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This article discusses a study that aimed to evaluate the role of speckle tracking echocardiography (STE) in distinguishing between small-for-gestational age (SGA) and fetal growth restriction (FGR) in fetuses at risk for late-onset FGR. The study included non-anomalous singleton pregnancies with suspected late-onset FGR and used ultrasound clips of the fetal heart to perform offline STE. The results showed differences in right ventricular strain between SGA, FGR, and evolving FGR, suggesting increased cardiac deformation in the latter group. However, no differences in STE parameters were found between SGA and FGR. [Extracted from the article]

This article, titled "Accurate AI measurements of ventricular area in second trimester fetal ultrasound video clips," discusses the use of artificial intelligence (AI) in measuring ventricular size in fetal ultrasounds. The study aimed to evaluate an AI system that could automate the measurement of right and left ventricle area in ultrasound video clips. The AI system used the entire video clip to measure the ventricular chamber end-diastolic area and provided a delimitation of the ventricles on a representative frame. The results showed that AI-aided measurements were similar to AI alone, indicating that AI measurement of the ventricles is a promising tool for accurate and reproducible cardiac assessment in fetal ultrasounds. [Extracted from the article]

This article discusses the performance of an artificial intelligence (AI) software in automatically detecting anatomical structures and characteristics on fetal ultrasound images. The study collected 643 fetal ultrasound exams from various centers in North America and Europe. The AI software showed high sensitivity and specificity in detecting different anatomical structures, such as fetal brain, thorax and heart, CRL/NT/Profile, placenta, and sex. The findings suggest that this AI software could be a valuable tool in supporting fetal ultrasound practitioners by providing objective evaluation of captured images for quality assessment. [Extracted from the article]

This article presents the findings of a national audit conducted in France to assess the quality of ultrasound practices related to fetal heart assessment in obstetrical ultrasounds. The researchers used deep learning tools to analyze 9,626 anonymized ultrasound files, consisting of 228,036 images at T2 and 161,535 images at T3, performed by 912 operators across the country. The results showed that 37.5% of the files were complete, with significant differences between regions. The average number of images per scan and the qualitative assessment of exam quality also varied significantly between regions. The study concludes that there is room for improvement in the overall quality of ultrasound reports. [Extracted from the article]

This article discusses a study conducted on fetuses with late-onset fetal growth restriction (FGR) to investigate patterns of cardiac remodeling and evaluate fetal cardiac function using speckle tracking fetal echocardiography (STE). The study found three distinct cardiac remodeling phenotypes: a morphologically normal heart, a morphologically elongated heart, and a morphologically globular heart. The comparison of cardiac functional parameters using STE showed differences in left and right ventricular strain among the phenotypes. This study highlights the existence of different cardiac remodeling phenotypes in fetuses with late-onset FGR and their association with variations in ventricular strain. [Extracted from the article]

This article explores the use of knowledge distillation technology in the fine segmentation of fetal echocardiographic images. The study collected 1300 ultrasound images of fetal hearts at three-vessel and trachea (3VT) views and divided them into training, validation, and testing sets. The results showed that the knowledge distillation algorithm training segmentation model achieved better results than other models, improving the accuracy of image recognition for doctors with less experience. This research suggests that the use of this technology can enhance the diagnosis of fetal heart conditions. [Extracted from the article]

This article presents a new artificial intelligence (AI) method for analyzing ultrasound videos of the fetal heart. The method automatically segments the three-vessel view (3VV) and characterizes its structures by analyzing morphological features. The researchers manually segmented the pulmonary artery (PA), aorta (Ao), and superior vena cava (SVC) in a set of frames to support the understanding of morphology. The results show that the method achieves accurate segmentations and performs at a high frame rate, making it suitable for real-time implementation. This technology could be used to detect congenital heart defects in ultrasound videos of the fetal heart. [Extracted from the article]

