Progression of Truncal Valve regurgitation during fetal life: a retrospective multicenter study

Progression of Truncal Valve regurgitation during fetal life: a retrospective multicenter study | 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 Progression of Truncal Valve regurgitation during fetal life: a retrospective multicenter study Irene Borzillo, Alessandra Toscano, Marco Masci, Kristen Gosnell, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6339803/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 04 Nov, 2025 Read the published version in Pediatric Cardiology → Version 1 posted 12 You are reading this latest preprint version Abstract Background Truncal valve regurgitation is a key factor impacting outcomes in patients with truncus arteriosus. Patients with moderate or greater regurgitation have elevated risk for early and late postoperative mortality. While the influence of regurgitation on postnatal outcomes is well-documented, its progression during fetal life is less understood. Our goal is to provide accurate prognostic information to parents by describing how truncal valve regurgitation evolves throughout pregnancy and whether this progression is related to cusp morphology, type of truncus arteriosus, or genetic abnormalities. Materials and Methods This retrospective multicenter study includes fetuses diagnosed with truncus arteriosus between January 2003 and April 2024. We analyzed the progression of truncal valve regurgitation by comparing first and second trimester fetal echocardiograms, as well as early postnatal echocardiograms. Regurgitation was assessed semi-quantitatively and classified as none, absent, moderate, or severe. The primary endpoint was to describe how truncal valve regurgitation progresses during fetal life and to assess whether it is associated with cusp number, truncus arteriosus type, or genetic abnormalities. Results Out of 56 initial fetal echocardiograms, 10 pregnancies were terminated, 4 cases were excluded due to moderate or severe regurgitation in the first trimester, 5 cases did not confirm a diagnosis of truncus arteriosus, and 4 were lost to follow-up. Comparing the second with the third trimester fetal echocardiogram, 2 patients progressed from absent/mild to moderate. When only third trimester echocardiogram was available, due to late referral, only 1 patient progressed from absent/mild to moderate regurgitation compared with postnatal assessment. Bicuspid and quadricuspid valves were more likely to exhibit progressive regurgitation (p = 0.049), while no significant association was found with genetic abnormalities or the type of truncus arteriosus. Conclusion Truncal valve regurgitation rarely progresses during fetal life and it is more likely to occur in cases with bicuspid or quadricuspid valves. These findings may be useful in counseling families with fetuses diagnosed with minimal truncal valve regurgitation, helping to set realistic expectations regarding postnatal outcomes. The counseling can be somewhat reassuring that the risk of progression to more significant truncal regurgitation is fairly low. Truncus arteriosus regurgitation fetal echocardiogram congenital heart disease Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 1. Introduction Truncus arteriosus (TA) represents 2–4% of all congenital heart defects. In this cardiac defect the arterial trunk and semilunar valves fail to separate during embryogenesis, resulting in a single artery suppling systemic, pulmonary, and coronary circulations [ 1 ] (Fig. 1 ). Given advances in fetal echocardiography, the frequency of prenatally diagnosis of TA, has improved over time [ 2 ]. Before availability of surgery, mortality in the first year of life was 80% for TA patients [ 3 ]. The outcomes in patients with TA are known to be impacted by several extracardiac and anatomic variables. For example, the incidence of 22q11 deletion syndrome is 35.5% in TA patients [ 4 ] and22q11 deletion syndrome is a risk factor for adverse outcomes including an increased length of hospital stay [ 5 ]. From an anatomic standpoint, an abnormal number of truncal cusps, presence of truncal valve dysplasia, are associated with truncal valve regurgitation. In addition, the degree of truncal valve regurgitation influences patient outcomes. Moderate or severe truncal valve regurgitation is a risk factor for late truncal valve reoperation or late severe truncal valve regurgitation [ 7 ] due to lack of durable valve repair. Valve replacement options, require frequent truncal valve reoperations. Patients with moderate or greater regurgitation have elevated risk for early and late postoperative mortality [ 8 ]. Truncal valve regurgitation could determine congestive heart failure due to increased ventricular end-diastolic pressure and could be responsible for developing coronary ischemia compromising diastolic coronary perfusion [ 8 ]. In patients who have a fetal diagnosis of TA, our goal as fetal cardiologists is to provide accurate information regarding anticipated outcomes for the child. These discussions include the known factors that impact long-term outcomes, however, the potential progression of truncal valve regurgitation during gestation has not been studied. Therefore, the aim of this study is to assess whether a minimal amount of truncal valve regurgitation may progress during fetal life. In the context of fetal TA diagnosis, providing accurate prognostic information is crucial for guiding parental expectations and decision-making. Understanding how truncal valve regurgitation evolves during gestation is particularly important for fetal cardiologists, as it can significantly impact counseling. Parents often seek clear information on the severity of the condition and its potential progression, which directly influences discussions about postnatal outcomes, possible interventions, and long-term prognosis. However, while the factors affecting long-term outcomes are well-known, the potential progression of truncal valve regurgitation during fetal life remains largely unexplored. Determining whether minimal truncal valve regurgitation worsens or remains stable during gestation, is fundamental to providing parents with accurate, evidence-based guidance. We hypothesize that the degree of regurgitation remains relatively stable throughout gestation, consistent with findings on the initial neonatal echocardiogram. 