Evaluating fetal pulmonary vascular development in congenital heart disease: a comparative study using the McGoon index and multiple parameters of fetal echocardiography

Evaluating fetal pulmonary vascular development in congenital heart disease: a comparative study using the McGoon index and multiple parameters of fetal echocardiography | 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 Evaluating fetal pulmonary vascular development in congenital heart disease: a comparative study using the McGoon index and multiple parameters of fetal echocardiography Chenke Pan, Bowen Zhao, Mei Pan, Yunkai Luo, Yunyun Zhang, Bin Ying This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4117262/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 Purpose: The purpose of this study was to evaluate the value of MGI and multiple parameters in the diagnosis of congenital heart disease with different pulmonary circulation blood volumes. Methods: This study included 349 fetuses categorized into three groups: Group A consisted of 258 fetuses with no discernible abnormalities identified through echocardiography; Group B included 71 fetuses with decreased pulmonary blood flow or pulmonary atresia; and Group C comprised 20 fetuses with reduced or detached aortic flow. The MGI and Z-scores were measured and compared among these groups. Results: Significant variations were noted in the aortic outflow Z-scores (AO-Zs), pulmonary artery (PA), PA Z-scores (PA-Zs), PA/AO, right PA , and MGI among the three groups (all p < 0.05). Among fetuses with decreased pulmonary blood flow or pulmonary atresia, PA, PA-Zs, and MGI in fetuses with reverse DA flow perfusion were lower than those in the DA forward perfusion group. Conclusion: Fetal echocardiography, incorporating the MGI and multiple parameters, not only allows for the evaluation of pulmonary blood flow and pulmonary vascular development of the fetus but also enables the observation of changes in pulmonary blood flow and MGI development across different gestational weeks. congenital heart disease McGoon index Z-score fetal echocardiography pulmonary artery Figures Figure 1 Figure 2 Introduction In the 1980s, the McGoon index (MGI) and pulmonary artery index, also known as the Nakata index, emerged as pivotal tools for evaluating pulmonary vascular development in patients with congenital heart disease (CHD), MGI gained recognition as a comprehensive indicator for assessing the overall development of the pulmonary vascular bed [ 1 , 2 ].Clinically, both MGI and Nakata index serve as crucial surgical indicators for primary radical surgery in Tetralogy of Fallot syndrome (TOF), offering an important reference basis for preoperative evaluation, surgical selection, and postoperative intervention in TOF patients, closely impacting prognosis [ 3 , 4 ]. Study has shown a high correlation between echocardiography and values measured by cardiovascular angiography, highlighting the accuracy of MGI in assessing pulmonary artery (PA) development and guiding surgical decisions [ 5 ]. Traditionally, MGI was primarily applied in the evaluation of adult or pediatric CHD. However, given that fetal hemodynamics and lung development differ from those after birth, recent years have seen an emerging interest in exploring the application of MGI in the fetal period. The study by Guo Yong et al. [ 6 ] on TOF fetuses indicated a significantly lower MGI compared to that of normal fetuses, suggesting potential adverse effects of CHD on PA development during the fetal period. Notably, they observed a significant linear positive correlation between the sum of RPA and LPA diameter (RPA + LPA) and fetal lung volume, suggesting that the two-dimensional ultrasound (US) measurement of RPA + LPA can, to some extent, reflect fetal lung development.In addition,it reported that the MGI of fetuses with moderate to severe pulmonary artery stenosis is significantly lower than that of normal fetuses and fetuses with mild PS [ 7 ]. Z-score refers to the standard deviation of the actual data compared with the average data, so the application of Z-score can more accurately evaluate the development of pulmonary arteries.In this study, we employed echocardiography to compare MGI and Z-scores in fetuses with different types of CHD under different pulmonary flow states. Our aim is to explore the application value of MGI combined with Z-score in fetuses with decreased pulmonary blood flow or pulmonary atresia, offering crucial insights for prenatal consultation and perinatal production planning in fetuses with CHD. Materials and methods Patients We prospectively collected data from a total of 349 fetuses who underwent echocardiography at the Department of Diagnostic Ultrasound & Echocardiography, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, between June 2020 and August 2021. The fetuses were categorized into three groups: the normal control group (Group A) and two case groups (Group B and Group C). Group A comprised 258 normal fetuses, undergoing a systematic scan based on fetal echocardiography standards [1] , which revealed no obvious abnormalities. These fetuses were further subdivided into four subgroups according to gestational weeks. Group B included 71 fetuses with decreased pulmonary blood flow or pulmonary atresia, categorized into two subgroups based on the presence or absence of retrograde flow in the ductus arteriosus (DA). Group B encompassed various CHD types, such as isolated pulmonary stenosis (PS), PS with ventricular septal defect (PA-VSD), double outlet right ventricle with PS (DORV-PS), DORV with pulmonary atresia (DORV-PA), TOF, hypoplastic right heart syndrome with PA (HRHS-PA), hypoplastic right heart syndrome with PS (HRHS-PS), tricuspid atresia with PS and ventricular septal defect (TA-VSD-PS), transposition of the great arteries with PS (TGA-PS), TOF with pulmonary atresia (TOF-PA), and PA with severe tricuspid regurgitation. Group C consisted of 21 fetuses with decreased aortic blood flow or interruption of the aortic arch, encompassing CHD types such as aortic stenosis (AS), coarctation of the aorta, interruption of the aorta, and hypoplastic left heart syndrome, as well as DORV with AS(DORV-AS). Inclusion criteria involved an estimated gestational age (GA) ranging from 18 to 33 + 6 weeks based on ultrasonography. Exclusion criteria encompassed cases with poor echocardiographic image quality, extracardiac abnormalities, cardiomyopathy, oligohydramnios, intrathoracic mass, and multiple gestation pregnancies. Additionally, Types IV in the PA/VSD Boston classification were excluded from this study due to atresia of the pulmonary valve (PV), MPA, LPA and RPA, making it impossible to visualize LPA and RPA. Echocardiography All ultrasonographic examinations were conducted by a senior physician with over 10 years of expertise in fetal echocardiography, utilizing high-resolution US equipment (Voluson E10, Convex Volume Probe RIC5-9-D,General Rlectric Medical Systems,Aipf Austria; Philips Epiq 7C, Controlled Array Probe S8-3, S5-1,Philips Medical Systems International, Best, The Netherlands). US settings for fetal echocardiography were standardized, and a comprehensive fetal heart echocardiographic examination was administered. Each patient underwent a detailed assessment, encompassing standard biometric measurements such as biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL). GA was determined through the measurement of fetal crown-rump length in the first trimester and subsequently determined using biological indicators measured using 2D-US. The cardiothoracic ratio (CTR) was computed by dividing the cardiac diameter by the thoracic diameter, both measured in the four-chamber view. The PA and AO were measured at end-systole to derive the PA/AO ratio. The dynamics of the LPA, RPA, DAO at the diaphragm level, and arterial catheter (DA) were visually assessed. LPA, RPA, and DAO were measured at end-systole at least three times, and the averages were calculated(location for Fig. 1 ,Fig. 2 ). The MGI was expressed using the equation [2] : MGI = (summed diameter of RPA and LPA [RPA + LPA]) / diameter of DAO. Z-score: Z-scores were calculated following statistical analysis methods outlined by Royston and Wright [ 8 ], leveraging regression equations established by previous studies within the study group [ 9 – 11 ]: AO Predicted values mean = 0.101 × FL − 0.012, PA Predicted values mean = 0.114 × FL + 0.028, AO Predicted SD = 0.005919 × FL + 0.016, and PA Predicted SD = 0.0113 × FL + 0.0122. Z-scores were computed using the equations: AO Z-score = (Actually measured AO − Predicted AO according to FL) / Predicted SD of AO; PA-Zs = (Actually measured PA − Predicted PA according to FL) / Predicted SD of PA. Subsequent