The aim of this study was to characterize the normality of the fetal circulatory system through the time between ventricular systoles of the ductus venosus in the three gestational trimesters in healthy fetuses using nonlinear methods of the complexity of the signal. A prospective cohort study was conducted at the Instituto de Medicina Integral Prof. Fernando Figueira (IMIP) from December 2019 to May 2020. Pregnant women between 11 and 14 weeks, with intrauterine pregnancy and healthy fetus were included. Patients with multiple gestation, positive screening for congenital malformation, including heart disease, and under 18 years of age were excluded. Doppler velocimetry ultrasonography of the ductus venosus was performed between the 11th and 14th weeks, 20th and 24th weeks, and 28th and 32nd weeks of gestation, and then the sound signal was extracted and segmented from the videos. To compare the means between the gestational trimesters of the approximate entropy (ApEn) and Lempel-Ziv complexity (CLZ) of the time between ventricular systoles, the Friedman test was used, with a significance level of 5%. No statistically significant difference was found between the 1st, 2nd, and 3rd trimesters regarding the mean ApEn (P=0.281) and CLZ (P=0.595) of the time between ventricular systoles of the ductus venosus. Ductus venosus systolic time was not sensitive to differentiate fetal cardiovascular dynamics between gestational trimesters. This study pioneered the characterization of cardiovascular normality by nonlinear parameters of the fetal ductus venosus in all three trimesters.

Twin reversed arterial perfusion (TRAP) sequence or acardiac twin is a rare and severe complication of monochorionic multiple pregnancies. Acardiac twin accounts for 10% of all TRAP sequences, which is the most morphologically developed acardius. We present an undiagnosed TRAP sequence case up to 24 weeks of gestation who underwent successful amnioreduction, radiofrequency ablation (RFA), and intrauterine transfusion (IUT). During follow-up, hydrops of surviving co-twin disappeared, and fetal heart function improved. Finally, a healthy girl weighing 2400 g was born at 36 weeks of gestation. To our knowledge, this is the first reported acardiac twin pregnancy, which requires IUT, in addition to RFA, due to late diagnosis. Therefore, this case report presents successful management options for TRAP sequence cases diagnosed late in pregnancy. [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]

Objective: To determine whether changes in fetal heart function according to glycemic control in pregnant women with Type 1 and Type 2 diabetes using spectral tissue Doppler imaging (TDI) and M‐mode imaging. Methods: This study included 68 pregestational diabetic women (DM) at 30–32 gestational weeks. All participants were divided into two groups: type 1(n = 17) and type 2(n = 51), and then these groups were divided into the subgroups as well‐controlled and poorly controlled, according to fasting glucose (FG) and 1‐h postprandial glucose (PPG) values. Cardiac parameters were compared for well‐ and poorly‐controlled groups with TDI and M‐mode imaging. The correlation of cardiac parameters with FG, PPG, and HbA1c values was evaluated. Their roles in predicting neonatal outcomes were also assessed. Results: Thickness measurements, early diastolic annular peak velocity (E'), late diastolic annular peak velocity (A'), tissue isovolumetric relaxation time (IRT'), and tissue myocardial performance index (MPI') were increased in both poorly controlled groups. Tissue ejection time (ET') was significantly reduced in the poorly controlled groups, while tissue isovolumetric contraction time (ICT') was not significantly changed in any group. Tricuspid, mitral, and septal annular plane excursions (TAPSE, MAPSE, and SAPSE, respectively) were significantly decreased in all poorly controlled subgroups. E', E'/A', MPI', IRT', ET', and M‐mode imaging parameters significantly correlated with FG notably. Conclusion: Maternal hyperglycemia leads to subtle changes in systolic and diastolic functions both in the interventricular septum and ventricles, so it is essential to ensure glycemic control in both Type 1 and Type 2 DM. [ABSTRACT FROM AUTHOR]

Developmental research has attempted to untangle the exact signals that control heart growth and size, with knockout studies in mice identifying pivotal roles for Wnt and Hippo signaling during embryonic and fetal heart growth. Despite this improved understanding, no clinically relevant therapies are yet available to compensate for the loss of functional adult myocardium and the absence of mature cardiomyocyte renewal that underlies cardiomyopathies of multiple origins. It remains of great interest to understand which mechanisms are responsible for the decline in proliferation in adult hearts and to elucidate new strategies for the stimulation of cardiac regeneration. Multiple signaling pathways have been identified that regulate the proliferation of cardiomyocytes in the embryonic heart and appear to be upregulated in postnatal injured hearts. In this Review, we highlight the interaction of signaling pathways in heart development and discuss how this knowledge has been translated into current technologies for cardiomyocyte production. [ABSTRACT FROM AUTHOR]

