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Measurements of fetal atrial size, shape, and contractility have been previously reported using the TomTec fetal heart speckle tracking analysis software, which currently is no longer available in the marketplace. At the present time, the only software available for speckle-tracking analysis of the fetal heart is fetalHQ, which analyzes the fetal heart ventricles using the same algorithms as the TomTec software used for speckle-tracking analysis. This communication will review how to use the fetalHQ software to measure the size, shape, and contractility of the atrial chambers., (© 2024 American Institute of Ultrasound in Medicine.)

Objective: Prediction of fetal growth restriction (FGR) and small of gestational age (SGA) infants by using various ultrasound cardiac parameters in a logistic regression model., Methods: In this retrospective study we obtained standardized ultrasound images of 357 fetuses between the 20th and 39th week of gestation, 99 of these fetuses were between the 3rd and 10th growth percentile, 61 smaller than 3rd percentile and 197- appropriate for gestational age over the 10th percentile (control group). Several cardiac parameters were studied. The cardiothoracic ratio and sphericity of the ventricles was calculated. A binary logistic regression model was developed for prediction of growth restriction using the cardiac and biometric parameters., Results: There were noticeable differences between the control and study group in the sphericity of the right ventricle (p = 0.000), left and right longitudinal ventricle length (p right  = 0.000, p left  = 0.000), left ventricle transverse length (p = 0.000), heart diameter (p = 0.002), heart circumference (p = 0.000), heart area (p = 0.000), and thoracic diameter limited by the ribs (p = 0.002). There was no difference of the cardiothoracic ratio between groups. The logistic regression model achieved a prediction rate of 79.4 % with a sensitivity of 74.5 % and specificity of 83.2 %., Conclusion: The heart of growth restricted infants is characterized by a more globular right ventricle, shorter ventricle length and smaller thorax diameter. These parameters could improve prediction of FGR and SGA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: To explore the cytological characteristics of tetralogy of Fallot (TOF), we collected samples and investigated the differences in the cytological classification between normal fetal hearts and fetal hearts with congenital defects. We then performed single-cell sequencing analysis to search for possible differential genes of disease markers., Methods: Here, the right ventricles of a heart sample with TOF and a healthy human fetal heart sample were analyzed through single-cell sequencing. Data quality control filtering, comparison, quantification, and identification of recovered cells on the raw data were performed using Cell Ranger, thereby ultimately obtaining gene expression matrices for each cell. Subsequently, Seurat was used for cell filtration, standardization, cell subgroup classification, differential expression gene analysis of each subgroup, and marker gene screening., Results: Bioinformatic analysis identified 9,979 and 15,224 cells from the healthy and diseased samples, respectively, with an average read depth of 25,000/cell. The cardiomyocyte cell populations, derived from the abnormal samples identified through the first-level graph-based analysis, were separated into six distinct cell clusters., Conclusion: Our study provides some information on TOF in a fetus, which can offer a new reference for the early detection and treatment of TOF by comparing defective heart cells with normal heart cells., (© 2024 S. Karger AG, Basel.)

Objectives: Assessment of myocardial strain by feature tracking magnetic resonance imaging (FT-MRI) in human fetuses with and without congenital heart disease (CHD) using cardiac Doppler ultrasound (DUS) gating., Methods: A total of 43 human fetuses (gestational age 28-41 weeks) underwent dynamic cardiac MRI at 3 T. Cine balanced steady-state free-precession imaging was performed using fetal cardiac DUS gating. FT-MRI was analyzed using dedicated post-processing software. Endo- and epicardial contours were manually delineated from fetal cardiac 4-chamber views, followed by automated propagation to calculate global longitudinal strain (GLS) of the left (LV) and right ventricle (RV), LV radial strain, and LV strain rate., Results: Strain assessment was successful in 38/43 fetuses (88%); 23 of them had postnatally confirmed diagnosis of CHD (e.g., coarctation, transposition of great arteries) and 15 were heart healthy. Five fetuses were excluded due to reduced image quality. In fetuses with CHD compared to healthy controls, median LV GLS (- 13.2% vs. - 18.9%; p < 0.007), RV GLS (- 7.9% vs. - 16.2%; p < 0.006), and LV strain rate (1.4 s -1 vs. 1.6 s -1 ; p < 0.003) were significantly higher (i.e., less negative). LV radial strain was without a statistically significant difference (20.7% vs. 22.6%; p = 0.1). Bivariate discriminant analysis for LV GLS and RV GLS revealed a sensitivity of 67% and specificity of 93% to differentiate between fetuses with CHD and healthy fetuses., Conclusion: Myocardial strain was successfully assessed in the human fetus, performing dynamic fetal cardiac MRI with DUS gating. Our study indicates that strain parameters may allow for differentiation between fetuses with and without CHD., Clinical Relevance Statement: Myocardial strain analysis by cardiac MRI with Doppler ultrasound gating and feature tracking may provide a new diagnostic approach for evaluation of fetal cardiac function in congenital heart disease., Key Points: • MRI myocardial strain analysis has not been performed in human fetuses so far. • Myocardial strain was assessed in human fetuses using cardiac MRI with Doppler ultrasound gating. • MRI myocardial strain may provide a new diagnostic approach to evaluate fetal cardiac function., (© 2024. The Author(s).)

Objective: To describe international surveillance and treatment strategies for managing anti-SSA/Ro autoantibody positive pregnancies., Study Design: An electronic REDCap questionnaire was distributed to Fetal Heart Society and North American Fetal Therapy Network members which queried institution-based risk stratification, surveillance methods/frequency, conduction abnormality treatments, and postnatal anti-SSA/Ro pregnancy assessment., Results: 101 responses from 59 centers (59% US, 17% international) were collected. Most (79%) do not risk stratify pregnancies by anti-SSA/Ro titer; those that do use varied cutoff values. Many pregnant rheumatology patients are monitored for cardiac abnormalities regardless of maternal anti-SSA/Ro status. Surveillance strategies were based on maternal factors (anti-SSA/Ro status 85%, titer 25%, prior affected child 79%) and monitoring durations varied. Most respondents treat 2° and 3° fetal atrioventricular block, commonly with dexamethasone and/or IVIG., Conclusions: Wide variation exists in current fetal cardiac surveillance and treatment for anti-SSA/Ro autoantibody positive pregnancies, highlighting the need for evidence-based protocols to optimize care.

The heart is the central organ of the circulatory system, and its proper development is vital to maintain human life. As fetal heart development is complex and poorly understood, we use single-cell RNA sequencing to profile the gene expression landscapes of human fetal hearts from the four-time points: 8, 10, 11, 17 gestational weeks (GW8, GW10, GW11, GW17), and identified 11 major types of cells: erythroid cells, fibroblasts, heart endothelial cells, ventricular cardiomyocytes, atrial cardiomyocytes, macrophage, DCs, smooth muscle, pericytes, neural cells, schwann cells. In addition, we identified a series of differentially expressed genes and signaling pathways in each cell type between different gestational weeks. Notably, we found that ANNEXIN, MIF, PTN, GRN signalling pathways were simple and fewer intercellular connections in GW8, however, they were significantly more complex and had more intercellular communication in GW10, GW11, and GW17. Notably, the interaction strength of OSM signalling pathways was gradually decreased during this period of time (from GW8 to GW17). Together, in this study, we presented a comprehensive and clear description of the differentiation processes of all the main cell types in the human fetal hearts, which may provide information and reference data for heart regeneration and heart disease treatment., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

