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Purpose: Fetal heart diseases significantly contribute to neonatal mortality. Improved prenatal diagnostics enable defect detection before delivery, emphasizing the need for a personalized approach to address anomalies and predict outcomes. Categorizing diseases into risk classes aids obstetricians in counseling and delivery decisions. This study classifies fetal heart diseases by severity, examining factors related to maternal, fetal, and delivery that affect neonatal mortality. The aim is to identify key determinants of neonatal mortality and create an individual approach to assess and manage risks in the first days of a newborn's life. Methods: A prospective study from 2019 to 2023 at a tertiary care institute involved pregnant women diagnosed with fetal heart disease. 382 women were categorized into three groups based on potential risk for hemodynamic instability at birth: Group-1 (no or low risk, n = 114), Group-2 (moderate risk, n = 201), and Group-3 (high risk, n = 67). Antenatal follow-up used fetal echocardiography. The study explored the association between maternal–fetal-delivery-related factors and neonatal mortality, with statistical significance set at p < 0.05. Results: Significant associations with neonatal mortality were found in cases with birth weight < 2500 g (p = 0.002), presence of genitourinary system anomaly (p = 0.001), group-2 and 3 heart disease (p < 0.001), and induction of labor (p = 0.01). Conclusion: Factors influencing neonatal mortality in fetal heart disease cases include heart disease severity (group-3 heart disease), low birth weight, and extracardiac anomalies. While labor induction with prostaglandin ± oxytocin appears to elevate neonatal mortality, this observation requires further validation with larger sample sizes. Obstetricians should consider selective use of prostaglandin for labor induction. [ABSTRACT FROM AUTHOR]

Objective: To examine the effect of intrahepatic cholestasis of pregnancy (ICP) on fetal heart morphology. Methods: This case–control study was conducted with 40 women with ICP and 54 pregnant controls. Fetal heart quantification based on speckle tracking technology was used to assess the morphology of the fetal right and left ventricles. Routine ventricular size parameters, global and 24‐segment spherical indices (SIs) were measured and compared between groups. Results: The routine fetal cardiac parameters, global and right‐ventricular SIs did not differ between the ICP and control groups. The left‐ventricular apical (segments 16‐24) SIs were lower in the ICP group than in the control group (P <.05), with no significant difference in the other left‐ventricular segments. Conclusions: Subclinical morphological changes were observed in the left ventricular apical segments of the fetal hearts in women with ICP, which indicates an intrauterine environment with high bile acid concentrations. Twenty‐four‐segment SIs can be used to effectively evaluate these changes. [ABSTRACT FROM AUTHOR]

Background: Prenatal ultrasound is the preferred modality for diagnosing fetal congenital heart disease. Given issues of physician proficiency and hospital distribution, we propose a dynamic sequential cross-sectional scanning (SCS) to explore the feasibility of cardiac screening by sonographers with less than 5 years of experience in ultrasound. Materials and methods: Twenty residents were randomly divided into two groups, receiving training in the American Institute of Ultrasound in Medicine (AIUM) fetal echocardiography and the SCS method. According to the needs of training, the professional staff developed the theoretical knowledge question bank, the CHD ultrasonic video disease bank, and the assessment scale. Trainees completed the pre-training examination, theory and skill operation training, and post-training assessment. For the two groups, the theoretical knowledge, skill operation and disease diagnosis were analyzed statistically before and after training. Results: After training, the trainees in both groups had significantly improved knowledge and diagnostic abilities, their diagnostic thinking about CHD was clear, and they could identify major or even all structural abnormalities and make a definite diagnosis. In terms of skill operation, both groups could complete all required scanning within the specified time. The scanning time of the SCS group was significantly lower than that of the AIUM group, and the effect of the receptor site in the AIUM group was significantly higher than that in the SCS group. Conclusion: SCS can be used as a new rapid fetal cardiac scanning method and try to popularize among echocardiographer. [ABSTRACT FROM AUTHOR]

Objective: Biallelic titin truncating variants (TTNtv) have been associated with a wide phenotypic spectrum, ranging from complex prenatal muscle diseases with dysmorphic features to adult‐onset limb‐girdle muscular dystrophy, with or without cardiac involvement. Given the size and complexity of TTN, reaching an unequivocal molecular diagnosis and precise disease prognosis remains challenging. Methods: In this case series, 12 unpublished cases and one already published case with biallelic TTNtv were collected from multiple international medical centers between November 2022 and September 2023. TTN mutations were detected through exome or genome sequencing. Information about familial and personal clinical history was collected in a standardized form. RNA‐sequencing and analysis of TTN exon usage were performed on an internal sample cohort including postnatal skeletal muscles, fetal skeletal muscles, postnatal heart muscles, and fetal heart muscles. In addition, publicly available RNA‐sequencing data was retrieved from ENCODE. Results: We generated new RNA‐seq data on TTN exons and identified genotype–phenotype correlations with prognostic implications for each titinopathy patient (whether worsening or improving in prenatal and postnatal life) using percentage spliced in (PSI) data for the involved exons. Interestingly, thanks to exon usage, we were also able to rule out a titinopathy diagnosis in one prenatal case. Interpretation: This study demonstrates that exon usage provides valuable insights for a more exhaustive clinical interpretation of TTNtv; additionally, it may serve as a model for implementing personalized medicine in many other genetic diseases, since most genes undergo alternative splicing. [ABSTRACT FROM AUTHOR]

Fetal heart monitoring, as a crucial part of fetal monitoring, can accurately reflect the fetus's health status in a timely manner. To address the issues of high computational cost, inability to observe fetal heart morphology, and insufficient accuracy associated with the traditional method of calculating the fetal heart rate using a four-channel maternal electrocardiogram (ECG), a method for extracting fetal QRS complexes from a single-channel non-invasive fetal ECG based on a multi-feature fusion neural network is proposed. Firstly, a signal entropy data quality detection algorithm based on the blind source separation method is designed to select maternal ECG signals that meet the quality requirements from all channel ECG data, followed by data preprocessing operations such as denoising and normalization on the signals. After being segmented by the sliding window method, the maternal ECG signals are calculated as data in four modes: time domain, frequency domain, time–frequency domain, and data eigenvalues. Finally, the deep neural network using three multi-feature fusion strategies—feature-level fusion, decision-level fusion, and model-level fusion—achieves the effect of quickly identifying fetal QRS complexes. Among the proposed networks, the one with the best performance has an accuracy of 95.85% and sensitivity of 97%. [ABSTRACT FROM AUTHOR]

Congenital heart defects are leading causes of neonatal mortality and are often associated with placental abnormalities, but mechanisms linking placenta and heart development are poorly understood. Herein, we investigated a potential signaling network connecting the placenta and nascent heart in mice. We found that fetal hearts exposed to media conditioned by placental tissue or differentiated wild-type trophoblast stem (TS) cells, but not undifferentiated TS cells, showed increased heart rate and epicardial cell outgrowth. This effect was not observed when hearts were exposed to media from TS cells lacking OVO-Like 2, a transcription factor required for trophoblast differentiation and placental development. Trophoblasts released abundant extracellular vesicles into media, and these vesicles were sufficient to mediate cardio-promoting effects. Our findings provide a potential mechanism whereby the placenta communicates with the fetal heart to promote cardiac morphogenesis, and offers insight into the link between poor placentation and a higher incidence of heart defects. Poor development of the placenta is linked with heart problems. This study reveals that extracellular vesicles from placental trophoblasts promote heart development in mice, shedding light on how placental health affects cardiac formation. [ABSTRACT FROM AUTHOR]