Purpose: Abnormal flow in the ductus venosus (DV) has been reported to be associated with adverse perinatal outcome, chromosomal abnormalities, and congenital heart defects (CHD). Aneuploid fetuses have increased risk of CHD, but there are discrepancies on the performance of this markers in euploid fetuses. The aim of this meta-analysis was to establish the predictive accuracy of DV for CHD. Methods: MEDLINE, EMBASE, and CINAHL were searched from inception to February 2022. No language or geographical restrictions were applied. Inclusion criteria regarded observational and randomized studies concerning first-trimester DV flow as CHD marker. Random effect meta-analyses to calculate risk ratio (RR) with 95% confidence interval (CI), hierarchical summary receiver-operating characteristics (HSROC), and bivariate models to evaluate diagnostic accuracy were used. Primary outcome was the diagnostic performance of DV in detecting prenatal CHD by means of area under the curve (AUROC). Subgroup analysis for euploid, high-risk, and normal NT fetuses was performed. Quality assessment of included papers was performed using QUADAS-2. Results: Twenty two studies, with a total of 204.829 fetuses undergoing first trimester scan with DV Doppler evaluation, fulfilled the inclusion criteria for this systematic review. Overall, abnormal DV flow at the time of first trimester screening was associated to an increased risk of CHD (RR 6.9, 95% CI 3.7–12.6; I2 = 95.2%) as well in unselected (RR: 6.4, 95% CI 2.5–16.4; I2 = 93.3%) and in euploid (RR: 6.45, 95% CI 3.3–12.6; I2 = 95.8%) fetuses. The overall diagnostic accuracy of abnormal DV in detecting CHD was good in euploid fetuses with an AUROC of 0.81 (95% CI 0.78–0.84), but it was poor in the high-risk group with an AUROC of 0.66 (95% CI 0.62–0.70) and in the unselected population with an AUROC of 0.44 (95% CI 0.40–0.49). Conclusions: Abnormal DV in the first trimester increases the risk of CHD with a moderate sensitivity for euploid fetuses. In combination with other markers (NT, TV regurgitation) could be helpful to identify fetuses otherwise considered to be at low risk for CHD. In addition to the improvement of the fetal heart examination in the first trimester, this strategy can increase the detection of major CHD at earlier stage of pregnancy. [ABSTRACT FROM AUTHOR]

Transamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) can attenuate placental inflammation and minimize intrauterine growth restriction (IUGR). We sought to determine whether MSC-based TRASCET could mitigate fetal cardiopulmonary effects of IUGR. Pregnant Sprague–Dawley dams were exposed to alternating 12-h hypoxia (10.5% O2) cycles in the last fourth of gestation. Their fetuses (n = 155) were divided into 4 groups. One group remained untreated (n = 42), while three groups received volume-matched intra-amniotic injections of either saline (sham; n = 34), or of syngeneic amniotic fluid-derived MSCs, either in their native state (TRASCET; n = 36) or "primed" by exposure to interferon-gamma and interleukin-1beta before administration in vivo (TRASCET-primed; n = 43). Normal fetuses served as additional controls (n = 30). Multiple morphometric and biochemical analyses were performed at term for select markers of cardiopulmonary development and inflammation previously shown to be affected by IUGR. Among survivors (75%; 117/155), fetal heart-to-body weight ratio was increased in both the sham and untreated groups (P < 0.001 for both) but normalized in the TRASCET and TRASCET-primed groups (P = 0.275, 0.069, respectively). Cardiac b-type natriuretic peptide levels were increased in all hypoxia groups compared with normal (P < 0.001), but significantly decreased from sham and untreated in both TRASCET groups (P < 0.0001–0.005). Heart tumor necrosis factor-alpha levels were significantly elevated in sham and TRASCET groups (P = 0.009, 0.002), but normalized in the untreated and TRASCET-primed groups (P = 0.256, 0.456). Lung transforming growth factor-beta levels were significantly increased in both sham and untreated groups (P < 0.001, 0.003), but normalized in both TRASCET groups (P = 0.567, 0.303). Similarly, lung endothelin-1 levels were elevated in sham and untreated groups (P < 0.001 for both), but normalized in both TRASCET groups (P = 0.367, 0.928). We conclude that TRASCET with MSCs decreases markers of fetal cardiac strain, insufficiency, and inflammation, as well as of pulmonary fibrosis and hypertension in the rodent model of IUGR. [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]

