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

Background: Novel ultrasound technology and software processing allow offline evaluation of tricuspid annular plane systolic excursion and mitral annular plane systolic excursion measurements. We wished to compare both novel 4D matrix (eM6C) and conventional (RAB6-D) transducers with variable settings (electronic spatiotemporal image correlation, spatiotemporal image correlation and four-dimensional real time) to determine if there was a significant difference in absolute value, quality and repeatability of the resultant reconstructed image and M-mode trace. Methods: A blinded prospective cross-sectional study of normal fetuses from 23 to 38 weeks' gestation were recruited. After routine sonography, four-dimensional volumes were stored and analysed using GE 4DView™ software. Statistical analysis explored variability, correlations and repeatability of the measurements with chi-square analysis, intraclass correlations and the Bland–Altman comparison plots. A scoring system was devised for image quality. Results: Eighteen participants generated 282 data volumes. Absolute values demonstrated some inconsistencies for both tricuspid annular plane systolic excursion and mitral annular plane systolic excursion measurements with variations between transducers: the highest for the RAB6-D/spatiotemporal image correlation setting and the lowest for the four-dimensional real-time settings. The RAB6-D/spatiotemporal image correlation setting was the most repeatable combination (intraclass correlation coefficient = 0.85). Poorest image quality (M-mode trace, four-chamber view, annuli) came from the RAB6-D/four-dimensional real-time combination with the eM6C/electronic spatiotemporal image correlation and RAB6-D/spatiotemporal image correlation settings being nearly identical. Conclusion: We show that transducer and setting combinations influence absolute tricuspid annular plane systolic excursion/mitral annular plane systolic excursion measurements, so need to be articulated in future research. The transducer setting (electronic spatiotemporal image correlation/spatiotemporal image correlation/four-dimensional real time) was a more significant factor than the type of transducer (conventional vs matrix). Subjective image evaluation does not correlate well with repeatability of image acquisition. Further studies are needed to compare measurements using four-dimensional post-processing tools against conventional real-time measurements. [ABSTRACT FROM AUTHOR]

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

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

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

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]

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

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

Congenital heart malformations are the most common cause of fetal and infant mortality, with an incidence of 4-13 per 1000 live births. Antenatal ultrasound evaluation of the fetal heart has developed over the past 30 years, and has allowed the detection of many abnormalities in the first trimester of pregnancy. Prenatal screening for fetal malformations is mandatory, allowing a better pregnancy counseling and greatly improving the neonatal prognosis. According to the Romanian Society of Obstetrics and Gynecology (SOGR), the evaluation of the fetal heart starting from the first trimester of pregnancy is mandatory. Due to technological advances, the fetal heart can be assessed in detail as early as the first trimester, which allows for adequate counseling of the couple facing a malformative heart pathology in their fetus, allows the termination of pregnancy at a legally optimal gestational age, or, when the ultrasound assessment does not reveal any fetal malformation, it assures the couple about the normal course of the pregnancy. The evaluation of the fetal heart using standard plans of examination is performed in each trimester of pregnancy. We present a series of cardiac mal)formations detected antenatally in our clinic, using standard assessment views. The purpose of this study is to emphasize that most lesions involving the ejection tracts of the arteries at the base of the heart are associated with varying degrees of disruption of the alignment, arrangement, size, or number of the three vessels, thus with an abnormal appearance of the standard cross-section of three vessels. In all cases, the three-vessel view of the heart revealed an abnormal appea)rance, helping us to diagnose major cardiac malformations. This plan can be easily obtained in all trimesters of pregnancy, providing sufficient information to detect many major conotruncal malformations. [ABSTRACT FROM AUTHOR]

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

Barrett's esophagus is a condition where the distal third of the esophagus changes its epithelial lining from nonkeratinized stratified squamous to simple columnar. This cross-sectional descriptive study was conducted to characterize the esophageal mucosa in the third trimester of pregnancy and determine possible variants in its development and was carried out in the Morphology Laboratory of the Health Faculty of the Industrial University of Santander, Colombia, with 45 human fetuses in the third trimester of gestation (weeks 25-40). A section of the distal esophagus and the first portion of the cardial region of the stomach were obtained, and the histological sections were subjected to a fixation process with 5 % formaldehyde solution. The sections were stained with hematoxylin and eosin and were evaluated for the presence of epithelial change or glands in the esophageal lamina propria. The change from nonkeratinized stratified squamous epithelium to simple columnar epithelium was observed in the esophageal mucosa in five fetuses (11.1 %). In 15 cases (33.3 %), the presence of mucous glands underlying the epithelium was determined. In two fetuses, simple columnar epithelium was observed in the esophageal mucosa and underlying submucosal glands (4.4 %). The lack of replacement of the columnar epithelium by squamous epithelium in the distal third of the esophagus and the presence of mucous glands in the last third of gestation may suggest the presentation of Barret's esophagus in adulthood and thus, a predisposition to develop esophageal adenocarcinoma. [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]

Prednisone is frequently used to treat rheumatoid diseases in pregnant women because of its high degree of safety. Whether prenatal prednisone exposure (PPE) negatively impacts fetal articular cartilage development is unclear. In this study, we simulated a clinical prednisone treatment regimen to examine the effects of different timings and doses of PPE on cartilage development in female and male fetal mice. Prednisone doses (0.25, 0.5, and 1 mg/kg/d) was administered to Kunming mice at different gestational stages (0–9 gestational days, GD0–9), mid-late gestation (GD10–18), or during the entire gestation (GD0–18) by oral gavage. The amount of matrix aggrecan (ACAN) and collagen type II a1(COL2a1), and expression of transforming growth factor β1 (TGFβ1) signaling pathway also demonstrated that the chondrocyte count and ACAN and COL2a1 expression reduced in fetal mice with early and mid-late PPE, with the reduction being more significant in the mice with early PPE than that in those with PPE at other stages. Prenatal exposure to different prednisone doses prevented the reduction of TGFβ signaling pathway-related genes [TGFβR1, SMAD family member 3 (Smad3), SRY-box9 (SOX9)] as well as ACAN and COL2a1 mRNA expression levels in fetal mouse cartilage, with the most significant decrease after 1 mg/kg·d PPE. In conclusion, PPE can inhibit/restrain fetal cartilage development, with the greatest effect at higher clinical dose (1 mg/kg·d) and early stage of pregnancy (GD0–9), and the mechanism may be related to TGFβ signaling pathway inhibition. The result of this study provide a theoretical and experimental foundation for the rational clinical use of prednisone. [Display omitted] • Prenatal prednisone exposure (PPE) can inhibit fetal cartilage development. • The toxic effect of PPE was at higher clinical dose and early stage of pregnancy. • The toxic mechanism of PPE may be related to TGFβ signaling pathway inhibition. [ABSTRACT FROM AUTHOR]

