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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]

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]

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]

Mitochondria undergo a myriad of changes during pre-implantation embryo development, including shifts in activity levels and mitochondrial DNA (mtDNA) replication. However, how these distinct aspects of mitochondrial function are linked and their responsiveness to diverse stressors is not well understood. Here, we show that mtDNA content increased between 8-cell embryos and the blastocyst stage, with similar copy numbers per cell in the inner cell mass (ICM) and trophectoderm (TE). In contrast, mitochondrial membrane potential (MMP) was higher in TE than ICM. Culture in ambient oxygen (20% O2) altered both aspects of mitochondrial function: the mtDNA copy number was upregulated in ICM, while MMP was diminished in TE. Embryos cultured in 20% O2 also exhibited delayed development kinetics, impaired implantation, and reduced mtDNA levels in E18 fetal liver. A model of oocyte mitochondrial stress using rotenone showed only a modest effect on on-time development and did not alter the mtDNA copy number in ICM; however, following embryo transfer, mtDNA was higher in the fetal heart. Lastly, endogenous mitochondrial dysfunction, induced by maternal age and obesity, altered the blastocyst mtDNA copy number, but not within the ICM. These results demonstrate that mitochondrial activity and mtDNA content exhibit cell-specific changes and are differentially responsive to diverse types of oxidative stress during pre-implantation embryogenesis. [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]

Developments in medicine and biology in recent decades have led to a significant increase in our knowledge of the complex interactions between the microbiota and human health. In the context of perinatal medicine and neonatology, particular attention is being paid to the potential impact of the maternal microbiota on fetal development. Among the many aspects of this relationship, the question of the impact of dysbiosis on the development of fetal heart defects is an important one. In this article, we present an analysis of recent research and scientific evidence on the relationship between a pregnant woman's microbiota and the development of fetal heart defects. We also discuss potential intervention strategies, including the role of probiotics and diet in optimising the maternal microbiota. [ABSTRACT FROM AUTHOR]

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

Human pluripotent stem cells have been employed in generating organoids, yet their immaturity compared to fetal organs and the limited induction of all constituent cell types remain challenges. Porcine fetal progenitor cells have emerged as promising candidates for co-culturing with human progenitor cells in regeneration and xenotransplantation research. This study focused on identifying proper preservation methods for porcine fetal kidneys, hearts, and livers, aiming to optimize their potential as cell sources. Extracted from fetal microminiature pigs, these organs were dissociated before and after cryopreservation–thawing, with subsequent cell quality evaluations. Kidney cells, dissociated and aggregated after vitrification in a whole-organ form, were successfully differentiated into glomeruli and tubules in vivo. In contrast, freezing hearts and livers before dissociation yielded suboptimal results. Heart cells, frozen after dissociation, exhibited pulsating heart muscle cells similar to non-frozen hearts. As for liver cells, we developed a direct tissue perfusion technique and successfully obtained highly viable liver parenchymal cells. Freezing dissociated liver cells, although inferior to their non-frozen counterparts, maintained the ability for colony formation. The findings of this study provide valuable insights into suitable preservation methods for porcine fetal cells from kidneys, hearts, and livers, contributing to the advancement of regeneration and xenotransplantation research. [ABSTRACT FROM AUTHOR]

The increasing popularity of electronic cigarettes (e-cigarettes) as an alternative to conventional tobacco products has raised concerns regarding their potential adverse effects. The cardiovascular system undergoes intricate processes forming the heart and blood vessels during fetal development. However, the precise impact of e-cigarette smoke and aerosols on these delicate developmental processes remains elusive. Previous studies have revealed changes in gene expression patterns, disruptions in cellular signaling pathways, and increased oxidative stress resulting from e-cigarette exposure. These findings indicate the potential for e-cigarettes to cause developmental and cardiovascular harm. This comprehensive review article discusses various aspects of electronic cigarette use, emphasizing the relevance of cardiovascular studies in Zebrafish for understanding the risks to human health. It also highlights novel experimental approaches and technologies while addressing their inherent challenges and limitations. [ABSTRACT FROM AUTHOR]

Fetal hyperthyroidism can occur secondary to maternal autoimmune hyperthyroidism. The thyroid-stimulating hormone receptor antibody (TRAb) transferred from the mother to the fetus stimulates the fetal thyroid and causes fetal thyrotoxicosis. Fetuses with this condition are difficult to detect, especially after maternal Graves disease therapy. Here, we present two cases of fetal hyperthyroidism with maternal hypothyroidism and review the assessment and intrauterine therapy for fetal hyperthyroidism. Both women were referred at 22+ and 23+ weeks of gestation with abnormal ultrasound findings, including fetal heart enlargement, pericardial effusion, and fetal tachycardia. Both women had a history of Graves disease while in a state of hypothyroidism with a high titer of TRAb. A sonographic examination showed a diffusely enlarged fetal thyroid with abundant blood flow. Invasive prenatal testing revealed no significant chromosomal aberration. Low fetal serum TSH and high TRAb levels were detected in the cord blood. Fetal hyperthyroidism was considered, and maternal oral methimazole (MMI) was administered as intrauterine therapy, with the slowing of fetal tachycardia, a reduction in fetal heart enlargement, and thyroid hyperemia. During therapy, maternal thyroid function was monitored, and the dosage of maternal levothyroxine was adjusted accordingly. Both women delivered spontaneously at 36+ weeks of gestation, and neonatal hyperthyroidism was confirmed in both newborns. After methimazole and propranolol drug treatment with levothyroxine for 8 and 12 months, both babies became euthyroid with normal growth and development. [ABSTRACT FROM AUTHOR]

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

Maternal immune activation results in altered levels of cytokines in the maternal–fetal system, which has a negative impact on fetal development, including the gonadotropin-releasing hormone (GnRH) system, which is crucial for the reproduction. Suppression of GnRH–neuron migration may be associated with cytokine imbalances, and primarily with proinflammatory cytokine interleukin (IL)-6. This study aimed to determine the effects of IL-6 and monoclonal antibody to IL-6 or IL-6R or polyclonal IgG on the formation of migration route of GnRH–neurons in ex vivo and in vivo rodent models on day 11.5 of embryonic development. The increased level of IL-6 in mouse nasal explants suppressed peripherin-positive fiber outgrowth, while this led to an increase in the number of GnRH–neurons in the nose and olfactory bulbs and a decrease in their number in the fetal brain. This effect is likely to be realized via IL-6 receptors along the olfactory nerves. The suppressive effect of IL-6 was diminished by monoclonal antibodies to IL-6 or its receptors and by IgG. [ABSTRACT FROM AUTHOR]