Background and Objectives: CTG test is a non-invasive investigative modality that is simple to perform and interpret, as well as widely accepted by patients. This test involves the use of Doppler- detected fetal heart rate acceleration that corresponds to fetal movements perceived by the mother. Owing to its cost-effectiveness and ease of application, it is used as a part of antenatal surveillance in developing countries. To analyze and monitor CTG changes in high and low-risk pregnancies as a part of antepartum surveillance and to correlate CTG with perinatal outcomes. Methods: A prospective observational study was conducted in the department of obstetrics, government medical college, Guntur. 200 pregnant females were enrolled in this study after they full filled the selection criteria. Patients were subjected to admission CTG and fetal heart rate was monitored. Perinatal outcomes were assessed. Results: 63% of the 200 patients had high-risk pregnancies. 61.5% needed operative delivery while 38.5% of the cases had NVD. APGAR score at 1 minute was <6 In 40%, & >7 in 60% of the cases. APGAR score at 5 minutes was <7 In 20% and 80% of the cases it was >8. Beat-to-beat variability was absent in 44% of the cases. There was a statistically significant association between perinatal outcome and beat-to-beat FHR variability. A significant association was observed between diagnosis and CST. Conclusion: Admission CTG is an effective, inexpensive, non-invasive technique to detect fetal hypoxia at early stages in low-and high-risk pregnancies, especially in developing countries with an increased workload and fewer resources. [ABSTRACT FROM AUTHOR]

Objectives: Ultrasound screening during early pregnancy is vital in preventing congenital disabilities. For example, nuchal translucency (NT) thickening is associated with fetal chromosomal abnormalities, particularly trisomy 21 and fetal heart malformations. Obtaining accurate ultrasound standard planes of a fetal face during early pregnancy is the key to subsequent biometry and disease diagnosis. Therefore, we propose a lightweight target detection network for early pregnancy fetal facial ultrasound standard plane recognition and quality assessment. Methods: First, a clinical control protocol was developed by ultrasound experts. Second, we constructed a YOLOv4 target detection algorithm based on the backbone network as GhostNet and added attention mechanisms CBAM and CA to the backbone and neck structure. Finally, key anatomical structures in the image were automatically scored according to a clinical control protocol to determine whether they were standard planes. Results: We reviewed other detection techniques and found that the proposed method performed well. The average recognition accuracy for six structures was 94.16%, the detection speed was 51 FPS, and the model size was 43.2 MB, and a reduction of 83% compared with the original YOLOv4 model was obtained. The precision for the standard median sagittal plane was 97.20%, and the accuracy for the standard retro‐nasal triangle view was 99.07%. Conclusions: The proposed method can better identify standard or non‐standard planes from ultrasound image data, providing a theoretical basis for automatic acquisition of standard planes in the prenatal diagnosis of early pregnancy fetuses. [ABSTRACT FROM AUTHOR]

SlowflowHD is a Doppler Ultrasound modality that is typically geared toward visualization of small‐size vessels and low velocity blood flow. In this commentary, we emphasize the importance of implementing the use of SlowflowHD as an adjunct to traditional Doppler modalities in the echocardiography screening in both the first and second trimester. This modality carries many characteristics that allow it to overcome the limitations of our current ultrasound modalities and facilitate mapping of the entirety of the fetal heart. The clinical implications are significant in regard to earlier acquisition of diagnostic information to guide decision‐making and patient counseling. [ABSTRACT FROM AUTHOR]