Objectives: To develop a mediastinal shift angle (MSA) measurement method applicable to right-sided congenital diaphragmatic hernia (RCDH) in fetal MRI and to validate the predictive value of MSA in RCDH. Methods: Twenty-seven fetuses with isolated RCDH and 53 controls were included in our study. MSA was measured on MRI axial image at the level of four-chamber view of the fetal heart. The angle between the sagittal midline landmark line and the left boundary landmark line touching tangentially the lateral wall of the left ventricle was used to quantify MSA for RCDH. Appropriate statistical analyses were performed to determine whether MSA can be regarded as a valid predictive tool for postnatal outcomes. Furthermore, predictive performance of MSA was compared with that of lung area to head circumference ratio (LHR), observed/expected LHR (O/E LHR), total fetal lung volume (TFLV), and observed/expected TFLV (O/E TFLV). Results: MSA was significantly higher in the RCDH group than in the control group. MSA, LHR, O/E LHR, TFLV, and O/E TFLV were all correlated with postnatal survival, pulmonary hypertension (PH), and extracorporeal membrane oxygenation (ECMO) therapy (p < 0.05). Value of the AUC demonstrated good predictive performance of MSA for postnatal survival (0.901, 95%CI: (0.781–1.000)), PH (0.828, 95%CI: (0.661–0.994)), and ECMO therapy (0.813, 95%CI: (0.645–0.980)), which was similar to O/E TFLV but slightly better than TFLV, O/E LHR, and LHR. Conclusions: We developed a measurement method of MSA for RCDH for the first time and demonstrated that MSA could be used to predict postnatal survival, PH, and ECMO therapy in RCDH. Clinical relevance statement: Newly developed MRI assessment method of fetal MSA in RCDH offers a simple and effective risk stratification tool for patients with RCDH. Key Points: • We developed a measurement method of mediastinal shift angle for right-sided congenital diaphragmatic hernia for the first time and demonstrated its feasibility and reproducibility. • Mediastinal shift angle can predict more prognostic information other than survival in right-sided congenital diaphragmatic hernia with good performance. • Mediastinal shift angle can be used as a simple and effective risk stratification tool in right-sided congenital diaphragmatic hernia to improve planning of postnatal management. [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]

The article explores the potential of automated 2D speckle-tracking echocardiography (2DST) in fetal cardiac function assessment. It discusses how 2DST, traditionally used in adult and pediatric cardiac evaluations, can now be applied to fetal hearts. It further highlights advancements like the FetalHQ® software, designed to analyze fetal cardiac shape and function using DICOM images.

Human cerebellum encompasses numerous neurons, exhibiting a distinct developmental paradigm from cerebrum. Here we conducted scRNA-seq, scATAC-seq and spatial transcriptomic analyses of fetal samples from gestational week (GW) 13 to 18 to explore the emergence of cellular diversity and developmental programs in the developing human cerebellum. We identified transitory granule cell progenitors that are conserved across species. Special patterns in both granule cells and Purkinje cells were dissected multidimensionally. Species-specific gene expression patterns of cerebellar lobes were characterized and we found that PARM1 exhibited inconsistent distribution in human and mouse granule cells. A novel cluster of potential neuroepithelium at the rhombic lip was identified. We also resolved various subtypes of Purkinje cells and unipolar brush cells and revealed gene regulatory networks controlling their diversification. Therefore, our study offers a valuable multi-omics landscape of human fetal cerebellum and advances our understanding of development and spatial organization of human cerebellum. [ABSTRACT FROM AUTHOR]

Regulation of gene expression through enhancers is one of the major processes shaping the structure and function of the human brain during development. High-throughput assays have predicted thousands of enhancers involved in neurodevelopment, and confirming their activity through orthogonal functional assays is crucial. Here, we utilized Massively Parallel Reporter Assays (MPRAs) in stem cells and forebrain organoids to evaluate the activity of ~ 7000 gene-linked enhancers previously identified in human fetal tissues and brain organoids. We used a Gaussian mixture model to evaluate the contribution of background noise in the measured activity signal to confirm the activity of ~ 35% of the tested enhancers, with most showing temporal-specific activity, suggesting their evolving role in neurodevelopment. The temporal specificity was further supported by the correlation of activity with gene expression. Our findings provide a valuable gene regulatory resource to the scientific community. [ABSTRACT FROM AUTHOR]

The article discusses a case of a 25-year-old primigravida with a fetus showing mirror-image dextrocardia and thoracic-abdominal discordance, detected through fetal echocardiography. Three-dimensional high-definition live tissue virtual dissection, including HD-live tissue rendering and 3D/4D spatiotemporal image correlation HD-live color rendering, was utilized to comprehensively analyze the complex cardiac morphology.