measurements and calculations were conducted by another physician with > 3 years of experience in fetal echocardiography. Statistical analysis Statistical analysis was performed using SPSS v26.0 software. Count data are presented as examples, and measurement data are expressed as mean ± SD or median (min-max). Reproducibility of LPA, RPA, and DAO was assessed using the intra-class correlation coefficient (ICC). Intergroup differences were compared using t-test, Mann–Whitney U test, or analysis of variance (ANOVA). Statistically significant differences were indicated by p < 0.05. Results 1.Baseline patient characteristics Initially, 402 fetuses were considered for this study, with 52 (12.9%) subsequently excluded based on predefined exclusion criteria. Ultimately, 350 fetuses were included for the analysis. A detailed comparison of each parameter among the three groups is presented in Table 1 . Table 1 Characteristics of each group Characteristics Group A(n = 258) Group B(n = 71) Group C(n = 21) p MA(years) 29.56 ± 4.36 30.13 ± 4.24 32.85 ± 4.78 bc 0.005 GA (weeks) 25.46 ± 3.68 25.54 ± 3.16 25.50 ± 4.21 0.970 CTR 0.27 ± 0.03 0.28 ± 0.05 0.26 ± 0.03 0.206 AO(mm) 3.75 ± 0.89 4.91 ± 1.08 a 3.34 ± 0.87 c < 0.01 AO-Zs -1.79 ± 1.08 0.89 ± 2.04 a -2.82 ± 1.44 bc < 0.01 PA(mm) 4.79 ± 1.04 3.78 ± 1.01 a 5.49 ± 1.32 bc < 0.01 PA-Zs -1.14 ± 0.88 -2.70 ± 1.50 a -0.09 ± 1.90 bc < 0.01 PA/AO 1.29 ± 0.09 0.79 ± 0.23 a 1.75 ± 0.40 bc < 0.01 LPA(mm) 2.52 ± 0.64 2.25 ± 0.64 a 2.69 ± 0.76 c < 0.01 RPA(mm) 2.67 ± 0.70 2.42 ± 0.62 a 3.01 ± 0.89 bc < 0.01 DAO(mm) 3.81 ± 0.86 4.04 ± 0.83 3.97 ± 0.98 0.133 MGI 1.37 ± 0.21 1.16 ± 0.19 a 1.47 ± 0.35 bc < 0.01 DA(mm) 3.14 ± 0.82 3.06 ± 0.76 3.84 ± 1.03 bc < 0.01 MA, GA:gestational age; CTR, cardiothoracic ratio; AO, aortic outflow; AO-Zs, AO Z-scores; PA, pulmonary artery; PA-Zs, PA Z-scores; LPA, left PA; RPA, right PA; DAO, descending aorta; MGI, McGoon index. a Group A vs Group B; b Group A vs Group C; c Group B vs Group C Statistical analysis revealed no significant differences in GA, CTR, and DAO among the three groups (all p > 0.05). However, there was a statistically significant difference in fetal AC in Group C compared with that in Groups A and B. Significant differences were also observed in AO-Zs, PA, PA-Zs, PA/AO ratio, PA/AO-Zs, RPA, MGI. Notably, there was no statistical difference in AO between Group B and Groups A and C and LPA between Groups A and C, A and C, between Groups A and B, and between Groups A and C, B and C. In Group B, 53 fetuses had a PA-Z < − 2, 44 had MGI < 1.2, and 69 had PA/AO < 1.2. 2. Differences in various parameters across gestational weeks Comparison of various parameters among different gestational weeks in the normal control group is detailed in Table 2 . No significant differences were observed in CTR, MGI, AO-Zs, or PA-Zs among the four groups; however, statistically significant differences were identified in AO, PA, LPA, RPA, DAO, and DA(location for table Table 2 ). Table 2 Comparison of different parameters between different gestational weeks in the normal control group Characteristics 18-(n = 39) 22-(n = 86) 26-(n = 106) 30-(n = 27) p CTR 0.27 ± 0.03 0.27 ± 0.03 0.26 ± 0.02 0.28 ± 0.04 0.141 AO(mm) 2.55 ± 0.64 3.44 ± 0.48 4.08 ± 0.49 5.12 ± 0.82 < 0.01 AO-Zs −1.72 ± 1.17 −1.74 ± 1.08 −1.93 ± 0.94 −1.47 ± 1.38 0.21 PA(mm) 3.40 ± 0.76 4.44 ± 0.56 5.16 ± 0.54 6.45 ± 0.97 < 0.01 PA-Zs −1.17 ± 1.06 −1.10 ± 0.88 −1.25 ± 0.73 −0.76 ± 1.05 0.08 PA/AO 1.35 ± 0.11 1.30 ± 0.09 1.27 ± 0.09 1.26 ± 0.05 < 0.01 LPA(mm) 1.75 ± 0.36 2.35 ± 0.50 2.76 ± 0.50 3.28 ± 0.43 < 0.01 RPA(mm) 1.72 ± 0.33 2.44 ± 0.51 2.97 ± 0.46 3.58 ± 0.45 < 0.01 DAO(mm) 2.65 ± 0.49 3.49 ± 0.58 4.21 ± 0.48 5.02 ± 0.63 < 0.01 MGI 1.34 ± 0.27 1.38 ± 0.20 1.37 ± 0.20 1.38 ± 0.18 0.788 DA(mm) 2.25 ± 0.36 2.89 ± 0.67 3.44 ± 0.63 4.16 ± 0.69 < 0.01 CTR, cardiothoracic ratio; AO, aortic outflow; AO-Zs, AO Z-scores; PA, pulmonary artery; PA-Zs, PA Z-scores; LPA, left PA; RPA, right PA; DAO, descending aorta; MGI, McGoon index. 3. Impact of fetal DA flow on PA development In the subset of 71 fetuses experiencing decreased pulmonary blood flow or pulmonary atresia, 33 exhibited reverse DA flow perfusion. Notably, this subgroup displayed lower values for PA, PA-Zs, LPA + RPA and MGI than the forward DA perfusion group. No significant difference was observed in AO and AO-Zs between these two groups. The correlation between the direction of fetal DA blood perfusion and PA development in fetuses with decreased pulmonary blood flow or pulmonary atresia is detailed in Table 3 . Table 3 Relationship between the direction of fetal DA blood perfusion and PA development in Group B Group The DA forward perfusion group(n = 38) The DA reverse perfusion group(n = 33) GA(week) 25.50 ± 3.13 25.58 ± 3.24 CTR 0.28 ± 0.04 0.26 ± 0.46 AO(mm) 5.00 ± 1.19 4.79 ± 0.93 AO-Zs 1.12 ± 2.33 0.61 ± 1.64 PA(mm) 4.07 ± 1.02 3.44 ± 0.91 * PA-Zs −2.25 ± 1.45 −3.22 ± 1.40 * PA/AO 0.84 ± 0.21 0.74 ± 0.24 LPA + RPA(mm) 4.95 ± 1.32 4.35 ± 0.96 * MGI 1.23 ± 0.17 1.07 ± 0.16 * DA(mm) 3.22 ± 0.84 2.87 ± 0.63 GA:gestational age; CTR, cardiothoracic ratio; AO, aortic outflow; AO-Zs, AO Z-scores; PA, pulmonary artery; PA-Zs, PA Z-scores; LPA, left PA; RPA, right PA; DAO, descending aorta; MGI, McGoon index. p < 0.05 compared with the DA forward perfusion group 4.Repeatability Within-group correlation coefficients for each parameter demonstrated excellent consistency, with ICC slightly lower in Group B than in the other two groups((location for Table 4 ). Table 4 ICC of different parameter measured by echocardiography in each group LPA RPA DAO Group A(n = 211) 0.956 0.966 0.977 Group B(n = 26) 0.901 0.842 0.910 Group C(n = 20) 0.980 0.904 0.965 Total 0.957 0.961 0.973 LPA, left pulmonary artery; RPA, right pulmonary artery; DAO, descending aorta. 5.Pregnancy outcome Among the 71 fetuses with CHD in case group B, 19 cases were lost to follow-up, the loss rate was 26.8%, 25 cases were induced labor, and 19 cases were born. Of the 19 neonates born, 1 died after giving up treatment due to poor condition (MGI = 1.37 at 22 weeks of gestation). One case underwent palliative surgery for TOF after birth and died of multiple organ failure (MGI = 1.20 at 24 weeks of gestation). 3 patients (MGI 1.05–1.22) required elective radical resection of TOF. 5 cases (MGI 0.88–1.35) underwent emergent or elective percutaneous balloon pulmonary valvuloplasty after birth. 9 cases (MGI 0.89–1.64) did well after birth and were followed up in the outpatient clinic without surgical intervention. Additionally, 50 fetuses randomly selected from the normal control group underwent delivery and pediatric echocardiography, revealing no cardiovascular malformations, except for patent foramen ovale and PDA (patent ductus arteriosus). Discussion The aim of this study was evaluating the value of McGoon index and multiple parameters measured by fetal echocardiography in assessing fetal pulmonary vascular development. In our investigation involving 71 fetuses with decreased pulmonary blood flow or pulmonary atresia in Group B, we observed that their MGI, PA-Zs, and PA/AO ratios were significantly smaller than those in the normal group. Conversely, the study of 21 fetuses with reduced or detached aortic flow in Group C revealed significantly greater values for MGI, PA-Zs, and PA/AO ratios than those in the other two groups. These findings, in conjunction with previous studies on CHD fetuses [ 9 – 11 ], suggest that fetal MGI serves as a valuable indicator for evaluating PA development during the prenatal period, which has great implications for the dynamic evaluation of cardiovascular development in advanced intrauterine CHD fetuses, guiding disease analysis and prognosis, and providing reasonable information for prenatal consultations. Subgroup analysis in Group B indicated that fetuses with backward DA flow had smaller values for PA, PA-Zs, LPA + RPA, and MGI than the forward DA perfusion group. This implies that reverse DA flow may signify more severe PS or pulmonary atresia, suggesting a more substantial impact on fetal pulmonary vascular development. In this study, we established a mean MGI of 1.37 ± 0.21 for a large sample of normal mid-to-late pregnant fetuses. Unlike previous studies, our normal fetal sample size covered the entire GA range for fetal echocardiography and was categorized into four groups based on GA. We observed no significant differences in fetal MGI across different GAs, indicating that MGI does not change with GA. In normal developing fetuses, quantitative indicators reflecting cardiovascular development, such as PA and its branches and AO growth, and non-cardiovascular parameters reflecting fetal growth and development, including BPD, HC, FL, and AC, are clearly correlated