Low blood flow through the fetal left heart is often conjectured as an etiology for hypoplastic left heart syndrome (HLHS). To investigate if a decrease in left heart flow results in growth failure, we generate left ventricular inflow obstruction (LVIO) in mid-gestation fetal lambs by implanting coils in their left atrium using an ultrasound-guided percutaneous technique. Significant LVIO recapitulates important clinical features of HLHS: decreased antegrade aortic valve flow, compensatory retrograde perfusion of the brain and ascending aorta (AAo) from the arterial duct, severe left heart hypoplasia, a non-apex forming LV, and a thickened endocardial layer. The hypoplastic AAo have miRNA-gene pairs annotating to cell proliferation that are inversely differentially expressed by bulk RNA-seq. Single-nucleus RNA-seq of the hypoplastic LV myocardium shows an increase in fibroblasts with a reciprocal decrease in cardiomyocyte nuclei proportions. Fibroblasts, cardiomyocytes and endothelial cells from hypoplastic myocardium have increased expression of extracellular matrix component or fibrosis genes with dysregulated fibroblast growth factor signaling. Hence, a severe sustained (~ 1/3 gestation) reduction in fetal left heart flow is sufficient to cause left heart hypoplasia. This is accompanied by changes in cellular composition and gene expression consistent with a pro-fibrotic environment and aberrant induction of mesenchymal programs. A fetal lamb model of mitral stenosis shows that sustained reduction in fetal left heart flow causes left heart hypoplasia and sequencing analysis identifies changes associated with pro-fibrotic environment and aberrant induction of mesenchymal programs. [ABSTRACT FROM AUTHOR]

Background: Researchers have long suspected a mutual interaction between maternal and fetal heart rhythms, referred to as maternal-fetal cardiac coupling (MFCC). While several studies have been published on this phenomenon, they vary in terms of methodologies, populations assessed, and definitions of coupling. Moreover, a clear discussion of the potential clinical implications is often lacking. Subsequently, we perform a scoping review to map the current state of the research in this field and, by doing so, form a foundation for future clinically oriented research on this topic. Methods: A literature search was performed in PubMed, Embase, and Cochrane. Filters were only set for language (English, Dutch, and German literature were included) and not for year of publication. After screening for the title and the abstract, a full-text evaluation of eligibility followed. All studies on MFCC were included which described coupling between heart rate measurements in both the mother and fetus, regardless of the coupling method used, gestational age, or the maternal or fetal health condition. Results: 23 studies remained after a systematic evaluation of 6,672 studies. Of these, 21 studies found at least occasional instances of MFCC. Methods used to capture MFCC are synchrograms and corresponding phase coherence indices, cross-correlation, joint symbolic dynamics, transfer entropy, bivariate phase rectified signal averaging, and deep coherence. Physiological pathways regulating MFCC are suggested to exist either via the autonomic nervous system or due to the vibroacoustic effect, though neither of these suggested pathways has been verified. The strength and direction of MFCC are found to change with gestational age and with the rate of maternal breathing, while also being further altered in fetuses with cardiac abnormalities and during labor. Conclusion: From the synthesis of the available literature on MFCC presented in this scoping review, it seems evident that MFCC does indeed exist and may have clinical relevance in tracking fetal well-being and development during pregnancy. [ABSTRACT FROM AUTHOR]

Fetal stages are critical periods for brain development. However, the protein molecular signature and dynamics of the human brain remain unclear due to sampling difficulty and ethical limitations. Non-human primates present similar developmental and neuropathological features to humans. This study constructed a spatiotemporal proteomic atlas of cynomolgus macaque brain development from early fetal to neonatal stages. Here we showed that (1) the variability across stages was greater than that among brain regions, and comparisons of cerebellum vs. cerebrum and cortical vs. subcortical regions revealed region-specific dynamics across early fetal to neonatal stages; (2) fluctuations in abundance of proteins associated with neural disease suggest the risk of nervous disorder at early fetal stages; (3) cross-species analysis (human, monkey, and mouse) and comparison between proteomic and transcriptomic data reveal the proteomic specificity and genes with mRNA/protein discrepancy. This study provides insight into fetal brain development in primates. Proteomic data covering fetal and neonatal primate brain development in the primate brain is needed to understand development and changes in functional gene products. Here, the authors show the dynamic proteomic changes of the cynomolgus macaque brain during the development from early fetal to neonatal stages by constructing a spatiotemporal proteomic atlas. [ABSTRACT FROM AUTHOR]