This study presents the initial results of a pilot project using the Elucis Virtual Reality (VR) platform for fetal heart segmentation. Twelve fetal heart cases, ranging in gestational age from 24 to 30 weeks, including various cardiac conditions, were reconstructed using 3D models facilitated by the Elucis platform's integration of automated algorithms and manual adjustments. The models, which were evaluated by four experts in virtual and 3D printed formats, were of high quality and offered improved visuospatial visualization and detailed anatomical insights. This research highlights the potential of VR technology to improve prenatal diagnosis and planning for complex cardiac conditions, suggesting significant implications for continuing medical education and clinical practice in fetal cardiology., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Fetuses affected by intrauterine growth restriction have an increased risk of developing heart disease and failure in adulthood. Compared with controls, late gestation intrauterine growth-restricted (IUGR) fetal sheep have fewer binucleated cardiomyocytes, reflecting a more immature heart, which may reduce mitochondrial capacity to oxidize substrates. We hypothesized that the late gestation IUGR fetal heart has a lower capacity for mitochondrial oxidative phosphorylation. Left (LV) and right (RV) ventricles from IUGR and control (CON) fetal sheep at 90% gestation were harvested. Mitochondrial respiration (states 1-3, Leak Omy , and maximal respiration) in response to carbohydrates and lipids, citrate synthase (CS) activity, protein expression levels of mitochondrial oxidative phosphorylation complexes (CI-CV), and mRNA expression levels of mitochondrial biosynthesis regulators were measured. The carbohydrate and lipid state 3 respiration rates were lower in IUGR than CON, and CS activity was lower in IUGR LV than CON LV. However, relative CII and CV protein levels were higher in IUGR than CON; CV expression level was higher in IUGR than CON. Genes involved in lipid metabolism had lower expression in IUGR than CON. In addition, the LV and RV demonstrated distinct differences in oxygen flux and gene expression levels, which were independent from CON and IUGR status. Low mitochondrial respiration and CS activity in the IUGR heart compared with CON are consistent with delayed cardiomyocyte maturation, and CII and CV protein expression levels may be upregulated to support ATP production. These insights will provide a better understanding of fetal heart development in an adverse in utero environment. KEY POINTS: Growth-restricted fetuses have a higher risk of developing and dying from cardiovascular diseases in adulthood. Mitochondria are the main supplier of energy for the heart. As the heart matures, the substrate preference of the mitochondria switches from carbohydrates to lipids. We used a sheep model of intrauterine growth restriction to study the capacity of the mitochondria in the heart to produce energy using either carbohydrate or lipid substrates by measuring how much oxygen was consumed. Our data show that the mitochondria respiration levels in the growth-restricted fetal heart were lower than in the normally growing fetuses, and the expression levels of genes involved in lipid metabolism were also lower. Differences between the right and left ventricles that are independent of the fetal growth restriction condition were identified. These results indicate an impaired metabolic maturation of the growth-restricted fetal heart associated with a decreased capacity to oxidize lipids postnatally., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

Background: Novel ultrasound technology and software processing allow offline evaluation of tricuspid annular plane systolic excursion and mitral annular plane systolic excursion measurements. We wished to compare both novel 4D matrix (eM6C) and conventional (RAB6-D) transducers with variable settings (electronic spatiotemporal image correlation, spatiotemporal image correlation and four-dimensional real time) to determine if there was a significant difference in absolute value, quality and repeatability of the resultant reconstructed image and M-mode trace., Methods: A blinded prospective cross-sectional study of normal fetuses from 23 to 38 weeks' gestation were recruited. After routine sonography, four-dimensional volumes were stored and analysed using GE 4DView™ software. Statistical analysis explored variability, correlations and repeatability of the measurements with chi-square analysis, intraclass correlations and the Bland-Altman comparison plots. A scoring system was devised for image quality., Results: Eighteen participants generated 282 data volumes. Absolute values demonstrated some inconsistencies for both tricuspid annular plane systolic excursion and mitral annular plane systolic excursion measurements with variations between transducers: the highest for the RAB6-D/spatiotemporal image correlation setting and the lowest for the four-dimensional real-time settings. The RAB6-D/spatiotemporal image correlation setting was the most repeatable combination (intraclass correlation coefficient = 0.85). Poorest image quality (M-mode trace, four-chamber view, annuli) came from the RAB6-D/four-dimensional real-time combination with the eM6C/electronic spatiotemporal image correlation and RAB6-D/spatiotemporal image correlation settings being nearly identical., Conclusion: We show that transducer and setting combinations influence absolute tricuspid annular plane systolic excursion/mitral annular plane systolic excursion measurements, so need to be articulated in future research. The transducer setting (electronic spatiotemporal image correlation/spatiotemporal image correlation/four-dimensional real time) was a more significant factor than the type of transducer (conventional vs matrix). Subjective image evaluation does not correlate well with repeatability of image acquisition. Further studies are needed to compare measurements using four-dimensional post-processing tools against conventional real-time measurements., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s) 2024.)

This article comprehensively reviews the literature concerning prenatal ultrasound findings of isolated total anomalous pulmonary venous return (TAPVR) and the application of specific sonographic markers to differentiate among the TAPVR types. These markers can be categorized as direct and indirect, based on either morphological features or hemodynamic changes in TAPVR. Indirect markers include the ventricular disproportion, an increased distance between the left atrium (LA) and the descending aorta, as well as the dilatation of superior vena cava or coronary sinus for supracardiac or cardiac TAPVR, along with abnormal pulmonary venous spectral Doppler patterns. Direct markers predominantly focus on the absence of a connection between the pulmonary veins and the LA. Some direct markers are specific to certain TAPVR types, such as the vertical vein. Diagnosing isolated TAPVR can pose challenges, but following a sequential approach can improve detection rates and outcomes. In cases with equivocal findings, additional follow-ups are recommended. The sequential approach described in the current article provides a step-wise methodology and sonographic markers for prenatal diagnosis of TAPVR, which can be utilized by fetal-maternal medicine specialists, obstetricians, and radiological technicians to ensure timely interventions., Competing Interests: Dr. Tung-Yao Chang, an editor at Journal of Medical Ultrasound, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper., (Copyright: © 2024 Journal of Medical Ultrasound.)

Purpose: In adults and fetuses, N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a marker of cardiac failure and myocardial remodelling. We examined the effect of anemia and intrauterine transfusion (IUT) on NT-proBNP concentrations in fetuses with anemia and established gestational age-dependent reference values of a control group., Methods: We analyzed NT-proBNP levels in anemic fetuses that underwent serial intrauterine transfusions (IUT), focusing on different causes and severity of anemia and comparing the results to a non-anemic control group., Results: In the control group, the average NT-proBNP concentration was 1339 ± 639 pg/ml, decreasing significantly with increasing gestational age (R = - 74.04, T = - 3.65, p = 0.001). Subjects had significantly higher NT-proBNP concentrations before initiation of IUT therapy (p < 0.001), showing fetuses with parvovirus B19 (PVB19) infection having the highest concentrations. Hydropic fetuses also showed an increased NT-proBNP concentration compared to non-hydropic fetuses (p < 0.001). During the course of therapy, NT-proBNP concentration before subsequent IUT decreased significantly from pathologically high levels, while MoM-Hb and MoM-MCA-PSV remained pathological., Conclusion: NT-pro BNP levels in non-anemic fetuses are higher than in postnatal life, decreasing with ongoing pregnancy. Anemia is a hyperdynamic state and its severity correlates with circulating NT-proBNP levels. Highest concentrations occur in fetuses with hydrops and with PVB19 infection, respectively. Treatment by IUT leads to a normalisation of NT-proBNP concentrations, so the measurement of its levels may be useful in therapy monitoring., (© 2023. The Author(s).)

Gestational hypoxia inhibits mitochondrial function in the fetal heart and placenta contributing to fetal growth restriction and organ dysfunction. NAD + deficiency may contribute to a metabolic deficit by inhibiting oxidative phosphorylation and ATP synthesis. We tested the effects of nicotinamide riboside (NR), an NAD + precursor, as a treatment for reversing known mitochondrial dysfunction in hypoxic fetal hearts. Pregnant guinea pigs were housed in room air (normoxia) or placed in a hypoxic chamber (10.5%O 2 ) for the last 14 days of gestation (term = 65 days) and administered either water or NR (1.6 mg/ml) in the drinking bottle. Fetuses were excised at term, and NAD + levels of maternal liver, placenta, and fetal heart ventricles were measured. Indices of mitochondrial function (complex IV activity, sirtuin 3 activity, protein acetylation) and ATP synthesis were measured in fetal heart ventricles of NR-treated/untreated normoxic and hypoxic animals. Hypoxia reduced fetal body weight in both sexes (p = 0.01), which was prevented by NR. Hypoxia had no effect on maternal liver NAD + levels but decreased (p = 0.04) placenta NAD + levels, the latter normalized with NR treatment. Hypoxia had no effect on fetal heart NAD + but decreased (p < 0.05) mitochondrial complex IV and sirtuin 3 activities, ATP content, and increased mitochondrial acetylation, which were all normalized with maternal NR. Hypoxia increased (p < 0.05) mitochondrial acetylation in female fetal hearts but had no effect on other mitochondrial indices. We conclude that maternal NR is an effective treatment for normalizing mitochondrial dysfunction and ATP synthesis in the hypoxic fetal heart., (© 2023. The Author(s).)