with the increase in GA, which has been confirmed in several studies that applied Z-score [ 12 – 15 ]. Because MGI is the ratio of LPA + RPA inner diameter to DAO, which reflects the relative proportion of fetal PA and AO development, the results of MGI and Z-scores are consistent. In normal developing fetuses, MGI remains relatively stable within the normal range and does not exhibit variation with GA. This contrasts with Guo et al.'s findings [ 16 ] in a study of 110 normal fetuses and 54 fetuses with reduced pulmonary blood flow CHD, where CTR, FLV/EFW, and MGI showed significant differences between the two groups. The variation in results may be attributed to the broader spectrum of diseases included in our study than the more specific inclusion criteria of TOF, PA-VSD, and PA-IVVS in Guo et al.’s study [ 16 ]. Evaluation of pulmonary vascular development is crucial in the surgical context, especially for PS, as it strongly influences postoperative outcomes. Laban et al. [ 17 ] reported that compared to neonates with respiratory distress syndrome(RDS), healthy neonates had significantly higher FLVs (p < 0.001).However, YEabdalla et al. [18] recommended that combining the mean FLV to the other parameters rather than using this measure alone .Clinical MGI assessment is a common practice in postnatal children and adults, providing an overview of pulmonary vascular bed growth in CHD patients. A low MGI often indicates lung hypoplasia and is associated with a poor prognosis [ 2 , 10 ]. Higher incidences of surgical death and heart failure have been reported in patients with PA dysplasia [ 1 ]. MGI has also been studied in children with congenital diaphragmatic hernia (CDH). Several studies [ 4 , 19 , 20 ] have suggested that among various prognostic factors in children with CDH, the extent of lung development is crucial, and the severity of pulmonary hypoplasia is considered the main limiting factor for survival, whereas MGI is positively correlated with pulmonary vascular development, serving as a prognostic factor for survival. From the follow-up in our study, we observed that patients with PS alone and MGI < 1.2 had a favorable prognosis. Notably, one patient with MGI 0.96 did not undergo surgery throughout the follow-up period. Similarly, two patients with TOF and MGI < 1.2 (MGI 1.17, 1.05) did not require surgical intervention and were generally in good condition. However, two deaths occurred due to TOF (MGI 1.20) and hypoplastic right heart syndrome (HRHS). This suggests that the cardiovascular structure and functional status of fetuses with severe PS can vary significantly postnatally, necessitating individualized treatment strategies based on each child's PA development [ 9 ]. Despite the overall better prognosis in isolated PS, MGI may still decrease. While MGI can be obtained through various methods such as cardiovascular angiography, CT, and echocardiography [ 21 ], the unique nature of the fetus places fetal echocardiography at the forefront of prenatal evaluation for cardiovascular structure and hemodynamics. Although MRI is utilized for the prenatal assessment of fetal brain and spine structures, its application in diagnosing fetal cardiovascular malformations is limited. The main challenges in fetal MGI measurement via echocardiography are obtaining clear images of the LPA, RPA, and DAO. This is dependent on the sonographer's ability to obtain standardized sections, which, in our study, was carried out by highly experienced physicians. Quantitative measurements of LPA, RPA, and DAO inner diameters were averaged from at least three measurements, resulting in a very good within-group correlation coefficient for each parameter. This ensured the high repeatability and accuracy of MGI measurements in our study. Our study has some limitations. First, the measurement of fetal MGI is challenging in early pregnancy and was, therefore, excluded from our study. With ongoing advancements in US technology, future studies may include more early pregnancies to explore the broader application of MGI throughout gestation. Additionally, this study follows a cross-sectional design, and no prenatal follow-up was conducted for the studied case group. Conducting multiple follow-ups for CHD fetuses throughout pregnancy could provide a more comprehensive understanding of MGI patterns and its utility during fetal development. Similarly, there is a lack of systematic follow-up on pulmonary vascular and pulmonary development in neonates and young children post-birth. A longitudinal systematic tracking of MGI changes both prenatally and postnatally would contribute to a more scientific assessment of pulmonary blood vessel development in fetuses, newborns, and young children under varying pulmonary blood flow conditions. This approach is crucial for analyzing fetal conditions, predicting prognosis, and informing prenatal consultations and postnatal treatments. Conclusion In conclusion, our study compared MGI, PA/AO, PA, and Z-scores in CHD fetuses with different pulmonary circulation blood volumes. The results demonstrate that MGI, combined with various parameter Z-scores, reliably evaluates pulmonary blood flow in different CHD fetuses, offering insights into pulmonary blood vessel development. The presence of reverse DA flow suggests more severe PS or pulmonary atresia, as indicated by smaller values in PA, PA-Zs, LPA + RPA, and MGI. This type of CHD may exert a more significant impact on fetal pulmonary vascular development. These findings have potential clinical applications in prognostic prediction and early intervention treatment. Through the analysis of a large number of normal fetal MGIs from 18 weeks to 33 + 6 weeks, we observed that fetal MGI remains relatively constant during this GA range and does not change with increasing GA. Declarations Funding This work was supported by foundation of Zhejiang Provincial Education Department(No.Y202146078). Conflicts of interests We have no financial relationships to disclose. Author Controbutions All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Chenke Pan, Mei Pan, Yunkai Luo and Yunyun Zhang. The first draft of the manuscript was written by Chenke Pan and all authors commented on previous versions of the manuscript.Bowen Zhao supervised the completion of the project and revised the manuscript. All authors read and approved the final manuscript. Ethics approval This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine (20200210-78). Consent to participate Informed consent was obtained from all individual participants included in the study. Data availability The datasets supporting the results of this study are available from the corresponding author on reasonable request. 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Evaluating mortality and disease severity in congenital diaphragmatic hernia using the McGoon and pulmonary artery indices. J Pediatr Surg. 2009 Nov;44(11):2101-6. doi: 10.1016/j.jpedsurg.2009.05.012. Additional Declarations No competing interests reported. Supplementary Files Tables1.doc 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-4117262","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":282213764,"identity":"bd100f11-a9ca-4635-880b-4188febd75e6","order_by":0,"name":"Chenke Pan","email":"","orcid":"","institution":"The Fourth Affiliated Hospital of Zhejiang University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Chenke","middleName":"","lastName":"Pan","suffix":""},{"id":282213765,"identity":"662c08a5-cd20-400f-b8e9-77f7d41aa24c","order_by":1,"name":"Bowen Zhao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyUlEQVRIiWNgGAWjYDACCTC2YWBsADJ4SNCSRqoWBobDEA5RWuRn9xh+sNxx3p55RgLjg7dtDPLmhLQwzjljLCF55jYz44wEZsO5bQyGOxsIaGGWyN3GINl2mw2ohU2at40hweAAAS1sEC3neIBa2H8TpYUHouWABMgWZqK0SMic/wz0S7IBY8/DZsk55yQMNxDSIj+7LfGz5A47e8P25IMf3pTZyBO0BQSYJRsYGAwbwJEpQYR6IGD8CFQsT5zaUTAKRsEoGIkAAJwlObtni0XeAAAAAElFTkSuQmCC","orcid":"","institution":"Department of Diagnostic Ultrasound \u0026 Echocardiography, Sir Run Run Shaw Hospital, Zhejiang University College of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Bowen","middleName":"","lastName":"Zhao","suffix":""},{"id":282213766,"identity":"06a655f6-8449-44e4-bd00-49d8800c2a17","order_by":2,"name":"Mei Pan","email":"","orcid":"","institution":"Department of Diagnostic Ultrasound \u0026 Echocardiography, Sir Run Run Shaw Hospital, Zhejiang University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Mei","middleName":"","lastName":"Pan","suffix":""},{"id":282213768,"identity":"18569baa-e62c-429f-b0d4-b5cbb9395881","order_by":3,"name":"Yunkai Luo","email":"","orcid":"","institution":"The Fourth Affiliated Hospital of Zhejiang University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yunkai","middleName":"","lastName":"Luo","suffix":""},{"id":282213770,"identity":"746df5ea-cb23-4851-8ee6-6898f63ce726","order_by":4,"name":"Yunyun Zhang","email":"","orcid":"","institution":"The Fourth Affiliated Hospital of Zhejiang University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yunyun","middleName":"","lastName":"Zhang","suffix":""},{"id":282213772,"identity":"f9ec6b0e-d6fa-40a0-8019-026bd246c52e","order_by":5,"name":"Bin Ying","email":"","orcid":"","institution":"The Fourth Affiliated Hospital of Zhejiang University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Bin","middleName":"","lastName":"Ying","suffix":""}],"badges":[],"createdAt":"2024-03-17 13:44:28","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4117262/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4117262/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":53417770,"identity":"913180f5-d95f-44a1-8b1c-8e8a2ab208fe","added_by":"auto","created_at":"2024-03-25 18:05:05","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":146261,"visible":true,"origin":"","legend":"\u003cp\u003eNormal fetal McGoon index was measured by ultrasound. Figure a shows measurement of LPA and RPA; Figure b shows measurements of DAO across the fetal diaphragm.