Simple Summary: Variations in the echogenicity of specific areas of the fetal kidneys, cortex and medulla are studied in this work during the last 10 days of pregnancy in bitches. The aim was to measure these variations and to identify any correlation with days before parturition (dbp). For this reason, 10 clinically healthy pregnant bitches (2–8 years old, 8.8–40.3 kg bw) were ultrasonographically evaluated from −10 to 0 days before parturition (dbp). Longitudinal kidney US scanning was performed on the three most caudal fetuses, and quantitative parameters were measured in their renal cortex and medulla, such as the mean gray level (MGL) and SD of a manually drawn region of interest (ROI), using specific (Fiji Image J 1.51h, Java 1.6 0_24 64 bit). software. The parameters affected by dbp only were the cortical SD (C-SD) and cortico-medullary SD (C/M-SD), which decreased as delivery approached, indicating a reduction in the heterogeneity of these structures. As they were only affected by dbp, and not by maternal and litter size, further studies may concentrate on those parameters in order to evaluate their usefulness for pregnancy monitoring and parturition prediction and their diagnostic value for the onset of renal pathologies in neonatal, pediatric and adult dogs. The objective of this study was to assess changes in the echogenicity of the cortex and medulla of canine fetal kidneys in relation to days before parturition (dbp), maternal size and litter size. Monitoring of 10 healthy pregnant bitches (2–8 years old, 8.8–40.3 kg bw) was conducted from −10 to 0 dbp using ultrasound. A single renal sonogram was obtained by scanning in a longitudinal section the three most caudal fetuses. The mean gray level (MGL) and SD of a manually drawn region of interest (ROI) in the renal cortex and medulla were measured using the Fiji Image J software (Image J 1.51h, Java 1.6 0_24 64 bit). A linear mixed model taking into account the maternal size as a fixed effect, dbp and litter size as covariates and the bitch as a random and repeated effect was used. The regression coefficients (b) were estimated. Cortical SD (C-SD) and cortico-medullary SD (C/M-SD) were influenced by dbp, with a significant decrease at the approaching day of parturition (b = 0.23 ± 0.06, p < 0.001 and b = 0.5 ± 0.02, p = 0.038, respectively). Maternal size had a significant impact on C/M-MGL with differences observed in large-sized (1.95 ± 0.13) compared to small- (1.41 ± 0.10, p = 0.027) and medium-sized bitches (1.51 ± 0.09, p = 0.016). The C/M-MGL was influenced by litter size, showing a decrease as the number of pups increased (b = −0.08 ± 0.03, p = 0.018). C-SD and C/M-SD were exclusively affected by dbp, and not by maternal and litter size. This suggests their potential as valuable parameters, warranting further investigations in future studies. [ABSTRACT FROM AUTHOR]

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

Simple Summary: About 15% of people born with congenital heart disease (CHD) have a specific genetic abnormality called a copy number variant. Most of their genetic tests, called chromosomal microarrays (CMAs), are considered normal. However, we suspected that some very small genetic deletions might be linked to CHD even though they were not reported in the test results. To investigate this, we investigated genetic test data from 319 patients with CHD. Then, we focused on genes in these small deletions that were somehow related to CHD, based on certain criteria like their association with CHD, their expression level in fetal hearts, and the potential impact of losing these genes. After analyzing the data, we found that these unreported small genetic deletions were slightly more likely to involve genes known to be related to CHD and also genes that might be important but were not recognized before. Our study suggests that "normal" genetic test data, which is readily available, can be valuable for discovering new genetic links to CHD. Also, smaller genetic deletions should be given more clinical attention for potential implications in CHD. About 15% of congenital heart disease (CHD) patients have a known pathogenic copy number variant. The majority of their chromosomal microarray (CMA) tests are deemed normal. Diagnostic interpretation typically ignores microdeletions smaller than 100 kb. We hypothesized that unreported microdeletions are enriched for CHD genes. We analyzed "normal" CMAs of 1762 patients who were evaluated at a pediatric referral center, of which 319 (18%) had CHD. Using CMAs from monozygotic twins or replicates from the same individual, we established a size threshold based on probe count for the reproducible detection of small microdeletions. Genes in the microdeletions were sequentially filtered by their nominal association with a CHD diagnosis, the expression level in the fetal heart, and the deleteriousness of a loss-of-function mutation. The subsequent enrichment for CHD genes was assessed using the presence of known or potentially novel genes implicated by a large whole-exome sequencing study of CHD. The unreported microdeletions were modestly enriched for both known CHD genes and those of unknown significance identified using their de novo mutation in CHD patients. Our results show that readily available "normal" CMA data can be a fruitful resource for genetic discovery and that smaller deletions should receive more attention in clinical evaluation. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to analyze the neonatal outcomes of fetuses with diagnosed functional cardiovascular abnormalities, also considering the connection with neonatal hyperbilirubinemia. Materials and Methods: It was an observational study of 100 neonates who had fetal echocardiography examinations in the third trimester (mean gestational age during the last echocardiography was 34 ± 3 weeks and mean birth weight was 3550 g). There were two groups: A: normal heart anatomy + no functional anomalies; group B: normal heart anatomy + functional abnormalities. Hyperbilirubinemia was defined as a bilirubin level of >10 mg%. Results: In group A, there were 72 cases and only 5 cases despite having normal heart anatomy and normal heart study that presented additional problems. In group B (28 cases), the prenatal functional findings included tricuspid regurgitation (TR) (15 cases, 53%), pericardial effusion (4 cases, 14%), myocardial hypertrophy (4 cases, 14%), cardiomegaly (2 cases, 7%), abnormal bidirectional blood flow across the foramen ovale (3 cases, 11%), aneurysm of atrial septum (2 case, 7%), abnormal E/A ratio for mitral and tricuspid valve (1 case, 3%), bright spot (3 case, 11%), abnormal Doppler flow in ductus arteriosus compared to aortic arch (difference >60 cm/s) (1 case, 3%), supraventricular tachycardia (SVT) (1 case), and mitral regurgitation (1 case, 3%). In group A (n = 72 cases), bilirubin levels of >10 mg/dL were observed in 8% of newborns. In group B (n = 28), bilirubin levels of > 10 m/dL were observed in 46% of cases and TR was present in group B in 53% of cases (15/28 cases). The difference between group A and B in terms of elevated bilirubin levels was statistically significant (p < 0.001). Conclusions: In the case of fetal normal heart anatomy and normal heart study, a good neonatal outcome may be expected. When fetal cardiovascular functional abnormalities in normal heart anatomy are detected, with special attention paid to tricuspid valve regurgitation, a neonatal elevated bilirubin level (mean 11 mg/dL, range 10–15 mg/dL) may be expected. [ABSTRACT FROM AUTHOR]

Injury to skeletal muscle through trauma, physical activity, or disease initiates a process called muscle regeneration. When injured myofibers undergo necrosis, muscle regeneration gives rise to myofibers that have myonuclei in a central position, which contrasts the normal, peripheral position of myonuclei. Myofibers with central myonuclei are called regenerating myofibers and are the hallmark feature of muscle regeneration. An important and underappreciated aspect of muscle regeneration is the maturation of regenerating myofibers into a normal sized myofiber with peripheral myonuclei. Strikingly, very little is known about processes that govern regenerating myofiber maturation after muscle injury. As knowledge of myofiber formation and maturation during embryonic, fetal, and postnatal development has served as a foundation for understanding muscle regeneration, this narrative review discusses similarities and differences in myofiber maturation during muscle development and regeneration. Specifically, we compare and contrast myonuclear positioning, myonuclear accretion, myofiber hypertrophy, and myofiber morphology during muscle development and regeneration. We also discuss regenerating myofibers in the context of different types of myofiber necrosis (complete and segmental) after muscle trauma and injurious contractions. The overall goal of the review is to provide a framework for identifying cellular and molecular processes of myofiber maturation that are unique to muscle regeneration. [ABSTRACT FROM AUTHOR]

Myocardial injury causes death to cardiomyocytes and leads to heart failure. The adult mammalian heart has very limited regenerative capacity. However, the heart from early postnatal mammals and from adult lower vertebrates can fully regenerate after apical resection or myocardial infarction. Thus, it is of particular interest to decipher the mechanism underlying cardiac regeneration that preserves heart structure and function. RNA-binding proteins, as key regulators of post-transcriptional gene expression to coordinate cell differentiation and maintain tissue homeostasis, display dynamic expression in fetal and adult hearts. Accumulating evidence has demonstrated their importance for the survival and proliferation of cardiomyocytes following neonatal and postnatal cardiac injury. Functional studies suggest that RNA-binding proteins relay damage-stimulated cell extrinsic or intrinsic signals to regulate heart regenerative capacity by reprogramming multiple molecular and cellular processes, such as global protein synthesis, metabolic changes, hypertrophic growth, and cellular plasticity. Since manipulating the activity of RNA-binding proteins can improve the formation of new cardiomyocytes and extend the window of the cardiac regenerative capacity in mammals, they are potential targets of therapeutic interventions for cardiovascular disease. This review discusses our evolving understanding of RNA-binding proteins in regulating cardiac repair and regeneration, with the aim to identify important open questions that merit further investigations. [ABSTRACT FROM AUTHOR]