Fetal sex has been associated with different development trajectories that cause structural and functional differences between the sexes throughout gestation. Fetal magnetocardiography (fMCG) recordings from 123 participants (64 females and 59 males; one recording/participant) from a database consisting of low-risk pregnant women were analyzed to explore and compare fetal development trajectories of both sexes. The gestational age of the recordings ranged from 28 to 38 weeks. Linear metrics in both the time and frequency domains were applied to study fetal heart rate variability (fHRV) measures that reveal the dynamics of short- and long-term variability. Rates of linear change with GA in these metrics were analyzed using general linear model regressions with assessments for significantly different variances and GA regression slopes between the sexes. The fetal sexes were well balanced for GA and sleep state. None of the fHRV measures analyzed exhibited significant variance heterogeneity between the sexes, and none of them exhibited a significant sex-by-GA interaction. The absence of a statistically significant sex-by-GA interaction on all parameters resulted in none of the regression slope estimates being significantly different between the sexes. With high-precision fMCG recordings, we were able to explore the variation in fHRV parameters as it relates to fetal sex. The fMCG-based fHRV parameters did not show any significant difference in rates of change with gestational age between sexes. This study provides a framework for understanding normal development of the fetal autonomic nervous system, especially in the context of fetal sex., (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Introduction: Cannabis is increasingly being consumed by pregnant women for recreational purposes as well as for its antiemetic and anxiolytic effects despite limited studies on its safety during pregnancy. Importantly, phytocannabinoids found in cannabis can pass through the placenta and enter the fetal circulation. Recent reports suggest gestational cannabis use is associated with negative fetal outcomes, including fetal growth restriction and perinatal intensive care, however, the effects of delta-9-tetrahydrocannabinol (THC) on fetal heart development remains to be elucidated. Materials and Methods: We aimed to determine the outcomes of maternal THC exposure on fetal heart development in mice by administering 0, 5, or 10 mg/kg/day of THC orally to C57BL/6 dams starting at embryonic day (E)3.5. Offspring were collected at E12.5 for molecular analysis, at E17.5 to analyze cardiac morphology or at postnatal day (PND)21 to assess heart function. Results: Maternal THC exposure in E17.5 fetuses resulted in an array of cardiac abnormalities with an incidence of 44% and 55% in the 5 and 10 mg/kg treatment groups, respectively. Maternal THC exposure in offspring resulted in ventricular septal defect, higher semilunar valve volume relative to orifice ratio, and higher myocardial wall thickness. Notably, cell proliferation within the ventricular myocardium was increased, and expression of multiple cardiac transcription factors was downregulated in THC-exposed E12.5 fetuses. Furthermore, heart function was compromised with lower left ventricular ejection fraction, fractional shortening, and cardiac output in PND21 pups exposed to THC compared to controls. Discussion: The results show that maternal THC exposure during gestation induces myocardial hyperplasia and semilunar valve thickening in the fetal heart and postnatal cardiac dysfunction. Our study suggests that maternal cannabis consumption may induce abnormalities in the developing heart and cardiac dysfunction in postnatal life.

Fetal critical aortic stenosis with evolving hypoplastic left heart syndrome (CAS-eHLHS) causes biomechanical and functional aberrations, leading to a high risk of progression to hypoplastic left heart syndrome (HLHS) at birth. Fetal aortic valvuloplasty (FAV) can resolve outflow obstruction and may reduce progression risk. However, it is currently difficult to accurately predict which patients will respond to the intervention and become functionally biventricular (BV) at birth, as opposed to becoming functionally univentricular (UV). This prediction is important for patient selection, parental counselling, and surgical planning. Therefore, we investigated whether biomechanics parameters from pre-FAV image-based computations could robustly distinguish between CAS-eHLHS cases with BV or UV outcomes in a retrospective cohort. To do so we performed image-based finite element biomechanics modelling of nine CAS-eHLHS cases undergoing intervention and six healthy fetal control hearts, and found that a biomechanical parameter, peak systolic myofibre stress, showed a uniquely large difference between BV and UV cases, which had a larger magnitude effect than echocardiography parameters. A simplified equation was derived for quick and easy estimation of myofibre stress from echo measurements via principal component analysis. When tested on a retrospective cohort of 37 CAS-eHLHS cases, the parameter outperformed other parameters in predicting UV versus BV outcomes, and thus has a high potential of improving outcome predictions, if incorporated into patient selection procedures. Physiologically, high myocardial stresses likely indicate a healthier myocardium that can withstand high stresses and resist pathological remodelling, which can explain why it is a good predictor of BV outcomes. KEY POINTS: Predicting the morphological birth outcomes (univentricular versus biventricular) of fetal aortic valvuloplasty for fetal aortic stenosis with evolving HLHS is important for accurate patient selection, parental counselling and management decisions. Computational simulations show that a biomechanics parameter, pre-intervention peak systolic myofibre stress, is uniquely robust in distinguishing between such outcomes, outperforming all echo parameters. An empirical equation was developed to quickly compute peak systolic myofibre stress from routine echo measurements and was the best predictor of outcomes among a wide range of parameters tested., (© 2024 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Congenital heart disease (CHD) accounts for nearly one-third of all congenital defects, and patients often require repeated heart valve replacements throughout their lives, due to failed surgical repairs and lack of durability of bioprosthetic valve implants. This objective of this study is to develop and in vitro test a fetal transcatheter pulmonary valve replacement (FTPVR) using sutureless techniques to attach leaflets, as an option to correct congenital defects such as pulmonary atresia with intact ventricular septum (PA/IVS), in utero. A balloon expandable design was analyzed using computational simulations to identify areas of failure. Five manufactured valves were assembled using the unique sutureless approach and tested in the fetal right heart simulator (FRHS) to evaluate hemodynamic characteristics. Computational simulations showed that the commissural loads on the leaflet material were significantly reduced by changing the attachment techniques. Hemodynamic analysis showed an effective orifice area of 0.08 cm 2 , a mean transvalvular pressure gradient of 7.52 mmHg, and a regurgitation fraction of 8.42%, calculated over 100 consecutive cardiac cycles. In conclusion, the FTPVR exhibited good hemodynamic characteristics, and studies with biodegradable stent materials are underway., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Objectives: Right aortic arch (RAA) is a rare anomaly with an incidence of 0.1 % in the adult population and low-risk fetuses. Our aim in this study was to evaluate associated anomalies and conditions according to subtypes., Methods: This was a retrospective study examining consecutive pregnancies diagnosed with RAA in our hospital between 2018 and 2022. Fetuses with RAA were divided into three groups, RAA with right-sided ductus arteriosus (RAA-RDA), RAA with left-sided ductus arteriosus (RAA-LDA), and RAA with a double aortic arch (RAA-DAA)., Results: A total of 81 fetuses were diagnosed as having RAA during the study period. The rate of cardiac anomalies (82.8 %) in the RAA-RDA group was higher than in the RAA-LDA (17.6 %) and RAA-DAA (22.2 %) groups (p<0.001). No statistically significant difference was found between the groups in terms of maternal age, diagnosis week, pregnancy outcome, extracardiac anomalies, and genetic anomalies. Three (8 %) of 36 fetuses with isolated RAA who resulted in live birth developed symptoms related to the vascular ring, and one (2.7 %) newborn with RAA-DAA underwent surgery., Conclusions: The incidence of cardiac anomalies is high in fetuses with RAA-RDA. Ultrasound examinations should be performed for cardiac anomalies and additional structural anomalies. Vascular ring formation is a rare but important complication due to compression risk to the trachea and esophagus., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Background: The ultrasound scan represents the first tool that obstetricians use in fetal evaluation, but sometimes, it can be limited by mobility or fetal position, excessive thickness of the maternal abdominal wall, or the presence of post-surgical scars on the maternal abdominal wall. Artificial intelligence (AI) has already been effectively used to measure biometric parameters, automatically recognize standard planes of fetal ultrasound evaluation, and for disease diagnosis, which helps conventional imaging methods. The usage of information, ultrasound scan images, and a machine learning program create an algorithm capable of assisting healthcare providers by reducing the workload, reducing the duration of the examination, and increasing the correct diagnosis capability. The recent remarkable expansion in the use of electronic medical records and diagnostic imaging coincides with the enormous success of machine learning algorithms in image identification tasks., Objectives: We aim to review the most relevant studies based on deep learning in ultrasound anomaly scan evaluation of the most complex fetal systems (heart and brain), which enclose the most frequent anomalies.