Fetal critical aortic stenosis with evolving hypoplastic left heart syndrome (CAS-eHLHS) can progress to a univentricular (UV) birth malformation. Catheter-based fetal aortic valvuloplasty (FAV) can resolve stenosis and reduce the likelihood of malformation progression. However, we have limited understanding of the biomechanical impact of FAV and subsequent LV responses. Therefore, we performed image-based finite element (FE) modeling of 4 CAS-eHLHS fetal hearts, by performing iterative simulations to match image-based characteristics and then back-computing physiological parameters. We used pre-FAV simulations to conduct virtual FAV (vFAV) and compared pre-FAV and post-FAV simulations. vFAV simulations generally enabled partial restoration of several physiological features toward healthy levels, including increased stroke volume and myocardial strains, reduced aortic valve (AV) and mitral valve regurgitation (MVr) velocities, reduced LV and LA pressures, and reduced peak myofiber stress. FAV often leads to aortic valve regurgitation (AVr). Our simulations showed that AVr could compromise LV and LA depressurization but it could also significantly increase stroke volume and myocardial deformational stimuli. Post-FAV scans and simulations showed FAV enabled only partial reduction of the AV dissipative coefficient. Furthermore, LV contractility and peripheral vascular resistance could change in response to FAV, preventing decreases in AV velocity and LV pressure, compared with what would be anticipated from stenosis relief. This suggested that case-specific post-FAV modeling is required to fully capture cardiac functionality. Overall, image-based FE modeling could provide mechanistic details of the effects of FAV, but computational prediction of acute outcomes was difficult due to a patient-dependent physiological response to FAV. [ABSTRACT FROM AUTHOR]

Background: Congenital cardiac malformations are a significant subset of developmental abnormalities, affecting approximately 6-8 per 1,000 live births and 2% of stillbirths. These malformations account for nearly one-quarter of all developmental anomalies, yet the etiology remains unknown in over 90% of cases. Hereditary factors and environmental conditions, such as high altitude and seasonal variations, have been implicated. The prevalence and types of congenital cardiac malformations in North India are not well-documented, prompting this study to investigate these aspects in adult and fetal cadavers at Bhagalpur. Materials and Methods: The study was conducted in the Department of Anatomy at Jawaharlal Nehru Medical College, Bhagalpur, using 25 adult and 45 fetal cadaver hearts, preserved in 10% formaldehyde solution. The hearts were dissected using a standardized method, examining and classifying malformations according to abnormalities in position, developmental progress, and visceral arches. Morphological features were assessed with tools including a dissection kit, magnifying lens, torch, probe, and measuring tape. Results: Out of 70 cases studied, 14 (20%) displayed congenital cardiac malformations, with a higher incidence in adults (24%) than in fetuses (17.78%). A total of 25 anomalies were identified among the 14 cases, with 10 types of anomalies observed. The most common malformation was atrial septal defect, followed by anomalous positions of the great arteries and cor biloculare. Coexistent external anomalies were found in 3 of the 14 cases (21.43%), affecting the face and multiple systems. Conclusion: The incidence of congenital cardiac malformations in Bhagalpur is consistent with findings from other regions of India and internationally. Atrial septal defect is the most prevalent malformation in this population, aligning with patterns observed in other Indian studies but differing from international reports. [ABSTRACT FROM AUTHOR]

The consumption of high fat–high energy diets (HF‐HEDs) continues to rise worldwide and parallels the rise in maternal obesity (MO) that predisposes offspring to cardiometabolic disorders. Although the underlying mechanisms are unclear, thyroid hormones (TH) modulate cardiac maturation in utero. Therefore, we aimed to determine the impact of a high fat–high energy diet (HF‐HED) on the hormonal, metabolic and contractility profile of the non‐human primate (NHP) fetal heart. At ∼9 months preconception, female baboons (Papiohamadryas) were randomly assigned to either a control diet or HF‐HED. At 165 days gestational age (term = 184 days), fetuses were delivered by Caesarean section under anaesthesia, humanely killed, and left ventricular cardiac tissue (Control (n = 6 female, 6 male); HF‐HED (n = 6 F, 6 M)) was collected. Maternal HF‐HED decreased the concentration of active cardiac TH (i.e. triiodothyronine (T3)), and type 1 iodothyronine deiodinase (DIO1) mRNA expression. Maternal HF‐HED decreased the abundance of cardiac markers of insulin‐mediated glucose uptake phosphorylated insulin receptor substrate 1 (Ser789) and glucose transporter 4, and increased protein abundance of key oxidative phosphorylation complexes (I, III, IV) and mitochondrial abundance in both sexes. Maternal HF‐HED alters cardiac TH status, which may induce early signs of cardiac insulin resistance. This may increase the risk of cardiometabolic disorders in later life in offspring born to these pregnancies. Key points: Babies born to mothers who consume a high fat–high energy diet (HF‐HED) prior to and during pregnancy are predisposed to an increased risk of cardiometabolic disorders across the life course.Maternal HF‐HED prior to and during pregnancy decreased thyroid hormone triiodothyronine (T3) concentrations and type 1 iodothyronine deiodinase DIO1 mRNA expression in the non‐human primate fetal heart.Maternal HF‐HED decreased markers of insulin‐dependent glucose uptake, phosphorylated insulin receptor substrate 1 and glucose transporter 4 in the fetal heart.Maternal HF‐HED increased mitochondrial abundance and mitochondrial OXPHOS complex I, III and IV in the fetal heart.Fetuses from HF‐HED pregnancies are predisposed to cardiometabolic disorders that may be mediated by changes in T3, placing them on a poor lifetime cardiovascular health trajectory. [ABSTRACT FROM AUTHOR]

Atrioventricular (AV) accessory pathways (APs) provide additional electrical connections between the atria and ventricles, resulting in severe electrical disturbances. It is generally accepted that APs originate in the altered annulus fibrosus maturation in the late prenatal and perinatal period. However, current experimental methods cannot address their development in specific locations around the annulus fibrosus because of the inaccessibility of late fetal hearts for electrophysiological investigation under physiological conditions. In this study, we describe an approach for optical mapping of the retrogradely perfused chick heart in the last third of the incubation period. This system showed stability for electrophysiological measurement for several hours. This feature allowed analysis of the number and functionality of the APs separately in each clinically relevant position. Under physiological conditions, we also recorded the shortening of the AV delay with annulus fibrosus maturation and analyzed ventricular activation patterns after conduction through APs at specific locations. We observed a gradual regression of AP with an area-specific rate (left-sided APs disappeared first). The results also revealed a sudden drop in the number of active APs between embryonic days 16 and 18. Accessory myocardial AV connections were histologically documented in all positions around the annulus fibrosus even after hatching. The fact that no electrically active AP was present at this stage highlights the necessity of electrophysiological evaluation of accessory atrioventricular connections in studying AP formation. NEW & NOTEWORTHY: We present the use of retrograde perfusion and optical mapping to investigate, for the first time, the regression of accessory pathways during annulus fibrosus maturation, separately examining each clinically relevant location. The system enables measurements under physiological conditions and demonstrates long-lasting stability compared with other approaches. This study offers applications of the model to investigate electrical and/or functional development in late embryonic development without concern about heart viability. [ABSTRACT FROM AUTHOR]