2. Methods Data collection, study population and study design This retrospective two-center cohort study was approved by the institutional review boards at both institutions (University of California San Francisco [UCSF] Benioff Children’s Hospital and Bambino Gesù Pediatric Hospital of Rome [OPBG]). We included all fetal diagnosis of TA at the two participating centers seen between January 2003 and April 2024. Both institutions are tertiary referral centers for congenital heart disease (CHD). Maternal and neonatal electronic medical records to obtain maternal demographic and pregnancy information, pregnancy outcomes, neonatal mortality, and morbidity data were reviewed. At UCSF Benioff Children’s Hospital, fetal echocardiography was performed using Voluson E10 and Vivid E95 (GE Healthcare). At OPBG, fetal echocardiography was performed using Philips EPIQ CVx ultrasound machine. Inclusion criteria were: fetal diagnosis of TA between January 2003 and April 2024 and minimal TV regurgitation. Minimal TV regurgitation was defined as mild or less (ex. none or trivial). Exclusion criteria were: termination of pregnancy, diagnosis of cardiac defect other than TA on postnatal echocardiogram or autopsy, tricuspid valve regurgitation greater than mild on the first fetal echocardiogram. A total of 56 fetal echoes were defined in the database (Fig. 2 ). We evaluated up to two fetal echocardiograms for each pregnant person: one at the time of diagnosis (during the second trimester of pregnancy) and one during the third trimester. In patients with multiple echocardiograms in the same trimester, we included the first echocardiogram performed in each trimester. The fetal diagnosis of TA was confirmed in each patient by postnatal echocardiography performed in the first hours of life. The fetal heart was examined based on a segmental approach, according to the American Society of Echo Guidelines [ 9 ]. Echocardiographic measurements were performed by experts in fetal and postnatal echocardiography at each center. TV annulus diameter was measured at the hinge points. Truncal valve stenosis was defined as none, minimal, moderate or severe. There are no published values for normal truncal valve velocities, therefore we used previously established cut-offs by Volpe et al to define: mild or no truncal valve stenosis when continuous-wave Doppler maximum velocity (Vmax) was less than 2 m/s, moderate stenosis when the velocity ranged from > 2 to 3 m/s and severe stenosis when the velocity was > 3 m/s [ 10 ]. We used the documented degree of regurgitation in the echo reports, which were read by experts in fetal echo. The degree of truncal valve regurgitation was graded as absent, mild, moderate or severe: mild as a very small insufficiency jet visible with color Doppler, moderate truncal valve insufficiency as a notable regurgitation jet parallel to the whole length of the anterior mitral valve leaflet, severe regurgitation as an extensive color Doppler retrograde flow into the ventricles. Ventricular function was assessed qualitatively. We used the Edward and Collet classification to define the type of truncus [ 1 ]. Independent variables were pregnancy characteristics, the presence of fetal genetic or extracardiac abnormalities, and fetal-echo variables. Endpoints The primary endpoint was assessing the frequency of progression of truncal regurgitation during the fetal life and establishing whether risk of truncal valve regurgitation progression is related to number of tricuspid valve cusps, genetic abnormalities, or to the type of truncus arteriosus. Statistical analysis Variables with a discrete distribution were summarized as counts and percentages, while those with a continuous distribution were presented as mean and standard deviation or median and interquartile range for non-parametric data. All statistical analysis was performed in SPSS version 26.0 (IBM, Armonk, NY). We used chi-square or Fisher’s tests for normal categorical covariables to determine significance (p < 0.05). 3. Results We identified 56 patients with a fetal diagnosis of TA on fetal echocardiograms performed between January 2003 and April 2024. Among these patients, 10 terminated the pregnancy, 4 fetuses were excluded for presence of moderate or severe truncal regurgitation already present at the second trimester fetal echocardiogram, 5 were excluded for a postnatal cardiac diagnosis other than TA and 4 patients were lost to follow-up (Figure 2) Outcomes Maternal and fetal characteristics are displayed in Table 1. Among the study population, 6 patients (18%) died in the neonatal period, 2 (6%) died during the fetal period, and 25 (75%) were alive in the first year. As expected, based on prior literature, genetic abnormalities and extracardiac defects were common (Table 2). 2 patients had in utero fetal demise. This was not related to the truncal valve regurgitation that in these cases was mild. Table 3 shows the progression of the regurgitation. Comparing the patients who had both second and third trimester fetal echocardiogram, the truncal valve regurgitation progressed to moderate in 2 cases (10%). Comparing the patients who had both second trimester fetal echocardiogram and post-natal assessment the truncal valve regurgitation progressed from absent/mild to moderate in 4 cases (19%). When only third trimester echocardiogram was available, due to late referral, only 1 patient (10%) progressed from absent/mild to moderate regurgitation compared to postnatal assessment. (Figure 3). Additional echocardiographic findings are shown in Table 4. As shown in Figure 4, we found that bicuspid and quadricuspid truncal valves were more likely to progress to at least moderate truncal valve insufficiency (p=0.049). Neither presence of genetic abnormalities nor type of truncus arteriosus were statistically significant in relation to progression of truncal valve regurgitation (Figures 5 and 6). 4. Discussion Our study demonstrated that the presence of minimal truncal regurgitation on second and third trimester fetal echocardiograms is unlikely to progress by initial neonatal echocardiogram. We found: The progression of TV regurgitation from none/mild in the second trimester fetal echocardiogram to moderate by postnatal echocardiogram is 10%. Quadricuspid and bicuspid TVs are more likely to progress to moderate truncal regurgitation. This is the largest study evaluating progression of minimal/no truncal valve regurgitation in the fetal life to the neonatal period. Not surprisingly, the TV morphology was related to progression of TV regurgitation, due to the dysplastic structure of the valve. Although determining number of TV leaflets is not always possible on fetal echocardiograms, this may become more helpful in fetal counseling as fetal imaging continues to improve. Interestingly, the presence of 22q11 deletion syndrome was not statistically significant in predicting worsening TV regurgitation, however our patient population is small and additional multicenter studies would be helpful. In any case, the