A well-developed heart is essential for embryonic survival. There are constant interactions between cardiac tissue motion and blood flow, which determine the heart shape itself. Hemodynamic forces are a powerful stimulus for cardiac growth and differentiation. Therefore, it is particularly interesting to investigate how the blood flows through the heart and how hemodynamics is linked to a particular species and its development, including human. The appropriate patterns and magnitude of hemodynamic stresses are necessary for the proper formation of cardiac structures, and hemodynamic perturbations have been found to cause malformations via identifiable mechanobiological molecular pathways. There are significant differences in cardiac hemodynamics among vertebrate species, which go hand in hand with the presence of specific anatomical structures. However, strong similarities during development suggest a common pattern for cardiac hemodynamics in human adults. In the human fetal heart, hemodynamic abnormalities during gestation are known to progress to congenital heart malformations by birth. In this chapter, we discuss the current state of the knowledge of the prenatal cardiac hemodynamics, as discovered through small and large animal models, as well as from clinical investigations, with parallels gathered from the poikilotherm vertebrates that emulate some hemodynamically significant human congenital heart diseases., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

In prenatal ultrasound screening, rapid and accurate recognition of the fetal heart ultrasound standard planes(FHUSPs) can more objectively predict fetal heart growth. However, the small size and movement of the fetal heart make this process more difficult. Therefore, we design a deep learning-based FHUSP recognition network (FHUSP-NET), which can automatically recognize the five FHUSPs and detect tiny key anatomical structures at the same time. 3360 ultrasound images of five FHUSPs from 1300 mid-pregnancy pregnant women are included in this study. 10 fetal heart key anatomical structures are manually annotated by experts. We apply spatial pyramid pooling with a fully connected spatial pyramid convolution module to capture information about targets and scenes of different sizes as well as improve the perceptual ability and feature representation of the model. Additionally, we adopt the squeeze-and-excitation networks to improve the sensitivity of the model to the channel features. We also introduce a new loss function, the efficient IOU loss, which makes the model effective for optimizing similarity. The results demonstrate the superiority of FHUSP-NET in detecting fetal heart key anatomical structures and recognizing FHUSPs. In the detection task, the value of mAP@0.5, precision, and recall are 0.955, 0.958, and 0.931, respectively, while the accuracy reaches 0.964 in the recognition task. Furthermore, it takes only 13.6 ms to detect and recognize one FHUSP image. This method helps to improve ultrasonographers' quality control of the fetal heart ultrasound standard plane and aids in the identification of fetal heart structures in a less experienced group of physicians., Competing Interests: Declaration of competing interest We declare that we have no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The objective of this study was to assess the ascending and descending aorta area measurements by three-dimensional (3D) ultrasound using spatiotemporal image correlation (STIC) in the rendering mode comparing these measurements with pregestational diabetic mothers and assessing the reproducibility of the method., Methods: We carried out a retrospective cross-sectional study with 58 normal and nine fetuses from pregestational diabetic mothers between 20 and 33 + 6 weeks of gestation. Fetal heart volumes were acquired at the level of four-chamber view to obtain the reconstructed planes for the ascending and descending aorta areas in the rendering mode. Linear regression was performed to assess the correlation between the fetal aorta areas and gestational age (GA). To assess the intra- and interobserver reproducibility, we used the concordance correlation coefficient (CCC)., Results: The mean ascending and descending aorta areas were 0.12 (0.02-0.48) and 0.11 (0.04-0.39) cm 2 in normal fetuses, respectively. There was a moderate positive correlation between GA and ascending aorta area measurements (0.005676*GA - 0.01283; r = 0.53, P < 0.0001) and strong positive correlation between GA and descending aorta area (0.01095*GA - 0.1581; r = 0.68, P < 0.0001). We observed a weak intra- and interobserver reproducibility with CCC ranging from 0.05 to 0.91. The mean difference in the ascending and descending aorta area measurements of normal and fetuses of pregestational diabetic mothers was -0.03 cm 2 ( P = 0.276) and -0.03 cm 2 ( P = 0.231), respectively., Conclusion: The fetal ascending and descending aorta area measurements obtained by 3D ultrasound using STIC in the rendering mode increased with GA in normal fetuses. The method showed weak intra- and interobserver reproducibility., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Medical Ultrasound.)

Purpose: Fetal macrosomia may have serious effects on both mother and newborn, so it is important to correctly evaluate the fetal weight before delivery. Fetal routine biometry, height of the fundus of uterus, interventricular septal thickness seems to be very good but still not perfect. In our study the relation between fetal biventricular (AP) diameter and fetal foot length was elaborated in the 2nd and 3rd trimester of pregnancy., Material and Methods: The analyzed group ( n  = 423 fetuses) was divided into 2 subgroups: a control group ( n  = 109 fetuses) with normal biometry, normal heart anatomy and normal cardiac function, no extracardiac malformation, no extracardiac anomalies, gestational age ranged from 17.5 to 37.1 weeks of gestation, born at term with birth weight 3000-3600 g, and a study group ( n  = 314 fetuses) with gestational age 17.5-39.5 weeks. Among the study group there were 20 patients ( n  = 20 fetuses) with macrosomia defined as a neonatal birth weight of greater than or equal to 4000 g. The control group was used to generate normograms on fetal AP, foot length and AP/Foot Index. The Statistica 13.3 and Excel 365 software were used to calculate the sensitivity, specificity, positive predictive value and negative predictive values., Results: In control group, the mean biventricular fetal heart (AP) measurement was 23 mm (12.9 mm-38 mm), the mean foot length was 43 mm (24 mm-71 mm), and the mean AP/Foot Index was 0.52 (0.40-0.65). The value of the AP/Foot Index in the second trimester of the control group was 0.53, whereas the AP/Foot Index in the third trimester of pregnancy was 0.51. The use of standard fetal biometry resulted in the prediction of macrosomia in 20%, whereas the AP/Foot index in addition to standard fetal biometry enabled the detection of 65% of macrosomia., Conclusions: The AP/Foot Index higher than 0.52 has greater sensitivity and negative predictive value to detect macrosomia compared to standard ultrasound fetal biometry.

The purpose of this article is to describe the evaluation of a variety of congenital heart diseases (CHDs) using three-dimensional (3D) ultrasound with different software, such as Cristal Vue, Realistic Vue, LumiFlow, and Spatiotemporal Image Correlation (STIC), with HDlive and HDlive Flow Silhouette modes. These technologies provide realistic images of the fetal heart and cardiac vessels using a fixed virtual light source that allows the operator to freely select a better light source position to enhance the cardiovascular anatomical details. In addition, Fetal Intelligent Navigation Echocardiography (FINE) technology, also known as "5D Heart" or "5D", is a technology that enables the automatic reconstruction of the nine standard fetal echocardiographic views and can alert non-specialists to suspected CHD. Through the use of artificial intelligence, an ultrasound machine is able to perform automatic anatomical and functional measurements. In addition, hese technologies enable the reconstruction of fetal cardiac structures in realistic images, improving the depth perception and resolution of anatomic cardiac details and blood vessels compared to those of standard two-dimensional (2D) ultrasound.