Human cardiac development and regeneration modeling are crucial areas of research that hold immense promise for advancing regenerative medicine and treating cardiovascular diseases. Understanding the intricate process of cardiac development, from the formation of the primitive heart tube to the maturation of the fetal heart, provides insights into potential therapeutic strategies for cardiac regeneration. This article explores the key stages of cardiac development, factors influencing cardiac regeneration, current models for studying regenerative processes, challenges and opportunities in regenerative medicine, future directions in cardiac development research, clinical applications of regenerative modeling, and the implications for healthcare. By delving into these aspects, researchers and healthcare professionals can gain a deeper understanding of how to harness the regenerative potential of the human heart for improved patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Obstetric ultrasound is considered important for determining gestational age, identifying single or multiple pregnancies, locating the placenta and fetal anomalies and monitoring fetal growth and pregnancy-related complications in order to improve patient management. Objectives: To explore health professionals' perspectives on different aspects of obstetric ultrasound in Tanzania regarding self-reported skills in performing ultrasound examinations and what could improve access to and utilization of obstetric ultrasound in the clinical setting. Design: Cross-sectional study. Material and Methods: Data was collected between November and December 2017 using a questionnaire based on previous qualitative research results from the CROss Country UltraSound Study (CROCUS Study). Seventeen healthcare facilities in 5 urban and semiurban municipalities in the Dar-es-Salaam region were included, with 636 health professionals participating (physicians, n = 307 and midwives/nurses, n = 329). Results: Most health professionals (82% physicians, 81% midwives/nurses) believed that obstetric ultrasound was decisive in the clinical management of pregnancy. Results indicate proficiency gaps across disciplines: 51% of physicians and 48.8% of midwives/nurses reported no or low-level skills in assessing cervical length. Similarly, deficiencies were observed in evaluating the four-chamber view of the fetal heart (physicians: 51%, midwives/nurses: 61%), aorta, pulmonary artery (physicians: 60.5%, midwives/nurses: 65%) and Doppler assessments (umbilical artery: physicians 60.6%, midwives/nurses 56.1%). Compared to midwives/nurses, physicians were significantly more likely to agree or strongly agree that utilization would improve with more ultrasound machines (odds ratio (OR) 2.13; 95% confidence intervals (CI) 1.26–3.61), better quality of ultrasound machines (OR 2.27; 95% CI 1.10–4.69), more training for health professionals currently performing ultrasound (OR 2.11; 95% CI 1.08–4.17) and more physicians trained in ultrasound (OR 2.51; 95% CI 1.30–4.87). Conclusions: Improving the provision of obstetric ultrasound examinations in Tanzania requires more and better-quality ultrasound machines, enhanced training for health professionals and an increased number of physicians trained in ultrasound use. To further increase the accessibility and utilization of obstetric ultrasound in maternity care in Tanzania, it is essential to provide training for midwives in basic obstetric ultrasound techniques. Plain language summary: A study reporting on health professionals' insights and skills regarding pregnancy scans in Tanzania This study, conducted in Tanzania, explores health professionals' perspectives on obstetric ultrasound, an important component believed to increase antenatal care attendance in low-income countries. The research was carried out through a cross-sectional study involving 636 health professionals, primarily physicians and midwives/nurses, to assess their self-reported skills in performing obstetric ultrasound examinations and identify factors that could enhance access to and utilization of obstetric ultrasound in clinical settings. The findings highlight that most health professionals view obstetric ultrasound as crucial in managing pregnancy. However, there is a notable discrepancy in the perceived skills between physicians and midwives/nurses, especially in basic obstetric ultrasound examinations. A majority of health professionals reported either no skills or low-level skills in assessing various aspects like cervical length, fetal heart (four-chamber views), aorta, pulmonary artery and Doppler (umbilical artery). The study suggests that improving access and utilization of obstetric ultrasound could be achieved through increased availability of quality ultrasound machines and enhanced training. Physicians expressed a stronger belief in the positive impact of more ultrasound machines, better machine quality, additional training for current ultrasound examiners and more physicians trained in ultrasound. The data underscores the potential for enhancing obstetric ultrasound provision in Tanzania by investing in better technology, providing more training for healthcare professionals and increasing the number of physicians skilled in ultrasound use. Furthermore, the study recommends targeted training for midwives to enhance their proficiency in basic obstetric ultrasound, ultimately contributing to improved accessibility and utilization of obstetric ultrasound in maternity care in Tanzania. [ABSTRACT FROM AUTHOR]

Multiple complex biological processes take place during pregnancy, including the migration of fetal cells to maternal circulation and their subsequent engraftment in maternal tissues, where they form microchimerisms. Fetal microchimerisms have been identified in several tissues; nevertheless, their functional role remains largely unknown. Different reports suggest these cells contribute to tissue repair and modulate the immune response, but they have also been associated with pre-eclampsia and tumor formation. In the maternal heart, cells of fetal origin can contribute to different cell lineages after myocardial infarction. However, the functional role of these cells and their effect on cardiac function and repair are unknown. In this work, we found that microchimerisms of fetal origin are present in the maternal circulation and graft in the heart. To determine their functional role, WT female mice were crossed with male mice expressing the diphtheria toxin (DT) receptor. Mothers were treated with DT to eliminate microchimerisms and the response to myocardial infarction was investigated. We found that removal of microchimerisms improved cardiac contraction in postpartum and post-infarction model females compared to untreated mice, where DT administration had no significant effects. These results suggest that microchimerisms play a detrimental role in the mother following myocardial infarction. [ABSTRACT FROM AUTHOR]

Finite Element simulations are a robust way of investigating cardiac biomechanics. To date, it has only been performed with the left ventricle (LV) alone for fetal hearts, even though results are likely different with biventricular (BiV) simulations. In this research, we conduct BiV simulations of the fetal heart based on 4D echocardiography images to show that it can capture the biomechanics of the normal healthy fetal heart, as well as those of fetal aortic stenosis better than the LV alone simulations. We found that performing LV alone simulations resulted in overestimation of LV stresses and pressures, compared to BiV simulations. Interestingly, inserting a compliance between the LV and right ventricle (RV) in the lumped parameter model of the LV only simulation effectively resolved these overestimations, demonstrating that the septum could be considered to play a LV-RV pressure communication role. However, stresses and strains spatial patterns remained altered from BiV simulations after the addition of the compliance. The BiV simulations corroborated previous studies in showing disease effects on the LV, where fetal aortic stenosis (AS) drastically elevated LV pressures and reduced strains and stroke volumes, which were moderated down with the addition of mitral regurgitation (MR). However, BiV simulations enabled an evaluation of the RV as well, where we observed that effects of the AS and MR on pressures and stroke volumes were generally much smaller and less consistent. The BiV simulations also enabled investigations of septal dynamics, which showed a rightward shift with AS, and partial restoration with MR. Interestingly, AS tended to enhance RV stroke volume, but MR moderated that down. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Cardiotocography (CTG) measurements are critical for assessing fetal wellbeing during monitoring, and accurate assessment requires well-traceable CTG signals. The current FHR calculation algorithm, based on autocorrelation to Doppler ultrasound (DUS) signals, often results in periods of loss owing to its inability to differentiate signals. We hypothesized that classifying DUS signals by type could be a solution and proposed that an artificial intelligence (AI)-based approach could be used for classification. However, limited studies have incorporated the use of AI for DUS signals because of the limited data availability. Therefore, this study focused on evaluating the effectiveness of semi-supervised learning in enhancing classification accuracy, even in limited datasets, for DUS signals. Data comprising fetal heartbeat, artifacts, and two other categories were created from non-stress tests and labor DUS signals. With labeled and unlabeled data totaling 9,600 and 48,000 data points, respectively, the semi-supervised learning model consistently outperformed the supervised learning model, achieving an average classification accuracy of 80.9%. The preliminary findings indicate that applying semi-supervised learning to the development of AI models using DUS signals can achieve high generalization accuracy and reduce the effort. This approach may enhance the quality of fetal monitoring. [ABSTRACT FROM AUTHOR]

Objective The purposes of the study were to develop reference ranges and maturation patterns of fetal cardiac function parameters measured by speckle tracking echocardiography (STE) using multiple biometric variables at 17 to 24 weeks' gestation among Thai fetuses and to compare with other previous reports. Study Design The four-chamber view of the fetal heart in 79 healthy fetuses was suitably analyzed by STE to establish the best-fit regression model. The 95% reference intervals and Z -score equations of fetal cardiac function parameters were computed. Results The fractional area change of both ventricles, left ventricular (LV) end-diastolic and end-systolic volumes, LV stroke volume, LV cardiac output (CO), and LV CO per kilogram were all increased according to gestational age (GA) and five fetal biometric measurements. However, the global longitudinal strain, basal-apical length fractional shortening (BAL-FS), BAL annular free wall and septal wall FS, BAL free wall and septal wall annular plane systolic excursions, 24-segment transverse width FS, as well as LV ejection fraction were all independent of GA or other somatic characteristics. There were varying development patterns between fetal right and left ventricles of these cardiac function indices across the gestation period. Conclusion Our study created Z -score and corresponding centile calculators, 5th and 95th centile reference tables, and corresponding graphs and determined the normal evolution across gestation using multiple somatic growth and age variables between 17 and 24 gestational weeks. These nomograms serve as an essential prerequisite for quantitatively evaluating fetal cardiac contractility and allow for precisely detecting early changes in the fetal heart function. Key Points Most fetal cardiac function measurements were correlated with all the independent variables. Fetal ventricular function parameters have their own characteristic maturation changes. Racial variability may not occupy an important place for fetal myocardial function during these GA. [ABSTRACT FROM AUTHOR]