A code is generally defined as a system of signals or symbols for communication. Experimental evidence is synthesized for the presence and utility of such communication in heart rate variability (HRV) with particular attention to fetal HRV: HRV contains signatures of information flow between the organs and of response to physiological or pathophysiological stimuli as signatures of states (or syndromes). HRV exhibits features of time structure, phase space structure, specificity with respect to (organ) target and pathophysiological syndromes, and universality with respect to species independence. Together, these features form a spatiotemporal structure, a phase space, that can be conceived of as a manifold of a yet-to-be-fully understood dynamic complexity. The objective of this article is to synthesize physiological evidence supporting the existence of HRV code: hereby, the process-specific subsets of HRV measures indirectly map the phase space traversal reflecting the specific information contained in the code required for the body to regulate the physiological responses to those processes. The following physiological examples of HRV code are reviewed, which are reflected in specific changes to HRV properties across the signal–analytical domains and across physiological states and conditions: the fetal systemic inflammatory response, organ-specific inflammatory responses (brain and gut), chronic hypoxia and intrinsic (heart) HRV (iHRV), allostatic load (physiological stress due to surgery), and vagotomy (bilateral cervical denervation). Future studies are proposed to test these observations in more depth, and the author refers the interested reader to the referenced publications for a detailed study of the HRV measures involved. While being exemplified mostly in the studies of fetal HRV, the presented framework promises more specific fetal, postnatal, and adult HRV biomarkers of health and disease, which can be obtained non-invasively and continuously. [ABSTRACT FROM AUTHOR]

This study investigated whether using multiwalled carbon nanotubes (MWCNTs) as a carrier for dibutyl phthalate (DBP) could delay the degradation rate of DBP in mice and increase its estrogen-like interference effect. Pregnant Balb/C mice were divided into four groups and exposed to different treatments via tail-vein injection every 3 days until gestational day 20. The female and male mice were then sacrificed for toxicological study. The results showed that the combination of MWCNTs and DBP resulted in a higher fetal mortality rate than if the mice were exposed to MWCNTs or DBP alone. H&E staining showed that the estrous period of the exposed mice was delayed, the development of oocytes was blocked in the combination group, the number of spermatogenic cells decreased, and the quality of sperm decreased. Our experiment showed that the expression levels of the genes involved in sex hormone synthesis in the testis and ovaries were significantly increased after combined treatment compared with the MWCNT group (p < 0.01). The study suggests that DBP degradation is delayed when absorbed on MWCNTs, which increases its estrogen-like interference and interferes with fetal development, ultimately leading to increased fetal mortality. [ABSTRACT FROM AUTHOR]

(1) Objectives: In utero functional cardiac assessments using echocardiography have become increasingly important. The myocardial performance index (MPI, Tei index) is currently used to evaluate fetal cardiac anatomy, hemodynamics and function. An ultrasound examination is highly examiner-dependent, and training is of enormous significance in terms of proper application and subsequent interpretation. Future experts will progressively be guided by applications of artificial intelligence, on whose algorithms prenatal diagnostics will rely on increasingly. The objective of this study was to demonstrate the feasibility of whether less experienced operators might benefit from an automated tool of MPI quantification in the clinical routine. (2) Methods: In this study, a total of 85 unselected, normal, singleton, second- and third-trimester fetuses with normofrequent heart rates were examined by a targeted ultrasound. The modified right ventricular MPI (RV-Mod-MPI) was measured, both by a beginner and an expert. A calculation was performed semiautomatically using a Samsung Hera W10 ultrasound system (MPI+™, Samsung Healthcare, Gangwon-do, South Korea) by taking separate recordings of the right ventricle's in- and outflow using a conventional pulsed-wave Doppler. The measured RV-Mod-MPI values were assigned to gestational age. The data were compared between the beginner and the expert using a Bland-Altman plot to test the agreement between both operators, and the intraclass correlation was calculated. (3) Results: The mean maternal age was 32 years (19 to 42 years), and the mean maternal pre-pregnancy body mass index was 24.85 kg/m2 (ranging from 17.11 to 44.08 kg/m2). The mean gestational age was 24.44 weeks (ranging from 19.29 to 36.43 weeks). The averaged RV-Mod-MPI value of the beginner was 0.513 ± 0.09, and that of the expert was 0.501 ± 0.08. Between the beginner and the expert, the measured RV-Mod-MPI values indicated a similar distribution. The statistical analysis showed a Bland-Altman bias of 0.01136 (95% limits of agreement from −0.1674 to 0.1902). The intraclass correlation coefficient was 0.624 (95% confidence interval from 0.423 to 0.755). (4) Conclusions: For experts as well as for beginners, the RV-Mod-MPI is an excellent diagnostic tool for the assessment of fetal cardiac function. It is a time-saving procedure, offers an intuitive user interface and is easy to learn. There is no additional effort required to measure the RV-Mod-MPI. In times of reduced resources, such assisted systems of fast value acquisition represent clear added value. The establishment of the automated measurement of the RV-Mod-MPI in clinical routine should be the next level in cardiac function assessment. [ABSTRACT FROM AUTHOR]

In the central nervous system (CNS) there are a greater number of glial cells than neurons (between five and ten times more). Furthermore, they have a greater number of functions (more than eight functions). Glia comprises different types of cells, those of neural origin (astrocytes, radial glia, and oligodendroglia) and differentiated blood monocytes (microglia). During ontogeny, neurons develop earlier (at fetal day 15 in the rat) and astrocytes develop later (at fetal day 21 in the rat), which could indicate their important and crucial role in the CNS. Analysis of the phylogeny reveals that reptiles have a lower number of astrocytes compared to neurons and in humans this is reversed, as there have a greater number of astrocytes compared to neurons. These data perhaps imply that astrocytes are important and special cells, involved in many vital functions, including memory, and learning processes. In addition, astrocytes are involved in different mechanisms that protect the CNS through the production of antioxidant and anti-inflammatory proteins and they clean the extracellular environment and help neurons to communicate correctly with each other. The production of inflammatory mediators is important to prevent changes in brain homeostasis. On the contrary, excessive, or continued production appears as a characteristic element in many diseases, such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and in neurodevelopmental diseases, such as bipolar disorder, schizophrenia, and autism. Furthermore, different drugs and techniques have been developed to reverse oxidative stress and/or excess of inflammation that occurs in many CNS diseases, but much remains to be investigated. This review attempts to highlight the functional relevance of astrocytes in normal and neuropathological conditions by showing the molecular and cellular mechanisms of their role in the CNS. [ABSTRACT FROM AUTHOR]