Introduction: This study aims to investigate non-invasive electrocardiography as a method for the detection of congenital heart disease (CHD) with the help of artificial intelligence., Material and Methods: An artificial neural network was trained for the identification of CHD using non-invasively obtained fetal electrocardiograms. With the help of a Bayesian updating rule, multiple electrocardiographs were used to increase the algorithm's performance., Results: Using 122 measurements containing 65 healthy and 57 CHD cases, the accuracy, sensitivity, and specificity were found to be 71%, 63%, and 77%, respectively. The sensitivity was however 75% and 69% for CHD cases requiring an intervention in the neonatal period and first year of life, respectively. Furthermore, a positive effect of measurement length on the detection performance was observed, reaching optimal performance when using 14 electrocardiography segments (37.5 min) or more. A small negative trend between gestational age and accuracy was found., Conclusions: The proposed method combining recent advances in obtaining non-invasive fetal electrocardiography with artificial intelligence for the automatic detection of CHD achieved a detection rate of 63% for all CHD and 75% for critical CHD. This feasibility study shows that detection rates of CHD might improve by using electrocardiography-based screening complementary to the standard ultrasound-based screening. More research is required to improve performance and determine the benefits to clinical practice., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objectives: Blood-flow pattern is an essential factor in cardiovascular development. Recently, blood speckle-tracking echocardiography (BST) based on high-frame-rate ultrasound has emerged as a promising technique for the assessment of blood-flow patterns and properties. The objectives of this study were to determine the feasibility of BST in the fetus and to assess intracardiac blood-flow patterns of fetuses with a congenital heart defect (CHD) using this technique., Methods: This was a prospective study consisting of 35 normal fetuses, 35 fetuses with left-sided obstructive lesion (LSOL) and 35 fetuses with right-sided obstructive lesion (RSOL). BST images of fetal intracardiac regions of interest (ROIs), including the left ventricle (LV), right ventricle (RV), ascending aorta (AAo), aortic arch (AA), descending aorta (DAo) and pulmonary artery (PA), were obtained and analyzed. The feasibility of BST was assessed, and blood-flow pattern and number of vortices in the ROIs were recorded., Results: The median gestational age of the fetuses was 24.7 weeks (range, 19.6-34.3 weeks). BST was feasible in 81.6% of cases, and the cut-off value of depth for an adequate BST image was ≤ 7.9 cm. There were no differences in the presence of vortex/turbulent blood flow in the LV or RV among the three groups. Vortex/turbulent blood flow in the AAo was detected in 0% (0/35), 14.3% (5/35) and 57.1% (20/35) of cases in the control, LSOL and RSOL groups, respectively. The respective values were 5.7% (2/35), 14.3% (5/35) and 51.4% (18/35) for the AA; 0% (0/35), 48.6% (17/35) and 0% (0/35) for the DAo; and 0% (0/35), 40.0% (14/35) and 51.4% (18/35) for the PA. With the exception of the DAo in the RSOL group, vortex/turbulent flow in the great artery ROIs was significantly more common in the LSOL and RSOL groups than in controls (P < 0.01). In the LSOL group, the number of vortices in the AAo, AA, DAo and PA was significantly greater compared with that in controls (P < 0.01). In the RSOL group, the number of vortices in the LV, AAo, AA and PA was significantly greater compared with that in controls (P < 0.01)., Conclusions: Fetuses with CHD were more likely to exhibit vortex/turbulent blood flow and increased number of vortices in the great arteries compared with healthy controls. Further research is needed to determine the biomechanical effect of blood-flow patterns, especially vortex flow, on fetal cardiovascular structure and function. © 2023 International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 International Society of Ultrasound in Obstetrics and Gynecology.)

Congenital heart disease (CHD) is the leading cause of death from malformations in the first year of life and carries a significant burden to the family when the diagnosis is made in the prenatal period. We recognize the significance of family counseling following a fetal CHD diagnosis. However, we have observed that most research focuses on assessing the emotional state of family members rather than examining the counseling process itself. The objective of this study was to identify and summarize the findings in the literature on family counseling in cases of diagnosis of CHD during pregnancy, demonstrating gaps and suggesting future research on this topic. Eight databases were searched to review the literature on family counseling in cases of CHD diagnosis during pregnancy. A systematic search was conducted from September to October 2022. The descriptors were "congenital heart disease", "fetal heart", and "family counseling". The inclusion criteria were studies on counseling family members who received a diagnosis of CHD in the fetus (family counseling was defined as any health professional who advises mothers and fathers on the diagnosis of CHD during the gestational period), how the news is expressed to family members (including an explanation of CHD and questions about management and prognosis), empirical and qualitative studies, quantitative studies, no publication deadline, and any language. Out of the initial search of 3719 reports, 21 articles were included. Most were cross-sectional (11) and qualitative (9) studies, and all were from developed countries. The findings in the literature address the difficulties in effectively conducting family counseling, the strengths of family counseling to be effective, opportunities to generate effective counseling, and the main challenges in family counseling.

The objective of the present study was to demonstrate the blood flow velocities, blood flow rate (BFR; bpm) with the accurate ratio of both systolic and diastolic velocities points (S/D) in addition to Doppler indices (resistive and pulsatility index [RI and PI]) in both fetal [fetal heart (FH), fetal abdominal aorta (Ab. A), and umbilical artery (UM.A)] and maternal [Middle uterine artery (MU.A)] sides during the last month of gestation. Ten Zaraibi (Egyptian Nubian) goats weighing 40-50kg and aged from 5-7 years were examined twice per month till reached the last month of pregnancy. Then all females were examined every 5 days starting from day -35 till day -1 before kidding.The pregnant goats were examined by ultrasonic and Doppler indices were recorded with Doppler scanning (7.5 -12 MHz, with colored and spectral graph to form the perfect wave to assess Doppler measurements). The obtained data were analyzed using analysis of variance. Results indicated that on the fetal side; the maximum point of velocity (MSV; cm/sec) in the FH and BFRwere elevated from day -35 till day -10 with a slight decline at days -5 and -1 at the peripartum period (P < 0.05), while FH.PI and S/D ratio declined till day -1(P < 0.05). In addition, the fetal Ab. A, and UM.A PI, RI, and S/D ratio declined from day -35 till day -1 at the peripartum period with a significant increase in the peak systolic velocity (PSV) and BFR(P < 0.05). However, non-significant changes in the end diastolic velocity (EDV) were detected. On the maternal side, the MU.A PI and S/D declined from day -35 till day -1 with an elevation of both PSV and BFRat the same time points (P < 0.05). In conclusion, the Doppler evaluation of fetal and maternal blood flow vessels is important to give complete information that directly affects the health status of the mother and fetus., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Study Question: Do spontaneously conceived (SC) fetuses from subfertile couples show the same signs of cardiac remodeling as those observed after IVF treatments?, Summary Answer: As opposed to fetuses from IVF, SC fetuses from subfertile couples do not show cardiac remodeling and present a similar cardiac structure and function to those of SC fetuses from fertile couples., What Is Known Already: Subjects conceived by IVF present signs of cardiac remodeling and suboptimal function in utero and during childhood, including larger atria, more globular and thicker ventricles, reduced longitudinal motion, and impaired relaxation as compared to SC individuals from fertile couples. There are no previous publications investigating the independent cardiac programming effects of infertility in SC fetuses from subfertile couples (with time-to-pregnancy (TTP) over 12 months)., Study Design, Size, Duration: A prospective cohort study of 289 singleton pregnancies exposed and not exposed to subfertility recruited from 2019 to 2021, including 96 SC pregnancies from fertile couples (TTP under 12 months), 97 SC from subfertile couples (TTP over 12 months), and 96 from IVF after fresh embryo transfer. Fetal echocardiography was performed in all pregnancies. Epidemiological data and perinatal outcomes were collected in all pregnancies. The overall attrition rate was 15.7%., Participants/materials, Setting, Methods: SC from subfertile couples and IVF pregnancies were identified as eligible at pregnancy diagnosis, and eligible SC pregnancies from fertile couples who attended our maternal-fetal unit were invited to participate at third trimester, being matched to the other groups by maternal age. Fetal echocardiography was performed at 29-34 weeks of pregnancy to assess cardiac structure and function, and results were adjusted by parental age, maternal smoking status, child's birth order, birthweight centile, gestational age, and estimated fetal weight at scan., Main Results and the Role of Chance: Parental age, ethnicity, BMI, and smoking exposure, median gestational age and estimated fetal weight were similar in all study groups. There were no significant differences in infertility duration or etiology between the subfertile and the IVF populations (TTP: subfertile median 35 months (interquartile range 20-48) versus IVF: 47 (25-61); P-value = 0.051). While both fertile and subfertile SC groups presented similar fetal cardiac results, IVF fetuses showed larger atria (right atria-to-heart ratio: IVF mean 18.9% (SD 3.4) versus subfertile 17.8% (3.5) versus fertile 17.6% (3.3); adjusted P-value < 0.001), more globular ventricles (right ventricular sphericity index: IVF 1.56 (0.25) versus subfertile 1.72 (0.26) versus fertile 1.72 (0.26); <0.001), and thicker myocardial walls (relative wall thickness: IVF 0.86 (0.22) versus subfertile 0.64 (0.13) versus fertile 0.64 (0.18); <0.001). Whereas SC fetuses from fertile and subfertile couples had preserved cardiac function, IVF fetuses showed signs of suboptimal systolic and diastolic function, with reduced tricuspid ring displacement (IVF 7.26 mm (1.07) versus subfertile 8.04 mm (1.18) versus fertile 7.89 mm (1.51); <0.001) and increased left myocardial performance index (IVF 0.49 (0.08) versus subfertile 0.45 (0.09) versus fertile 0.45 (0.10); <0.001). A sub-analysis including only unexplained infertility cases in subfertile SC and IVF groups showed similar results., Limitations, Reasons for Caution: The fetal cardiac changes reported here are subclinical, and most of the cardiovascular parameters were within normal ranges. Although echocardiographic changes are recognized as potential cardiovascular risk factors, their association with long-term cardiovascular disease remains to be demonstrated., Wider Implications of the Findings: Subfertility per se does not seem to be associated to fetal cardiac remodeling, which has been previously described in IVF fetuses. Future studies are warranted to further investigate other factors related to the observed fetal cardiac changes associated with ART., Study Funding/competing Interest(s): This project has been partially funded with support from the Erasmus + Programme of the European Union (Framework Agreement number: 2013-0040). This publication reflects the views only of the author, and the Commission cannot be held responsible for any use, which may be made of the information contained therein. Additionally, the research leading to these results has received funding from 'la Caixa' Foundation under grant agreement LCF/PR/GN18/10310003, the Instituto de Salud Carlos III (PI15/00130, PI16/00861, PI17/00675, PI18/00073, INT21/00027)-co-funded by the European Union, Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK) and AGAUR 2017 SGR grant no 1531. The authors have no conflicts of interest to declare., Trial Registration Number: N/A., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The fetal pulmonary circulation represents less than 25% of the fetal cardiac output. In comparison with the pulmonary arteries, studies on pulmonary veins are few and limited, and many questions remain to be answered. The literature reports that pulmonary veins play an important role in regulating vascular flow, forming an active segment of the pulmonary circulation. The development of more sophisticated ultrasonography technology has allowed the investigation of the extraparenchymal pulmonary veins and their waveform. The recognition of the pulmonary vein anatomy in echocardiography is important for the diagnosis of anomalous pulmonary venous connections, with a significant impact on prognosis. On the other hand, the identification of the normal pulmonary vein waveform seems to be a reliable way to study left heart function, with potential applicability in fetal and maternal pathology. Thus, the goal of this narrative review was to provide a clinically oriented perspective of the available literature on this topic., (© 2023. The Author(s).)