The prenatal diagnosis of fetal heart disease potentially influences parental decision-making regarding pregnancy termination. Existing literature indicates that the severity, whether in complexity or lethality, significantly influences parental decisions concerning abortion. However, questions remain as to how fetal heart disease severity impacts parental decisions, given recent advancements in postsurgical outcomes. Therefore, we investigated risk factors associated with parents' decision-making regarding abortion following a prenatal diagnosis of fetal heart disease. Our analysis included 73 (terminated: n = 37; continued: n = 36) pregnancies with a fetal heart disease diagnosed before 22 weeks of gestation. Increased gestational age at diagnosis reduced the likelihood of parents' decision on termination (Model 1: adjusted odds ratio, 0.94; 95% confidence interval 0.89–0.99; Model 2: 0.95 0.90–0.997). Critical disease (5.25; 1.09–25.19) and concurrent extracardiac or genetic abnormalities (Model 1: 4.19, 1.21–14.53; Model 2: 5.47, 1.50–19.96) increased the likelihood of choosing abortion. Notably, complex disease did not significantly influence parental decisions (0.56; 0.14–2.20). These results suggest that parental decision-making regarding abortion may be influenced by earlier gestational age at diagnosis, the lethality of heart disease, and extracardiac or genetic abnormalities, but not its complexity if prenatal diagnosis and parental counseling are provided at a cardiovascular-specialized facility. [ABSTRACT FROM AUTHOR]

Objectives: Due to the government's liberalization of epidemic control, the current 2019 novel coronavirus disease (COVID‐19) has started to spread widely within China. This study aimed to use the fetal heart quantification (fetal HQ) technique to assess the cardiac function and morphology of the fetuses of pregnant women diagnosed with COVID‐19 in the early stages of pregnancy. Methods: Exactly 86 pregnant women diagnosed with COVID‐19 infection in early pregnancy (COVID‐19 group) and 90 healthy pregnant women (control group) who underwent fetal echocardiography were prospectively included in this study. The fetal HQ technique was applied to compare the differences in the global sphericity index (GSI), global strain values (GS), fractional area change (FAC), and 24‐segment fractional shortening (FS) of the left and right ventricles, between the COVID‐19 group and the control group. Results: Compared with the control group, the differences in GS and 24‐segment FS of the left ventricle in the COVID‐19 group were not statistically significant. However, the COVID‐19 group showed lower GSI values compared with the control group (1.24 vs 1.28). FAC (48.12%) of the left ventricle and GS (−23.55%), FAC (41.74%) of the right ventricle in the COVID‐19 group were reduced compared with FAC (50.50%) of the left ventricle and GS (−27.63%), FAC (46.01%) of the right ventricle in the control group. Segmental analysis revealed reduced FS in segments 20–24 in the COVID‐19 group compared with the control group. Right ventricular GS was an independent predictor of adverse pregnancy outcome with an optimal cutoff value of −18.66%. Conclusions: The results suggest that COVID‐19 infection in early pregnancy may have a negative impact on fetal cardiac morphology and function. Fetal HQ may offer a new assessment method for the early identification of fetal cardiac alterations in pregnant women infected with COVID‐19. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the feasibility and reliability of tricuspid and mitral annular plane systolic excursion measurements (TAPSE and MAPSE) applying M-mode spatiotemporal image correlation (STIC) technology in low-risk pregnancies. An initial retrospective pilot study was carried out to assess repeatability, followed by a larger mixed cross-sectional and prospective longitudinal study, both evaluating low-risk singleton pregnancies between 22+6 and 39+1 weeks. As only annuli capture was necessary, STIC acquisition parameters were set to the minimum volume angle of 15° and acquisition time of 7.5 s. A total of 330 volumes were analysed offline applying STIC M-mode. Acquisition rates were 96.9 % for TAPSE and 93.7 % MAPSE in the pilot study (n=32) and 98.0 % for both in the longitudinal study (n=102). Both study designs revealed good repeatability for both sides of the heart, with higher intraclass correlation coefficients (ICCs) for TAPSE (0.84–0.94) compared to MAPSE (0.80–0.88). Good repeatability was demonstrated for both sides of the heart, more so for TAPSE than MAPSE, with ICCs for TAPSE 0.84–0.91 and MAPSE 0.75–0.76, comparable to prior ICCs for STIC repeatability. Modified STIC acquisition settings specifically tailored for capturing the longitudinal annular displacement may improve STIC TAPSE and MAPSE acquisition rates, optimising image quality for precise measurement and potentially bringing these modalities closer to clinical application. [ABSTRACT FROM AUTHOR]

Cardiotocography (CTG) is widely used to assess fetal well-being. CTG is typically obtained using ultrasound and autocorrelation methods, which extract periodicity from the signal to calculate the heart rate. However, during labor, maternal vessel pulsations can be measured, resulting in the output of the maternal heart rate (MHR). Since the autocorrelation output is displayed as fetal heart rate (FHR), there is a risk that obstetricians may mistakenly evaluate the fetal condition based on MHR, potentially overlooking the necessity for medical intervention. This study proposes a method that utilizes Doppler ultrasound (DUS) signals and artificial intelligence (AI) to determine whether the heart rate obtained by autocorrelation is of fetal origin. We developed a system to simultaneously record DUS signals and CTG and obtained data from 425 cases. The midwife annotated the DUS signals by auditory differentiation, providing data for AI, which included 30,160 data points from the fetal heart and 2160 data points from the maternal vessel. Comparing the classification accuracy of the AI model and a simple mathematical method, the AI model achieved the best performance, with an area under the curve (AUC) of 0.98. Integrating this system into fetal monitoring could provide a new indicator for evaluating CTG quality. [ABSTRACT FROM AUTHOR]

Evaluation of the fetal heart involves two approaches. The first describes a screening protocol in which the heart is imaged in transverse planes that includes the four‐chamber view (4CV), left and right outflow tracts, and the 3‐vessel‐tracheal view. The second approach is a fetal echocardiogram that requires additional cardiac images as well as evaluating ventricular function using diagnostic tools such as M‐mode and pulsed Doppler ultrasound. Speckle tracking analysis of the ventricular and atrial endocardium of the fetal heart has focused primarily on computing longitudinal global strain. However, the technology enabling this measurement to occur has recently been adapted to enable the clinician to obtain numerous additional measurements of the size, shape, and contractility of the ventricles and atrial chambers. By using the increased number of measurements derived from speckle tracking analysis, we have reported the ability to screen for tetralogy of Fallot, D‐transposition of the great arteries (D‐TGA), and coarctation of the aorta by only imaging the 4CV. In addition, we have found that measurements derived from speckle tracking analysis of the ventricular and atrial chambers can be used to compute the risk for emergent neonatal balloon atrial septostomy in fetuses with D‐TGA. The purpose of this review is to consolidate our experience in one source to provide perspective on the benefits of speckle tracking analysis to measure the size, shape, and contractility of the ventricles and atria imaged in the 4CV in fetuses with congenital heart defects. [ABSTRACT FROM AUTHOR]