(1) Background: The objective of this study was to investigate the diagnostic value of chromosomal microarray analysis (CMA) for congenital heart defects (CHDs) with different cardiac phenotypes and extracardiac abnormalities (ECAs) and to explore the pathogenic genetic factors of CHDs. (2) Methods: We collected fetuses diagnosed with CHDs by echocardiography at our hospital from January 2012 to December 2021. We analyzed the CMA results of 427 fetuses with CHDs. We then categorized the CHD into different groups according to two dimensions: different cardiac phenotypes and whether it was combined with ECAs. The correlation between the numerical chromosomal abnormalities (NCAs) and copy number variations (CNVs) with CHDs was analyzed. Statistical analyses, including Chi-square tests and t-tests, were performed on the data using IBM SPSS and GraphPad Prism. (3) Results: In general, CHDs with ECAs increased the detection rate for CA, especially the conotruncal defects. CHD combined with the thoracic and abdominal walls and skeletal, thymic and multiple ECAs, were more likely to exhibit CA. Among the CHD phenotypes, VSD and AVSD were associated with NCA, while DORV may be associated with NCA. The cardiac phenotypes associated with pCNVs were IAA (type A and B), RAA, TAPVC, CoA and TOF. In addition, IAA, B, RAA, PS, CoA and TOF were also associated with 22q11.2DS. The length distribution of the CNV was not significantly different between each CHD phenotype. We detected twelve CNV syndromes, of which six syndromes may be related to CHDs. The pregnancy outcome in this study suggests that termination of pregnancy with fetal VSD and vascular abnormality is more dependent on genetic diagnosis, whereas the outcome in other phenotypes of CHDs may be associated with other additional factors. (4) Conclusions: CMA examination for CHDs is still necessary. We should identify the existence of fetal ECAs and specific cardiac phenotypes, which are helpful for genetic counseling and prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Congenital heart defect (CHD) is the most common birth defect that affects the structure of the heart from birth. A possible reason for this occurrence could be alterations in the properties of the stem cells associated with fetal heart development. In this study, we compared the growth and cardiomyogenic potential of fetal-derived amniotic fluid mesenchymal stem cells (AF-MSCs) from isolated congenital heart defective fetuses (ICHD) with AF-MSCs of normal fetuses. The ICHD AF-MSCs showed a defect in the ability to grow efficiently and displayed increased senescence and DNA damage processes compared to normal AF-MSCs. Furthermore, the ICHD AF-MSCs showed cardiomyogenic differentiation defects that were accompanied by decreased expression of various proteins, including cardiac progenitor markers, transcription factors, and structural proteins, which are necessary for proper heart development. Overall, our study highlights that these defects in AF-MSCs of ICHD fetuses possibly contribute to CHDs and may lead to improper heart development. Amniotic fluid mesenchymal stromal cells (AF-MSCs) represent an autologous cell source to ameliorate congenital heart defects (CHDs) in children. The AF-MSCs, having cardiomyogenic potential and being of fetal origin, may reflect the physiological and pathological changes in the fetal heart during embryogenesis. Hence, the study of defects in the functional properties of these stem cells during fetal heart development will help obtain a better understanding of the cause of neonatal CHDs. Therefore, in the present study, we compared the proliferative and cardiomyogenic potential of AF-MSCs derived from ICHD fetuses (ICHD AF-MSCs) with AF-MSCs from structurally normal fetuses (normal AF-MSCs). Compared to normal AF-MSCs, the ICHD AF-MSCs showed comparable immunophenotypic MSC marker expression and adipogenic and chondrogenic differentiation potential, with decreased proliferation, higher senescence, increased expression of DNA-damaged genes, and osteogenic differentiation potential. Furthermore, the expression of cardiac progenitor markers (PDGFR-α, VEGFR-2, and SSEA-1), cardiac transcription factors (GATA-4, NKx 2-5, ISL-1, TBX-5, TBX-18, and MeF-2C), and cardiovascular markers (cTNT, CD31, and α-SMA) were significantly reduced in ICHD AF-MSCs. Overall, these results suggest that the AF-MSCs of ICHD fetuses have proliferation defects with significantly decreased cardiomyogenic differentiation potential. Thus, these defects in ICHD AF-MSCs highlight that the impaired heart development in ICHD fetuses may be due to defects in the stem cells associated with heart development during embryogenesis. [ABSTRACT FROM AUTHOR]

Hyperglycemia during gestation can disrupt fetal heart development and increase postnatal cardiovascular disease risk. It is therefore imperative to identify early biomarkers of hyperglycemia during gestation-induced fetal heart damage and elucidate the underlying molecular pathomechanisms. Clinical investigations of diabetic adults with heart dysfunction and transgenic mouse studies have revealed that overexpression or increased expression of TNNI3K, a heart-specific kinase that binds troponin cardiac I, may contribute to abnormal cardiac remodeling, ventricular hypertrophy, and heart failure. Optimal heart function also depends on the precise organization of contractile and excitable tissues conferred by intercellular occlusive, adherent, and communicating junctions. The current study evaluated changes in embryonic heart development and the expression levels of sarcomeric proteins (troponin I, desmin, and TNNI3K), junctional proteins, glucose transporter-1, and Ki-67 under fetal hyperglycemia. Stage 22HH Gallus domesticus embryos were randomly divided into two groups: a hyperglycemia (HG) group, in which individual embryos were injected with 30 mmol/L glucose solution every 24 h for 10 days, and a no-treatment (NT) control group, in which individual embryos were injected with physiological saline every 24 h for 10 days (stage 36HH). Embryonic blood glucose, height, and weight, as well as heart size, were measured periodically during treatment, followed by histopathological analysis and estimation of sarcomeric and junctional protein expression by western blotting and immunostaining. Hyperglycemic embryos demonstrated delayed heart maturation, with histopathological analysis revealing reduced left and right ventricular wall thickness (−39% and −35% vs. NT). Immunoexpression levels of TNNI3K and troponin 1 increased (by 37% and 39%, respectively), and desmin immunofluorescence reduced (by 23%). Embryo-fetal hyperglycemia may trigger an increase in the expression levels of TNNI3K and troponin I, as well as dysfunction of occlusive and adherent junctions, ultimately inducing abnormal cardiac remodeling. [ABSTRACT FROM AUTHOR]

Simple Summary: Our study represents an innovative attempt to describe fetal skeleton development during the first part of gestation in sheep using ultrasonography associated with a differential staining technique that allows the observation of the first ossification processes. The timing of ossification and the growth rate of skeletal components are very important to assess normal prenatal growth. This knowledge may be useful for gestational management and early diagnosis of skeletal diseases, especially in the early period of pregnancy when bone growth is very fast in the ovine species. Increased knowledge of the developmental processes during gestation could provide valuable information on potential alterations in embryonic/fetal development. We examined the development of ovine conceptus between the 20th and 70th day of gestation with three convergent analyses: (1) uterus ultrasound examination and measurement (eco) of crown–rump length (CRL) and biparietal diameter (BPD) of the conceptus; (2) direct measurement (vivo) of CRL and BPD of the conceptus outside the uterus (3) osteo–cartilage dynamics during development by differential staining. No significant differences were observed between eco and vivo measurements for CRL and BPD in all examined concepti. CRL and BPD, instead, showed a significant positive linear correlation with gestational age. The study of osteogenesis dynamics has demonstrated a completely cartilaginous ovine fetus at up to 35 days of gestation. The ossification begins in the skull (40th day) and is almost complete between the 65th and the 70th of pregnancy. Our study highlighted that CRL and BPD are accurate parameters for gestational age estimation in the first part of sheep pregnancy and provides an overview of osteochondral temporal dynamics. Furthermore, tibia ossification is a valid parameter to estimate fetal age by ultrasound. [ABSTRACT FROM AUTHOR]

To date, cardiotocography (CTG) is the only non-invasive and cost-effective tool available for continuous monitoring of the fetal health. In spite of a marked growth in the automation of the CTG analysis, it still remains a challenging signal processing task. Complex and dynamic patterns of fetal heart are poorly interpreted. Particularly, the precise interpretation of the suspected cases is fairly low by both visual and automated methods. Also, the first and second stage of labor produce very different fetal heart rate (FHR) dynamics. Thus, a robust classification model takes both stages into consideration separately. In this work, the authors propose a machine-learning-based model, which was applied separately to both the stages of labor, using standard classifiers such as SVM, random forest (RF), multi-layer perceptron (MLP), and bagging to classify the CTG. The outcome was validated using the model performance measure, combined performance measure, and the ROC-AUC. Though AUC-ROC was sufficiently high for all the classifiers, the other parameters established a better performance by SVM and RF. For suspicious cases the accuracies of SVM and RF were 97.4% and 98%, respectively, whereas sensitivity was 96.4% and specificity was 98% approximately. In the second stage of labor the accuracies were 90.6% and 89.3% for SVM and RF, respectively. Limits of agreement for 95% between the manual annotation and the outcome of SVM and RF were (−0.05 to 0.01) and (−0.03 to 0.02). Henceforth, the proposed classification model is efficient and can be integrated into the automated decision support system. [ABSTRACT FROM AUTHOR]