\u003c/p\u003e\n\u003cp\u003eLPA:left pulmonary artery,RPA:right pulmonary artery,DAO:descending aorta\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4117262/v1/ba43cf6ae0e6dbbc0b668353.png"},{"id":53417773,"identity":"64dff378-01b1-4318-afae-9e63608fa135","added_by":"auto","created_at":"2024-03-25 18:05:05","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":236186,"visible":true,"origin":"","legend":"\u003cp\u003eTOF fetal McGoon index was measured by ultrasound. Figure a shows measurement of LPA and RPA; Figure b shows measurements of DAO across the fetal diaphragm.\u003c/p\u003e\n\u003cp\u003eTOF:Tetralogy of Fallot syndrome,LPA:left pulmonary artery,RPA:right pulmonary artery,DAO:descending aorta\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4117262/v1/cde50b70f6ae12791b947df0.png"},{"id":54849333,"identity":"59aeb978-639f-4e46-b0e6-ce21f9d3ffb9","added_by":"auto","created_at":"2024-04-17 15:50:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":841726,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4117262/v1/c9cece8c-524c-4076-9444-b6020da88456.pdf"},{"id":53417774,"identity":"a38dc07d-9f23-4e16-8bd4-7ecc621bda3a","added_by":"auto","created_at":"2024-03-25 18:05:05","extension":"doc","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":38912,"visible":true,"origin":"","legend":"","description":"","filename":"Tables1.doc","url":"https://assets-eu.researchsquare.com/files/rs-4117262/v1/2bfbe80e078ebbc9fb09c717.doc"}],"financialInterests":"No competing interests reported.","formattedTitle":"Evaluating fetal pulmonary vascular development in congenital heart disease: a comparative study using the McGoon index and multiple parameters of fetal echocardiography","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIn the 1980s, the McGoon index (MGI) and pulmonary artery index, also known as the Nakata index, emerged as pivotal tools for evaluating pulmonary vascular development in patients with congenital heart disease (CHD), MGI gained recognition as a comprehensive indicator for assessing the overall development of the pulmonary vascular bed [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].Clinically, both MGI and Nakata index serve as crucial surgical indicators for primary radical surgery in Tetralogy of Fallot syndrome (TOF), offering an important reference basis for preoperative evaluation, surgical selection, and postoperative intervention in TOF patients, closely impacting prognosis [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Study has shown a high correlation between echocardiography and values measured by cardiovascular angiography, highlighting the accuracy of MGI in assessing pulmonary artery (PA) development and guiding surgical decisions [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Traditionally, MGI was primarily applied in the evaluation of adult or pediatric CHD. However, given that fetal hemodynamics and lung development differ from those after birth, recent years have seen an emerging interest in exploring the application of MGI in the fetal period.\u003c/p\u003e \u003cp\u003eThe study by Guo Yong et al. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] on TOF fetuses indicated a significantly lower MGI compared to that of normal fetuses, suggesting potential adverse effects of CHD on PA development during the fetal period. Notably, they observed a significant linear positive correlation between the sum of RPA and LPA diameter (RPA\u0026thinsp;+\u0026thinsp;LPA) and fetal lung volume, suggesting that the two-dimensional ultrasound (US) measurement of RPA\u0026thinsp;+\u0026thinsp;LPA can, to some extent, reflect fetal lung development.In addition,it reported that the MGI of fetuses with moderate to severe pulmonary artery stenosis is significantly lower than that of normal fetuses and fetuses with mild PS [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eZ-score refers to the standard deviation of the actual data compared with the average data, so the application of Z-score can more accurately evaluate the development of pulmonary arteries.In this study, we employed echocardiography to compare MGI and Z-scores in fetuses with different types of CHD under different pulmonary flow states. Our aim is to explore the application value of MGI combined with Z-score in fetuses with decreased pulmonary blood flow or pulmonary atresia, offering crucial insights for prenatal consultation and perinatal production planning in fetuses with CHD.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003eWe prospectively collected data from a total of 349 fetuses who underwent echocardiography at the Department of Diagnostic Ultrasound \u0026amp; Echocardiography, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, between June 2020 and August 2021. The fetuses were categorized into three groups: the normal control group (Group A) and two case groups (Group B and Group C). Group A comprised 258 normal fetuses, undergoing a systematic scan based on fetal echocardiography standards\u003csup\u003e[1]\u003c/sup\u003e, which revealed no obvious abnormalities. These fetuses were further subdivided into four subgroups according to gestational weeks. Group B included 71 fetuses with decreased pulmonary blood flow or pulmonary atresia, categorized into two subgroups based on the presence or absence of retrograde flow in the ductus arteriosus (DA). Group B encompassed various CHD types, such as isolated pulmonary stenosis (PS), PS with ventricular septal defect (PA-VSD), double outlet right ventricle with PS (DORV-PS), DORV with pulmonary atresia (DORV-PA), TOF, hypoplastic right heart syndrome with PA (HRHS-PA), hypoplastic right heart syndrome with PS (HRHS-PS), tricuspid atresia with PS and ventricular septal defect (TA-VSD-PS), transposition of the great arteries with PS (TGA-PS), TOF with pulmonary atresia (TOF-PA), and PA with severe tricuspid regurgitation. Group C consisted of 21 fetuses with decreased aortic blood flow or interruption of the aortic arch, encompassing CHD types such as aortic stenosis (AS), coarctation of the aorta, interruption of the aorta, and hypoplastic left heart syndrome, as well as DORV with AS(DORV-AS). Inclusion criteria involved an estimated gestational age (GA) ranging from 18 to 33\u0026thinsp;+\u0026thinsp;6 weeks based on ultrasonography. Exclusion criteria encompassed cases with poor echocardiographic image quality, extracardiac abnormalities, cardiomyopathy, oligohydramnios, intrathoracic mass, and multiple gestation pregnancies. Additionally, Types IV in the PA/VSD Boston classification were excluded from this study due to atresia of the pulmonary valve (PV), MPA, LPA and RPA, making it impossible to visualize LPA and RPA.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eEchocardiography\u003c/h2\u003e \u003cp\u003eAll ultrasonographic examinations were conducted by a senior physician with over 10 years of expertise in fetal echocardiography, utilizing high-resolution US equipment (Voluson E10, Convex Volume Probe RIC5-9-D,General Rlectric Medical Systems,Aipf Austria; Philips Epiq 7C, Controlled Array Probe S8-3, S5-1,Philips Medical Systems International, Best, The Netherlands). US settings for fetal echocardiography were standardized, and a comprehensive fetal heart echocardiographic examination was administered. Each patient underwent a detailed assessment, encompassing standard biometric measurements such as biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL). GA was determined through the measurement of fetal crown-rump length in the first trimester and subsequently determined using biological indicators measured using 2D-US.