presence of DiGeorge syndrome is associated with a series of complications that also make perioperative management more complex [ 5 ]. Studies have demonstrated that Di George syndrome and congenital hearts disease have an unfavorable neurodevelopmental outcome. This appears to be more related to the presence of 22qdelation syndrome rather than to the underlying cardiac defect [ 11 ]. Prenatal detection of 22qDS is important. As showed by Freud et al [ 12 ], it was associated with improved delivery management and less cardiac and noncardiac morbidity, in comparison with postnatal detection. We believe that larger studies are needed to assess how genetic abnormalities impact on the Truncal valve dysplasia. Existing data suggests that TV dysfunction may be an important predictor of pre-surgical mortality due to ventricular remodeling and dysfunction [ 13 ], our study findings may have an important impact on how we counsel patients with a fetal diagnosis of TA. In addition, patients who require truncal valve intervention have higher risk of mortality probably due to an increased complexity, the higher utilization of mechanical circulatory support, and longer length of stay [ 14 ], increased need for reoperation [ 12 ]. One of the largest series of infant TA repair was reported by Ebert [ 15 ], of the 11 deaths in Ebert’s original series, 8 patients had moderate or greater truncal valve regurgitation. Similarly, McElhinney [ 16 ] demonstrated that a moderate or greater degree of pre-repair truncal valve regurgitation was associated with a significantly greater likelihood of later truncal valve replacement. Prenatal counseling is crucial because allows time for parental decision-making regarding continuation or termination of pregnancy, prenatal genetic testing, site of delivery and postnatal cardiac care, and discussion about the option of palliative care. Having a prenatal diagnosis allows time for parents to process the emotions of shock, and disappointment and allows them to be mentally and emotionally prepared for the postnatal hospitalization and medical needs [ 17 ]. From our results we can say that when counseling fetal patients with no/mild truncal valve regurgitation, we can be somewhat reassuring that the risk of progression to more significant truncal regurgitation is fairly low. Anyhow, should be considered that the regurgitation of the TA is not the only finding that contributes to the surgery complexity. These risk factors included associated interrupted aortic arch, discontinuous pulmonary arteries, comorbidities often related to the TA in relation with the genetic abnormalities [ 18 ]. Prenatal care should also focus on addressing other risk factors, which are likely to influence surgical complexity and overall prognosis. 10 patients in our study were late referral. Early diagnosis is essential in parents’ decision making; this highlights the importance, whenever possible, of referring patients for a fetal echocardiogram at least in the second trimester of pregnancy. 5. Limitations This is a retrospective study conducted in two tertiary centers, but TA is a rare congenital heart disease and the number of patients is small. More big multicenter studies are needed to assess the fetus echocardiography predictor outcomes. 6. Conclusion When truncal valve regurgitation is minimal at initial fetal echocardiogram, the risk of progression during gestation is low. Progression of truncal valve regurgitation is more likely in patients with quadricuspid or bicuspid truncal valves. In this small study, there was no statistically significant association between progression of truncal valve regurgitation and either genetic abnormalities or type of truncus arteriosus. These findings may be useful in fetal counseling for these patients with minimal truncal valve regurgitation and instead focus on other anatomic and extracardiac findings that may impact postnatal outcomes. Declarations Author Contribution N.C had the idea of the project, I:B wrote the main manuscript, M.M. and K.G helped in collected datasets. Alla authors reviwied the manuscript References Collett RW, Edwards JE (1949) Persistent truncus arteriosus; a classification according to anatomic types. Surg Clin North Am 29:1245–1270. 10.1016/s0039-6109(16)32803-1 Marginean C et al (2018) Prenatal diagnosis of the fetal common arterial trunk. A case series. Med Ultrasonogr 1(1):100–104 Marcelletti C, McGoon DC, Mair DD (1976) The natural history of truncus arteriosus. Circulation 54(1):108–111 Peyvandi S, Lupo PJ, Garbarini J et al (2013) 22q11.2 deletions in patients with conotruncal defects: data from 1,610 consecutive cases. Pediatr Cardiol 34:1687–1694 O’Byrne ML, Yang W, Mercer-Rosa L et al (2014) 22q11.2 Deletion syndrome is associated with increased perioperative events and more complicated postoperative course in infants undergoing infant operative correction of truncus arteriosus communis or interrupted aortic arch. J Thorac Cardiovasc Surg 148:1597–1605 Epub 2014 Feb 10 Patrick WL et al (2016) Anatomic Factors Associated With Truncal Valve Insufficiency and the Need for Truncal Valve Repair. 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J Am Soc Echocardiography: official publication Am Soc Echocardiography vol 36(7):679–723 Volpe P, Paladini D, Marasini M, Buonadonna AL, Russo MG, Caruso G, Marzullo A, Vassallo M, Martinelli P, Gentile M (2003) Common arterial trunk in the fetus: characteristics, associations, and outcome in a multicentre series of 23 cases. Heart 89(12):1437–1441. 10.1136/heart.89.12.1437 Willen A, Feys H, Adriaens T, Nelissen L, Mertens L, Gewillig M, Devriendt K, Fryns JP (2005) Early motor development in young children with 22q.11 deletion syndrome and a conotruncal heart defect. Dev Med Child Neurol 47:797–802 Freud LR, Galloway S, Crowley TB, Moldenhauer J, Swillen A, Breckpot J, Borrell A, Vora NL, Cuneo B, Hoffman H, Gilbert L, Nowakowska B, Geremek M, Kutkowska-Kaźmierczak A, Vermeesch JR, Devriendt K, Busa T, Sigaudy S, Vigneswaran T, Simpson JM, Dungan J, Gotteiner N, Gloning KP, Digilio MC, Unolt M, Putotto C, Marino B, Repetto G, Fadic M, Garcia-Minaur S, Achón Buil A, Thomas MA, Fruitman D, Beecroft T, Hui PW, Oskarsdottir S, Bradshaw R, Criebaum A, Norton ME, Lee T, Geiger M, Dunnington L, Isaac J, Wilkins-Haug L, Hunter L, Izzi C, Toscano M, Ghi T, McGlynn J, Romana Grati F, Emanuel BS, Gaiser K, Gaynor JW, Goldmuntz E, McGinn DE, Schindewolf E, Tran O, Zackai EH, Yan Q, Bassett AS, Wapner R, McDonald-McGinn DM (2024) Prenatal vs postnatal diagnosis of 22q11.2 deletion syndrome: cardiac and noncardiac outcomes through 1 year of age. Am J Obstet Gynecol 230(3):368. .e1-368.e12Epub 2023 Sep 16 Martínez-Quintana E, Portela-Torrón F (2019) Truncus arteriosus and truncal valve regurgitation. Transl Pediatr 8(5):360–362. 