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]

Background: Misoprostol is widely used for cervical ripening and labour induction as it is heat‐stable and inexpensive. Oral misoprostol 25 μg given 2‐hourly is recommended over vaginal misoprostol 25 μg given 6‐hourly, but the need for 2‐hourly fetal monitoring makes oral misoprostol impractical for routine use in high‐volume obstetric units in resource‐constrained settings. Objectives: To compare the efficacy and safety of oral misoprostol initiated at 25 or 50 μg versus 25 μg vaginal misoprostol given at 4‐ to 6‐hourly intervals for labor induction in women at or beyond term (≥ 37 weeks) with a single viable fetus and an unscarred uterus. Search Strategy: We identified eligible randomized, parallel‐group, labor‐induction trials from recent systematic reviews. We additionally searched PubMed, Cochrane CENTRAL, Epistemonikos, and clinical trials registries from February 1, 2020 to December 31, 2022 without language restrictions. Database‐specific keywords for cervical priming, labor induction, and misoprostol were used. Selection Criteria: We excluded labor‐induction trials exclusively in women with ruptured membranes, in the third trimester, and those that initiated misoprostol at doses not specified in the review's objectives. The primary outcomes were vaginal birth within 24 h, cesarean section, perinatal mortality, neonatal morbidity, and maternal morbidity. The secondary outcomes were uterine hyperstimulation with fetal heart rate changes, and oxytocin augmentation. Data Collection and Analysis: Two or more authors selected studies independently, assessed risk of bias, and extracted data. We derived pooled weighted risk ratios with 95% confidence intervals (CIs) for each outcome, subgrouping trials by the dose and frequency of misoprostol regimens. We used the I2 statistic to quantify heterogeneity and the random‐effects model for meta‐analysis when appropriate. We used the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach to assess certainty (confidence) in the effect estimates. Main Results: Thirteen trials, from Canada, India, Iran, and the US, randomizing 2941 women at ≥37 weeks of gestation with an unfavorable cervix (Bishop score <6), met the eligibility criteria. Five misoprostol regimens were compared: 25 μg oral versus 25 μg vaginal, 4‐hourly (three trials); 50 μg oral versus 25 μg vaginal, 4‐hourly (five trials); 50 μg followed by 100 μg oral versus 25 μg vaginal, 4‐hourly (two trials); 50 μg oral, 4‐hourly versus 25 μg vaginal, 6‐hourly (one trial); and 50 μg oral versus 25 μg vaginal, 6‐hourly (two trials). The overall certainty in the evidence ranged from moderate to very low, due to high risk of bias in 11/13 trials (affecting all outcomes), unexplained heterogeneity (1/7 outcomes), indirectness (1/7 outcomes), and imprecision (4/7 outcomes). Vaginal misoprostol probably increased vaginal deliveries within 24 h compared with oral misoprostol (risk ratio [RR] 0.82, 95% CI 0.70–0.96; 11 trials, 2721 mothers; moderate‐certainty evidence); this was more likely with 4‐hourly than with 6‐hourly vaginal regimens. The risk of cesarean sections did not appreciably differ (RR 1.00, 95% CI 0.80–1.26; 13 trials, 2941 mothers; very low‐certainty evidence), although oral misoprostol 25 μg 4‐hourly probably increased this risk compared with 25 μg vaginal misoprostol 4‐hourly (RR 1.69, 95% CI 1.21–2.36; three trials, 515 mothers). The risk of perinatal mortality (RR 0.67, 95% CI 0.11–3.90; one trial, 196 participants; very low‐certainty evidence), neonatal morbidity (RR 0.84, 95% CI 0.67–1.06; 13 trials, 2941 mothers; low‐certainty evidence), and maternal morbidity (RR 0.83, 95% CI 0.48–1.44; 6 trials; 1945 mothers; moderate‐certainty evidence) did not differ appreciably. The risk of uterine hyperstimulation with fetal heart rate changes may be lower with oral misoprostol (RR 0.70, 95% CI 0.52–0.95; 10 trials, 2565 mothers; low‐certainty evidence). Oxytocin augmentation was probably more frequent with oral compared with vaginal misoprostol (RR 1.29, 95% CI 1.10–1.51; 13 trials, 2941 mothers; moderate‐certainty evidence). Conclusions: Low‐dose, 4‐ to 6‐hourly vaginal misoprostol regimens probably result in more vaginal births within 24 h and less frequent oxytocin use compared with low‐dose, 4‐ to 6‐hourly, oral misoprostol regimens. Vaginal misoprostol may increase the risk of uterine hyperstimulation with fetal heart changes compared with oral misoprostol, without increasing the risk of perinatal mortality, neonatal morbidity, or maternal morbidity. Indirect evidence indicates that 25 μg vaginal misoprostol 4‐hourly may be more effective and as safe as the recommended 6‐hourly vaginal regimen. This evidence could inform clinical decisions in high‐volume obstetric units in resource‐constrained settings. Synopsis: Vaginal misoprostol 25 μg 4‐hourly may be an effective, safe, and pragmatic alternative to currently recommended labor‐induction regimens in high‐volume obstetric units in resource‐constrained settings. [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]