Recent studies in experimental animals found that oral exposure to micro- and nano-plastics (MNPs) during pregnancy had multiple adverse effects on outcomes and progeny, although no study has yet identified the translocation of ingested MNPs to the placenta or fetal tissues, which might account for those effects. We therefore assessed the placental and fetal translocation of ingested nanoscale polystyrene MNPs in pregnant rats. Sprague Dawley rats (N = 5) were gavaged on gestational day 19 with 10 mL/kg of 250 µg/mL 25 nm carboxylated polystyrene spheres (PS25C) and sacrificed after 24 h. Hyperspectral imaging of harvested placental and fetal tissues identified abundant PS25C within the placenta and in all fetal tissues examined, including liver, kidney, heart, lung and brain, where they appeared in 10–25 µm clusters. These findings demonstrate that ingested nanoscale polystyrene MNPs can breach the intestinal barrier and subsequently the maternal–fetal barrier of the placenta to access the fetal circulation and all fetal tissues. Further studies are needed to assess the mechanisms of MNP translocation across the intestinal and placental barriers, the effects of MNP polymer, size and other physicochemical properties on translocation, as well as the potential adverse effects of MNP translocation on the developing fetus. [ABSTRACT FROM AUTHOR]

Fetal heart failure (FHF) is a condition of inability of the fetal heart to deliver adequate blood flow for tissue perfusion in various organs, especially the brain, heart, liver and kidneys. FHF is associated with inadequate cardiac output, which is commonly encountered as the final outcome of several disorders and may lead to intrauterine fetal death or severe morbidity. Fetal echocardiography plays an important role in diagnosis of FHF as well as of the underlying causes. The main findings supporting the diagnosis of FHF include various signs of cardiac dysfunction, such as cardiomegaly, poor contractility, low cardiac output, increased central venous pressures, hydropic signs, and the findings of specific underlying disorders. This review will present a summary of the pathophysiology of fetal cardiac failure and practical points in fetal echocardiography for diagnosis of FHF, focusing on essential diagnostic techniques used in daily practice for evaluation of fetal cardiac function, such as myocardial performance index, arterial and systemic venous Doppler waveforms, shortening fraction, and cardiovascular profile score (CVPs), a combination of five echocardiographic markers indicative of fetal cardiovascular health. The common causes of FHF are reviewed and updated in detail, including fetal dysrhythmia, fetal anemia (e.g., alpha-thalassemia, parvovirus B19 infection, and twin anemia-polycythemia sequence), non-anemic volume load (e.g., twin-to-twin transfusion, arteriovenous malformations, and sacrococcygeal teratoma, etc.), increased afterload (intrauterine growth restriction and outflow tract obstruction, such as critical aortic stenosis), intrinsic myocardial disease (cardiomyopathies), congenital heart defects (Ebstein anomaly, hypoplastic heart, pulmonary stenosis with intact interventricular septum, etc.) and external cardiac compression. Understanding the pathophysiology and clinical courses of various etiologies of FHF can help physicians make prenatal diagnoses and serve as a guide for counseling, surveillance and management. [ABSTRACT FROM AUTHOR]

Down syndrome (DS), a complex disorder that is caused by the trisomy of chromosome 21 (Hsa21), is a major cause of congenital heart defects (CHD). Interestingly, only about 50% of individuals with Hsa21 trisomy manifest CHD. Here we review the genetic basis of CHD in DS, focusing on genes that regulate extracellular matrix (ECM) organization. The overexpression of Hsa21 genes likely underlies the molecular mechanisms that contribute to CHD, even though the genes responsible for CHD could only be located in a critical region of Hsa21. A role in causing CHD has been attributed not only to protein-coding Hsa21 genes, but also to genes on other chromosomes, as well as miRNAs and lncRNAs. It is likely that the contribution of more than one gene is required, and that the overexpression of Hsa21 genes acts in combination with other genetic events, such as specific mutations or polymorphisms, amplifying their effect. Moreover, a key function in determining alterations in cardiac morphogenesis might be played by ECM. A large number of genes encoding ECM proteins are overexpressed in trisomic human fetal hearts, and many of them appear to be under the control of a Hsa21 gene, the RUNX1 transcription factor. [ABSTRACT FROM AUTHOR]

Simple Summary: The presentation of equine dystocias to a referral clinic varies significantly. This case report describes the clinical and postmortem findings of a case of uterine body constriction in a late gestation mare that precluded normal vaginal delivery, ultimately resulting in fetal mortality with humane euthanasia of the mare. Gross examination revealed a circumferential, tan, fibrous band at the base of the uterine body that constricted the uterus and was adhered to the left and right ovaries, supporting the diagnosis of a uterine body constriction. A 13-year-old multiparous Quarter Horse mare was presented to the Michigan State University's, Large Animal Emergency service for dystocia. Clinical evaluation revealed a minimally dilated cervix on vaginal examination, with a palpable deceased fetus. Postmortem evaluation following owner-elected humane euthanasia revealed a circumferential, tan, fibrous band at the base of the uterine body that constricted the uterus and was adhered to the left and right ovaries. A routine histologic section of the incarcerating cord attached to the ovary consisted predominately of dense fibrous connective tissue, large blood vessels, and a central oviduct suggestive of a rent in the broad ligament. To the authors' knowledge, this is the first case report to describe uterine body constriction that precluded vaginal delivery of a fetus in a late gestation mare. [ABSTRACT FROM AUTHOR]

Fetal brain tissue segmentation is essential for quantifying the presence of congenital disorders in the developing fetus. Manual segmentation of fetal brain tissue is cumbersome and time-consuming, so using an automatic segmentation method can greatly simplify the process. In addition, the fetal brain undergoes a variety of changes throughout pregnancy, such as increased brain volume, neuronal migration, and synaptogenesis. In this case, the contrast between tissues, especially between gray matter and white matter, constantly changes throughout pregnancy, increasing the complexity and difficulty of our segmentation. To reduce the burden of manual refinement of segmentation, we proposed a new deep learning-based segmentation method. Our approach utilized a novel attentional structural block, the contextual transformer block (CoT-Block), which was applied in the backbone network model of the encoder–decoder to guide the learning of dynamic attentional matrices and enhance image feature extraction. Additionally, in the last layer of the decoder, we introduced a hybrid dilated convolution module, which can expand the receptive field and retain detailed spatial information, effectively extracting the global contextual information in fetal brain MRI. We quantitatively evaluated our method according to several performance measures: dice, precision, sensitivity, and specificity. In 80 fetal brain MRI scans with gestational ages ranging from 20 to 35 weeks, we obtained an average Dice similarity coefficient (DSC) of 83.79%, an average Volume Similarity (VS) of 84.84%, and an average Hausdorff95 Distance (HD95) of 35.66 mm. We also used several advanced deep learning segmentation models for comparison under equivalent conditions, and the results showed that our method was superior to other methods and exhibited an excellent segmentation performance. [ABSTRACT FROM AUTHOR]