Chronic intrauterine hypoxia is a significant pregnancy complication impacting fetal heart growth, metabolism, and mitochondrial function, contributing to cardiovascular programming of the offspring. PGC1α (peroxisome proliferator-activated receptor γ co-activator 1α) is the master regulator of mitochondrial biogenesis. We investigated the effects of hypoxia on PGC1α expression following exposure at different gestational ages. Time-mated pregnant guinea pigs were exposed to normoxia (NMX, 21% O 2 ) or hypoxia (HPX, 10.5% O 2 ) at either 25-day (early-onset) or 50-day (late-onset) gestation, and all fetuses were extracted at term (term = ~65-day gestation). Expression of nuclear PGC1α, sirtuin 1 (SIRT1), AMP-activated protein kinase (AMPK), and mitochondrial sirtuin 3 (SIRT3) was measured, along with SIRT3 activity and mitochondrial acetylation of heart ventricles of male and female fetuses. Early-onset hypoxia increased (P<0.05) fetal cardiac nuclear PGC1α and had no effect on mitochondrial acetylation of either growth-restricted males or females. Late-onset hypoxia had either no effect or decreased (P<0.05) PCC1α expression in males and females, respectively, but increased (P<0.05) mitochondrial acetylation in both sexes. Hypoxia had variable effects on expression of SIRT1, AMPK, SIRT3, and SIRT3 activity depending on the sex. The capacity of the fetal heart to respond to hypoxia differs depending on the gestational age of exposure and sex of the fetus. Further, the effects of late-onset hypoxia on fetal heart function impose a greater risk to male than female fetuses, which has implications toward cardiovascular programming effects of the offspring., (© 2023. The Author(s).)

As presently conceptualised, the artificial placenta (AP) is an experimental life support platform for extremely preterm infants (i.e. 400-600 g; 21-23 +6 weeks of gestation) born at the border of viability. It is based around the oxygenation of the periviable fetus using gas-exchangers connected to the fetal vasculature. In this system, the lung remains fluid-filled and the fetus remains in a quiescent state. The AP has been in development for some sixty years. Over this time, animal experimental models have evolved iteratively from employing external pump-driven systems used to support comparatively mature fetuses (generally goats or sheep) to platforms driven by the fetal heart and used successfully to maintain extremely premature fetuses weighing around 600 g. Simultaneously, sizable advances in neonatal and obstetric care mean that the nature of a potential candidate patient for this therapy, and thus the threshold success level for justifying its adoption, have both changed markedly since this approach was first conceived. Five landmark breakthroughs have occurred over the developmental history of the AP: i) the first human studies reported in the 1950's; ii) foundation animal studies reported in the 1960's; iii) the first extended use of AP technology combined with fetal pulmonary resuscitation reported in the 1990s; iv) the development of AP systems powered by the fetal heart reported in the 2000's; and v) the adaption of this technology to maintain extremely preterm fetuses (i.e. 500-600 g body weight) reported in the 2010's. Using this framework, the present paper will provide a review of the developmental history of this long-running experimental system and up-to-date assessment of the published field today. With the apparent acceleration of AP technology towards clinical application, there has been an increase in the attention paid to the field, along with some inaccurate commentary regarding its potential application and merits. Additionally, this paper will address several misrepresentations regarding the potential application of AP technology that serve to distract from the significant potential of this approach to greatly improve outcomes for extremely preterm infants born at or close to the present border of viability., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Congenital heart defects (CHD) remain the most common class of birth defect worldwide, affecting 1 in every 110 live births. A host of clinical and morphological indicators of placental dysfunction are observed in pregnancies complicated by fetal CHD and, with the recent emergence of single-cell sequencing capabilities, the molecular and physiological associations between the embryonic heart and developing placenta are increasingly evident. In CHD pregnancies, a hostile intrauterine environment may negatively influence and alter fetal development. Placental maldevelopment and dysfunction creates this hostile in-utero environment and may manifest in the development of various subtypes of CHD, with downstream perfusion and flow-related alterations leading to yet further disruption in placental structure and function. The adverse in-utero environment of CHD-complicated pregnancies is well studied, however the specific etiological role that the placenta plays in CHD development remains unclear. Many mouse and rat models have been used to characterize the relationship between CHD and placental dysfunction, but these paradigms present substantial limitations in the assessment of both the heart and placenta. Improvements in non-invasive placental assessment can mitigate these limitations and drive human-specific investigation in relation to fetal and placental development. Here, we review the clinical, structural, and molecular relationships between CHD and placental dysfunction, the CHD subtype-dependence of these changes, and the future of Placenta-Heart axis modeling and investigation., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aim: We aimed to investigate fetal cardiac output (CO) in pregnancies with preterm premature rupture of membranes (PPROM) and its relationship with umbilical cord pH., Methods: This was a prospective study in total 90 pregnancies at 24-37 weeks gestation including 42 pregnancies with PPROM and 48 that healthy controls. Fetal cardiac function including combined, left and right CO z-scores were compared. The neonates in the PPROM group were separated with umbilical cord pH above and below 7.25, and cardiac output was compared between groups., Results: In PPROM group, CCO z-score, left cardiac output (LCO) z-score, and right cardiac output (RCO) were significantly lower compared to healthy pregnancies (p = .036, p = .001, p = .032, respectively), while RCO z-score showed no significant differences between the two groups. The aortic annulus and pulmonary artery annulus z-scores were measured smaller in the PPROM group (p = .000 and p = .001, respectively). In PPROM group, the fetal LCO z-score was significantly lower in neonates with an umbilical cord pH of 7.25 or less (p = .048)., Conclusion: This study provides evidence that fetal CCO is lower in PPROM compared with healthy pregnancies. Reduced LCO z-scores may be useful for predicting adverse neonatal outcomes in pregnancies with PPROM., (© 2023 Wiley Periodicals LLC.)