Obstetricians utilize cardiotocography (CTG) to assess the fetal heart and lungs during pregnancy. It can help determine if the foetus is healthy, in doubt, or suffering from disease by providing data on the fetal heart rate and uterine breathing. The analysis of CTG data has typically made use of machine learning (ML) techniques such as support vector machines and decision trees to forecast fetal health and enhance the detection procedure. Fetal heart rate and uterine contraction timing were recorded by CTG. Monitoring fetal health and ensuring normal fetal growth and development throughout pregnancy rely heavily on CTG intelligent categorization. Pregnancies with a higher risk of problems are the most common cases in which CTG is used to evaluate the health of the fetus. ML algorithms are utilized to evaluate state of the foetal health based on CTG-obtained factors. Compared to ML techniques, ensemble models have been shown to increase detection speed and effectiveness. Ensemble modeling refers to the practice of combining the scores or distributions from multiple related but distinct analytical models. In order to predict foetal health, ensemble models such as Boosting, AdaBoost, Extreme Gradient Boosting, Light gradient boost method (LightGBM), and stack models were used in the paper. When the outcomes are compared, the proposed stack model using logistic regression, decision tree, random forest and LightGBM proved to obtain the best performance with 96.71% success rate. The proposed methodology, which can be used to classify foetal health based on Fetal Heart Rate (FHR) data, is more efficient and superior to existing machine learning models, which have already been taken into consideration. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Veterinary Journal / Revue Vétérinaire Canadienne is the property of Canadian Veterinary Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Few existing reports have investigated the copy number variants (CNVs) in fetuses with central nervous system (CNS) anomalies. To gain further insights into the genotype–phenotype relationship, we conducted chromosomal microarray analysis (CMA) to reveal the pathogenic CNVs (pCNVs) that were associated with fetal CNS anomalies. We enrolled 5,460 pregnant women with different high-risk factors who had undergone CMA. Among them, 57 subjects with fetal CNS anomalies were recruited. Of the subjects with fetal CNS anomalies, 23 were given amniocentesis, which involved karyotype analysis and CMA to detect chromosomal abnormalities. The other 34 cases only underwent CMA detection using fetal abortive tissue. In this study, we identified five cases of chromosome aneuploid and nine cases of pCNVs in the fetuses, with a chromosomal aberration detection rate of 24.56% (14/57). In the 23 cases that were given both karyotype and CMA analysis, one case with trisomy 18 was detected by karyotyping. Moreover, CMA revealed a further three cases of pCNVs, including the 1p36.33p36.31, 7q11.23, and 1q21.1q21.2 microdeletions, with a 13.04% (3/23) increase in CMA yield over the karyotype analysis. Additionally, three cases of trisomy 13, one case of trisomy 21, and six cases of pCNVs were detected in the other 34 fetuses where only CMA was performed. Furthermore, a higher chromosomal aberration detection rate was observed in the extra CNS anomaly group than in the isolated CNS anomaly group (40.91% vs 14.29%). In conclude, several pathogenic CNVs were identified in the fetuses with CNS anomalies using CMA. Among the detected CNVs, ZIC2, GNB1, and NSUN5 may be the candidate genes that responsible for fetal CNS anomalies. Our findings provides an additional reference for genetic counseling regarding fetal CNS anomalies and offers further insight into the genotype–phenotype relationship. [ABSTRACT FROM AUTHOR]

Recent data showed that prenatal alcohol exposure (PAE) impairs the "placenta-brain" axis controlling fetal brain angiogenesis in human and preclinical models. Placental growth factor (PlGF) has been identified as a proangiogenic messenger between these two organs. CD146, a partner of the VEGFR-1/2 signalosome, is involved in placental angiogenesis and exists as a soluble circulating form. The aim of the present study was to investigate whether placental CD146 may contribute to brain vascular defects described in fetal alcohol spectrum disorder. At a physiological level, quantitative reverse transcription polymerase chain reaction experiments performed in human placenta showed that CD146 is expressed in developing villi and that membrane and soluble forms of CD146 are differentially expressed from the first trimester to term. In the mouse placenta, a similar expression pattern of CD146 was found. CD146 immunoreactivity was detected in the labyrinth zone and colocalized with CD31-positive endothelial cells. Significant amounts of soluble CD146 were quantified by ELISA in fetal blood, and the levels decreased after birth. In the fetal brain, the membrane form of CD146 was the majority and colocalized with microvessels. At a pathophysiological level, PAE induced marked dysregulation of CD146 expression. The soluble form of CD146 decreased in both placenta and fetal blood, whereas it increased in the fetal brain. Similarly, the expression of several members of the CD146 signalosome, such as VEGFR2 and PSEN, was differentially impaired between the two organs by PAE. At a functional level, targeted repression of placental CD146 by in utero electroporation (IUE) of CRISPR/Cas9 lentiviral plasmids resulted in (i) a decrease in cortical vessel density, (ii) a loss of radial vascular organization, and (iii) a reduced density of oligodendrocytes. Statistical analysis showed that the more the vasculature was impaired, the more the cortical oligodendrocyte density was reduced. Altogether, these data support that placental CD146 contributes to the proangiogenic "placenta-brain" axis and that placental CD146 dysfunction contributes to the cortical oligo-vascular development. Soluble CD146 would represent a promising placental biomarker candidate representative of alcoholinduced neurovascular defects in neonates, as recently suggested by PlGF (patents WO2016207253 and WO2018100143). [ABSTRACT FROM AUTHOR]

Background: Hyperglycemia during pregnancy can affect fetal heart in many ways, including causing cardiac malformation, leading to hypertrophic cardiomyopathy and cardiac dysfunction. Echocardiographic evaluation can assist identify alterations in heart structure, morphology and function, enabling prompt monitoring and management. However, according to earlier research, the cardiac alterations are modest in hyperglycemic mothers' fetuses, and might not be detectable using conventional methods and it is also unclear whether these changes are related to the metabolism of mothers. Fetal Heart Quantification (Fetal HQ) can assess ventricular geometry and function more sensitively and thoroughly, and identify sub-clinical cardiac dysfunction. The purpose of this study was to evaluate fetal heart by Fetal HQ in fetuses of hyperglycemic mothers who either had pre-gestational or gestational diabetes and to correlate them with maternal metabolic indices. Methods: The fetuses of 25 gestational age-matched control mothers, 48 women with gestational diabetes mellitus (GDM), and 11 women with diabetes mellitus (DM) were included in the prospective case-control research. Using fetal echocardiography and speckle tracking echocardiography (STE), the heart of the fetus was evaluated. Differences in the groups' anthropometric, metabolic, and cardiac parameters were examined. It was assessed whether maternal features, prenatal glucose, lipids, and maternal hemoglobin A1c (HbA1c) correlated with fetal cardiac parameters. Results: The LV EDV and ESV were significantly higher in the GDM group as compared to the DM group (p < 0.05). The GSI% was significantly lower in the GDM group compared with the control (p < 0.05). The LV SV and CO of the GDM group were both significantly higher compared with the DM group (p < 0.05). There was a significant decrease in RV FS for segments 1–7 in GDM fetuses compared to the control (p < 0.05) and for segments 5–10 compared to DM (p < 0.05). Fetal cardiac morphology and function indices correlate with maternal pregestational weight, BMI, early pregnancy fast glucose, lipids, and glycemic control levels. Conclusions: Fetuses exposed to gestational diabetes have altered heart morphology and function that is linked to maternal metabolic parameters, which presents a special indication for performing geometry and function cardiac assessment. Fetal HQ can be employed to evaluate the fetal cardiac shape and function in fetuses exposed to gestational diabetes. [ABSTRACT FROM AUTHOR]