The progress in fetal cardiology allows for the early diagnosis of congenital heart defects, but there is still a lack of data on the psychological situation of parents expecting a child with a congenital heart defect. In this cross-sectional study, 77 parents (45 women and 32 men) expecting a child with a heart defect were interviewed with different questionnaires. The standardized Hospital Anxiety and Depression Scale (HADS) questionnaire was used to assess the psychological state of the parents. Various statistical procedures were performed to determine the prevalence, risk factors, and predictors of anxiety and depression. The prevalence for prenatal anxiety was 11.8% and for depressed mood 6.6%, whereas the postnatal prevalence was 25% for anxiety and 16.7% for depressed mood. The mother is influential in protecting against depression as a contact person (p = 0.035). Women were more affected by anxiety and depression than men (p = 0.036). A significant and positive correlation was observed between anxiety and depression before birth (ρ = 0.649, p < 0.001) and after birth (ρ = 0.808, p < 0.001). The level of education correlated negatively with depression (p = 0.016) and anxiety (p = 0.017) before birth. Significantly higher anxiety and depression scores were not observed among health and social workers (p = 0.084), first-time mothers (p = 0.190), and parents whose pregnancies were due to medical assistance (p = 0.051). Close collaboration between maternal-fetal care units, pediatric cardiologists and psychiatric/psychosomatic disciplines is a possible strategy to reduce stress in parents. Therefore, an expert team of professionals, educating with understandable terms and sufficient knowledge about fetal heart disease in parenting counseling, is required. The support of affected parents can positively impact the treatment of the child and should be integrated into the daily routine of the clinic. [ABSTRACT FROM AUTHOR]

Fetal echocardiography has limited prognostic ability in the evaluation of left-sided congenital heart defects (left heart defects). Cord blood cardiovascular biomarkers could improve the prognostic evaluation of left heart defects. A multicenter prospective cohort (2013–2019) including fetuses with left heart defects (aortic coarctation, aortic stenosis, hypoplastic left heart, and multilevel obstruction (complex left heart defects) subdivided according to their outcome (favorable vs. poor), and control fetuses were evaluated in the third trimester of pregnancy at three referral centers in Spain. Poor outcome was defined as univentricular palliation, heart transplant, or death. Cord blood concentrations of N-terminal precursor of B-type natriuretic peptide, Troponin I, transforming growth factor β, placental growth factor, and soluble fms-like tyrosine kinase-1 were determined. A total of 45 fetuses with left heart defects (29 favorable and 16 poor outcomes) and 35 normal fetuses were included, with a median follow-up of 3.1 years (interquartile range 1.4–3.9). Left heart defects with favorable outcome showed markedly increased cord blood transforming growth factor β (normal heart median 15.5 ng/mL (6.8–21.4) vs. favorable outcome 51.7 ng/mL (13.8–73.9) vs. poor outcome 25.1 ng/mL (6.9–39.0), p = 0.001) and decreased placental growth factor concentrations (normal heart 17.9 pg/mL (13.8–23.9) vs. favorable outcome 12.8 pg/mL (11.7–13.6) vs. poor outcome 11.0 pg/mL (8.8–15.4), p < 0.001). Poor outcome left heart defects had higher N-terminal precursor of B-type natriuretic peptide (normal heart 508.0 pg/mL (287.5–776.3) vs. favorable outcome 617.0 pg/mL (389.8–1087.8) vs. poor outcome 1450.0 pg/mL (919.0–1645.0), p = 0.001) and drastically reduced soluble fms-like tyrosine kinase-1 concentrations (normal heart 1929.7 pg/mL (1364.3–2715.8) vs. favorable outcome (1848.3 pg/mL (646.9–2313.6) vs. poor outcome 259.0 pg/mL (182.0–606.0), p < 0.001). Results showed that fetuses with left heart defects present a distinct cord blood biomarker profile according to their outcome. [ABSTRACT FROM AUTHOR]

Long-term monitoring of a fetus with heart failure is an undeniable challenge for prenatal cardiology. Echocardiography is constrained by many fetal and maternal factors, and it is difficult to maintain the reproducibility of the measured and analyzed parameters. In our study, we presented the possibilities of using modern speckle tracking technology in combination with standard echocardiography parameters that may be insufficient or less sensitive in the context of monitoring life-threatening fetal conditions. Our analysis shows the superiority of the parameters used to assess fetal cardiac architecture, such as the GSI Global sphericity Index, and fetal cardiac function, such as the FAC fractional area change and the EF ejection fraction, which temporal change may indicate a worsening condition of the fetus with heart failure. The significant increase in the parameters of fetal heart size in speckle tracking allows for an improved echocardiographic diagnosis and monitoring of the fetus with heart failure and the prognostic conclusions about the clinical condition after birth. Significant decreases in FAC for the left and right ventricles and EF for the left ventricle may indicate an unfavourable prognosis for the monitored fetus due to heart failure. [ABSTRACT FROM AUTHOR]

Simple Summary: The prenatal stage of life can be divided into embryonic and fetal periods. While the course of the embryonic period has been investigated to some degree, the fetal period has been described only in general. The details of stomach development in the fetal period are unknown in any domesticated mammals excluding swine. This study describes changes in equine stomach morphology, shape, and location between the 4th and 11th months of pregnancy. The equine stomach with all its anatomical parts is already developed at four months of gestation. During further development, the stomach dimensions change and the shape of the stomach evolves from medium-wide to wide and from slightly bent to strongly bent. The gastric mucosa become differentiated as the fetal period progresses, forming typical anatomical features. Our statistical analysis of the majority of the metric parameters revealed that their growth rate was faster than the increase in crown–rump length. This study proved that dynamic development of the equine stomach can be traced not only in the embryo but also in the fetus. In this way, the study fills the knowledge gap concerning this part of prenatal life in horses. Studies of equine stomach prenatal development are very rare, and descriptions usually focus on the processes taking place in the embryonic period. Only general information about gastric organogenesis in the fetal period is available in embryology textbooks on domestic mammals. The material for our study included twenty half-breed horse fetuses divided into three age groups on the basis of known fetal age (verified using the CRL method). Our study consists of the topographical, morphological, and morphometrical description of stomach development between the 4th and 11th months of gestation. Even though the skeletotopy, syntopy, and holotopy of the stomach in the fetal period seems to be relatively unchanged, the organ shape and the proportions between its anatomical parts differed in fetuses from the three age groups. The achieved results were statistically elaborated to estimate the dynamics of the stomach shape. This can be described as changing from medium-wide to wide and from slightly bent to sharply bent. A nonlinear correlation of all metric values with CRL in all age groups was observed. A positive allometric growth rate of different intensity was seen in all metric parameters. All the values increased as the fetal period progressed. Only the parietal surface growth rate gradually changed from strongly positive allometric in the first age group to strongly negative allometric in the third age group. A difference between the non-glandular and glandular mucosa of the stomach was visible in the first group. Development of a well-distinguishable plicated edge margin began in the second age group together with gastric pits and gastric areas. The third age group showed a well-developed gastric groove and angular incisura. [ABSTRACT FROM AUTHOR]

Dietary exposure to Bisphenol A (BPA), an industrial chemical present in food containers, affects nutrient metabolism in the myocardium of offspring during intrauterine life. Using a murine model, we observed that fetal hearts from mothers exposed to BPA (2.5 μg/kg/day) for 20 days before mating and for all of the gestation had decreased expression of glucose transporter-1 (GLUT1), the principal sugar transporter in the fetal heart, and increased expression of fatty acid cluster of differentiation 36 transporter (CD36), compared to control fetuses from vehicle-treated mothers. We confirmed the suppression of GLUT1 by exposing fetal heart organotypic cultures to BPA (1 nM) for 48 h but did not detect changes in CD36 compared to controls. During pregnancy, the placenta continuously releases extracellular vesicles such as exosomes into fetal circulation. These vesicles influence the growth and development of fetal organs. When fetal heart cultures were treated with cord blood-derived exosomes isolated from BPA-fed animals, GLUT1 expression was increased by approximately 40%. Based on our results, we speculate that exosomes from cord blood, in particular placenta-derived nanovesicles, could contribute to the stabilization of the fetal heart metabolism by ameliorating the harmful effects of BPA on GLUT1 expression. [ABSTRACT FROM AUTHOR]