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

Background and Purpose: To perform a volumetric evaluation of the brain in fetuses with right or left congenital diaphragmatic hernia (CDH), and to compare brain growth trajectories to normal fetuses. Methods: We identified fetal MRIs performed between 2015 and 2020 in fetuses with a diagnosis of CDH. Gestational age (GA) range was 19‐40 weeks. Control subjects consisted of normally developing fetuses between 19 and 40 weeks recruited for a separate prospective study. All images were acquired at 3 Tesla and were processed with retrospective motion correction and slice‐to‐volume reconstruction to generate super‐resolution 3‐dimensional volumes. These volumes were registered to a common atlas space and segmented in 29 anatomic parcellations. Results: A total of 174 fetal MRIs in 149 fetuses were analyzed (99 controls [mean GA: 29.2 ± 5.2 weeks], 34 fetuses left‐sided CDH [mean GA: 28.4 ± 5.3 weeks], and 16 fetuses right‐sided CDH [mean GA: 27 ± 5.4 weeks]). In fetuses with left‐sided CDH, brain parenchymal volume was –8.0% (95% confidence interval [CI] [–13.1, –2.5]; p =.005) lower than normal controls. Differences ranged from –11.4% (95% CI [–18, –4.3]; p <.001) in the corpus callosum to –4.6% (95% CI [–8.9, –0.1]; p =.044) in the hippocampus. In fetuses with right‐sided CDH, brain parenchymal volume was –10.1% (95% CI [–16.8, –2.7]; p =.008) lower than controls. Differences ranged from –14.1% (95% CI [–21, –6.5]; p <.001) in the ventricular zone to –5.6% (95% CI [–9.3, –1.8]; p =.025) in the brainstem. Conclusion: Left and right CDH are associated with lower fetal brain volumes. [ABSTRACT FROM AUTHOR]

To determine reference curves for fetal aortic and pulmonary valve annulus area by three-dimensional ultrasonography using the spatio-temporal image correlation (STIC) in the rendering mode, and to ascertain its applicability in congenital heart disease (CHD). We performed a retrospective cross-sectional study of 328 normal fetuses and 42 fetuses with CHD between 20 and 33 weeks 6 days of gestation. The outflow plane view of the great vessels was used to measure the areas of the valvar annuli, and the measurements were performed in systole. A linear regression model adjusted according to the determination coefficient (R2) was utilized to construct the reference intervals. The concordance correlation coefficient (CCC) was used to calculate the reproducibility of the mitral and tricuspid valve areas. The mean ± standard deviation (SD) of the aortic and pulmonary valve annulus areas ranged from 6.6 ± 1.2 to 32.9 ± 1.1 mm2 and 10.7 ± 1.3 to 40.3 ± 1.2 mm2, respectively. We observed a linear relationship and strong positive correlation between the area of the aortic and pulmonary valve annuli with r=0.97 and 0.96, respectively. Good intra (CCC=0.99) and interobserver agreement (CCC=0.98) was observed for the measurement of the aortic valve annulus area. A good intra (CCC=0.99) and interobserver (CCC=0.97) agreement was also observed for the measurement of the pulmonary valve annulus area. The mean ± SD of the difference of the areas of the aortic and pulmonary valve annuli between the normal fetuses and those with CHD were −1.801 ± 1.429 mm2 (p=0.208) and −1.033 ± 1.467 mm2 (p<0.0001), respectively. The reference curves for the areas of the aortic and pulmonary valve annuli of fetal hearts were determined, and showed good inter and intraobserver reproducibility. The constructed reference curves showed applicability in different types of CHD. [ABSTRACT FROM AUTHOR]

Aim: The intraventricular pressure difference (IVPD) is the pressure difference in early diastole from the base to the apex of the ventricle. It is a useful marker for evaluating diastolic function because of its role as a suction force. This study investigated the changes in total and segmental IVPDs in normal fetuses throughout gestation to obtain normative data equations. Methods: One hundred thirty‐seven healthy pregnant women at 12–40 weeks of gestation were prospectively enrolled to evaluate IVPD. The color M mode was performed, and the image was evaluated using our own code to calculate the IVPD. Segmental IVPD was divided into mid to apex and base. Pearson's correlation coefficient was used to evaluate this relationship. Results: There was a significant, positive relationship between IVPD and gestational age in both ventricles (right ventricle [RV]: r = 0.800, left ventricle [LV]: r = 0.818). As for segmental IVPD, basal and mid‐apical IVPD also increased with gestation in both ventricles (RV: basal, r = 0.627; mid‐apical, r = 0.705; LV: basal r = 0.758; mid‐apical, r = 0.756). IVPG, which was calculated as IVPD/ventricular length, also showed a weak, positive relationship with gestation in both ventricles (RV r = 0.351, p < 0.001; LV r = 0.373, p < 0.001). Conclusion: The total and segmental IVPDs significantly increased linearly through time. [ABSTRACT FROM AUTHOR]