This study aimed to compare fetal myocardial performance index (MPI) between fetuses of pregnant women with gestational diabetes mellitus (GDM) and healthy controls and to evaluate the relationship between MPI and maternal glucose levels. This was a prospective study of 90 pregnant women, including 50 pregnancies with GDM (27 pregnancies with insulin-regulated GDM and 23 pregnancies with diet-regulated GDM) and 40 healthy controls. Isovolumetric contraction time (ICT) + isovolumetric relaxation time (IRT)/ejection time (ET) were used to calculate the MPI (MPI = [ICT + IRT]/ET). Fetal MPI, PR interval, E/A ratio, maternal plasma glucose levels on the day of MPI measurement, and neonatal outcomes were compared. The fetal left-MPI was significantly higher in the GDM group than healthy controls (0.43 ± 0.04 vs. 0.40 ± 0.06, p = 0.007). The best cut-off level for MPI was >0.41 to predict adverse perinatal outcomes (sensitivity: 70%, specificity: 68%, area under the curve: 0.715, 95% confidence interval: 0.5143-0.8205, p < 0.001). The fetal MPI values showed no correlation with maternal plasma fasting, postprandial glucose, and hemoglobin A1c (HbA1c) levels. Reduced E/A ratio, higher neonatal intensive care unit admissions, and the need for cesarean delivery were detected in the GDM group. Fetal MPI is impaired in women with GDM, and the need for insulin therapy is associated with higher MPI values and adverse neonatal outcomes. Fetal MPI can help detect fetuses with potential adverse outcome risks, owing to impaired fetal cardiac function., (© 2023 Japanese Teratology Society.)

Transamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) can attenuate placental inflammation and minimize intrauterine growth restriction (IUGR). We sought to determine whether MSC-based TRASCET could mitigate fetal cardiopulmonary effects of IUGR. Pregnant Sprague-Dawley dams were exposed to alternating 12-h hypoxia (10.5% O 2 ) cycles in the last fourth of gestation. Their fetuses ( n  = 155) were divided into 4 groups. One group remained untreated ( n  = 42), while three groups received volume-matched intra-amniotic injections of either saline (sham; n  = 34), or of syngeneic amniotic fluid-derived MSCs, either in their native state (TRASCET; n  = 36) or "primed" by exposure to interferon-gamma and interleukin-1beta before administration in vivo (TRASCET-primed; n  = 43). Normal fetuses served as additional controls ( n  = 30). Multiple morphometric and biochemical analyses were performed at term for select markers of cardiopulmonary development and inflammation previously shown to be affected by IUGR. Among survivors (75%; 117/155), fetal heart-to-body weight ratio was increased in both the sham and untreated groups ( P  < 0.001 for both) but normalized in the TRASCET and TRASCET-primed groups ( P  = 0.275, 0.069, respectively). Cardiac b-type natriuretic peptide levels were increased in all hypoxia groups compared with normal ( P  < 0.001), but significantly decreased from sham and untreated in both TRASCET groups ( P  < 0.0001-0.005). Heart tumor necrosis factor-alpha levels were significantly elevated in sham and TRASCET groups ( P  = 0.009, 0.002), but normalized in the untreated and TRASCET-primed groups ( P  = 0.256, 0.456). Lung transforming growth factor-beta levels were significantly increased in both sham and untreated groups ( P  < 0.001, 0.003), but normalized in both TRASCET groups ( P  = 0.567, 0.303). Similarly, lung endothelin-1 levels were elevated in sham and untreated groups ( P  < 0.001 for both), but normalized in both TRASCET groups ( P  = 0.367, 0.928). We conclude that TRASCET with MSCs decreases markers of fetal cardiac strain, insufficiency, and inflammation, as well as of pulmonary fibrosis and hypertension in the rodent model of IUGR.

Objectives: It has been belived that changes in diastolic blood velocities in the fetal ductus venosus were due to increased central venous pressure secondary to increased fetal heart strain during hypoxia or heart failure. There have been recent reports of changes in ductus venosus blood velocity without signs of increased fetal heart strain. The aim of this evaluation was to compare blood velocity in the right hepatic vein as a marker of increased central venous pressure in relationship to changes in ductus venosus blood velocity., Material and Methods: Fifty pregnancies suspected of fetal growth resitriction were evaluated by Doppler ultrasound. Blood velocity was recorded in the right hepatic vein, ducus venosus and in the umbilical vein. Placental blood flow was also recorded in the uterine and umbilical arteries as well as the fetal middle cerebral artery., Results: Increased umbilical artery pulsatility index was recorded in 19 fetuses and 20 has signes of brain sparing according to recordings in the middle cerebral artery. Abnormal blood velocity in the ductus venosus was recorded in 5 fetuses, none of these fetuses had an abnormal pulsatility in the right hepatic vein., Conclusions: Opening of the ductus venosus is not only related to fetal cardiac strain. This might indicate that the ductus venosus does not primarily open due to increased central venous pressure in moderate fetal hypoxia. Increased fetal cardiac strain might be a late event in the process of chronic fetal hypoxia.

The persistent left superior vena cava (PLSVC) is a common venous abnormality. However, malformation of the bilateral inferior venae cava (IVC) is extremely rare, with an incidence rate of .3%. IVC malformation is associated most frequently with heart defects and isomerism and often has a poor prognosis. We presented a case of vascular malformations in the fetus of bilateral caval veins with the interruption of the left-sided venous return with hemiazygos continuation in presence of a right-sided inferior caval vein. Also noted were the PLSVC and a dilated right heart with a widened pulmonary trunk. In this case, there were no heart defects or chromosomal abnormalities, and the newborn postpartum was in a good condition., (© 2023 Wiley Periodicals LLC.)

Background: Cardiac heart defects affect nearly 6-12 per 1000 live births in the general population and are more frequent than common trisomies., Aim: To assess the efficacy and technical limitations of first-trimester fetal heart evaluation in the 11-14 th -weeks' scan and comparison with the second-trimester anatomical exam by ultrasound., Material and Method: Between April 2015 and July 2020, medical records and ultrasound data of 3295 pregnancies who underwent first-trimester fetal anatomy exams by ultrasound were reviewed retrospectively. All ultrasound exams were performed by the same two operators (TUKD, OP) with transabdominal transducers. Fetal situs, four-chamber view, outflow tracts, and three-vessel trachea view are the cornerstones of first-trimester fetal heart examination. Conventional grayscale mode and high-definition power Doppler mode were utilized. The same operators re-examined all cases between the 18 and 23 weeks of gestation by ISUOG guidelines., Results: We performed a combined transvaginal and transabdominal approach for only 101 cases (3.06%). The mean maternal age was 31.28 ± 4.43, the median gestational age at the first-trimester ultrasound exam was 12.4 weeks, and the median CRL was 61.87 mm (range was 45.1-84 mm). Even combined approach situs, cardiac axis, and four-chamber view could not be visualized optimally in 28 cases (0.7%). Outflow tracts were visualized separately in 80% (2636 in 3295) cases. Three vessel-trachea views were obtained in 85.4% (2814 in 3295) cases by high-definition Doppler mode. There were 47 fetuses with cardiac defects in 3295 pregnancies with the known pregnancy outcome. Ten cases had abnormal karyotype results. Thirty-two fetuses with cardiac anomalies (9.7 in 1000 pregnancies) were detected in the first-trimester examination, and the remaining 15 (4.55 in 1000 pregnancies) cases were diagnosed in the second-trimester examination. The prevalence of congenital cardiac anomalies was 14.25 in 1000 pregnancies. Fifteen cases were missed in the first-trimester exam. Also, ten fetuses which had abnormal cardiac findings in the first-trimester exam were not confirmed in the second-trimester exam. Sensitivity, specificity, positive, and negative predictive values were calculated as 65.3%, 99.7%, 66.8%, and 99.67%, respectively., Conclusion: Late first-trimester examination of the fetus is feasible and allows earlier detection of many structural abnormalities of the fetus, including congenital heart defects. Suspicious and isolated cardiac abnormal findings should be re-examined and confirmed in the second-trimester exam. Previous abdominal surgery, high BMI, and subtle cardiac defects can cause missed cardiac abnormalities., Competing Interests: None