Despite recent breakthroughs in diagnosis and treatment, congenital heart defects (CHDs) continue to be the leading cause of death among newborns. Fetal echocardiography is the most effective and non-invasive method for the prenatal diagnosis of CHDs. However, the challenge of obtaining standard views can lead to a low diagnostic accuracy. To explore new methods for training, the combined use of cardiovascular casting, computed tomography (CT) scanning, and virtual ultrasound generation methods was studied to preserve the cardiac structures of a fetus in digital form. The feasibility of the proposed workflow was verified by testing three fetal heart specimens collected after the termination of pregnancy. As a result, the anatomical structures were imaged clearly by a CT scan after cardiovascular casting, and the virtually generated ultrasound images based on the use of the Public software Library for UltraSound imaging research (PLUS) toolkit successfully demonstrated both the standard views and the views with diagnostic values for the visualization of the cardiovascular structures. This solution provides great data extensibility while being simple and cost-effective for end users. Therefore, the proposed method could provide a promising educational system for trainees to understand standard views of fetal echocardiography and the corresponding anatomical correlations. [ABSTRACT FROM AUTHOR]

Congenital ventricular diverticulum (CVD) is a cardiac malformation defined as an outpouching lesion of a ventricle with normal contractility and thickness, and the advancement of prenatal sonography has led to its prenatal diagnosis. In the prenatal period, CVD is reported in association with pericardial effusion, arrhythmia, and fetal hydrops or as an isolated condition. With the development of prenatal echocardiography, CVD can be diagnosed from the early stage of pregnancy, and prenatal procedures, such as pericardiocentesis, are also possible. Spatiotemporal image correlation (STIC) acquisition, a novel approach for the clinical evaluation of fetal hearts, provides easy-to-use techniques for acquiring data from fetal hearts and helping visualization with two-dimensional and three-dimensional (3D) cine sequences. Furthermore, the speckle-tracking technique enables a more comprehensive evaluation of the shape, continuity, and function of the fetal heart. These recent techniques have never been used for CVD diagnosis and evaluation. Here, we present a case of right-sided CVD, which is the first in which STIC acquisition and cardiac function assessment with the speckle-tracking technique were used to assist in the diagnosis and evaluation. [ABSTRACT FROM AUTHOR]

Although the rate of preterm birth has increased in recent decades, a number of preterm infants have escaped death due to improvements in perinatal and neonatal care. Antenatal glucocorticoid (GC) therapy has significantly contributed to progression in lung maturation; however, its potential effects on other organs remain controversial. Furthermore, the effects of antenatal GC therapy on the fetal heart show both pros and cons. Translational research in animal models indicates that constant fetal exposure to antenatal GC administration is sufficient for lung maturation. We have established a premature fetal rat model to investigate immature cardiopulmonary functions in the lungs and heart, including the effects of antenatal GC administration. In this review, we explain the mechanisms of antenatal GC actions on the heart in the fetus compared to those in the neonate. Antenatal GCs may contribute to premature heart maturation by accelerating cardiomyocyte proliferation, angiogenesis, energy production, and sarcoplasmic reticulum function. Additionally, this review specifically focuses on fetal heart growth with antenatal GC administration in experimental animal models. Moreover, knowledge regarding antenatal GC administration in experimental animal models can be coupled with that from developmental biology, with the potential for the generation of functional cells and tissues that could be used for regenerative medical purposes in the future. [ABSTRACT FROM AUTHOR]

Background: The most commonly known cardiac effect of gestational diabetes mellitus (GD) in the fetus is hypertrophic cardiomyopathy, but recent studies show that it is preceded by subclinical cardiac dysfunction. This study aimed to assess the effect of GD on fetal cardiac geometry and contractility by two-dimensional speckle-tracking technology. Methods: We performed a prospective observational study that included 33 pregnant patients with GD and 30 healthy individuals. For all fetuses, a four-chamber 3 s cine-loop was recorded and analyzed with Fetal Heart Quantification (FetalHQ®), a novel proprietary speckle-tracking software. The following cardiac indices were calculated: global sphericity index (GSI), global longitudinal strain (GLS), fractional area change (FAC), and 24-segment end-diastolic diameter (EDD), fractional shortening (FS), and sphericity index (SI) for both ventricles. Demographic and cardiac differences between the two groups were analyzed, as well as intra-rater and inter-rater reliability. Results: There were significant changes in right ventricular FAC and FS for segments 4–24 in fetuses exposed to GD (−1 SD, p < 0.05). No significant differences were detected for GSI, GLS, EDD, or SI for either ventricle. Conclusions: Fetuses exposed to GD present impaired right ventricular contractility, especially in the mid and apical segments. [ABSTRACT FROM AUTHOR]

Simple Summary: The present study aimed to determine the effects of maternal dietary supplementation combining hydroxytyrosol and n3 polyunsaturated fatty acids (n3-PUFA) from day 35 to day 100 of gestation on the fatty acid (FA) composition of the offspring tissues of the Iberian pig. No effects were found in the plasma FA composition of the dams but higher levels of n3-PUFA were found in the plasma and different tissues (muscle, liver, and brain) of the supplemented fetuses. These findings may have important implications for piglets' health and may offer guidance for achieving human dietary n3-PUFA recommendations. Intrauterine Growth Restriction (IUGR) is a major problem in pig production and different strategies, mainly maternal supplementation with different agents, are currently being studied. The combination of hydroxytyrosol and n3-PUFA seems to be a promising treatment to counteract IUGR, since the combination may help improve n3-PUFA composition and lower the inflammatory status of IUGR piglets. The aim of the present study is to determine the effects of a maternal supplementation, from day 35 to day 100 of pregnancy, with linseed oil and hydroxytyrosol on the fetal FA composition. The results showed higher n3 levels, including eicosapentaenoic and docosahexaenoic FA in the offspring from treated gilts, which showed lower n6-PUFA/n3-PUFA (n6/n3) ratios. Saturated and monounsaturated fatty acids were also affected by treatment, especially in the muscle and brain. Thus, a maternal supplementation with linseed oil and hydroxytyrosol affected the fetal FA tissue composition, which could have implications in pig production due to the improvement of the piglets' health status. [ABSTRACT FROM AUTHOR]

Simple Summary: Reactivation of the fetal cardiac gene program, such as those encoding atrial and brain natriuretic peptides (ANP and BNP, respectively), is a characteristic feature of failing hearts. We previously revealed that a transcriptional repressor, neuron-restrictive silencer factor (NRSF), also called repressor element-1-silencing transcription factor (REST), plays a crucial role in the transcriptional control of ANP, BNP and other fetal cardiac genes through collaboration with various other transcription factors to maintain physiological cardiac function and electrical stability. Increased production of ANP and BNP prevents the progression of heart failure, but reactivation of Gαo and fetal-type cardiac ion channels (T-type Ca2+ and HCN channels) leads to deteriorated cardiac function and lethal arrhythmias observed in mice with disturbed NRSF function. Epigenetic regulators with which NRSF forms a complex modify histone acetylation and methylation, thereby participating in NRSF-mediated transcriptional regulation. Further comprehensive studies will lead to clarification of the molecular mechanisms underlying the development of cardiac dysfunction and heart failure. Reactivation of fetal cardiac genes, including those encoding atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), is a key feature of pathological cardiac remodeling and heart failure. Intensive studies on the regulation of ANP and BNP have revealed the involvement of numerous transcriptional factors in the regulation of the fetal cardiac gene program. Among these, we identified that a transcriptional repressor, neuron-restrictive silencer factor (NRSF), also named repressor element-1-silencing transcription factor (REST), which was initially detected as a transcriptional repressor of neuron-specific genes in non-neuronal cells, plays a pivotal role in the transcriptional regulation of ANP, BNP and other fetal cardiac genes. Here we review the transcriptional regulation of ANP and BNP gene expression and the role of the NRSF repressor complex in the regulation of cardiac gene expression and the maintenance of cardiac homeostasis. [ABSTRACT FROM AUTHOR]