10.21037/tp.2019.02.01 PMID: 31993347; PMCID: PMC6970119 Kaza AK, Burch PT, Pinto N et al (2010) Durability of truncal valve repair. Ann Thorac Surg 90:1307–1312 Ebert PA, Turley K, Stanger P, Hoffman JI, Heymann MA, Rudolph AM (1984) Surgical treatment of truncus arteriosus in the first 6 months of life. Ann Surg 200:451–456 McElhinney DB, Reddy VM, Rajasinghe HA, Mora BN, Silverman NH, Hanley FL (1998) Trends in the management of truncal valve insufficiency. Ann Thorac Surg 65:517–524 Lee CK (2017) Prenatal Counseling of Fetal Congenital Heart Disease. Curr Treat options Cardiovasc Med vol 19(1):5 Naimo PS, Fricke TA, Lee MGY, d'Udekem Y, Weintraub RG, Brizard CP, Konstantinov IE (2020) Long-term outcomes following repair of truncus arteriosus and interrupted aortic arch. Eur J Cardiothorac Surg. ;57(2):366–372. 10.1093/ejcts/ezz176 . PMID: 31209463 Tables Tables 1 to 4 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Tabe1generalcharacteristics.docx Table2.GeneticandExtracardiacabnormalitiesdocx.docx Table3Truncalvalveprogression.docx Tabe4Echocardiographyfindings.docx Cite Share Download PDF Status: Published Journal Publication published 04 Nov, 2025 Read the published version in Pediatric Cardiology → Version 1 posted Editorial decision: Revision requested 21 Apr, 2025 Reviews received at journal 15 Apr, 2025 Reviewers agreed at journal 10 Apr, 2025 Reviews received at journal 10 Apr, 2025 Reviewers agreed at journal 09 Apr, 2025 Reviewers agreed at journal 09 Apr, 2025 Reviewers agreed at journal 06 Apr, 2025 Reviewers agreed at journal 04 Apr, 2025 Reviewers invited by journal 04 Apr, 2025 Editor assigned by journal 31 Mar, 2025 Submission checks completed at journal 31 Mar, 2025 First submitted to journal 30 Mar, 2025 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. 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1","display":"","copyAsset":false,"role":"figure","size":1223775,"visible":true,"origin":"","legend":"\u003cp\u003e22 weeks Fetal echocardiogram, Truncus Type 1\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-6339803/v1/fa448528ec96df935e5096ac.png"},{"id":82120604,"identity":"b0cd1b8e-e33e-4b3e-b133-4074f9be8fe7","added_by":"auto","created_at":"2025-05-07 03:17:00","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":170901,"visible":true,"origin":"","legend":"\u003cp\u003eSelection Flow of Study population\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-6339803/v1/fc619c19fa2bd8f0859acadb.png"},{"id":82125339,"identity":"9f02dab9-7faf-4080-8086-186d47837cee","added_by":"auto","created_at":"2025-05-07 03:49:00","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":156852,"visible":true,"origin":"","legend":"\u003cp\u003eProgression of Truncal Valve regurgitation in fetal life and compared to Neonatal Period\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-6339803/v1/bc7f2692264a46529f2a18b9.png"},{"id":82121841,"identity":"427aa3b1-c1f3-49c3-9d7f-77e0cc75402c","added_by":"auto","created_at":"2025-05-07 03:25:00","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":51182,"visible":true,"origin":"","legend":"\u003cp\u003eProgression of Truncal Valve regurgitation in relation with numbers of Leaflets\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-6339803/v1/f45567959067c65b5900d8ec.png"},{"id":82120593,"identity":"86da3509-5bfd-482e-87b6-8caf0993e614","added_by":"auto","created_at":"2025-05-07 03:17:00","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":56169,"visible":true,"origin":"","legend":"\u003cp\u003eProgression of Truncal Valve regurgitation in relation with Type of Truncus\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-6339803/v1/a1b89c3451db820a7cc692d0.png"},{"id":82121848,"identity":"6187aecc-434a-4d12-9924-88bf517387bc","added_by":"auto","created_at":"2025-05-07 03:25:00","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":279349,"visible":true,"origin":"","legend":"\u003cp\u003eProgression of Truncal Valve regurgitation in relation with Genetic Abnormalities.\u003c/p\u003e","description":"","filename":"Figure6.png","url":"https://assets-eu.researchsquare.com/files/rs-6339803/v1/1be4bf9700e2d97347a5faad.png"},{"id":95564191,"identity":"b1b86e74-8c24-48d1-b0fb-f435e505fe41","added_by":"auto","created_at":"2025-11-10 16:08:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2349793,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6339803/v1/ff92c3b5-a9ee-43a1-a5e6-1ba88e205405.pdf"},{"id":82123461,"identity":"52c553d8-74d1-4acb-a62a-51728b48f9cb","added_by":"auto","created_at":"2025-05-07 03:33:00","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":15454,"visible":true,"origin":"","legend":"","description":"","filename":"Tabe1generalcharacteristics.docx","url":"https://assets-eu.researchsquare.com/files/rs-6339803/v1/3340d7892500b11f8915d313.docx"},{"id":82120592,"identity":"bbd33036-8c52-4454-bcad-e27ecc8352e5","added_by":"auto","created_at":"2025-05-07 03:17:00","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":13190,"visible":true,"origin":"","legend":"","description":"","filename":"Table2.GeneticandExtracardiacabnormalitiesdocx.docx","url":"https://assets-eu.researchsquare.com/files/rs-6339803/v1/3d08f1ff27a854abc6a4d63b.docx"},{"id":82121844,"identity":"4f696b52-d3e0-425c-a53e-e0de86e2b135","added_by":"auto","created_at":"2025-05-07 03:25:00","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":17304,"visible":true,"origin":"","legend":"","description":"","filename":"Table3Truncalvalveprogression.docx","url":"https://assets-eu.researchsquare.com/files/rs-6339803/v1/3612f07aca6c9a5dff426377.docx"},{"id":82121838,"identity":"891bf4cf-2a7f-4cae-9be1-b7cd69158e99","added_by":"auto","created_at":"2025-05-07 03:25:00","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":13436,"visible":true,"origin":"","legend":"","description":"","filename":"Tabe4Echocardiographyfindings.docx","url":"https://assets-eu.researchsquare.com/files/rs-6339803/v1/35cf9dac2b27aa1aa491fc7f.