Objectives: Congenital ventricular aneurysms or diverticulum (VA/VD) are rare cardiac anomalies with lack prenatal evaluation data. The present study aimed to provide the prenatal characteristics and outcomes from a tertiary center and the use of new techniques to evaluate the shape and contractility of these fetuses., Methods: Ten fetuses were diagnosed with VA or VD, and 30 control fetuses were enrolled. Fetal echocardiography was performed to make the diagnosis. The prenatal echo characteristics and follow-up data were carefully reviewed. The shape and contractility measurements of the four-chamber view (4CV) and both ventricles were measured and computed using fetal fetal heart quantification (HQ)., Results: A total of 10 fetuses were enrolled, including 4 cases of left ventricular diverticulum, 5 cases of left ventricular aneurysm, and 1 case of right ventricular aneurysm (RVA). Four cases chose to terminate the pregnancy. The RVA was associated with a perimembranous ventricular septal defect. Two cases had fetal arrhythmia, and one case had pericardial effusion. After birth, one case underwent surgical resection at five years old. The 4CV global sphericity index (SI) of free-wall located ventricular outpouching (VO) was significantly lower than the apical ones and the control group ( p  < 0.01). Four of five apical left VOs had significant higher (>95th centile) SI in base segments, and three of four left VOs in the free-wall had significant lower (< 5th centile) SI in the majority of 24 segments. Compared to the control group, the left ventricle (LV) global longitudinal strain, ejection fraction, and fractional area change were significantly decreased ( p  < 0.01), while the LV cardiac output of the cases was in the normal range. The transverse fraction shortening of the affected segments of ventricles was significantly lower than the other ventricle segments ( p  < 0.01)., Conclusions: Fetal HQ is a promising technique to evaluate the shape and contractility of congenital ventricular aneurysm and diverticulum., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer FL declared a shared parent affiliation with the authors to the handling editor at the time of review., (© 2023 Zhao, Wu, Jiao, Zhang, Jing, Wu and Chen.)

Background: Many aspects of care for fetuses and neonates with congenital heart disease (CHD) fall outside standard practice guidelines, leading to the potential for significant variation in clinical care for this vulnerable population., Methods: We conducted a cross-sectional survey of site sponsors of the Children's Hospitals Neonatal Consortium, a multicenter collaborative of 41 Level IV neonatal intensive care units to assess key areas of clinical practice variability for patients with fetal and neonatal CHD., Results: We received responses from 31 centers. Fetal consult services are shared by neonatology and pediatric cardiology at 70% of centers. Three centers (10%) routinely perform fetal magnetic resonance imaging (MRI) for women with pregnancies complicated by fetal CHD. Genetic testing for CHD patients is routine at 76% of centers. Preoperative brain MRI is standard practice at 5 centers (17%), while cerebral NIRS monitoring is regularly used at 14 centers (48%). Use of electroencephalogram (EEG) after major cardiac surgery is routine in 5 centers (17%). Neurodevelopmental follow-up programs are offered at 30 centers (97%)., Conclusions: Many aspects of fetal and neonatal CHD care are highly variable with evolving shared multidisciplinary models., Impact: Many aspects of fetal and neonatal CHD care are highly variable. Genetic testing, placental examination, preoperative neuroimaging, and postoperative EEG monitoring carry a high yield of finding abnormalities in patients with CHD and these tests may contribute to more precise prognostication and improve care. Evidence-based standards for prenatal and postnatal CHD care may decrease inter-center variability., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objectives: The aim of this study was to evaluate the agreement between visual and automatic methods in assessing the adequacy of fetal cardiac views obtained during second trimester ultrasonographic examination., Methods: In a prospective observational study frames of the four-chamber view left and right outflow tracts, and three-vessel trachea view were obtained from 120 consecutive singleton low-risk women undergoing second trimester ultrasound at 19-23 weeks of gestation. For each frame, the quality assessment was performed by an expert sonographer and by an artificial intelligence software (Heartassist™). The Cohen's κ coefficient was used to evaluate the agreement rates between both techniques., Results: The number and percentage of images considered adequate visually by the expert or with Heartassist™ were similar with a percentage >87 % for all the cardiac views considered. The Cohen's κ coefficient values were for the four-chamber view 0.827 (95 % CI 0.662-0.992), 0.814 (95 % CI 0.638-0.990) for left ventricle outflow tract, 0.838 (95 % CI 0.683-0.992) and three vessel trachea view 0.866 (95 % CI 0.717-0.999), indicating a good agreement between the two techniques., Conclusions: Heartassist™ allows to obtain the automatic evaluation of fetal cardiac views, reached the same accuracy of expert visual assessment and has the potential to be applied in the evaluation of fetal heart during second trimester ultrasonographic screening of fetal anomalies., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Clinically serious congenital heart valve defects arise from improper growth and remodeling of endocardial cushions into leaflets. Genetic mutations have been extensively studied but explain less than 20% of cases. Mechanical forces generated by beating hearts drive valve development, but how these forces collectively determine valve growth and remodeling remains incompletely understood. Here, we decouple the influence of those forces on valve size and shape, and study the role of YAP pathway in determining the size and shape. The low oscillatory shear stress promotes YAP nuclear translocation in valvular endothelial cells (VEC), while the high unidirectional shear stress restricts YAP in cytoplasm. The hydrostatic compressive stress activated YAP in valvular interstitial cells (VIC), whereas the tensile stress deactivated YAP. YAP activation by small molecules promoted VIC proliferation and increased valve size. Whereas YAP inhibition enhanced the expression of cell-cell adhesions in VEC and affected valve shape. Finally, left atrial ligation was performed in chick embryonic hearts to manipulate the shear and hydrostatic stress in vivo. The restricted flow in the left ventricle induced a globular and hypoplastic left atrioventricular (AV) valves with an inhibited YAP expression. By contrast, the right AV valves with sustained YAP expression grew and elongated normally. This study establishes a simple yet elegant mechanobiological system by which transduction of local stresses regulates valve growth and remodeling. This system guides leaflets to grow into proper sizes and shapes with the ventricular development, without the need of a genetically prescribed timing mechanism., Competing Interests: MW, BL, SS, CD, FL, JB No competing interests declared, (© 2023, Wang et al.)

Objective: This study aimed to report our experience in qualitative and quantitative evaluation of fetal complete vascular ring (CVR) using fetal cardiovascular magnetic resonance imaging (MRI) to improve prenatal diagnosis and make early postnatal management possible., Methods: A retrospective case-control study was performed on cases of CVR diagnosed using fetal cardiovascular MRI, and confirmed by postnatal imaging diagnosis. Associated abnormalities were recorded. The diameters of aortic arch isthmus (AoI) and ductus arteriosus (DA), and tracheal diameters in fetuses with tracheal compression were measured and compared with those of the control group., Results: All fetal CVR cases in this study included right aortic arch (RAA) with aberrant left subclavian artery (ALSA) and left DA ( n  = 93), double aortic arch (DAA) ( n  = 29), RAA with mirror-image branching and retroesophageal left ductus arteriosus (RLDA) ( n  = 8). Compared with the control group, the diameters of AoI in fetuses with DAA were decreased ( p  < 0.001), and the diameters of DA in fetuses with RAA with ALSA and left DA were increased ( p  < 0.001). The diameters of AoI and DA were positively correlated with gestational age (GA) in the normal control group (both p  < 0.001); The diameters of AoI and DA were also positively correlated with GA in RAA with ALSA and left DA subgroup (both p  < 0.001) and RAA with mirror-image branching and RLDA subgroup (AoI: p  = 0.003; DA: p  = 0.002); The diameters of DA were positively associated with GA in DAA subgroup ( p  < 0.001), however, there was no linear tendency between the diameters of AoI and GA in the DAA subgroup ( p  = 0.074). There were CVR fetuses with associated intracardiac malformation ( n  = 13), especially ventricular septal defect rather than complex heart disease, and extracardiac malformation ( n  = 14). Sixteen fetuses were shown the airway compression whose tracheal diameters were smaller than the normal ( p  < 0.001)., Conclusions: The altered diameters of AoI and DA can be detected and measured in CVR fetuses using fetal cardiovascular MRI. Fetal CVR can occur alone or with intracardiac and extracardiac malformation. Fetal CVR can be associated with prenatal airway compression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Zhang, Zhu and Dong.)