Right ventricular (RV) function is one of the critical factors affecting the prognosis of fetuses with hypoplastic left heart syndrome (HLHS). Our study objectives included assessment of cardiac function and comprehensive measurement of cardiac microstructure. We retrospectively studied 42 fetuses diagnosed as HLHS by echocardiography. Myocardial deformation of the right ventricular wall was calculated automatically in offline software. Postmortem cardiac imaging for three control fetal hearts and four HLHS specimens was performed by a 9.4T DTI scanner. Myocardial deformation parameters of the RV (including strain, strain rate, and velocity) were significantly lower in HLHS fetuses (all p < 0.01). FA values increased (0.18 ± 0.01 vs. 0.21 ± 0.02; p < 0.01) in HLHS fetuses, but MD reduced (1.3 ± 0.15 vs. 0.88 ± 0.13; p < 0.001). The HLHS fetuses' RV lateral base wall (−7.31 ± 51.91 vs. −6.85 ± 31.34; p = 0.25), middle wall (1.71 ± 50.92 vs. −9.38 ± 28.18; p < 0.001), and apical wall (−6.19 ± 46.61 vs. −11.16 ± 29.86, p < 0.001) had HA gradient ascent but HA gradient descent in the anteroseptal wall (p < 0.001) and inferoseptal wall (p < 0.001). RV basal lateral wall HA degrees were correlated with RVGLS (R2 = 0.97, p = 0.02). MD values were positively correlated with RVGLS (R2 = 0.93, p = 0.04). Our study found morphological and functional changes of the RV in HLHS fetuses, and cardiac function was related to the orientation patterns of myocardial fibers. It may provide insight into understanding the underlying mechanisms of impaired RV performance in HLHS. [ABSTRACT FROM AUTHOR]

This work is devoted to the problems of one of the most common screening examinations used in medical practice: fetal cardiotocography (CTG). The technology of ultrasonic monitoring of fetal heart rate (HR) variations has been used for more than 70 years. During this time, it has undergone many upgrades and has been characterized several times as a hopelessly outdated routine technology. Over the past 5–7 years, many in-depth studies and review papers on cardiotocography have appeared, which revealed both the problems and prospects of the technology. Basically, hopes are associated with artificial intelligence, which should increase the accuracy of the analysis of initially inaccurate measurements obtained using ultrasonic testing. At the same time, after the introduction of pulsed operating modes and the appearance of multi-chip sensors, the quality of the original signal remains practically unchanged. This circumstance makes the prospects of the technology very problematic. However, until now, there has not been a reliable replacement for this screening, which is equally safe, non-invasive, and accessible to a wide range of specialists, medical institutions, and patients. The paper discusses and substantiates proposals for improving the technology based on original (different from traditional CTG) methods of processing information received from ultrasonic sensors, which, in the author's opinion, allow for solving the main problems of CTG: identifying the correct direction of radiation to the fetal heart and to reliably evaluate beat-to-beat heart rate. [ABSTRACT FROM AUTHOR]

(1) Objective: To scrutinize the reliability and the clinical value of routinely used fetal intelligent navigation echocardiography (FINE) static mode (5DHeartStatic™) for accelerated semiautomatic volumetric assessment of the normal fetal heart. (2) Methods: In this study, a total of 296 second and third trimester fetuses were examined by targeted ultrasound. Spatiotemporal image correlation (STIC) volumes of the fetal heart were acquired for further volumetric assessment. In addition, all fetal hearts were scanned by a fast acquisition time volume (1 s). The volumes were analyzed using the FINE software. The data were investigated regarding the number of properly reconstructed planes and cardiac axis. (3) Results: A total of 257 volumes were included for final analysis. The mean gestational age (GA) was 23.9 weeks (14.3 to 37.7 weeks). In 96.9 (standard acquisition time, FINE standard mode) and 94.2% (fast acquisition time, FINE static mode) at least seven planes were reconstructed properly (p = 0.0961, not significant). Regarding the overall depiction rate, the standard mode was able to reconstruct 96.9% of the planes properly, whereas the static mode showed 95.2% of the planes (p = 0.0098). Moreover, there was no significant difference between the automatic measurement of the cardiac axis (37.95 + 9.14 vs. 38.00 + 8.92 degrees, p = 0.8827, not significant). (4) Conclusions: Based on our results, the FINE static mode technique is a reliable method. It provides similar information of the cardiac anatomy compared to conventional STIC volumes assessed by the FINE method. The FINE static mode has the potential to minimize the influence of motion artifacts during volume acquisition and might therefore be helpful concerning volumetric cardiac assessment in daily routine. [ABSTRACT FROM AUTHOR]

The fetal echocardiogram is useful for monitoring and diagnosing cardiovascular diseases in the fetus in utero. Importantly, it can be used for assessing prenatal congenital heart disease, for which timely intervention can improve the unborn child's outcomes. In this regard, artificial intelligence (AI) can be used for the automatic analysis of fetal heart ultrasound images. This study reviews nondeep and deep learning approaches for assessing the fetal heart using standard four-chamber ultrasound images. The state-of-the-art techniques in the field are described and discussed. The compendium demonstrates the capability of automatic assessment of the fetal heart using AI technology. This work can serve as a resource for research in the field. [ABSTRACT FROM AUTHOR]

Bovine viral diarrhea virus (BVDV) infection during early gestation results in persistently infected (PI) immunotolerant calves that are the primary reservoirs of the virus. Pathologies observed in PI cattle include congenital defects of the brain, heart, and bone as well as marked functional defects in their immune system. It was hypothesized that fetal BVDV infection alters T cell activation and signaling genes by epigenetic mechanisms. To test this, PI and control fetal splenic tissues were collected on day 245 of gestation, 170 days post maternal infection. DNA was isolated for reduced representation bisulfite sequencing, protein was isolated for proteomics, both were analyzed with appropriate bioinformatic methods. Within set parameters, 1951 hypermethylated and 691 hypomethylated DNA regions were identified in PI compared to control fetuses. Pathways associated with immune system, neural, cardiac, and bone development were associated with heavily methylated DNA. The proteomic analysis revealed 12 differentially expressed proteins in PI vs. control animals. Upregulated proteins were associated with protein processing, whereas downregulated proteins were associated with lymphocyte migration and development in PI compared to control fetal spleens. The epigenetic changes in DNA may explain the immune dysfunctions, abnormal bone formation, and brain and heart defects observed in PI animals. [ABSTRACT FROM AUTHOR]

Acoustic shadows are common artifacts in medical ultrasound imaging. The shadows are caused by objects that reflect ultrasound such as bones, and they are shown as dark areas in ultrasound images. Detecting such shadows is crucial for assessing the quality of images. This will be a pre-processing for further image processing or recognition aiming computer-aided diagnosis. In this paper, we propose an auto-encoding structure that estimates the shadowed areas and their intensities. The model once splits an input image into an estimated shadow image and an estimated shadow-free image through its encoder and decoder. Then, it combines them to reconstruct the input. By generating plausible synthetic shadows based on relatively coarse domain-specific knowledge on ultrasound images, we can train the model using unlabeled data. If pixel-level labels of the shadows are available, we also utilize them in a semi-supervised fashion. By experiments on ultrasound images for fetal heart diagnosis, we show that our method achieved 0.720 in the DICE score and outperformed conventional image processing methods and a segmentation method based on deep neural networks. The capability of the proposed method on estimating the intensities of shadows and the shadow-free images is also indicated through the experiments. [ABSTRACT FROM AUTHOR]