Introduction: Increased fetal heart rate variability (IFHRV), defined as fetal heart rate (FHR) baseline amplitude changes of >25 beats per minute with a duration of ≥1 min, is an early sign of intrapartum fetal hypoxia. This study evaluated the level of agreement of machine learning (ML) algorithms-based recognition of IFHRV patterns with expert analysis. Methods: Cardiotocographic recordings and cardiotocograms from 4,988 singleton term childbirths were evaluated independently by two expert obstetricians blinded to the outcomes. Continuous FHR monitoring with computer vision analysis was compared with visual analysis by the expert obstetricians. FHR signals were graphically processed and measured by the computer vision model labeled SALKA. Results: In visual analysis, IFHRV pattern occurred in 582 cardiotocograms (11.7%). Compared with visual analysis, SALKA recognized IFHRV patterns with an average Cohen's kappa coefficient of 0.981 (95% CI: 0.972–0.993). The sensitivity of SALKA was 0.981, the positive predictive rate was 0.822 (95% CI: 0.774–0.903), and the false-negative rate was 0.01 (95% CI: 0.00–0.02). The agreement between visual analysis and SALKA in identification of IFHRV was almost perfect (0.993) in cases (N = 146) with neonatal acidemia (i.e., umbilical artery pH <7.10). Conclusions: Computer vision analysis by SALKA is a novel ML technique that, with high sensitivity and specificity, identifies IFHRV features in intrapartum cardiotocograms. SALKA recognizes potential early signs of fetal distress close to those of expert obstetricians, particularly in cases of neonatal acidemia. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to explore the correlation between fetal aberrant right subclavian artery (ARSA) and chromosomal disorders, with a specific focus on Down syndrome and DiGeorge syndrome. Methods: From November 2017 to February 2020, we conducted fetal anomaly screening and assessed the fetal heart in 8494 at our institution. The right subclavian artery tracing was assessed using Doppler ultrasonography following the 3-vessel and tracheal views (3VTV) in the fetal heart scan. Results: ARSA was found in 31 fetuses, which accounts for 0.36% of the total of 8494 fetuses. 96.8% of fetuses with ARSA were found to have normal chromosomal analysis. We identified only one case of trisomy 21 as the chromosomal condition present. In 80% of the identified ARSA, there were no additional associated findings. Conclusion: ARSA is a rare condition that often does not manifest any concomitant abnormalities. The majority of ARSA instances identified in the second trimester are euploid. If ARSA is the only sonographic finding during fetal anomaly screening and there are no maternal or laboratory risk factors, further evaluation with non-invasive diagnostics may be recommended. Non-invasive genetic testing may be used for additional investigation. [ABSTRACT FROM AUTHOR]

Introduction: Neonatal presentation of coarctation of the aorta (CoA) is a potentially life-threatening condition that is difficult to diagnose in fetal life. We therefore sought to validate and compare novel metrics that may add diagnostic value for fetal CoA, including the diastolic to systolic aortic isthmus VTI ratio (VTId:VTIs), ascending aorta to descending aorta angle (AAo-DAo), transverse aorta to descending aorta angle (TAo-DAo), and LV longitudinal strain (LVS), then to evaluate whether these novel metrics improve specificity to identify fetuses at the highest risk for postnatal CoA without compromising sensitivity. Methods: Retrospective cohort study of fetuses followed a prospective clinical pathway and previously classified as mild, moderate, or high-risk for CoA based on standard fetal echo metrics. Novel metrics were retrospectively measured in a blinded manner. Results: Among fetuses with prenatal concern for CoA, VTId:VTIs, AAo-DAo angle, TAo-DAo angle, and LVS were significantly different between surgical and non-surgical cases (p < 0.01 for all variables). In the subgroup of moderate- and high-risk fetuses, the standard high-risk criteria (flow reversal at the foramen ovale or aortic arch) did not discriminate effectively between surgical and non-surgical cases. VTId:VTIs, AAo-Dao angle, Tao-DAo angle, and LVS all demonstrated greater discrimination than standard high-risk criteria, with specificity of 100% and PPV (positive predictive value) of 78–100%. Conclusions: The incorporation of novel metrics added diagnostic value to our clinical pathway for fetal CoA with higher specificity than the previous high-risk criteria. The incorporation of these metrics into the evaluation of fetuses at moderate- or high-risk for surgical CoA may improve prenatal counseling, allow for more consistent surgical planning, and ultimately optimize hospital resource allocation. Plain Language Summary: Coarctation of the aorta is challenging to diagnosis in fetal life. New fetal echocardiographic techniques have been developed to help predict the development of surgical coarctation of the aorta after birth but have not been externally validated or compared to each other. We sought to validate these metrics and compare their utility in predicting surgical coarctation of the aorta in a retrospective cohort of previously identified fetuses at risk for coarctation of the aorta. We found that among fetuses with prenatal concern for coarctation of the aorta, novel metrics were significantly different between surgical and non-surgical cases. Our results indicate that the incorporation of novel metrics can add diagnostic value for fetal coarctation of the aorta with higher specificity than previous high-risk criteria, without compromising the sensitivity of the low-risk group. The ability to identify fetuses at the highest risk for surgical coarctation may improve prenatal counseling, allow for more consistent surgical planning, and ultimately optimize hospital resource allocation. [ABSTRACT FROM AUTHOR]

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Background: Hypothyroidism is a common endocrine disruption observed in utero that adversely affects fetal growth and maturation leading to long-term impacts on health; however, the exact molecular mechanisms by which these deleterious effects occur are unknown. We hypothesize that fetal hypothyroidism during late gestation will disrupt cell cycle regulation in a tissue-specific manner. To evaluate this, eight pregnant gilts were dosed with either methimazole or an equivalent negative control during days 85–106 out of 114 days of gestation (n = 4/group). Following treatment, the gilts were humanely euthanized, and tissue samples of fetal heart, ileum, kidney, lung, liver, muscle, spleen, and thymus taken from two male and two female fetuses (n = 32) from each gilt. Results: The relative expression of three cell cycle promoters (CDK1, CDK2, and CDK4), and one cell cycle inhibitor (CDKN1A) was compared in each tissue to determine the effect of hypothyroidism on the developing fetus. All of the eight tissues examined experienced at least one significant up- or downregulation in the expression of the aforementioned genes as a result of treatment with methimazole. Substantial changes were observed in the liver and muscle, with the latter experiencing significant downregulations of CDK1, CDK2, and CDK4 as a result of treatment. In addition, all tissues were examined for changes in protein content, which further elucidated the impact of hypothyroidism on the fetal liver by the observation of a marked increase in protein content in the methimazole-treated group. Finally, the heart and liver were histologically examined for evidence of cellular hyperplasia and hypertrophy by measuring average nuclei density and size in each tissue, with the results showing a significant decrease in average nuclei size in the liver of hypothyroid fetuses. Conclusions: Collectively, these findings indicate the occurrence of organ-specific disruptions in cell cycle progression as a result of in utero hypothyroidism, which may explain the long term and widespread effects of hypothyroidism on fetal development. [ABSTRACT FROM AUTHOR]

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, LeakOmy, 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. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess the impact of gestational diabetes mellitus (GDM) on fetal heart structure and function using a technique called fetal heart quantification (Fetal HQ), with a focus on mitochondrial dynamics, which employs advanced imaging technology for comprehensive analysis. Methods: A total of 180 fetuses with normal heart structures, aged 24-40 weeks of gestation, were examined. A 2-3 s cine loop in the standard four-chamber oblique view was captured and analyzed using the speckle-tracking technique with Fetal HQ. Various echocardiographic parameters were evaluated, including four-chamber view (4CV), global spherical index (GSI), global longitudinal strain (GLS), 24-segment spherical index (SI), ventricular fractional area change (FAC), cardiac output (CO), and stroke volume (SV). These parameters were compared between the GDM group and the control group during two gestational periods: 24+0 to 28+0 weeks and 28+1 to 40+1 weeks. Statistical analysis was performed using independent samples t-tests and Mann-Whitney U tests to identify significant differences. Results: Twenty fetuses from mothers with GDM and 40 from the control group were recruited at 24+0 to 28+0 weeks. At 28+1 to 40+1 weeks, 40 fetuses from mothers with GDM and 80 from the control group were recruited. The fetal left ventricular global longitudinal function was similar between the GDM and control groups. However, compared to the controls, right ventricular function in theGDM group was lower only at 28+1 to 40+1 weeks. In the GDM group, the global spherical index (GSI) was lower than in the control group at 28+1 to 40+1 weeks (1.175 vs. 1.22; p = 0.001). There were significant decreases in ventricular FAC (38.74% vs. 42.83%; p < 0.0001) and 4CV GLS for the right ventricle (-22.27% vs. -26.31%; p = 0.005) at 28+1 to 40+1 weeks. Conclusion: Our findings suggest that GDM is associated with decreased right ventricular function in the fetal heart, particularly during the later stages of pregnancy (28+1 to 40+1 weeks), compared to fetuses from healthy pregnancies. The Fetal HQ technique represents a valuable tool for evaluating the structure and function of fetal hearts affected by GDM during the advanced stages of pregnancy. [ABSTRACT FROM AUTHOR]