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Progression of Truncal Valve regurgitation during fetal life: a retrospective multicenter study","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eTruncus arteriosus (TA) represents 2\u0026ndash;4% of all congenital heart defects. In this cardiac defect the arterial trunk and semilunar valves fail to separate during embryogenesis, resulting in a single artery suppling systemic, pulmonary, and coronary circulations [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Given advances in fetal echocardiography, the frequency of prenatally diagnosis of TA, has improved over time [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Before availability of surgery, mortality in the first year of life was 80% for TA patients [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The outcomes in patients with TA are known to be impacted by several extracardiac and anatomic variables. For example, the incidence of 22q11 deletion syndrome is 35.5% in TA patients [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] and22q11 deletion syndrome is a risk factor for adverse outcomes including an increased length of hospital stay [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. From an anatomic standpoint, an abnormal number of truncal cusps, presence of truncal valve dysplasia, are associated with truncal valve regurgitation. In addition, the degree of truncal valve regurgitation influences patient outcomes. Moderate or severe truncal valve regurgitation is a risk factor for late truncal valve reoperation or late severe truncal valve regurgitation [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] due to lack of durable valve repair. Valve replacement options, require frequent truncal valve reoperations. Patients with moderate or greater regurgitation have elevated risk for early and late postoperative mortality [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Truncal valve regurgitation could determine congestive heart failure due to increased ventricular end-diastolic pressure and could be responsible for developing coronary ischemia compromising diastolic coronary perfusion [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn patients who have a fetal diagnosis of TA, our goal as fetal cardiologists is to provide accurate information regarding anticipated outcomes for the child. These discussions include the known factors that impact long-term outcomes, however, the potential progression of truncal valve regurgitation during gestation has not been studied. Therefore, the aim of this study is to assess whether a minimal amount of truncal valve regurgitation may progress during fetal life. In the context of fetal TA diagnosis, providing accurate prognostic information is crucial for guiding parental expectations and decision-making. Understanding how truncal valve regurgitation evolves during gestation is particularly important for fetal cardiologists, as it can significantly impact counseling. Parents often seek clear information on the severity of the condition and its potential progression, which directly influences discussions about postnatal outcomes, possible interventions, and long-term prognosis. However, while the factors affecting long-term outcomes are well-known, the potential progression of truncal valve regurgitation during fetal life remains largely unexplored. Determining whether minimal truncal valve regurgitation worsens or remains stable during gestation, is fundamental to providing parents with accurate, evidence-based guidance. We hypothesize that the degree of regurgitation remains relatively stable throughout gestation, consistent with findings on the initial neonatal echocardiogram.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cp\u003e \u003cem\u003eData collection, study population and study design\u003c/em\u003e \u003c/p\u003e \u003cp\u003e This retrospective two-center cohort study was approved by the institutional review boards at both institutions (University of California San Francisco [UCSF] Benioff Children\u0026rsquo;s Hospital and Bambino Ges\u0026ugrave; Pediatric Hospital of Rome [OPBG]). We included all fetal diagnosis of TA at the two participating centers seen between January 2003 and April 2024. Both institutions are tertiary referral centers for congenital heart disease (CHD). Maternal and neonatal electronic medical records to obtain maternal demographic and pregnancy information, pregnancy outcomes, neonatal mortality, and morbidity data were reviewed.\u003c/p\u003e \u003cp\u003eAt UCSF Benioff Children\u0026rsquo;s Hospital, fetal echocardiography was performed using Voluson E10 and Vivid E95 (GE Healthcare). At OPBG, fetal echocardiography was performed using Philips EPIQ CVx ultrasound machine.\u003c/p\u003e \u003cp\u003eInclusion criteria were: fetal diagnosis of TA between January 2003 and April 2024 and minimal TV regurgitation. Minimal TV regurgitation was defined as mild or less (ex. none or trivial). Exclusion criteria were: termination of pregnancy, diagnosis of cardiac defect other than TA on postnatal echocardiogram or autopsy, tricuspid valve regurgitation greater than mild on the first fetal echocardiogram.\u003c/p\u003e \u003cp\u003eA total of 56 fetal echoes were defined in the database (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eWe evaluated up to two fetal echocardiograms for each pregnant person: one at the time of diagnosis (during the second trimester of pregnancy) and one during the third trimester. In patients with multiple echocardiograms in the same trimester, we included the first echocardiogram performed in each trimester. The fetal diagnosis of TA was confirmed in each patient by postnatal echocardiography performed in the first hours of life.\u003c/p\u003e \u003cp\u003eThe fetal heart was examined based on a segmental approach, according to the American Society of Echo Guidelines [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Echocardiographic measurements were performed by experts in fetal and postnatal echocardiography at each center. TV annulus diameter was measured at the hinge points. Truncal valve stenosis was defined as none, minimal, moderate or severe. There are no published values for normal truncal valve velocities, therefore we used previously established cut-offs by Volpe et al to define: mild or no truncal valve stenosis when continuous-wave Doppler maximum velocity (Vmax) was less than 2 m/s, moderate stenosis when the velocity ranged from \u0026gt;\u0026thinsp;2 to 3 m/s and severe stenosis when the velocity was \u0026gt;\u0026thinsp;3 m/s [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe used the documented degree of regurgitation in the echo reports, which were read by experts in fetal echo. The degree of truncal valve regurgitation was graded as absent, mild, moderate or severe: mild as a very small insufficiency jet visible with color Doppler, moderate truncal valve insufficiency as a notable regurgitation jet parallel to the whole length of the anterior mitral valve leaflet, severe regurgitation as an extensive color Doppler retrograde flow into the ventricles. Ventricular function was assessed qualitatively.\u003c/p\u003e \u003cp\u003eWe used the Edward and Collet classification to define the type of truncus [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIndependent variables were pregnancy characteristics, the presence of fetal genetic or extracardiac abnormalities, and fetal-echo variables.