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Background: Developing a combined artificial intelligence (AI) and ultrasound imaging to provide an accurate, objective, and efficient adjunctive diagnostic approach for fetal heart ventricular septal defects (VSD). Methods: 1,451 fetal heart ultrasound images from 500 pregnant women were comprehensively analyzed between January 2016 and June 2022. The fetal heart region was manually labeled and the presence of VSD was discriminated by experts. The principle of five-fold cross-validation was followed in the training set to develop the AI model to assist in the diagnosis of VSD. The model was evaluated in the test set using metrics such as mAP@0.5, precision, recall, and F1 score. The diagnostic accuracy and inference time were also compared with junior doctors, intermediate doctors, and senior doctors. Results: The mAP@0.5, precision, recall, and F1 scores for the AI model diagnosis of VSD were 0.926, 0.879, 0.873, and 0.88, respectively. The accuracy of junior doctors and intermediate doctors improved by 6.7% and 2.8%, respectively, with the assistance of this system. Conclusions: This study reports an AI-assisted diagnostic method for VSD that has a high agreement with manual recognition. It also has a low number of parameters and computational complexity, which can also improve the diagnostic accuracy and speed of some physicians for VSD. [ABSTRACT FROM AUTHOR]

Objective: The main objective of this study is to investigate whether there is a difference in the occurrence of MSAF between fever and nonfever–pregnant women during the COVID‐19 pandemic. Study Design: We conducted a multicenter retrospective study including pregnant women during the COVID‐19 pandemic. Among the 400 pregnant women included in the final data analysis, 238 had fever during delivery, while 162 nonfever–pregnant women met the inclusion and exclusion criteria and served as controls. We collected various obstetric and neonatal parameters for both groups of patients, compared, and statistically tested the significance of these parameters. For parameters with significant statistical differences and clinical significance, we performed logistic regression analysis to explore potential risk factors for MSAF. Result: In a sample of 400 parturients, a total of 69 individuals (17.25%) were discovered to have MSAF with the prevalence increasing to 21.85% in the fever population. A statistically significant association was observed between fever during pregnancy and MSAF, with a higher risk of development observed in fever–pregnant women compared to nonfever ones. Specifically, the odds of developing MSAF increased by a factor of 0.979 in fever‐pregnant women compared to nonfever ones, as determined by a logistic regression model (OR = 1.979, 95% CI = 1.061∼3.693, p = 0.032). Moreover, pregnant women with COVID‐19 infection had a significantly higher risk of developing MSAF, with the odds increasing by a factor of 2.567 compared to uninfected pregnant women (OR = 3.567, 95% CI = 1.622∼7.845, p = 0.002). In addition, the study also identified abnormal fetal heart monitoring (p < 0.05) and gestational age (p < 0.05) as independent risk factors for the occurrence of MSAF. Conclusion: For pregnant women infected with COVID‐19, the rate of MSAF disturbance significantly increases, therefore, it is necessary to pay more attention to fetal heart changes and amniotic fluid conditions, and actively managing labor is beneficial for improving delivery outcomes. [ABSTRACT FROM AUTHOR]

During vaginal delivery, the delivery requires the fetal head to mold to accommodate the geometric constraints of the birth canal. Excessive molding can produce brain injuries and long-term sequelae. Understanding the loading of the fetal brain during the second stage of labor (fully dilated cervix, active pushing, and expulsion of fetus) could thus help predict the safety of the newborn during vaginal delivery. To this end, this study proposes a finite element model of the fetal head and maternal canal environment that is capable of predicting the stresses experienced by the fetal brain at the onset of the second phase of labor. Both fetal and maternal models were adapted from existing studies to represent the geometry of full-term pregnancy. Two fetal positions were compared: left-occiput-anterior and left-occiput-posterior. The results demonstrate that left-occiput-anterior position reduces the maternal tissue deformation, at the cost of higher stress in the fetal brain. In both cases, stress is concentrated underneath the sutures, though the location varies depending on the presentation. In summary, this study provides a patient-specific simulation platform for the study of vaginal delivery and its effect on both the fetal brain and maternal anatomy. Finally, it is suggested that such an approach has the potential to be used by obstetricians to support their decision-making processes through the simulation of various delivery scenarios. [ABSTRACT FROM AUTHOR]

The article discusses the consensus opinion from the Fetal Heart Society on the acute maternal hyperoxygenation (MH) protocol. Acute MH testing can help understand fetal pulmonary vascular reactivity and simulate postnatal circulatory shifts. The document provides a standardized approach to conducting acute MH testing, including indications, timing, oxygen administration, fetal echocardiography assessments, and interpretation of findings. The consensus opinion aims to guide fetal cardiac centers interested in implementing acute MH testing for clinical and research purposes. [Extracted from the article]