Fetal abdominal subcutaneous soft tissue thickness (FASSTT) is a key indicator in evaluating fetal growth, development, and nutritional status. Currently, manual measurement in FASSTT faces the problems of difficulty in positioning, time consumption, and inaccurate measurement. Therefore, this article proposes an automatic measurement scheme for FASSTT. Firstly, a U‐shaped attention network VGG‐SeUnet is proposed to automatically segment the subcutaneous soft tissue area of the fetal abdomen. Secondly, based on the segmentation results, a morphological method is proposed to obtain FASSTT. Specifically, the segmentation network uses VGG16 as the encoder and connects the decoder through jump connections for multi‐scale fusion. We introduce channel attention to jump connections, which enables the model to select key channels for feature fusion. At the same time, the model uses the proposed DF_Loss function for training to solve the problem of sample imbalance. Based on the segmentation results, a morphological distance transformation algorithm is proposed to obtain FASSTT by drawing the maximum inscribed circle and calculating its diameter. The method is evaluated on a fetal abdominal circumference ultrasound dataset containing 135 samples. The DSC, mIOU, mPA, Precision and Recall of the segmentation experiments reache 88.9%, 81.02%, 90.44%, 86.38%, and 90.44% respectively. The difference between FASSTT's result from that provided by radiologist is 0.0615 cm in Average Error (AVE) and 0.081 cm in Root Mean Square Error (RMSE). The overall performance of this algorithm is superior to existing methods with excellent performance, and the measurement error is less than 1 millimeter. This result proves that the proposed scheme in this paper can achieve automated measurement of FASSTT and assist doctors in subsequent evaluation of fetal development and nutritional status. [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]

Fetal congenital heart block is a widely recognized complication of pregnancies with anti Ro/La antibodies. Less common presentations, including dilated cardiomyopathy, myocarditis, valvular insufficiency, and endocardial fibroelastosis, have also been described in these fetuses. We present two cases where recognition of isolated basal echogenicity of the fetal heart, an unconventional manifestation of anti-SSA antibodies during pregnancy, led to a suspicion and ultimately diagnosis of antibody positivity in the mother. These cases highlight the importance of being aware of this rare manifestation of anti-SSA antibodies during pregnancy, as early recognition of antibody positivity may lead to improve fetal and maternal outcomes. [ABSTRACT FROM AUTHOR]

Objectives: The acceptance of conventional autopsy (CA), the gold standard method for investigating fetal death, often remains problematic. Post-mortem magnetic resonance imaging (PMMRI) is increasingly advocated, particularly for neurologic malformations. However, PMMRI performances to diagnose non-neurologic malformations remain unclear. We aim to clarify whether a full body CA remains needed after prenatal ultrasound (US) and PMMRI in assessing non-neurologic fetal malformations. Methods: In this retrospective IRB-approved study, during a 6-year period, all fetuses who underwent PMMRI, prenatal US, and full body CA were included. Body abnormalities were identified in US, PMMRI, and CA reports. US and PMMRI images were all reviewed. All abnormalities were graded as major (2 points) or minor (1 point). Each technique (US, PMMRI, CA) was given a score by adding all grading points. In each fetus, results were compared for both separate and combined US and PMMRI to CA. Sensitivity and specificity were calculated for detecting major abnormalities. Results: Fifty fetuses were included. The score of CA, US, and PMMRI was respectively 53, 37, and 46. Compared with US-PMMRI, CA added information in 2 cases (4%) with major abnormalities and 7 cases (14%) with minor abnormalities. PMMRI and US were concordant in 36/50 (72%) fetuses. Separate US/PMMRI sensitivities and specificities for detecting major body malformations respectively were 80%/80% and 100%/94%. Combined US-PMMRI had a sensitivity of 90% and a specificity of 94%. Two cardiac malformations (2/6) were only described by CA. Conclusions: After prenatal US and PMMRI, few additional fetal body malformations are discovered with CA. Nevertheless, fetal heart autopsy remains mandatory. Clinical relevance statement: A cardiac conventional autopsy complemented by prenatal ultrasound and post-mortem MRI allows to detect all major fetal body abnormalities. With this efficient and much less invasive approach, a higher acceptance rate of fetal autopsy can be expected. Key Points: • Excepting cardiac malformations, most major fetal body malformations can reliably be identified by prenatal US combined with post-mortem MRI. • In the post-mortem diagnosis of fetal body malformations, a conventional autopsy limited to the fetal heart might replace a full body autopsy after a well-conducted prenatal US and post-mortem MRI. [ABSTRACT FROM AUTHOR]

Primigravida has impacts related to preparedness for the transition into motherhood. Thus, its can disrupt the attachment between the mother and the fetus. This study aimed to determine the effects of prenatal spiritual-based stimulation on maternalfetal attachment. This study employed a quasi-experimental design with a control group and was conducted among primigravida women in Indonesia. The study included 66 respondents selected through purposive sampling. They were divided into the intervention and control groups, each comprising 33 participants. The intervention group received prenatal spiritual-based stimulations, which involved auditory, kinesthetic, light, and temperature stimulations and were administered over a 12-week period. Data on maternal-fetal attachment were collected using the Prenatal Attachment Inventory (PAI), which had been tested for validity and reliability. Approval to use the instrument was obtained from its original author. Data analysis was performed using the Wilcoxon and Mann Whitney tests. The results showed that the Wilcoxon test yielded a p-value of 0.000 or significant differences were observed before and after intervention for the intervention group and 0.059 no significant differences were observed before and after the intervention for the control group. The Mann Whitney test revealed a p-value of 0.000, there were differences in the maternal-fetal attachment before and after the intervention. Therefore, spiritual-based prenatal stimulation is effective in enhancing maternal-fetal attachment. These results can provide a basis for pregnant women to apply spiritual-based prenatal stimulation interventions to enhance maternal-fetal attachment and health status. [ABSTRACT FROM AUTHOR]