\u003c/p\u003e \u003cp\u003e \u003cem\u003eEndpoints\u003c/em\u003e \u003c/p\u003e \u003cp\u003eThe primary endpoint was assessing the frequency of progression of truncal regurgitation during the fetal life and establishing whether risk of truncal valve regurgitation progression is related to number of tricuspid valve cusps, genetic abnormalities, or to the type of truncus arteriosus.\u003c/p\u003e \u003cp\u003e \u003cem\u003eStatistical analysis\u003c/em\u003e \u003c/p\u003e \u003cp\u003eVariables with a discrete distribution were summarized as counts and percentages, while those with a continuous distribution were presented as mean and standard deviation or median and interquartile range for non-parametric data. All statistical analysis was performed in SPSS version 26.0 (IBM, Armonk, NY). We used chi-square or Fisher\u0026rsquo;s tests for normal categorical covariables to determine significance (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003eWe identified 56 patients with a fetal diagnosis of TA on fetal echocardiograms performed between January 2003 and April 2024. Among these patients, 10 terminated the pregnancy, 4 fetuses were excluded for presence of moderate or severe truncal regurgitation already present at the second trimester fetal echocardiogram, 5 were excluded for a postnatal cardiac diagnosis other than TA and 4 patients were lost to follow-up (Figure 2)\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eOutcomes\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eMaternal and fetal characteristics are displayed in Table 1. Among the study population, 6 patients (18%) died in the neonatal period, 2 (6%) died during the fetal period, and 25 (75%) were alive in the first year.\u003c/p\u003e\n\u003cp\u003eAs expected, based on prior literature, genetic abnormalities and extracardiac defects were common (Table 2).\u003c/p\u003e\n\u003cp\u003e2 patients had in utero fetal demise. This was not related to the truncal valve regurgitation that in these cases was mild. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 3 shows the progression of the regurgitation. Comparing the patients who had both second and third trimester fetal echocardiogram, the truncal valve regurgitation progressed to moderate in 2 cases (10%).\u003c/p\u003e\n\u003cp\u003eComparing the patients who had both second trimester fetal echocardiogram and post-natal assessment the truncal valve regurgitation progressed from absent/mild to moderate in 4 cases (19%). When only third trimester echocardiogram was available, due to late referral, only 1 patient (10%) progressed from absent/mild to moderate regurgitation compared to postnatal assessment.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(Figure 3).\u003c/p\u003e\n\u003cp\u003eAdditional echocardiographic findings are shown in Table 4.\u003c/p\u003e\n\u003cp\u003eAs shown in Figure 4, we found that bicuspid and quadricuspid truncal valves were more likely to progress to at least moderate truncal valve insufficiency (p=0.049). \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNeither presence of genetic abnormalities nor type of truncus arteriosus were statistically significant in relation to progression of truncal valve regurgitation (Figures 5 and 6).\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eOur study demonstrated that the presence of minimal truncal regurgitation on second and third trimester fetal echocardiograms is unlikely to progress by initial neonatal echocardiogram. We found:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eThe progression of TV regurgitation from none/mild in the second trimester fetal echocardiogram to moderate by postnatal echocardiogram is 10%.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eQuadricuspid and bicuspid TVs are more likely to progress to moderate truncal regurgitation.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eThis is the largest study evaluating progression of minimal/no truncal valve regurgitation in the fetal life to the neonatal period.\u003c/p\u003e \u003cp\u003eNot surprisingly, the TV morphology was related to progression of TV regurgitation, due to the dysplastic structure of the valve. Although determining number of TV leaflets is not always possible on fetal echocardiograms, this may become more helpful in fetal counseling as fetal imaging continues to improve. Interestingly, the presence of 22q11 deletion syndrome was not statistically significant in predicting worsening TV regurgitation, however our patient population is small and additional multicenter studies would be helpful.\u003c/p\u003e \u003cp\u003eIn any case, the presence of DiGeorge syndrome is associated with a series of complications that also make perioperative management more complex [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eStudies have demonstrated that Di George syndrome and congenital hearts disease have an unfavorable neurodevelopmental outcome. This appears to be more related to the presence of 22qdelation syndrome rather than to the underlying cardiac defect [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Prenatal detection of 22qDS is important. As showed by Freud et al [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], it was associated with improved delivery management and less cardiac and noncardiac morbidity, in comparison with postnatal detection.\u003c/p\u003e \u003cp\u003eWe believe that larger studies are needed to assess how genetic abnormalities impact on the Truncal valve dysplasia.\u003c/p\u003e \u003cp\u003eExisting data suggests that TV dysfunction may be an important predictor of pre-surgical mortality due to ventricular remodeling and dysfunction [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], our study findings may have an important impact on how we counsel patients with a fetal diagnosis of TA. In addition, patients who require truncal valve intervention have higher risk of mortality probably due to an increased complexity, the higher utilization of mechanical circulatory support, and longer length of stay [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], increased need for reoperation [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. One of the largest series of infant TA repair was reported by Ebert [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], of the 11 deaths in Ebert\u0026rsquo;s original series, 8 patients had moderate or greater truncal valve regurgitation. Similarly, McElhinney [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] demonstrated that a moderate or greater degree of pre-repair truncal valve regurgitation was associated with a significantly greater likelihood of later truncal valve replacement.