Objective: To compare fetal cardiac function in pregnant women with iron deficiency anemia (IDA) vs healthy pregnant controls. Methods: This was a single‐center, prospective, case–control study conducted in a tertiary hospital between November 2022 and September 2023. Women diagnosed with IDA who attended as outpatients at the pregnancy follow‐up clinic at 30–34 weeks' gestation or who were hospitalized for intravenous iron treatment owing to profound anemia were included. The control group consisted of randomly selected gestational‐age‐matched pregnant women with no obstetric complications or comorbidities and who did not have anemia. Patients underwent two‐dimensional imaging, followed by pulsed‐wave Doppler and M‐mode and tissue Doppler imaging (TDI) to evaluate fetal cardiac function. A fetal cardiac score was calculated using systolic, diastolic and global hemodynamic function parameters, and was compared between patients with IDA and those without. The fetal cardiac score was also assessed according to the severity of anemia in the IDA group. Results: A total of 150 patients, comprising 50 patients with IDA and 100 healthy pregnant women at 30–34 weeks' gestation, were included in the study. Of the patients with IDA, 20 had mild, 18 had moderate and 12 had severe anemia. The fetal myocardial performance index and isovolumetric relaxation time were significantly higher in the IDA group compared with the control group (P < 0.0001 for both), while isovolumetric contraction time was similar. Among the fetal tricuspid and mitral valve diastolic parameters, the E, A and E/A values were significantly lower in the IDA group (P < 0.05 for all). Mitral (MAPSE) and tricuspid (TAPSE) annular plane systolic excursions were significantly lower in the IDA group (P < 0.05 for both). The IDA group also had significantly lower values for the TDI parameters mitral and tricuspid E′, A′, S′ and E′/A′ ratio and a significantly higher E/E′ ratio (P < 0.05 for all). Among the IDA subgroups, a significant decrease was observed in the tricuspid and mitral A, E and E/A ratio in fetuses whose mothers had severe anemia (P = 0.001). M‐mode Doppler analysis revealed significantly lower fetal TAPSE and MAPSE in the patient group with severe maternal anemia (P = 0.001 for both). According to the subgroup comparison of TDI findings, the fetuses of mothers with severe anemia had significantly lower tricuspid and mitral E′, A′, S′ and E′/A′ ratio values and a significantly higher E/E′ ratio (P < 0.05 for all). The fetal cardiac score was significantly higher in the maternal IDA group compared with the control group (P < 0.001). A significant negative correlation was found between maternal hemoglobin level and fetal cardiac score (P < 0.001). Conclusions: We observed differences in fetal systolic and diastolic cardiac function in pregnancies with maternal IDA. Fetal cardiac function was affected more among patients with severe anemia. This study found an increased E/E′ ratio in the fetuses of pregnant women with IDA, suggesting decreased fetal heart maturation. Prenatal fetal cardiac evaluation, especially in women with severe anemia, can facilitate a more seamless transition to the postnatal period for these newborns. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

The article discusses the recent recommendations from the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) regarding the third-trimester obstetric ultrasound scan, focusing on the evaluation of the fetal heart. It suggests additional recommendations for clinicians implementing these guidelines, particularly in measuring the size of the fetal heart and assessing ventricular and outflow tract disproportion. The article provides detailed methods for measuring the fetal heart, calculating ratios, and identifying abnormalities associated with cardiomegaly and ventricular disproportion, offering calculators to aid in the evaluation process. [Extracted from the article]

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]

Our previous study has demonstrated that the decline in cardiomyocytes proliferation capacity induced by maternal androgen excess was mainly attributed to the accumulation of androsterone in the heart. However, the underlying mechanism by which androsterone inhibits cardiomyocytes proliferation remains unknown. In this study, pregnant mice were injected subcutaneously daily with dihydrotestosterone (DHT) from gestational day (GD) 16.5 to GD18.5. On GD18.5, fetal heart tissue was dissected and used for analyzing androgen receptor (AR) levels. H9c2 cells and primary cardiomyocytes, isolated from fetal hearts, were applied to investigate the mechanism. H9c2 cells under androsterone treatment were subjected to RNA sequencing analysis and the results showed that genes were primarily enriched in cell cycle and DNA replication pathways. Elevated AR levels were observed in fetal cardiac tissue in the maternal DHT‐treated group. Androsterone treatment increased the ratio of nuclear AR and cytoplasmic AR both in H9c2 cells and primary cardiomyocytes. The ablation and overexpression of AR can mildly reverse and aggravate cell cycle arrest induced by androsterone, respectively. ChIP‐qPCR analysis suggested that AR can directly repress cell cycle and DNA replication‐related gene expression, which was mediated by the recruitment of retinoblastoma protein (Rb). The repression of cell proliferation in response to androsterone was alleviated partly through the downregulation of Rb by siRNA transfection. In conclusion, AR repression to cell cycle and DNA replication‐related gene expression, mediated by recruitment of Rb, may be one of the potential mechanisms of cell cycle arrest in cardiomyocytes induced by androsterone. [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]