Purpose: Fetal echocardiography is widely used for the assessment of fetal heart development and detection of congenital heart disease (CHD). Preliminary examination of the fetal heart involves the four-chamber view which indicates the presence of all the four chambers and its structural symmetry. Examination of various cardiac parameters is generally done using the clinically selected diastole frame. This largely depends on the expertise of the sonographer and is prone to intra- and interobservational errors. To overcome this, automated frame selection technique is proposed for the recognition of fetal cardiac chamber from fetal echocardiography. Methods: Three techniques have been proposed in this research study to automate the process of determining the frame referred as "Master Frame" that can be used for the measurement of the cardiac parameters. The first method uses frame similarity measures (FSM) for the determination of the master frame from the given cine loop ultrasonic sequences. FSM makes use of similarity measures such as correlation, structural similarity index (SSIM), peak signal to noise ratio (PSNR), and mean square error (MSE) to identify the cardiac cycle, and all the frames in one cardiac cycle are superimposed to form the master frame. The final master frame is obtained by considering the average of the master frame obtained using each similarity measure. The second method uses averaging of ± 20% from the midframes (AMF). The third method uses averaging of all the frames (AAF) of the cine loop sequence. Both diastole and master frames have been annotated by the clinical experts, and their ground truths are compared for validation. No segmentation techniques have been used to avoid the variability of the performance of various segmentation techniques. All the proposed schemes were evaluated using six fidelity metrics such as Dice coefficient, Jaccard ratio, Hausdorff distance, structural similarity index, mean absolute error, and Pratt figure of merit. Results: The three proposed techniques were tested on the frames extracted from 95 ultrasound cine loop sequences between 19 and 32 weeks of gestation. The feasibility of the techniques was determined by the computation of fidelity metrics between the master frame derived and the diastole frame chosen by the clinical experts. The FSM-based identified master frame found to closely match with manually chosen diastole frame and also ensures statistically significant. The method also detects automatically the cardiac cycle. The resultant master frame obtained through AMF though found to be identical to that of the diastole frame, the size of the chambers found to be reduced that can lead to inaccurate chamber measurement. The master frame obtained through AAF was not found to be identical to that of clinical diastole frame. Conclusion: It can be concluded that the frame similarity measure (FSM)–based master frame can be introduced in the clinical routine for segmentation followed by cardiac chamber measurements. Such automated master frame selection also overcomes the manual intervention of earlier reported techniques in the literature. The fidelity metrics assessment further confirms the suitability of proposed master frame for automated fetal chamber recognition. [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]

Objective To assess the clinical significance of 16p13.11 microduplications encompassing NDE1 gene and study the genotype-phenotype correlation. Methods Sixty-one patients and 6, 144 controls who had undergone chromosome microarray analysis（CMA）for neurocognitive impairment or other reasons were analyzed and then divided into three groups: a group of patients with neurocognitive impairment, a prenatal group with abnormal nervous systems, and a prenatal group with normal nervous systems. The fetuses carrying 16p13.11 microduplications were followed up, and the detection rates for the three groups were statistically analyzed. Results 16p13.11 microduplications were not detectable in the group of patients with neurocognitive impairment and the prenatal group with abnormal nervous systems. However, 16p13.11 microduplications encompassing NDE1 gene were detectable in 13 fetuses in the prenatal group with normal nervous systems. Of these, one pregnancy was terminated because of fetal heart defect, the others chose to continue their pregnancy, and no other structural abnormalities were observed in the fetuses. A follow-up on postnatal health of the newborns revealed no apparent abnormalities. There was no significant difference in the detection rate of 16p13.11 microduplication among the three groups （P > 0.05）. Conclusions Combined with the characteristics of low penetrance, 16p13.11 microduplications encompassing the entire NDE1 gene may be benign variants;however, more large-scale studies are needed to evaluate the associated clinical phenotypes. Follow-up to adulthood is recommended for prenatal cases with 16p13.11 microduplication. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to evaluate whether selected prenatal markers obtained from fetal echocardiography can predict postnatal outcome in congenital diaphragmatic hernia (CDH) patients. We also aimed to verify the prognostic value of lung-to-head ratio (LHR). Material and methods: The study group included 29 fetuses with CDH. We analyzed potentially prognostic parameters measured using fetal echocardiography and fetal ultrasound. The assessed parameters were compared between the group of patients with CDH who survived to discharge (n = 21) and the subset of patients who died before discharge from hospital (n = 8). Results: In survivors, mean z-score for ascending aorta (AAo) diameter was 0.23 ±0.98 vs. - 1.82 ±1.04 in patients who died (t-test, p = 0.0015). In survivors, the main pulmonary artery/ascending aorta ratio was 1.22 ±0.17 vs. 1.46 ±0.21 in patients who died (t-test, p = 0.017). In survivors, the LHR was 1.81 ±0.96 vs. 0.95 ±0.6 in patients who died (t-test, p = 0.019). In survivors, the observed to expected LHR was 57 ±30% vs 30 ±18% in patients who died (t-test, p = 0.018). Conclusions: Narrowing of the ascending aorta in CDH fetuses is a poor prognostic factor associated with increased mortality in neonates. Our study also confirmed the prognostic value of LHR. [ABSTRACT FROM AUTHOR]