\u003c/p\u003e \u003cp\u003ePrenatal counseling is crucial because allows time for parental decision-making regarding continuation or termination of pregnancy, prenatal genetic testing, site of delivery and postnatal cardiac care, and discussion about the option of palliative care. Having a prenatal diagnosis allows time for parents to process the emotions of shock, and disappointment and allows them to be mentally and emotionally prepared for the postnatal hospitalization and medical needs [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFrom our results we can say that when counseling fetal patients with no/mild truncal valve regurgitation, we can be somewhat reassuring that the risk of progression to more significant truncal regurgitation is fairly low.\u003c/p\u003e \u003cp\u003eAnyhow, should be considered that the regurgitation of the TA is not the only finding that contributes to the surgery complexity. These risk factors included associated interrupted aortic arch, discontinuous pulmonary arteries, comorbidities often related to the TA in relation with the genetic abnormalities [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePrenatal care should also focus on addressing other risk factors, which are likely to influence surgical complexity and overall prognosis.\u003c/p\u003e \u003cp\u003e10 patients in our study were late referral. Early diagnosis is essential in parents\u0026rsquo; decision making; this highlights the importance, whenever possible, of referring patients for a fetal echocardiogram at least in the second trimester of pregnancy.\u003c/p\u003e"},{"header":"5. Limitations","content":"\u003cp\u003eThis is a retrospective study conducted in two tertiary centers, but TA is a rare congenital heart disease and the number of patients is small. More big multicenter studies are needed to assess the fetus echocardiography predictor outcomes.\u003c/p\u003e"},{"header":"6. Conclusion","content":"\u003cp\u003eWhen truncal valve regurgitation is minimal at initial fetal echocardiogram, the risk of progression during gestation is low. Progression of truncal valve regurgitation is more likely in patients with quadricuspid or bicuspid truncal valves. In this small study, there was no statistically significant association between progression of truncal valve regurgitation and either genetic abnormalities or type of truncus arteriosus. These findings may be useful in fetal counseling for these patients with minimal truncal valve regurgitation and instead focus on other anatomic and extracardiac findings that may impact postnatal outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eN.C had the idea of the project, I:B wrote the main manuscript, M.M. and K.G helped in collected datasets. Alla authors reviwied the manuscript\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCollett RW, Edwards JE (1949) Persistent truncus arteriosus; a classification according to anatomic types. Surg Clin North Am 29:1245\u0026ndash;1270. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s0039-6109(16)32803-1\u003c/span\u003e\u003cspan address=\"10.1016/s0039-6109(16)32803-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarginean C et al (2018) Prenatal diagnosis of the fetal common arterial trunk. A case series. Med Ultrasonogr 1(1):100\u0026ndash;104\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarcelletti C, McGoon DC, Mair DD (1976) The natural history of truncus arteriosus. Circulation 54(1):108\u0026ndash;111\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeyvandi S, Lupo PJ, Garbarini J et al (2013) 22q11.2 deletions in patients with conotruncal defects: data from 1,610 consecutive cases. Pediatr Cardiol 34:1687\u0026ndash;1694\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eO\u0026rsquo;Byrne ML, Yang W, Mercer-Rosa L et al (2014) 22q11.2 Deletion syndrome is associated with increased perioperative events and more complicated postoperative course in infants undergoing infant operative correction of truncus arteriosus communis or interrupted aortic arch. J Thorac Cardiovasc Surg 148:1597\u0026ndash;1605 Epub 2014 Feb 10\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePatrick WL et al (2016) Anatomic Factors Associated With Truncal Valve Insufficiency and the Need for Truncal Valve Repair. 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Pediatr Cardiol 44(8):1649\u0026ndash;1657. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00246-023-03231-9\u003c/span\u003e\u003cspan address=\"10.1007/s00246-023-03231-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003eEpub 2023 Jul 20. PMID: 37474609\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoon-Grady, Anita J et al (2023) Guidelines and Recommendations for Performance of the Fetal Echocardiogram: An Update from the American Society of Echocardiography. J Am Soc Echocardiography: official publication Am Soc Echocardiography vol 36(7):679\u0026ndash;723\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVolpe P, Paladini D, Marasini M, Buonadonna AL, Russo MG, Caruso G, Marzullo A, Vassallo M, Martinelli P, Gentile M (2003) Common arterial trunk in the fetus: characteristics, associations, and outcome in a multicentre series of 23 cases. Heart 89(12):1437\u0026ndash;1441. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/heart.89.12.1437\u003c/span\u003e\u003cspan address=\"10.1136/heart.89.12.1437\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWillen A, Feys H, Adriaens T, Nelissen L, Mertens L, Gewillig M, Devriendt K, Fryns JP (2005) Early motor development in young children with 22q.11 deletion syndrome and a conotruncal heart defect. Dev Med Child Neurol 47:797\u0026ndash;802\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFreud LR, Galloway S, Crowley TB, Moldenhauer J, Swillen A, Breckpot J, Borrell A, Vora NL, Cuneo B, Hoffman H, Gilbert L, Nowakowska B, Geremek M, Kutkowska-Kaźmierczak A, Vermeesch JR, Devriendt K, Busa T, Sigaudy S, Vigneswaran T, Simpson JM, Dungan J, Gotteiner N, Gloning KP, Digilio MC, Unolt M, Putotto C, Marino B, Repetto G, Fadic M, Garcia-Minaur S, Ach\u0026oacute;n Buil A, Thomas MA, Fruitman D, Beecroft T, Hui PW, Oskarsdottir S, Bradshaw R, Criebaum A, Norton ME, Lee T, Geiger M, Dunnington L, Isaac J, Wilkins-Haug L, Hunter L, Izzi C, Toscano M, Ghi T, McGlynn J, Romana Grati F, Emanuel BS, Gaiser K, Gaynor JW, Goldmuntz E, McGinn DE, Schindewolf E, Tran O, Zackai EH, Yan Q, Bassett AS, Wapner R, McDonald-McGinn DM (2024) Prenatal vs postnatal diagnosis of 22q11.2 deletion syndrome: cardiac and noncardiac outcomes through 1 year of age. 