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]

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. [Display omitted] • Gene expression map of human fetal hearts from the four-time points were identified. • Dynamic alteration of cell subpopulations and gene expression during heart development. • ANNEXIN, MIF, PTN, GRN, OSM signalling pathways are crucial in heart development. [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]

Objective Methods Results Conclusion Supported by remote signal processing techniques and wireless communication technology, remote electronic fetal monitoring (REFM) has emerged as a promising alternative to traditional electronic fetal monitoring (TEFM) in clinical practice. The aim of this study was to evaluate the comparability, accessibility, and clinical utility of REFM in contrast to TEFM.This was a multicenter prospective cohort study. A cohort of 2900 pregnant women were enrolled from three medical centers between June 1, 2021 and June 31, 2022. Among them, 800 utilized REFM, with 760 of them completing the self‐rating anxiety scale (SAS) and self‐rating depression scale (SDS) assessments using the devices for 1 month. The control group comprised 2100 pregnant women who did not use REFM. Additionally, 80 pregnant women concurrently employed both REFM and TEFM, and their respective curve coincidence rates were determined through curve fitting. Primary outcomes encompassed pregnancy outcomes in both groups, average curve coincidence rates between REFM and TEFM, as well as SDS and SAS scores.Among the 760 pregnant women who completed SAS and SDS assessments, their average SAS scores before and after 1 month of REFM usage were 43.09 ± 8.04 and 41.58 ± 6.59, respectively. Concurrently, the average SDS scores before and after 1 month of REFM usage were 45.45 ± 9.60 and 44.80 ± 9.17, respectively. A statistically significant decrease was observed in SAS scores (P = 0.005), whereas no significant difference was noted in SDS scores (P = 0.340). Furthermore, a statistically significant difference in the rate of adverse pregnancy outcomes (neonatal asphyxia) emerged between the two groups, those who employed REFM and those who did not (P = 0.021). In the subset of 80 pregnant women employing both REFM and TEFM, all 80 results showed precise congruence between the two methods. The average coincidence rate was determined to be 79.45% ± 12.64%.REFM contributes to improved pregnancy outcomes and exhibits a high level of concordance with TEFM, thereby accurately reflecting the quality of fetal heart monitoring. Additionally, REFM effectively mitigates pregnant women's anxiety. Thus, REFM demonstrates comparability, accessibility, and clinical utility. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusion To investigate the fetal heart using pulsed wave Doppler, M‐mode, and tissue Doppler imaging (TDI) in cases of intrahepatic cholestasis of pregnancy (ICP).This prospective study was conducted at a single tertiary center and included 35 patients with ICP and 70 healthy pregnant women at 28–36 weeks of pregnancy. Among the patients with ICP, 26 had serum bile acid (SBA) levels less than 40 μmol/L and nine had SBA levels of 40 μmol/L or greater. Pulsed wave Doppler, M‐mode, and TDI evaluations were performed on the patients to assess fetal cardiac function.The ICP group exhibited significantly higher myocardial performance index (MPI) and isovolumetric relaxation time (IRT), but similar isovolumetric contraction time (ICT). The tricuspid and mitral valve E, A, and E/A ratios were significantly reduced in the ICP group. The TDI parameters showed significantly reduced tricuspid and mitral valve E′/A′ ratios in the ICP group compared with the control group (P < 0.001). The E/E′ ratio was significantly increased in the ICP group (P < 0.001). According to the M‐mode Doppler findings, tricuspid and mitral annular plane systolic excursion values were significantly decreased in the ICP group (P = 0.005 and P = 0.001, respectively). In the subgroup analysis, MPI and IRT were significantly higher in the severe ICP group.ICP might induce changes in the fetal heart during the early systolic and diastolic phases. The detection of these early changes using M‐mode and TDI during the antenatal period can provide valuable insights into the condition of the fetus. [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]

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]

Prediction of fetal growth restriction (FGR) and small of gestational age (SGA) infants by using various ultrasound cardiac parameters in a logistic regression model. 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. 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 (pright = 0.000, pleft = 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 %. 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. [ABSTRACT FROM AUTHOR]

Abstract Background Developing a combined artificial intelligence (AI) and ultrasound imaging to provide an accurate, objective, and efficient adjunctive diagnostic approach for fetal heart ventricular septal defects (VSD). Methods 1,451 fetal heart ultrasound images from 500 pregnant women were comprehensively analyzed between January 2016 and June 2022. The fetal heart region was manually labeled and the presence of VSD was discriminated by experts. The principle of five-fold cross-validation was followed in the training set to develop the AI model to assist in the diagnosis of VSD. The model was evaluated in the test set using metrics such as mAP@0.5, precision, recall, and F1 score. The diagnostic accuracy and inference time were also compared with junior doctors, intermediate doctors, and senior doctors. Results The mAP@0.5, precision, recall, and F1 scores for the AI model diagnosis of VSD were 0.926, 0.879, 0.873, and 0.88, respectively. The accuracy of junior doctors and intermediate doctors improved by 6.7% and 2.8%, respectively, with the assistance of this system. Conclusions This study reports an AI-assisted diagnostic method for VSD that has a high agreement with manual recognition. It also has a low number of parameters and computational complexity, which can also improve the diagnostic accuracy and speed of some physicians for VSD.