Epicardial cells regulate heart growth by secreting numerous growth factors and undergoing lineage specification into other cardiac lineages. However, the lack of specificmarker genes for epicardial cells has hindered the understanding of this cell type in heart development. Through the analysis of a cardiac single cell mRNA sequencing dataset, we identified a novel epicardial gene named Keratin 19 (Krt19). Further analysis of the expression patterns of Krt19 and Wt1, a well-known epicardial gene, revealed their preferences in major cardiac cell types. Using lineage-tracing analysis, we analyzed Krt19-CreER labeled cells at multiple time windows and found that it labels epicardial cells at both embryonic and neonatal stages. Furthermore, we studied the function of epicardial cells using a diphtheria toxin A chain (DTA)-based cell ablation system. We discovered that Krt19-CreER labeled cells are essential for fetal heart development. Finally, we investigated the function of Krt19-CreER and Wt1-CreER labeled cells in neonatal mouse development. We observed that the Krt19-CreER; Rosa-DTA mice displayed a smaller size after tamoxifen treatment, suggesting the potential importance of Krt19-CreER labeled cells in neonatal mouse development. Additionally, we found that Wt1-CreER; Rosa-DTA mice died at early stages, likely due to defects in the kidney and spleen. In summary, we have identified Krt19 as a new epicardial cell marker gene and further explored the function of epicardial cells using the Krt19-CreER and Wt1-CreER-mediated DTA ablation system. [ABSTRACT FROM AUTHOR]

Background: Prenatal echocardiographic assessment of fetal cardiac function has become increasingly important. Fetal two‐dimensional speckle‐tracking echocardiography (2D‐STE) allows the determination of global and segmental functional cardiac parameters. Prenatal diagnostics is relying increasingly on artificial intelligence, whose algorithms transform the way clinicians use ultrasound in their daily workflow. The purpose of this study was to demonstrate the feasibility of whether less experienced operators can handle and might benefit from an automated tool of 2D‐STE in the clinical routine. Methods: A total of 136 unselected, normal, singleton, second‐ and third‐trimester fetuses with normofrequent heart rates were examined by targeted ultrasound. 2D‐STE was performed separately by beginner and expert semiautomatically using a GE Voluson E10 (FetalHQ®, GE Healthcare, Chicago, IL). Several fetal cardiac parameters were calculated (end‐diastolic diameter [ED], sphericity index [SI], global longitudinal strain [EndoGLS], fractional shortening [FS]) and assigned to gestational age (GA). Bland‐Altman plots were used to test agreement between both operators. Results: The mean maternal age was 33 years, and the mean maternal body mass index prior to pregnancy was 24.78 kg/m2. The GA ranged from 16.4 to 32.0 weeks (average 22.9 weeks). Averaged endoGLS value of the beginner was ‐18.57% ± 6.59 percentage points (pp) for the right and ‐19.58% ± 5.63 pp for the left ventricle, that of the expert ‐14.33% ± 4.88 pp and ‐16.37% ± 5.42 pp. With increasing GA, right ventricular endoGLS decreased slightly while the left ventricular was almost constant. The statistical analysis for endoGLS showed a Bland‐Altman‐Bias of ‐4.24 pp ± 8.06 pp for the right and ‐3.21 pp ± 7.11 pp for the left ventricle. The Bland‐Altman‐Bias of the ED in both ventricles in all analyzed segments ranged from ‐.49 mm ± 1.54 mm to ‐.10 mm ± 1.28 mm, that for FS from ‐.33 pp ± 11.82 pp to 3.91 pp ± 15.56 pp and that for SI from ‐.38 ±.68 to ‐.15 ±.45. Conclusions: Between both operators, our data indicated that 2D‐STE analysis showed excellent agreement for cardiac morphometry parameters (ED and SI), and good agreement for cardiac function parameters (EndoGLS and FS). Due to its complexity, the application of fetal 2D‐STE remains the domain of scientific‐academic perinatal ultrasound and should be placed preferably in the hands of skilled operators. At present, from our perspective, an implementation into clinical practice "on‐the‐fly" cannot be recommended. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to explore the parents' experiences of home monitoring of the fetal heart rhythm. Women with anti-SSA/Ro52 autoantibodies carry a 2%–3% risk of giving birth to a child with congenital heart block (CHB), following transplacental transfer and antibody-mediated inflammation in the fetal conduction system during 18th to 24th gestational week. Early detection and subsequent treatment have been reported to decrease morbidity and mortality. Therefore, home monitoring of the fetal heart rhythm by Doppler has been offered at our fetal cardiology center. This study was undertaken to explore the lived experience of the routine. Methods: Participants were recruited from a single fetal cardiology center. Consecutive sampling was used. The inclusion criteria were women with SSA/Ro52 antibodies who had undergone Doppler examinations within the last two and a half years at the hospital and had monitored the fetal heartbeat at home. A semi-structured questionnaire was created, and the participants were interviewed individually. The interviews were transcribed verbatim and analyzed according to qualitative content analysis. Results: The overall theme was defined as "walking on thin ice," with six underlying categories: reality, different strategies, gain and loss, healthcare providers, underlying tension, and conducting the examinations again, all with a focus on how to handle the home monitoring during the risk period. Conclusion: Both the mother and the co-parent expressed confidence in their own abilities and that the monitoring provided them with the advantage of growing a bond with the expected child. However, all the participants described a feeling of underlying tension during the risk period. The results show that home monitoring is not experienced as complicated or a burden for the parents-to-be and should be considered a vital part of the chain of care for mothers at risk for giving birth to a child with CHB. However, explaining the teamwork between the different caregivers, for the patients involved, their areas of expertise, and how they collaborate with the patient continues to be a pedagogic challenge and should be developed further. [ABSTRACT FROM AUTHOR]

The article focuses on the effects of prenatal exposure to tetrahydrocannabinol (THC) on fetal cardiac development. Topics include the study's investigation into THC's impact on extracellular matrix composition in fetal hearts, transcriptomic profiling revealing changes in vascular gene expression, and potential long-term implications of altered gene expression on cardiovascular health.