\u003c/p\u003e \u003cp\u003eThe cardiothoracic ratio (CTR) was computed by dividing the cardiac diameter by the thoracic diameter, both measured in the four-chamber view. The PA and AO were measured at end-systole to derive the PA/AO ratio.\u003c/p\u003e \u003cp\u003eThe dynamics of the LPA, RPA, DAO at the diaphragm level, and arterial catheter (DA) were visually assessed. LPA, RPA, and DAO were measured at end-systole at least three times, and the averages were calculated(location for Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e,Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The MGI was expressed using the equation \u003csup\u003e[2]\u003c/sup\u003e:\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eMGI = (summed diameter of RPA and LPA [RPA\u0026thinsp;+\u0026thinsp;LPA]) / diameter of DAO.\u003c/p\u003e \u003cp\u003eZ-score: Z-scores were calculated following statistical analysis methods outlined by Royston and Wright [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], leveraging regression equations established by previous studies within the study group [\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]: AO Predicted values mean\u0026thinsp;=\u0026thinsp;0.101 \u0026times; FL\u0026thinsp;\u0026minus;\u0026thinsp;0.012, PA Predicted values mean\u0026thinsp;=\u0026thinsp;0.114 \u0026times; FL\u0026thinsp;+\u0026thinsp;0.028, AO Predicted SD\u0026thinsp;=\u0026thinsp;0.005919 \u0026times; FL\u0026thinsp;+\u0026thinsp;0.016, and PA Predicted SD\u0026thinsp;=\u0026thinsp;0.0113 \u0026times; FL\u0026thinsp;+\u0026thinsp;0.0122. Z-scores were computed using the equations: AO Z-score = (Actually measured AO\u0026thinsp;\u0026minus;\u0026thinsp;Predicted AO according to FL) / Predicted SD of AO; PA-Zs = (Actually measured PA\u0026thinsp;\u0026minus;\u0026thinsp;Predicted PA according to FL) / Predicted SD of PA.\u003c/p\u003e \u003cp\u003eSubsequent measurements and calculations were conducted by another physician with \u0026gt;\u0026thinsp;3 years of experience in fetal echocardiography.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed using SPSS v26.0 software. Count data are presented as examples, and measurement data are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or median (min-max). Reproducibility of LPA, RPA, and DAO was assessed using the intra-class correlation coefficient (ICC). Intergroup differences were compared using t-test, Mann\u0026ndash;Whitney U test, or analysis of variance (ANOVA). Statistically significant differences were indicated by p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e1.Baseline patient characteristics\u003c/p\u003e \u003cp\u003eInitially, 402 fetuses were considered for this study, with 52 (12.9%) subsequently excluded based on predefined exclusion criteria. Ultimately, 350 fetuses were included for the analysis. A detailed comparison of each parameter among the three groups is presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of each group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGroup A(n\u0026thinsp;=\u0026thinsp;258)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGroup B(n\u0026thinsp;=\u0026thinsp;71)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGroup C(n\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMA(years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e29.56\u0026thinsp;\u0026plusmn;\u0026thinsp;4.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30.13\u0026thinsp;\u0026plusmn;\u0026thinsp;4.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32.85\u0026thinsp;\u0026plusmn;\u0026thinsp;4.78\u003csup\u003ebc\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGA (weeks)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e25.46\u0026thinsp;\u0026plusmn;\u0026thinsp;3.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.54\u0026thinsp;\u0026plusmn;\u0026thinsp;3.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25.50\u0026thinsp;\u0026plusmn;\u0026thinsp;4.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.970\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCTR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.26\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.206\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAO(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e3.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.91\u0026thinsp;\u0026plusmn;\u0026thinsp;1.08\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.34\u0026thinsp;\u0026plusmn;\u0026thinsp;0.87\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAO-Zs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e-1.79\u0026thinsp;\u0026plusmn;\u0026thinsp;1.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.89\u0026thinsp;\u0026plusmn;\u0026thinsp;2.04\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-2.82\u0026thinsp;\u0026plusmn;\u0026thinsp;1.44\u003csup\u003ebc\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePA(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e4.79\u0026thinsp;\u0026plusmn;\u0026thinsp;1.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.78\u0026thinsp;\u0026plusmn;\u0026thinsp;1.01\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.49\u0026thinsp;\u0026plusmn;\u0026thinsp;1.32\u003csup\u003ebc\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePA-Zs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e-1.14\u0026thinsp;\u0026plusmn;\u0026thinsp;0.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-2.70\u0026thinsp;\u0026plusmn;\u0026thinsp;1.50\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.09\u0026thinsp;\u0026plusmn;\u0026thinsp;1.90\u003csup\u003ebc\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePA/AO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.79\u0026thinsp;\u0026plusmn;\u0026thinsp;0.23\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.40\u003csup\u003ebc\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLPA(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e2.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.25\u0026thinsp;\u0026plusmn;\u0026thinsp;0.64\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.69\u0026thinsp;\u0026plusmn;\u0026thinsp;0.76\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRPA(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e2.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.42\u0026thinsp;\u0026plusmn;\u0026thinsp;0.62\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.89\u003csup\u003ebc\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDAO(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e3.81\u0026thinsp;\u0026plusmn;\u0026thinsp;0.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.04\u0026thinsp;\u0026plusmn;\u0026thinsp;0.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.97\u0026thinsp;\u0026plusmn;\u0026thinsp;0.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.133\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMGI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.37\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.19\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.35\u003csup\u003ebc\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDA(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e3.14\u0026thinsp;\u0026plusmn;\u0026thinsp;0.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.06\u0026thinsp;\u0026plusmn;\u0026thinsp;0.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.84\u0026thinsp;\u0026plusmn;\u0026thinsp;1.03\u003csup\u003ebc\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eMA, GA:gestational age; CTR, cardiothoracic ratio; AO, aortic outflow; AO-Zs, AO Z-scores; PA, pulmonary artery; PA-Zs, PA Z-scores; LPA, left PA; RPA, right PA; DAO, descending aorta; MGI, McGoon index.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ea\u003c/sup\u003eGroup A vs Group B; \u003csup\u003eb\u003c/sup\u003eGroup A vs Group C; \u003csup\u003ec\u003c/sup\u003eGroup B vs Group C\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eStatistical analysis revealed no significant differences in GA, CTR, and DAO among the three groups (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). However, there was a statistically significant difference in fetal AC in Group C compared with that in Groups A and B. Significant differences were also observed in AO-Zs, PA, PA-Zs, PA/AO ratio, PA/AO-Zs, RPA, MGI. Notably, there was no statistical difference in AO between Group B and Groups A and C and LPA between Groups A and C, A and C, between Groups A and B, and between Groups A and C, B and C. In Group B, 53 fetuses had a PA-Z\u0026thinsp;\u0026lt;\u0026thinsp;\u0026minus;\u0026thinsp;2, 44 had MGI\u0026thinsp;\u0026lt;\u0026thinsp;1.2, and 69 had PA/AO\u0026thinsp;\u0026lt;\u0026thinsp;1.2.