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. [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]

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]

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]

This article discusses the use of transvaginal SlowflowHD imaging technology to examine the development of embryonic and fetal hearts in the first trimester of pregnancy. The study found that by the 11th week of gestation, all major structures of the heart had developed. The article also mentions previous studies that used older technology to visualize cardiac structures, but the quality of the images was poor. The authors conclude that transvaginal SlowflowHD imaging provides a high-resolution and sensitive method for assessing cardiac structures in early pregnancy. The use of SlowflowHD has the potential to diagnose congenital heart anomalies and provide valuable diagnostic information on various heart conditions. However, it cannot determine flow direction and velocity, and further research is needed to explore its potential role in early fetal cardiac diagnosis. [Extracted from the article]

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 Methods Results Conclusions Commercial products currently available for sperm selection utilizing hyaluronic acid (HA) binding prior to intracytoplasmic sperm injection (ICSI) are widely used but have some disadvantages. To potentially circumvent these limitations, we compared ICSI using a self‐made hyaluronic acid (smHA) reagent with ICSI using SpermSlow.The binding of the reagents to spermatozoa on plastic‐ or glass‐bottom dishes was quantitated using spermatozoa that were isolated by density‐gradient centrifugation and swim‐up procedures (N = 10/group). Additionally, we investigated the relationship between the HA reagent used prior to ICSI and clinical outcomes after assisted reproduction with HA‐ICSI (N = 81).The smHA reagent exhibited extremely stable binding to human spermatozoa. The binding time of spermatozoa was significantly longer in the smHA reagent than in SpermSlow on both plastic and glass dishes (plastic: 60.0 ± 0.0 min vs. 2.7 ± 5.9 min, P < 0.001; glass: 60.0 ± 0.0 min vs. 2.5 ± 1.8 min, P < 0.001). There were no significant differences in the normal fertilization rate between HA‐ICSI with the smHA reagent (128/160, 80.0%) and HA‐ICSI with SpermSlow (171/231, 74.0%, P = 0.184). The frequency of the blastocyst development from the HA‐ICSI‐derived zygote was significantly higher with the smHA reagent (74/101, 73.3%) than with SpermSlow (76/131, 58.0%, P = 0.019). The rates of biochemical pregnancy, clinical pregnancy, fetal heart movement, live birth, and miscarriage were not significantly different between HA‐ICSI with the smHA reagent and HA‐ICSI with SpermSlow.The blastulation rate was higher for HA‐ICSI with the smHA reagent as compared with SpermSlow. Clinical outcomes, excluding blastulation, after HA‐ICSI were the same using smHA reagent and using SpermSlow. Spermatozoa binding to the smHA reagent was not attenuated over a 60‐min time course. In conclusion, this reagent may shorten and simplify HA‐ICSI procedures because smHA can be used with any dish material, making it easier to observe the spindle or assess intracytoplasmic morphology. [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]

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]

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: 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]

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]

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]

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]

We evaluated the outcomes of pregnancy in women with congenital heart disease (CHD) and their offspring in Taiwan. We also investigated how different severity levels may influence the outcomes. We used data (2009–2017) from the Birth Certificate Application database in Taiwan, which is linked to the National Health Insurance Research Database and Taiwan Maternal and Child Health Database. We identified 2990 women with CHD who had 4227 births. Based on the CHD subtypes, patients were further divided into "severe CHD" and "simple CHD" groups. Women with CHD have a significant risk of stillbirth. In maternal cardiac events, they had the highest risk of heart failure, followed by arrhythmia. The severity of CHD had a significant effect on the outcomes as well. The neonatal birth event that mothers with CHD have the highest risk of is preterm birth at < 32 weeks of gestation. The prominent difference in neonatal morbidities between mothers with severe and simple CHD is recurrent CHD in the offspring. The offspring of the severe CHD group had a higher risk of severe CHD, whereas those of the simple CHD group had a higher risk of simple CHD. During pregnancy, the monitoring of heart function and cardiac rhythm could be more intensive in mothers with CHD. In addition to accurately assessing fetal growth and development during antenatal care, mothers with severe CHD should be provided with careful fetal heart structure assessment and genetic testing along with counseling. [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]

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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]

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]

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]