• Early recognition of pregnancies destined to miscarry could allow couples to prepare for this common but often unexpected eventuality. • Using a large prospectively studied first trimester cohort, we have developed a prediction model with multivariable logistic regression for first trimester viability. • Simple ultrasound and demographic variables can be used to provide patients with an individualised risk of first trimester outcome. Early prediction of pregnancies destined to miscarry will allow couples to prepare for this common but often unexpected eventuality, and clinicians to allocate finite resources. We aimed to develop a prediction model combining clinical, demographic, and sonographic data as a clinical tool to aid counselling about first trimester pregnancy outcome. This is a prospective, observational cohort study conducted at Queen Charlotte's and Chelsea Hospital, UK from March 2014 to May 2019. Women with confirmed intrauterine pregnancies between 5 weeks and their dating scan (11–14 weeks) were recruited. Participants attended serial ultrasound scans in the first trimester and at each visit recorded symptoms of vaginal bleeding, pelvic pain, nausea and vomiting using validated scoring tools. Pregnancies were followed up until the dating scan (11–14 weeks). Univariate and multivariate analyses were performed to predict first trimester viability. A model was developed with multivariable logistic regression, variables limited by feature selection, and bootstrapping with multiple imputation was used for internal validation. 1403 women were recruited and after exclusions, data were available for 1105. 160 women (14.5 %) experienced first trimester miscarriage and 945 women (85.5 %) had viable pregnancies at 11–14 weeks' gestation. The average gestational age at the initial visit (calculated from the menstrual dates) was 7 + 1 weeks (+/-12.2 days). A multivariable logistic regression model was developed to predict first trimester viability and included the variables: mean gestational sac diameter, presence of fetal heart pulsations, difference in gestational age from last menstrual period and from mean sac diameter on ultrasonography, current folic acid usage and maternal age. The model demonstrated good performance (optimism-corrected area under curve (AUC) 0.84, 95 % CI 0.81–0.87; optimism-corrected calibration slope 0.969). We have developed and internally validated a model to predict first trimester viability with good accuracy prior to the 11–14 week dating scan, which now needs to be externally validated prior to clinical use. [ABSTRACT FROM AUTHOR]

The article discusses a multimedia tutorial that aims to enhance the screening examination of the fetal heart based on the ISUOG Practice Guidelines. The tutorial covers three topics: identifying the continuity of the ascending aorta with the aortic arch, measuring the size of the four-chamber view to identify cardiomegaly, and differentiating a pericardial effusion from a hypoechogenic rim. The tutorial provides step-by-step instructions and techniques to improve the screening process and accurately diagnose or exclude potential issues. The tutorial may be helpful for those conducting second or third-trimester screening examinations of the fetal heart. [Extracted from the article]

Background and Objective: Physiologically based pharmacokinetic (PBPK) models for pregnant women have recently been successfully used to predict maternal and umbilical cord pharmacokinetics (PK). Because there is very limited opportunity for conducting clinical and PK investigations for fetal drug exposure, PBPK models may provide further insights. The objectives of this study were to extend a whole-body pregnancy PBPK model by multiple compartments representing fetal organs, and to predict the PK of cefuroxime in the maternal and fetal plasma, the amniotic fluid, and several fetal organs. Methods: To this end, a previously developed pregnancy PBPK model for cefuroxime was updated using the open-source software Open Systems Pharmacology (PK-Sim®/MoBi®). Multiple compartments were implemented to represent fetal organs including brain, heart, liver, lungs, kidneys, the gastrointestinal tract (GI), muscles, and fat tissue, as well as another compartment lumping organs and tissues not explicitly represented. Results: This novel PBPK model successfully predicted cefuroxime concentrations in maternal blood, umbilical cord, amniotic fluid, and several fetal organs including heart, liver, and lungs. Further model validation with additional clinical PK data is needed to build confidence in the model. Conclusions: Being developed with an open-source software, the presented generic model can be freely re-used and tailored to address specific questions at hand, e.g., to assist the design of clinical studies in the context of drug research or to predict fetal organ concentrations of chemicals in the context of fetal health risk assessment. [ABSTRACT FROM AUTHOR]

Myocardial sleeve around human pulmonary veins plays a critical role in the pathomechanism of atrial fibrillation. Besides the well‐known arrhythmogenicity of these veins, there is evidence that myocardial extensions into caval veins and coronary sinus may exhibit similar features. However, studies investigating histologic properties of these structures are limited. We aimed to investigate the immunoreactivity of myocardial sleeves for intermediate filament desmin, which was reported to be more abundant in Purkinje fibers than in ventricular working cardiomyocytes. Sections of 16 human (15 adult and 1 fetal) hearts were investigated. Specimens of atrial and ventricular myocardium, sinoatrial and atrioventricular nodes, pulmonary veins, superior caval vein and coronary sinus were stained with anti‐desmin monoclonal antibody. Intensity of desmin immunoreactivity in different areas was quantified by the ImageJ program. Strong desmin labeling was detected at the pacemaker and conduction system as well as in the myocardial sleeves around pulmonary veins, superior caval vein, and coronary sinus of adult hearts irrespective of sex, age, and medical history. In the fetal heart, prominent desmin labeling was observed at the sinoatrial nodal region and in the myocardial extensions around the superior caval vein. Contrarily, atrial and ventricular working myocardium exhibited low desmin immunoreactivity in both adults and fetuses. These differences were confirmed by immunohistochemical quantitative analysis. In conclusion, this study indicates that desmin is abundant in the conduction system and venous myocardial sleeves of human hearts. [ABSTRACT FROM AUTHOR]