\u003c/p\u003e \u003cp\u003e2. Differences in various parameters across gestational weeks\u003c/p\u003e \u003cp\u003eComparison of various parameters among different gestational weeks in the normal control group is detailed in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. No significant differences were observed in CTR, MGI, AO-Zs, or PA-Zs among the four groups; however, statistically significant differences were identified in AO, PA, LPA, RPA, DAO, and DA(location for table Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of different parameters between different gestational weeks in the normal control group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18-(n\u0026thinsp;=\u0026thinsp;39)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22-(n\u0026thinsp;=\u0026thinsp;86)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26-(n\u0026thinsp;=\u0026thinsp;106)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30-(n\u0026thinsp;=\u0026thinsp;27)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCTR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.26\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e0.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.141\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAO(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e2.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.44\u0026thinsp;\u0026plusmn;\u0026thinsp;0.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e4.08\u0026thinsp;\u0026plusmn;\u0026thinsp;0.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e5.12\u0026thinsp;\u0026plusmn;\u0026thinsp;0.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAO-Zs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;1.72\u0026thinsp;\u0026plusmn;\u0026thinsp;1.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e\u0026minus;1.74\u0026thinsp;\u0026plusmn;\u0026thinsp;1.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e\u0026minus;1.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e\u0026minus;1.47\u0026thinsp;\u0026plusmn;\u0026thinsp;1.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePA(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e3.40\u0026thinsp;\u0026plusmn;\u0026thinsp;0.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e4.44\u0026thinsp;\u0026plusmn;\u0026thinsp;0.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e5.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e6.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePA-Zs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;1.17\u0026thinsp;\u0026plusmn;\u0026thinsp;1.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e\u0026minus;1.10\u0026thinsp;\u0026plusmn;\u0026thinsp;0.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e\u0026minus;1.25\u0026thinsp;\u0026plusmn;\u0026thinsp;0.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e\u0026minus;0.76\u0026thinsp;\u0026plusmn;\u0026thinsp;1.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePA/AO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.35\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.30\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e1.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e1.26\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLPA(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e2.35\u0026thinsp;\u0026plusmn;\u0026thinsp;0.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e2.76\u0026thinsp;\u0026plusmn;\u0026thinsp;0.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e3.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRPA(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.72\u0026thinsp;\u0026plusmn;\u0026thinsp;0.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e2.44\u0026thinsp;\u0026plusmn;\u0026thinsp;0.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e2.97\u0026thinsp;\u0026plusmn;\u0026thinsp;0.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e3.58\u0026thinsp;\u0026plusmn;\u0026thinsp;0.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDAO(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e2.65\u0026thinsp;\u0026plusmn;\u0026thinsp;0.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.49\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e4.21\u0026thinsp;\u0026plusmn;\u0026thinsp;0.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e5.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMGI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.34\u0026thinsp;\u0026plusmn;\u0026thinsp;0.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.38\u0026thinsp;\u0026plusmn;\u0026thinsp;0.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e1.37\u0026thinsp;\u0026plusmn;\u0026thinsp;0.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e1.38\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.788\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDA(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e2.25\u0026thinsp;\u0026plusmn;\u0026thinsp;0.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e2.89\u0026thinsp;\u0026plusmn;\u0026thinsp;0.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e3.44\u0026thinsp;\u0026plusmn;\u0026thinsp;0.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e4.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eCTR, cardiothoracic ratio; AO, aortic outflow; AO-Zs, AO Z-scores; PA, pulmonary artery; PA-Zs, PA Z-scores; LPA, left PA; RPA, right PA; DAO, descending aorta; MGI, McGoon index.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e3. Impact of fetal DA flow on PA development\u003c/p\u003e \u003cp\u003eIn the subset of 71 fetuses experiencing decreased pulmonary blood flow or pulmonary atresia, 33 exhibited reverse DA flow perfusion. Notably, this subgroup displayed lower values for PA, PA-Zs, LPA\u0026thinsp;+\u0026thinsp;RPA and MGI than the forward DA perfusion group. No significant difference was observed in AO and AO-Zs between these two groups. The correlation between the direction of fetal DA blood perfusion and PA development in fetuses with decreased pulmonary blood flow or pulmonary atresia is detailed in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRelationship between the direction of fetal DA blood perfusion and PA development in Group B\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe DA forward perfusion group(n\u0026thinsp;=\u0026thinsp;38)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eThe DA reverse perfusion group(n\u0026thinsp;=\u0026thinsp;33)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGA(week)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e25.50\u0026thinsp;\u0026plusmn;\u0026thinsp;3.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e25.58\u0026thinsp;\u0026plusmn;\u0026thinsp;3.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCTR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.26\u0026thinsp;\u0026plusmn;\u0026thinsp;0.46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAO(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e5.00\u0026thinsp;\u0026plusmn;\u0026thinsp;1.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e4.79\u0026thinsp;\u0026plusmn;\u0026thinsp;0.93\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAO-Zs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.12\u0026thinsp;\u0026plusmn;\u0026thinsp;2.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.61\u0026thinsp;\u0026plusmn;\u0026thinsp;1.64\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePA(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e4.07\u0026thinsp;\u0026plusmn;\u0026thinsp;1.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.44\u0026thinsp;\u0026plusmn;\u0026thinsp;0.91\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePA-Zs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;2.25\u0026thinsp;\u0026plusmn;\u0026thinsp;1.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e\u0026minus;3.22\u0026thinsp;\u0026plusmn;\u0026thinsp;1.40\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePA/AO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.84\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.74\u0026thinsp;\u0026plusmn;\u0026thinsp;0.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLPA\u0026thinsp;+\u0026thinsp;RPA(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e4.95\u0026thinsp;\u0026plusmn;\u0026thinsp;1.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e4.35\u0026thinsp;\u0026plusmn;\u0026thinsp;0.96\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMGI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.07\u0026thinsp;\u0026plusmn;\u0026thinsp;0.16\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDA(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e3.22\u0026thinsp;\u0026plusmn;\u0026thinsp;0.