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Ann Surg 200:451\u0026ndash;456\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcElhinney DB, Reddy VM, Rajasinghe HA, Mora BN, Silverman NH, Hanley FL (1998) Trends in the management of truncal valve insufficiency. Ann Thorac Surg 65:517\u0026ndash;524\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee CK (2017) Prenatal Counseling of Fetal Congenital Heart Disease. Curr Treat options Cardiovasc Med vol 19(1):5\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNaimo PS, Fricke TA, Lee MGY, d'Udekem Y, Weintraub RG, Brizard CP, Konstantinov IE (2020) Long-term outcomes following repair of truncus arteriosus and interrupted aortic arch. Eur J Cardiothorac Surg. ;57(2):366\u0026ndash;372. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/ejcts/ezz176\u003c/span\u003e\u003cspan address=\"10.1093/ejcts/ezz176\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 31209463\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 4 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pediatric-cardiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pedc","sideBox":"Learn more about [Pediatric Cardiology](http://link.springer.com/journal/246)","snPcode":"246","submissionUrl":"https://submission.nature.com/new-submission/246/3","title":"Pediatric Cardiology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Truncus arteriosus, regurgitation, fetal echocardiogram, congenital heart disease","lastPublishedDoi":"10.21203/rs.3.rs-6339803/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6339803/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTruncal valve regurgitation is a key factor impacting outcomes in patients with truncus arteriosus. Patients with moderate or greater regurgitation have elevated risk for early and late postoperative mortality. While the influence of regurgitation on postnatal outcomes is well-documented, its progression during fetal life is less understood. Our goal is to provide accurate prognostic information to parents by describing how truncal valve regurgitation evolves throughout pregnancy and whether this progression is related to cusp morphology, type of truncus arteriosus, or genetic abnormalities.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and Methods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective multicenter study includes fetuses diagnosed with truncus arteriosus between January 2003 and April 2024. We analyzed the progression of truncal valve regurgitation by comparing first and second trimester fetal echocardiograms, as well as early postnatal echocardiograms. Regurgitation was assessed semi-quantitatively and classified as none, absent, moderate, or severe. The primary endpoint was to describe how truncal valve regurgitation progresses during fetal life and to assess whether it is associated with cusp number, truncus arteriosus type, or genetic abnormalities.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOut of 56 initial fetal echocardiograms, 10 pregnancies were terminated, 4 cases were excluded due to moderate or severe regurgitation in the first trimester, 5 cases did not confirm a diagnosis of truncus arteriosus, and 4 were lost to follow-up. \u0026nbsp;Comparing the second with the third trimester fetal echocardiogram, 2 patients progressed from absent/mild to moderate. When only third trimester echocardiogram was available, due to late referral, only 1 patient progressed from absent/mild to moderate regurgitation compared with postnatal assessment.\u003c/p\u003e\n\u003cp\u003eBicuspid and quadricuspid valves were more likely to exhibit progressive regurgitation (p = 0.049), while no significant association was found with genetic abnormalities or the type of truncus arteriosus.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTruncal valve regurgitation rarely progresses during fetal life and it is more likely to occur in cases with bicuspid or quadricuspid valves. These findings may be useful in counseling families with fetuses diagnosed with minimal truncal valve regurgitation, helping to set realistic expectations regarding postnatal outcomes. The counseling can be somewhat reassuring that the risk of progression to more significant truncal regurgitation is fairly low.\u003c/p\u003e","manuscriptTitle":"Progression of Truncal Valve regurgitation during fetal life: a retrospective multicenter study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-07 03:16:55","doi":"10.21203/rs.3.rs-6339803/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-21T15:14:38+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-15T21:03:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"104478119826732746541502609165666281934","date":"2025-04-10T17:41:33+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-10T04:54:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"202809465835537191031220820663986779304","date":"2025-04-09T16:04:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"221802389071946811712088622954895841400","date":"2025-04-09T14:44:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"330423195233689811516352831298414614845","date":"2025-04-06T10:27:40+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"187920100727098229127063434798723458031","date":"2025-04-04T14:36:54+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-04T07:46:54+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-31T09:15:36+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-31T09:11:12+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pediatric Cardiology","date":"2025-03-30T17:55:28+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pediatric-cardiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pedc","sideBox":"Learn more about [Pediatric Cardiology](http://link.springer.com/journal/246)","snPcode":"246","submissionUrl":"https://submission.nature.com/new-submission/246/3","title":"Pediatric Cardiology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"34ca0e49-8597-4761-84ba-c9224279b529","owner":[],"postedDate":"May 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-11-10T16:05:37+00:00","versionOfRecord":{"articleIdentity":"rs-6339803","link":"https://doi.org/10.1007/s00246-025-04040-y","journal":{"identity":"pediatric-cardiology","isVorOnly":false,"title":"Pediatric Cardiology"},"publishedOn":"2025-11-04 15:58:11","publishedOnDateReadable":"November 4th, 2025"},"versionCreatedAt":"2025-05-07 03:16:55","video":"","vorDoi":"10.1007/s00246-025-04040-y","vorDoiUrl":"https://doi.org/10.1007/s00246-025-04040-y","workflowStages":[]},"version":"v1","identity":"rs-6339803","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6339803","identity":"rs-6339803","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}