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

[Objective] The structure and function of yak heart fatty acid binding protein 3 (FABP3) gene were analyzed and its expression levels in adult and fetal yak were detected to provide references for xploring biological functions of the gene in yak breeding. [Method] The FABP3 gene was amplified by PCR from heart tissue of Meiren yak, and bioinformatics analysis was carried out after the CDS region was obtained. The expression levels of FABP3 in heart, liver, spleen, lung, kidney, and muscle tissues of adult and fetal yak were detected by real-time quantitative PCR (RT-qPCR). [Result] The length of the coding egion of FABP3 was 402 bp, encoding 133 amino acids. The advanced structure of the protein included mainly β-turn and extended chain. There was no transmembrane region or signal peptide on yak FABP3 protein, indicating it was a stable protein with certain hydrophilicity. Homology analysis of the nucleotide and amino acid sequences of the CDS region showed that the FABP3 gene was conserved in cattle. Accordng to the phylogenetic tree, yak had the closest genetic relationship with wild yak and zebu, and the farhest genetic relationship with chicken. RT-qPCR results showed that the FABP3 gene was expressed in heart, liver, spleen, lung, kidney, and muscle tissues of adult and fetal yak. The expression in liver, spleen, kidney, and muscle of fetal cattle was significantly or extremely significantly higher than that of adult yak, and the expression level in lung of adult yak was significantly higher than that of fetal yak. [Conclusion] The FABP3 gene of yak was cloned, and its tissue expression pattern was explored. This study provided asic data for further study on the role of FABP3 in fat deposition. [ABSTRACT FROM AUTHOR]

Copyright of Acta Veterinaria Brasilica is the property of Acta Veterinaria Brasilica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

To explore the associations between high uterine artery pulsatility index (UtA-PI) values and congenital heart disease (CHD) risk and whether they differed between singleton and multiple pregnancies. This hospital-based cohort study involving 52,047 pregnant women who underwent prenatal examinations from 2012 to 2016. Infants born to the included pregnant women were followed until 42 days after birth to identify those with CHDs. Generalized estimating equations were used to estimate the associations of high right UtA-PI (> 95th percentile) values with maternal preeclampsia and fetal CHDs. Logistic regression analyses were conducted using path analysis models to quantify the effect of high right UtA-PI values on fetal CHD risk. A total of 42,552 women and 43,470 infants (147 with CHDs) were included. Preeclampsia risk was associated with a high right UtA-PI in singleton-pregnant women (adjusted PR, 3.01; 95% CI 2.57–3.52). CHD risk was marginally associated with a high right UtA-PI in singleton-pregnant women (adjusted PR, 2.26, 95% CI 1.03–4.95). Considering only two factors, 96.0% of the fetal CHD risk was mediated by preeclampsia in singleton-pregnant women, while 93.8% of the risk was related to a high right UtA-PI in multiple-pregnant women. A high right UtA-PI was marginally associated with an increased fetal CHD risk in singleton-pregnant women and might play an important role in multiple-pregnant women. Further studies are warranted to confirm these findings given the high loss to follow-up rate. [ABSTRACT FROM AUTHOR]

In this study, Wingless-type MMTV (mouse mammary tumor virus) integration site family member (WNT10B) gene was sequence characterized in the Indian water buffalo. Sequence analysis revealed an open reading frame of 1176 nucleotides in buffalo, encoding 391 amino acids long protein. Nineteen nucleotide variations were observed between cattle and buffalo resulting in six amino acid changes. Phylogenetic analysis showed the clustering of ruminant species together. Real-time expression analysis of WNT10B in tissues collected from different organs of fetal and adult buffalo, revealed, the gene being abundantly expressed in the rumen and liver of the fetus. The fetal ovary, heart, kidney, lung, testis and mammary gland showed moderate expression, while in adult tissues, expression was high in the ovary, testis, brain, kidney, small intestine and liver, whereas lower expression was observed in the adult rumen. Significant differences in WNT10B expression levels were found for the brain, small intestine, testes, kidney, heart, rumen, and ovary when adult and fetal tissues were compared. A moderate level of genetic variation was found between cattle and buffalo WNT10B and expression patterns in a variety of tissues in adult buffalo implies that in addition to possible roles in adipogenesis and hematopoiesis, the WNT10B gene might be playing a significant role in other regulatory pathways as well. [ABSTRACT FROM AUTHOR]

Background: Congenital heart defect (CHD) is the most common congenital abnormality, and it has long been a clinical and public health concern. Our previous findings have found Periostin (POSTN) and Pappalysin-1 (PAPPA) as potential biomarkers for fetal CHD. We aim to further elucidate POSTN's role in fetal heart development and explore the clinical applicability of POSTN and PAPPA as diagnostic marker for fetal CHD. This study is poised to establish a theoretical framework for mitigating the incidence of CHD and advance a novel approach for prenatal screening of fetal CHD. Methods: We verified differential expression of POSTN and PAPPA in gravida serum and fetal amniotic fluid based on our previous research. We established the Postn knockout mouse by CRISPR/Cas9 to investigate whether Postn deletion leads to cardiac abnormalities in mice. Besides, we explored the mechanism of POSTN on heart development through Postn knockout mouse model and cell experiments. Finally, we established the logistic regression model and decision curve analysis to evaluate the clinical utility of POSTN and PAPPA in fetal CHD. Results: We observed a significant decrease in POSTN and increase in PAPPA in the CHD group. Atrial septal defects occurred in Postn−/− and Postn± C57BL/6 fetal heart, while ventricular septal defects with aortic saddle were observed in Postn± C57BL/6 fetal heart. Disruption of the extracellular matrix (ECM) in cardiomyocytes and multiple abnormalities in cellular sub-organelles were observed in Postn knockout mice. POSTN may positively regulate cell behaviors and unsettle ECM via the TGFβ-Smad2/3 signaling pathway. The combination of serum biomarkers POSTN and PAPPA with Echocardiogram can enhance the diagnostic accuracy of CHD. Furthermore, the comprehensive model including POSTN, PAPPA, and two clinical indicators (NT and age) exhibits significantly higher predictive ability than the diagnosis group without the use of serum biomarkers or clinical indicators. Conclusions: It is the first evidence that Postn deletion leads to cardiac developmental abnormalities in fetal mice. This may involve the regulation of the TGFβ signaling pathway. Importantly, POSTN and PAPPA possess clinical utility as noninvasive prenatal promising screening indicators of CHD. [ABSTRACT FROM AUTHOR]