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e2.87\u0026thinsp;\u0026plusmn;\u0026thinsp;0.63\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eGA:gestational age; CTR, cardiothoracic ratio; AO, aortic outflow; AO-Zs, AO Z-scores; PA, pulmonary artery; PA-Zs, PA Z-scores; LPA, left PA; RPA, right PA; DAO, descending aorta; MGI, McGoon index.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.05 compared with the DA forward perfusion group\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e4.Repeatability\u003c/p\u003e \u003cp\u003eWithin-group correlation coefficients for each parameter demonstrated excellent consistency, with ICC slightly lower in Group B than in the other two groups((location for Table \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eICC of different parameter measured by echocardiography in each group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLPA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRPA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDAO\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup A(n\u0026thinsp;=\u0026thinsp;211)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.956\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.966\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.977\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup B(n\u0026thinsp;=\u0026thinsp;26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.901\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.842\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.910\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup C(n\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.980\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.904\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.965\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.957\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.961\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.973\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eLPA, left pulmonary artery; RPA, right pulmonary artery; DAO, descending aorta.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e5.Pregnancy outcome\u003c/p\u003e \u003cp\u003eAmong the 71 fetuses with CHD in case group B, 19 cases were lost to follow-up, the loss rate was 26.8%, 25 cases were induced labor, and 19 cases were born. Of the 19 neonates born, 1 died after giving up treatment due to poor condition (MGI\u0026thinsp;=\u0026thinsp;1.37 at 22 weeks of gestation). One case underwent palliative surgery for TOF after birth and died of multiple organ failure (MGI\u0026thinsp;=\u0026thinsp;1.20 at 24 weeks of gestation). 3 patients (MGI 1.05\u0026ndash;1.22) required elective radical resection of TOF. 5 cases (MGI 0.88\u0026ndash;1.35) underwent emergent or elective percutaneous balloon pulmonary valvuloplasty after birth. 9 cases (MGI 0.89\u0026ndash;1.64) did well after birth and were followed up in the outpatient clinic without surgical intervention.\u003c/p\u003e \u003cp\u003eAdditionally, 50 fetuses randomly selected from the normal control group underwent delivery and pediatric echocardiography, revealing no cardiovascular malformations, except for patent foramen ovale and PDA (patent ductus arteriosus).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe aim of this study was evaluating the value of McGoon index and multiple parameters measured by fetal echocardiography in assessing fetal pulmonary vascular development.\u003c/p\u003e \u003cp\u003eIn our investigation involving 71 fetuses with decreased pulmonary blood flow or pulmonary atresia in Group B, we observed that their MGI, PA-Zs, and PA/AO ratios were significantly smaller than those in the normal group. Conversely, the study of 21 fetuses with reduced or detached aortic flow in Group C revealed significantly greater values for MGI, PA-Zs, and PA/AO ratios than those in the other two groups. These findings, in conjunction with previous studies on CHD fetuses [\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], suggest that fetal MGI serves as a valuable indicator for evaluating PA development during the prenatal period, which has great implications for the dynamic evaluation of cardiovascular development in advanced intrauterine CHD fetuses, guiding disease analysis and prognosis, and providing reasonable information for prenatal consultations. Subgroup analysis in Group B indicated that fetuses with backward DA flow had smaller values for PA, PA-Zs, LPA\u0026thinsp;+\u0026thinsp;RPA, and MGI than the forward DA perfusion group. This implies that reverse DA flow may signify more severe PS or pulmonary atresia, suggesting a more substantial impact on fetal pulmonary vascular development.\u003c/p\u003e \u003cp\u003eIn this study, we established a mean MGI of 1.37\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21 for a large sample of normal mid-to-late pregnant fetuses. Unlike previous studies, our normal fetal sample size covered the entire GA range for fetal echocardiography and was categorized into four groups based on GA. We observed no significant differences in fetal MGI across different GAs, indicating that MGI does not change with GA. In normal developing fetuses, quantitative indicators reflecting cardiovascular development, such as PA and its branches and AO growth, and non-cardiovascular parameters reflecting fetal growth and development, including BPD, HC, FL, and AC, are clearly correlated with the increase in GA, which has been confirmed in several studies that applied Z-score [\u003cspan additionalcitationids=\"CR13 CR14\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Because MGI is the ratio of LPA\u0026thinsp;+\u0026thinsp;RPA inner diameter to DAO, which reflects the relative proportion of fetal PA and AO development, the results of MGI and Z-scores are consistent. In normal developing fetuses, MGI remains relatively stable within the normal range and does not exhibit variation with GA. This contrasts with Guo et al.'s findings [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] in a study of 110 normal fetuses and 54 fetuses with reduced pulmonary blood flow CHD, where CTR, FLV/EFW, and MGI showed significant differences between the two groups. The variation in results may be attributed to the broader spectrum of diseases included in our study than the more specific inclusion criteria of TOF, PA-VSD, and PA-IVVS in Guo et al.\u0026rsquo;s study [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEvaluation of pulmonary vascular development is crucial in the surgical context, especially for PS, as it strongly influences postoperative outcomes. Laban et al. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] reported that compared to neonates with respiratory distress syndrome(RDS), healthy neonates had significantly higher FLVs (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).However, YEabdalla et al. \u003csup\u003e[18]\u003c/sup\u003e recommended that combining the mean FLV to the other parameters rather than using this measure alone .Clinical MGI assessment is a common practice in postnatal children and adults, providing an overview of pulmonary vascular bed growth in CHD patients. A low MGI often indicates lung hypoplasia and is associated with a poor prognosis [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Higher incidences of surgical death and heart failure have been reported in patients with PA dysplasia [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. MGI has also been studied in children with congenital diaphragmatic hernia (CDH). Several studies [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] have suggested that among various prognostic factors in children with CDH, the extent of lung development is crucial, and the severity of pulmonary hypoplasia is considered the main limiting factor for survival, whereas MGI is positively correlated with pulmonary vascular development, serving as a prognostic factor for survival.\u003c/p\u003e \u003cp\u003eFrom the follow-up in our study, we observed that patients with PS alone and MGI\u0026thinsp;\u0026lt;\u0026thinsp;1.2 had a favorable prognosis. Notably, one patient with MGI 0.96 did not undergo surgery throughout the follow-up period. Similarly, two patients with TOF and MGI\u0026thinsp;\u0026lt;\u0026thinsp;1.2 (MGI 1.17, 1.05) did not require surgical intervention and were generally in good condition. However, two deaths occurred due to TOF (MGI 1.20) and hypoplastic right heart syndrome (HRHS). This suggests that the cardiovascular structure and functional status of fetuses with severe PS can vary significantly postnatally, necessitating individualized treatment strategies based on each child's PA development [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Despite the overall better prognosis in isolated PS, MGI may still decrease.