiothoracic ratio. Chinese Journal of Medical Imaging Technology, 37(9), 1363\u0026ndash;1367.\u003c/li\u003e\n\u003cli\u003eComstock CH. Normal fetal heart axis and position. Obstet Gynecol, 1987, 70:255-259．\u003c/li\u003e\n\u003cli\u003eSu, F. F., Wang, J. J., Yin, C. H., Yue, W. T., \u0026amp; Wu, Q. Q. (2019). Relationship between fetal cardiac axis angle and congenital heart disease in mid-pregnancy. Journal of Capital Medical University, 40(6), 838\u0026ndash;841.\u003c/li\u003e\n\u003cli\u003eVigneswaran T V,Kametas N A,Zinevich Y et al. Assessment of cardiac angle in fetuses with congenital heart disease at risk of 22q11.2 deletion. [J] .Ultrasound Obstet Gynecol, 2015, 46: 695-9.\u003c/li\u003e\n\u003cli\u003eSinkovskaya ES, Chaoui R, Karl K, et al. Fetal cardiac axis and congenital heart defects in early gestation [J]. Ultrasound Obstet Gynecol, 2015, 125(2): 453-460.\u003c/li\u003e\n\u003cli\u003eZheng MM, Tang HR, Zhang Y, Ru T, Li J, Xu BY, Xu Y, Hu YL. Contribution of the Fetal Cardiac Axis and V-Sign Angle in First-Trimester Screening for Major Cardiac Defects. J Ultrasound Med. 2019 May;38(5):1179-1187.\u003c/li\u003e\n\u003cli\u003ePang, C. Y., Li, X. Y., Huang, H., et al. (2021). Reference range study of fetal global sphericity index Z-score. Chinese Journal of Ultrasound in Medicine, 37(4), 446\u0026ndash;449. \u003c/li\u003e\n\u003cli\u003eLin, W. Z., Deng, X. D., Yin, L. L., et al. (2019). Reference values and clinical significance of fetal cardiac axis in early pregnancy. Chinese Journal of Medical Ultrasound (Electronic Edition), 16(4), 270\u0026ndash;274. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Early pregnancy, Fetus, V-sign angle, Cardiothoracic ratio, Global sphericity index, Cardiac axis, Congenital heart disease, Color Doppler ultrasound","lastPublishedDoi":"10.21203/rs.3.rs-7003626/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7003626/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective: \u003c/strong\u003eThis study aims to investigate the application value of four parameters, namely, V-angle (VSA), cardiothoracic ratio (CTR), global sphericity index (GSI), and cardiac axis (CAx), in the early detection of congenital heart disease (CHD) during the first trimester by using color Doppler ultrasound and increase the accuracy of CHD prediction in early pregnancy.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e:\u0026nbsp; A prospective study was conducted from January 2022 to March 2024 across two centers: Haidian District Maternal and Child Health Hospital in Beijing and Fujian Maternal and Child Health Hospital. A total of 2,529 normal fetuses and 50 fetuses with CHD underwent color Doppler fetal echocardiography between 11\u003csup\u003e+0\u003c/sup\u003e and 16\u003csup\u003e+0\u003c/sup\u003e weeks of gestation. The correlation between each parameter and gestational age (GA) during early pregnancy was analyzed. Normative reference ranges and diagnostic models were established and validated. The diagnostic efficacy of the four parameters for CHD was quantitatively assessed based on the established models, and their clinical application value was explored.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e In normal fetuses during early pregnancy, GA showed negative correlation with VSA, positive correlation while CTR and GSI, and no correlation with CAx. Z-score models and reference ranges for the four parameters were established across five different GA groups. The polynomial linear regression model significantly improved the detection rate of CHD compared with univariate regression models. The four parameters demonstrated statistical significance in different CHD subtypes, especially in severe forms of CHD, confirming their value as effective parameters for early CHD screening in fetuses.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e CAx, CTR, VSA, and CSI were identified as effective parameters for the early diagnosis of CHD in fetuses during the first trimester. This research has, for the first time, established normal reference value ranges for the four parameters in early pregnancy and developed a multiparameter joint prediction model. The findings provide quantifiable indicators for CHD screening and further enhance the accuracy of CHD prediction in early pregnancy.\u003c/p\u003e","manuscriptTitle":"Reference Ranges and Clinical Significance of Key Fetal Cardiac Parameters Measured by Color Doppler Ultrasound at 11+0 to 16+0 Weeks of Gestation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-23 07:24:43","doi":"10.21203/rs.3.rs-7003626/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1118379b-ef03-4f57-a167-8cd62c1148ee","owner":[],"postedDate":"July 23rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-07-23T07:24:43+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-23 07:24:43","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7003626","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7003626","identity":"rs-7003626","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}