Background: It remains unclear how the condition of glucose metabolism during pregnancy affects fetal outcomes. This study aimed to investigate the associations of gestational diabetes mellitus (GDM) and elevated glucose levels at each time point during oral glucose tolerance test (OGTT) with congenital heart disease (CHD) risk in offspring. Methods: We conducted a retrospective cohort study of mothers with singleton pregnancies of 20 weeks or more registered at Maternal and Child Health Centers in Fujian Province, China. The OGTT results and offspring CHD occurrence were collected. We used logistic regression to analyse the association between elevated blood glucose at each time point during OGTT and CHD. Results: A total of 71,703 normal and 533 CHD fetuses were included. Compared to the corresponding normal group, women with GDM, elevated blood glucose at different time points in OGTT (0 h ≥ 5.1 mmol/L, 1 h ≥ 10 mmol/L, and 2 h ≥ 8.5 mmol/L) showed an increased risk of CHD in offspring (adjusted OR = 1.41, 1.36, 1.37, and 1.41, all P < 0.05, respectively). Compared to group 1 (normal OGTT 0 h, 1 h and 2 h), the risk of CHD was higher in group 3 (normal OGTT 0 h and abnormal OGTT 1 h or 2 h) and group 4 (abnormal OGTT 0 h, 1 h and 2 h), OR = 1.53 and 2.21, all P < 0.05, respectively. Moreover, we divided participants by advanced maternal age, multipara, assisted reproduction, fetal sex, and others, similar associations were observed in the subgroup analyses. Conclusion: Elevated blood glucose at different time points during OGTT was associated with CHD in offspring. Fetuses of pregnant women with GDM should be screened for a high risk of CHD. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) play important roles in almost all biological processes. However, there is little research on the effects of lncRNAs on estrus and early fetal development. In this study, 12 lncRNA libraries were constructed by high-throughput sequencing using sheep ovaries at luteal phase, follicular phase, 30, and 45 days of pregnancy. The target genes of DElncRNAs were predicted as cis or trans, to which functional and pathway analysis were performed. A total of 21 125 mRNAs and 5084 lncRNAs were identified in 12 samples from Dolang sheep. Among these, 418 mRNAs and 49 lncRNAs were differentially expressed. 341 target genes of differentially expressed lncRNAs (DELs) were obtained for enrichment analyses using the GO and KEGG. GO enrichment and KEGG pathway analysis showed that differentially expressed mRNAs and lncRNA target genes were mainly involved in signal transduction, metabolic pathways, immune system, endocrine, AMPK signaling pathway, etc. It was realized that LOC105612389, BGIG9940_27655, RPS28, BGIG9940_27548 and BGIG9940_27563 lncRNA were significantly elevated at 30 and 45 days of gestation and were involved in early fetal development, which had a significant prognosis value for early pregnancy. Our study highlighted the putative contributions of lncRNAs in regulating expression of genes associated with early fetal development and regulation in sheep. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate fetal cardiac function in cases with overt and subclinical hypothyroidism and to determine the effect of levothyroxine (LT4) treatment and Anti‐thyroid peroxidase (Anti‐TPO) antibody status on fetal cardiac functions in cases with subclinical hypothyroidism. Methods: Within the scope of the study, fetuses of 23 overt hypothyroid, 52 subclinical hypothyroid and 250 control group pregnant women were evaluated. Fetal cardiac function was assessed via cardiac Doppler. Results: Isovolumetric relaxation time (IRT) and myocardial performance index (MPI) values in the overt hypothyroid group were significantly higher than both the subclinical hypothyroid group (p:.006, p:.000, respectively) and the control group (p:.000, p:.000, respectively). In addition, both IRT and MPI were significantly higher in the subclinical hypothyroid group than in the control group (p:.000, p:.000, respectively). In the subclinical hypothyroid group, there was no significant difference in terms of cardiac function parameters in the fetuses of pregnant women who received LT4 therapy and those who did not. When pregnant women with subclinical hypothyroidism were evaluated according to their Anti‐TPO antibody status, IRT and MPI values were found to be significantly higher in fetuses of Anti‐TPO (+) pregnant women (respectively, p:.005, p:.019). Conclusion: In the presence of maternal overt or subclinical hypothyroidism, fetal cardiac functions may be affected as early as the second trimester. Anti‐TPO antibody positivity in cases with subclinical hypothyroidism seems to negatively affect fetal cardiac functions. [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]

Background: One of the most important challenges to the mother during pregnancy is the implantation of a semi-allogenic fetus. Granulocyte Colony Stimulating Factor is a polypeptide glycoprotein mainly used in hematological diseases and post-chemotherapy, but it has recently gained some popularity as an immune-modulating agent in reproductive medicine. The study aimed to define the influence of repeated subcutaneous G-CSF administration in infertile females submits to intracytoplasmic sperm injection. Method: Ninety patients were taken from an outpatient infertility clinic and divided into two groups on the day of embryo transfer. The control group (49 patients) received no extra intervention, while the G-CSF group (41 patients) received a subcutaneous injection of G-CSF the first hour after embryo transfer, followed by weekly injections until a positive fetal heartbeat was detected. Result: In the G-CSF group, the implantation rate was 20.4% compared to 7.6% in the control. In the control group, the rates of both chemical and clinical pregnancy were 18.4%, whereas they were 48.8% and 43.9%, respectively, in the G-CSF group. Conclusion: The multiple doses of G-CSF significantly improved the implantation and pregnancy rates, so it is considered a promising drug in reproductive medicine. [ABSTRACT FROM AUTHOR]