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. [ABSTRACT FROM AUTHOR]

To investigate the association between birth weight to placental weight (BW/PW) ratio, and echocardiographic left ventricle (LV) morphology at birth, while accounting for other relevant perinatal factors. A prospective cohort study was conducted on neonates at NewYork-Presbyterian Brooklyn Methodist Hospital from 2014 to 2018, categorized by their BW/PW percentile. Missing data were imputed with principal component analysis. Chi-squared and one-way analysis of variance were used to compare BW/PW groups and the best regression model was selected using a genetic and backward stepwise algorithm. We analyzed 827 neonates in three BW/PW groups: small (n=16), normal (n=488), and large (n=323). Placental thickness and smallest diameter were positively correlated with several LV parameters, including inter-ventricular septal thickness during diastole (IVSd) (p=0.002, p<0.001) and systole (IVSs) (p=0.001, p<0.001), LV posterior wall thickness at end of diastole (LVPWd) (p=0.003, p<0.001) and systole (LVPWs) (p<0.001, p<0.001), LV mass (p=0.017, p<0.001), and LV mass/volume (p=0.011, p<0.001). The BW/PW ratio correlated with an increased shortening fraction (estimate=0.29, 95 % CI 0.03–0.55, p=0.027). PW correlated with IVSs (p=0.019), while the longest placental diameter was linked to a decrease in LV internal dimension during diastole (LVIDd) (estimate=−0.07, p=0.039), LV mass (estimate=−0.11, p=0.024), and LV mass/volume (estimate=−0.55, p=0.005). This study found that several placental factors, including the BW/PW ratio, can independently affect LV dimension and morphology, highlighting the importance of fetal growth and placental health in the physiological adaptation of the fetal heart. More research is needed to establish causation and inform newborn prevention strategies. [ABSTRACT FROM AUTHOR]

One of the most prevalent zoonotic illnesses in the world, toxoplasmosis, affects both humans and animals and is caused by the parasite Toxoplasma gondii. The infection will trigger the immune system to increase antibody production. This study aims to determine the dose of toxoplasma that causes necrosis in rats placental and fetal hearts. This study was laboratory experimental research with a Randomized Control Trial (RCT). The study design used a post-test only with a control group design. The Ig G variable obtained from the control group (CG) and treatment group 3 (TG3) is the most significant because the mean value difference was the largest (176.56). The Ig M variable obtained from the control group with treatment group 3 (TG3) is the most significant because the mean value difference is the largest (33.47). The fetus weight variable obtained from the control group with treatment group 3 (TG3) is the most significant because the mean value difference is the largest (2.6). The body length variable obtained from the control group between treatment group 3 (TG3) is the most significant because the mean value difference is the largest (1.26). There was a significant difference in placental tissue necrosis (p = 0.034) and heart (p = 0.025) between the control group (CG) and treatment group 3 (TG3). Therefore, there was a significant difference in Ig G, Ig M, fetus weight, body length, placental tissue necrosis, and fetal heart at the 10? dose compared to the 102, 101, and normal doses. [ABSTRACT FROM AUTHOR]

Background Our previous analyses of cardiomyocyte single-nucleus RNA sequencing (snRNAseq) data from the hearts of fetal pigs and pigs that underwent apical resection surgery on postnatal day (P) 1 (ARP1), myocardial infarction (MI) surgery on P28 (MIP28), both ARP1 and MIP28 (ARP1MIP28), or controls (no surgical procedure or CTL) identified 10 cardiomyocyte subpopulations (clusters), one of which appeared to be primed to proliferate in response to MI. However, the clusters composed of primarily proliferating cardiomyocytes still contained noncycling cells, and we were unable to distinguish between cardiomyocytes in different phases of the cell cycle. Here, we improved the precision of our assessments by conducting similar analyses with snRNAseq data for only the 1646 genes included under the Gene Ontology term "cell cycle." Methods Two cardiac snRNAseq datasets, one from mice (GEO dataset number GSE130699) and one from pigs (GEO dataset number GSE185289), were evaluated via our cell-cycle–specific analytical pipeline. Cycling cells were identified via the co-expression of 5 proliferation markers (AURKB, MKI67, INCENP, CDCA8, and BIRC5). Results The cell-cycle–specific autoencoder (CSA) algorithm identified 7 cardiomyocyte clusters in mouse hearts (mCM1 and mCM3-mCM8), including one prominent cluster of cycling cardiomyocytes in animals that underwent MI or Sham surgery on P1. Five cardiomyocyte clusters (pCM1, pCM3-pCM6) were identified in pig hearts, 2 of which (pCM1 and pCM4) displayed evidence of cell cycle activity; pCM4 was found primarily in hearts from fetal pigs, while pCM1 comprised a small proportion of cardiomyocytes in both fetal hearts and hearts from ARP1MIP28 pigs during the 2 weeks after MI induction, but was nearly undetectable in all other experimental groups and at all other time points. Furthermore, pseudotime trajectory analysis of snRNAseq data from fetal pig cardiomyocytes identified a pathway that began at pCM3, passed through pCM2, and ended at pCM1, whereas pCM3 was enriched for the expression of a cell cycle activator that regulates the G1/S phase transition (cyclin D2), pCM2 was enriched for an S-phase regulator (CCNE2), and pCM1 was enriched for the expression of a gene that regulates the G2M phase transition and mitosis (cyclin B2). We also identified 4 transcription factors (E2F8, FOXM1, GLI3, and RAD51) that were more abundantly expressed in cardiomyocytes from regenerative mouse hearts than from nonregenerative mouse hearts, from the hearts of fetal pigs than from CTL pig hearts, and from ARP1MIP28 pig hearts than from MIP28 pig hearts during the 2 weeks after MI induction. Conclusions The CSA algorithm improved the precision of our assessments of cell cycle activity in cardiomyocyte subpopulations and enabled us to identify a trajectory across 3 clusters that appeared to track the onset and progression of cell cycle activity in cardiomyocytes from fetal pigs. [ABSTRACT FROM AUTHOR]

Objective: Docosahexaenoic acid (DHA) is recommended routinely in pregnancy to promote fetal development. DHA has anti‐inflammatory activity, but its effects on the fetal heart and circulation are unknown. This study aimed to investigate whether maternal DHA supplementation in the third trimester affects maternal prostaglandin levels and fetal ductus arteriosus flow dynamics. Methods: This was a double‐blind randomized controlled trial with parallel groups conducted between 2018 and 2021. Pregnant women aged over 18 years with a normal fetus at 27–28 weeks' gestation showing no cardiac/extracardiac anomalies or ductal constriction were eligible for the trial. Women consuming substances with a known inhibitory effect on prostaglandin metabolism, such as non‐steroidal anti‐inflammatory drugs and polyphenol‐rich foods, were excluded. The intervention group received oral supplementation of omega‐3 with 450 mg/day of DHA for 8 weeks and the placebo group received capsules of soy lecithin for 8 weeks. Anthropometric measurements, assessment of polyphenol and omega‐3 consumption, fetal morphological ultrasound examination, fetal Doppler echocardiographic examination and blood sample collection were performed at the start of the study and the latter two were repeated at follow‐up. Prostaglandin E2 (PGE2) level and echocardiographic parameters were compared between the intervention and placebo groups and between baseline and follow‐up. Results: A total of 24 participants were included in each group. After 8 weeks, there were no significant differences between the intervention and placebo groups in maternal serum PGE2 level or Doppler echocardiographic parameters of ductal flow. No case of ductus arteriosus constriction was observed. The expected intragroup changes in cardiac morphology, as a result of advancing gestation, were present. Conclusions: Maternal DHA supplementation in the third trimester at a clinically recommended dose did not result in inhibition of PGE2 or constriction of the ductus arteriosus. These findings should be confirmed in postmarket surveillance studies with larger patient numbers in order to test the full safety profile of DHA and provide robust clinical reassurance. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Large-scale production and waste of plastic materials have resulted in widespread environmental contamination by the breakdown product of bulk plastic materials to micro- and nanoplastics (MNPs). The small size of these particles enables their suspension in the air, making pulmonary exposure inevitable. Previous work has demonstrated that xenobiotic pulmonary exposure to nanoparticles during gestation leads to maternal vascular impairments, as well as cardiovascular dysfunction within the fetus. Few studies have assessed the toxicological consequences of maternal nanoplastic (NP) exposure; therefore, the objective of this study was to assess maternal and fetal health after a single maternal pulmonary exposure to polystyrene NP in late gestation. We hypothesized that this acute exposure would impair maternal and fetal cardiovascular function. Pregnant rats were exposed to nanopolystyrene on gestational day 19 via intratracheal instillation. 24 h later, maternal and fetal health outcomes were evaluated. Cardiovascular function was assessed in dams using vascular myography ex vivo and in fetuses in vivo function was measured via ultrasound. Both fetal and placental weight were reduced after maternal exposure to nanopolystyrene. Increased heart weight and vascular dysfunction in the aorta were evident in exposed dams. Maternal exposure led to vascular dysfunction in the radial artery of the uterus, a resistance vessel that controls blood flow to the fetoplacental compartment. Function of the fetal heart, fetal aorta, and umbilical artery after gestational exposure was dysregulated. Taken together, these data suggest that exposure to NPs negatively impacts maternal and fetal health, highlighting the concern of MNPs exposure on pregnancy and fetal development. [ABSTRACT FROM AUTHOR]