\u003c/p\u003e \u003cp\u003eWhile MGI can be obtained through various methods such as cardiovascular angiography, CT, and echocardiography [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], the unique nature of the fetus places fetal echocardiography at the forefront of prenatal evaluation for cardiovascular structure and hemodynamics. Although MRI is utilized for the prenatal assessment of fetal brain and spine structures, its application in diagnosing fetal cardiovascular malformations is limited. The main challenges in fetal MGI measurement via echocardiography are obtaining clear images of the LPA, RPA, and DAO. This is dependent on the sonographer's ability to obtain standardized sections, which, in our study, was carried out by highly experienced physicians. Quantitative measurements of LPA, RPA, and DAO inner diameters were averaged from at least three measurements, resulting in a very good within-group correlation coefficient for each parameter. This ensured the high repeatability and accuracy of MGI measurements in our study.\u003c/p\u003e \u003cp\u003eOur study has some limitations. First, the measurement of fetal MGI is challenging in early pregnancy and was, therefore, excluded from our study. With ongoing advancements in US technology, future studies may include more early pregnancies to explore the broader application of MGI throughout gestation. Additionally, this study follows a cross-sectional design, and no prenatal follow-up was conducted for the studied case group. Conducting multiple follow-ups for CHD fetuses throughout pregnancy could provide a more comprehensive understanding of MGI patterns and its utility during fetal development. Similarly, there is a lack of systematic follow-up on pulmonary vascular and pulmonary development in neonates and young children post-birth. A longitudinal systematic tracking of MGI changes both prenatally and postnatally would contribute to a more scientific assessment of pulmonary blood vessel development in fetuses, newborns, and young children under varying pulmonary blood flow conditions. This approach is crucial for analyzing fetal conditions, predicting prognosis, and informing prenatal consultations and postnatal treatments.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, our study compared MGI, PA/AO, PA, and Z-scores in CHD fetuses with different pulmonary circulation blood volumes. The results demonstrate that MGI, combined with various parameter Z-scores, reliably evaluates pulmonary blood flow in different CHD fetuses, offering insights into pulmonary blood vessel development. The presence of reverse DA flow suggests more severe PS or pulmonary atresia, as indicated by smaller values in PA, PA-Zs, LPA\u0026thinsp;+\u0026thinsp;RPA, and MGI. This type of CHD may exert a more significant impact on fetal pulmonary vascular development. These findings have potential clinical applications in prognostic prediction and early intervention treatment. Through the analysis of a large number of normal fetal MGIs from 18 weeks to 33\u003csup\u003e+\u0026thinsp;6\u003c/sup\u003e weeks, we observed that fetal MGI remains relatively constant during this GA range and does not change with increasing GA.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by\u0026nbsp;foundation of Zhejiang Provincial Education Department(No.Y202146078).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe have no financial relationships to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Controbutions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by\u0026nbsp;Chenke Pan,\u0026nbsp;Mei Pan, Yunkai Luo and Yunyun Zhang. The first draft of the manuscript was written by\u0026nbsp;Chenke Pan\u0026nbsp;and all authors commented on previous versions of the manuscript.Bowen Zhao supervised the completion of the project and revised the manuscript.\u0026nbsp;All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by\u0026nbsp;the Ethics Committee of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine (20200210-78).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets supporting the results of this study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eNakata S, Imai Y, Takanashi Y, Kurosawa H, Tezuka K, Nakazawa M, Ando M, Takao A. A new method for the quantitative standardization of cross-sectional areas of the pulmonary arteries in congenital heart diseases with decreased pulmonary blood flow. 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Epub 2017 Oct 10.\u003c/li\u003e\n\u003cli\u003eLaban M, Mansour GM, Elsafty MS, Hassanin AS, EzzElarab SS. Prediction of neonatal respiratory distress syndrome in term pregnancies by assessment of fetal lung volume and pulmonary artery resistance index. Int J Gynaecol Obstet. 2015 Mar;128(3):246-50. doi: 10.1016/j.ijgo.2014.09.018.\u003c/li\u003e\n\u003cli\u003eKhalifa YEA, Aboulghar MM, Hamed ST, Tomerak RH, Asfour AM, Kamal EF. Prenatal prediction of respiratory distress syndrome by multimodality approach using 3D lung ultrasound, lung-to-liver intensity ratio tissue histogram and pulmonary artery Doppler assessment of fetal lung maturity. Br J Radiol. 2021 Dec;94(1128):20210577. doi: 10.1259/bjr.20210577.\u003c/li\u003e\n\u003cli\u003eCasaccia G, Crescenzi F, Dotta A, Capolupo I, Braguglia A, Danhaive O, Pasquini L, Bevilacqua M, Bagolan P, Corchia C, Orzalesi M. Birth weight and McGoon Index predict mortality in newborn infants with congenital diaphragmatic hernia. J Pediatr Surg. 2006 Jan;41(1):25-8; discussion 25-8. doi: 10.1016/j.jpedsurg.2005.10.002.\u003c/li\u003e\n\u003cli\u003eAggarwal S, Stockmann P, Klein MD, Natarajan G. Echocardiographic measures of ventricular function and pulmonary artery size: prognostic markers of congenital diaphragmatic hernia? J Perinatol. 2011 Aug;31(8):561-6. doi: 10.1038/jp.2011.3. \u003c/li\u003e\n\u003cli\u003eTakahashi S, Oishi Y, Ito N, Nanba Y, Tsukamoto K, Nakamura T, Ito Y, Hayashi S, Sago H, Kuroda T, Honna T. Evaluating mortality and disease severity in congenital diaphragmatic hernia using the McGoon and pulmonary artery indices. J Pediatr Surg. 2009 Nov;44(11):2101-6. doi: 10.1016/j.jpedsurg.2009.05.012.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"congenital heart disease, McGoon index, Z-score, fetal echocardiography, pulmonary artery","lastPublishedDoi":"10.21203/rs.3.rs-4117262/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4117262/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose: \u003c/strong\u003eThe purpose of this study was to evaluate the value of MGI and multiple parameters in the diagnosis of congenital heart disease with different pulmonary circulation blood volumes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eThis study included 349 fetuses categorized into three groups: Group A consisted of 258 fetuses with no discernible abnormalities identified through echocardiography; Group B included 71 fetuses with decreased pulmonary blood flow or pulmonary atresia; and Group C comprised 20 fetuses with reduced or detached aortic flow. The MGI and Z-scores were measured and compared among these groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Significant variations were noted in the aortic outflow Z-scores (AO-Zs), pulmonary artery (PA), PA Z-scores (PA-Zs), PA/AO, right PA , and MGI among the three groups (all p \u0026lt; 0.05). Among fetuses with decreased pulmonary blood flow or pulmonary atresia, PA, PA-Zs, and MGI in fetuses with reverse DA flow perfusion were lower than those in the DA forward perfusion group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eFetal echocardiography, incorporating the MGI and multiple parameters, not only allows for the evaluation of pulmonary blood flow and pulmonary vascular development of the fetus but also enables the observation of changes in pulmonary blood flow and MGI development across different gestational weeks.\u003c/p\u003e","manuscriptTitle":"Evaluating fetal pulmonary vascular development in congenital heart disease: a comparative study using the McGoon index and multiple parameters of fetal echocardiography","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-25 18:04:55","doi":"10.21203/rs.3.rs-4117262/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":"c764c4a8-d4de-4736-aa03-9bdc3ccd3746","owner":[],"postedDate":"March 25th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-05-28T14:21:04+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-25 18:04:55","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4117262","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4117262","identity":"rs-4117262","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}