Timely and reliable fetal monitoring is crucial to prevent adverse events during pregnancy and delivery. Fetal phonocardiography, i.e., the recording of fetal heart sounds, is emerging as a novel possibility to monitor fetal health status. Indeed, due to its passive nature and its noninvasiveness, the technique is suitable for long-term monitoring and for telemonitoring applications. Despite the high share of literature focusing on signal processing, no previous work has reviewed the technological hardware solutions devoted to the recording of fetal heart sounds. Thus, the aim of this scoping review is to collect information regarding the acquisition devices for fetal phonocardiography (FPCG), focusing on technical specifications and clinical use. Overall, PRISMA-guidelines-based analysis selected 57 studies that described 26 research prototypes and eight commercial devices for FPCG acquisition. Results of our review study reveal that no commercial devices were designed for fetal-specific purposes, that the latest advances involve the use of multiple microphones and sensors, and that no quantitative validation was usually performed. By highlighting the past and future trends and the most relevant innovations from both a technical and clinical perspective, this review will represent a useful reference for the evaluation of different acquisition devices and for the development of new FPCG-based systems for fetal monitoring. [ABSTRACT FROM AUTHOR]

Background: Congenital heart disease (CHD) is one of the most common birth defects in the world. It is the leading cause of infant mortality, necessitating an early diagnosis for timely intervention. Prenatal screening using ultrasound is the primary method for CHD detection. However, its effectiveness is heavily reliant on the expertise of physicians, leading to subjective interpretations and potential underdiagnosis. Therefore, a method for automatic analysis of fetal cardiac ultrasound images is highly desired to assist an objective and effective CHD diagnosis. Method: In this study, we propose a deep learning-based framework for the identification and segmentation of the three vessels—the pulmonary artery, aorta, and superior vena cava—in the ultrasound three vessel view (3VV) of the fetal heart. In the first stage of the framework, the object detection model Yolov5 is employed to identify the three vessels and localize the Region of Interest (ROI) within the original full-sized ultrasound images. Subsequently, a modified Deeplabv3 equipped with our novel AMFF (Attentional Multi-scale Feature Fusion) module is applied in the second stage to segment the three vessels within the cropped ROI images. Results: We evaluated our method with a dataset consisting of 511 fetal heart 3VV images. Compared to existing models, our framework exhibits superior performance in the segmentation of all the three vessels, demonstrating the Dice coefficients of 85.55%, 89.12%, and 77.54% for PA, Ao and SVC respectively. Conclusions: Our experimental results show that our proposed framework can automatically and accurately detect and segment the three vessels in fetal heart 3VV images. This method has the potential to assist sonographers in enhancing the precision of vessel assessment during fetal heart examinations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Morphology and function in a fetal heart with severe tricuspid regurgitation remains challenging. The aim of this study was to assess cardiac morphology and function in fetuses with severe tricuspid regurgitation by fetal heart quantification (HQ) and to assess the practical value of fetal HQ. Clinical information was analyzed for 63 pregnant women who underwent fetal cardiac ultrasonography. The women were divided into those who had a fetus with severe tricuspid regurgitation (n = 20) and those with a normal fetus (n = 40). The global sphericity index (GSI), fractional area change (FAC), and global longitudinal strain (GLS) of both ventricles and the sphericity index (SI) and fractional shortening (FS) of 24 segments were quantified by fetal HQ using speckle tracking imaging. Fetuses with severe tricuspid regurgitation had a significantly lower GSI (1.14 ± 0.10 vs. 1.26 ± 0.08, p < 0.001) and a higher GSI Z-score (-0.98 ± 1.01 vs. 0.25 ± 0.87, p < 0.001) as well as a significantly lower right ventricular FAC (36.50 ± 7.34% vs. 45.19 ± 3.39%, p < 0.001), FAC Z-score (-1.02 ± 1.41 vs. 0.49 ± 0.74, p < 0.001), and GLS (-21.01 ± 5.66% vs. 45.19 ± 3.49%, p < 0.001). The SI and SI Z-score were significantly lower in segments 1–18 of the right ventricle in fetuses with severe tricuspid regurgitation (p < 0.05); furthermore, FS of segments 1–12 and 19–24 and the FS Z-score of segments 18–24 were significantly lower in fetuses with severe tricuspid regurgitation (p < 0.05). Fetal HQ is useful for evaluation of cardiac morphology and function in fetuses with severe tricuspid regurgitation and can provide important reference information for both clinical diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: Prenatal diagnosis of Berry syndrome, a rare combination of cardiac anomalies including aortopulmonary window (APW), aortic origin of the right pulmonary artery (RPA), interrupted aortic arch (IAA), hypoplastic aortic arch, or coarctation of the aorta (COA), poses a significant challenge. Due to the rarity of the disease, and the limited case reports available to features the complex malformation of Berry syndrome postpartum, this article introduces an innovative approach to visually showcase this unusual disease. The proposed method provides a comprehensive display of the structural deformities, offering valuable insights for clinical practitioners seeking to comprehend this condition. Case presentation: In this report, we present a case where fetal echocardiography aided in diagnosing Berry syndrome, which was later confirmed through postpartum cardiovascular casting. Our experience highlights the importance of using the three-vessel view to diagnose APW and aortic origin of the right pulmonary artery. Additionally, obtaining true cross-sectional and sagittal views by continuously scanning from the three-vessel-trachea view to the long-axis view of the aortic arch is necessary to image IAA or coarctation of the aortic arch. Conclusions: Early and accurate prenatal diagnosis of Berry syndrome is feasible and our cardiovascular cast can perfectly display the microvascular morphology of the fetal heart, which may have great application prospects for postpartum diagnosis and teaching of complex cardiac abnormalities. [ABSTRACT FROM AUTHOR]

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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. 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). 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. 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. [ABSTRACT FROM AUTHOR]

Adult mesenchymal stem cells (MSCs) are a promising cell source for tissue regeneration. However, ex vivo expansion results in cell senescence; cells lose their proliferation and differentiation capacity. Fetal MSCs can offer an alternative due to their robust proliferation and differentiation capacities, as well as their immune privilege properties. Given the rejuvenation effect of the decellularized extracellular matrix (dECM) on adult MSCs, it remains unknown whether dECM influences the regenerative potential of fetal stem cells. In this study, passage five fetal nucleus pulposus cells (fNPCs) and fetal synovium-derived stem cells (fSDSCs) were expanded on dECMs deposited by fNPCs (NECM) and fSDSCs (SECM) for one passage, with expansion on tissue culture plastic (Plastic) as a control. We found that dECM-expanded fNPCs and fSDSCs exhibited both similarities and differences in the expression of stemness genes and surface markers. Expanded fNPCs yielded more differentiated pellets after chondrogenic induction but exhibited no adipogenic differentiation following adipogenic induction in both the Plastic and dECM groups than the corresponding fSDSC group. Despite a significant increase in fNPCs, the dECM-expanded fSDSCs exhibited no increase in chondrogenic potential; however, compared to the Plastic group, dECM-expanded fSDSCs exhibited a small increase in osteogenic potential and a great increase in adipogenic potential. These results suggest that fNPCs are more sensitive to NECM rejuvenation for cartilage tissue engineering and regeneration; in contrast, the dECMs exhibited limited effects on fSDSC rejuvenation in a chondrogenic capacity, except for enhanced adipogenic capacity following expansion on SECM. [ABSTRACT FROM AUTHOR]