Objective: Fetuses with congenital heart disease (CHD) are at increased risk of pregnancy loss compared with the general population. We aimed to assess the incidence, timing and risk factors of pregnancy loss in cases with major fetal CHD, overall and according to cardiac diagnosis. Methods: This was a retrospective, population‐level cohort study of fetuses and infants diagnosed with major CHD between 1997 and 2018 identified by the Utah Birth Defect Network (UBDN), excluding cases with termination of pregnancy and minor cardiovascular diagnoses (e.g. isolated aortic/pulmonary pathology and isolated septal defects). The incidence and timing of pregnancy loss were recorded, overall and according to CHD diagnosis, with further stratification based on presence of isolated CHD vs additional fetal diagnosis (genetic diagnosis and/or extracardiac malformation). Adjusted risk of pregnancy loss was calculated and risk factors were assessed using multivariable models for the overall cohort and prenatal diagnosis subgroup. Results: Of 9351 UBDN cases with a cardiovascular code, 3251 cases with major CHD were identified, resulting in a study cohort of 3120 following exclusion of cases with pregnancy termination (n = 131). There were 2956 (94.7%) live births and 164 (5.3%) cases of pregnancy loss, which occurred at a median gestational age of 27.3 weeks. Of study cases, 1848 (59.2%) had isolated CHD and 1272 (40.8%) had an additional fetal diagnosis, including 736 (57.9%) with a genetic diagnosis and 536 (42.1%) with an extracardiac malformation. The observed incidence of pregnancy loss was highest in the presence of mitral stenosis (< 13.5%), hypoplastic left heart syndrome (HLHS) (10.7%), double‐outlet right ventricle with normally related great vessels or not otherwise specified (10.5%) and Ebstein's anomaly (9.9%). The adjusted risk of pregnancy loss was 5.3% (95% CI, 3.7–7.6%) in the overall CHD population and 1.4% (95% CI, 0.9–2.3%) in cases with isolated CHD (adjusted risk ratio, 9.0 (95% CI, 6.0–13.0) and 2.0 (95% CI, 1.0–6.0), respectively, based on the general population risk of 0.6%). On multivariable analysis, variables associated with pregnancy loss in the overall CHD population included female fetal sex (adjusted odds ratio (aOR), 1.6 (95% CI, 1.1–2.3)), Hispanic ethnicity (aOR, 1.6 (95% CI, 1.0–2.5)), hydrops (aOR, 6.7 (95% CI, 4.3–10.5)) and additional fetal diagnosis (aOR, 6.3 (95% CI, 4.1–10)). On multivariable analysis of the prenatal diagnosis subgroup, years of maternal education (aOR, 1.2 (95% CI, 1.0–1.4)), presence of an additional fetal diagnosis (aOR, 2.7 (95% CI, 1.4–5.6)), atrioventricular valve regurgitation ≥ moderate (aOR, 3.6 (95% CI, 1.3–8.8)) and ventricular dysfunction (aOR, 3.8 (95% CI, 1.2–11.1)) were associated with pregnancy loss. Diagnostic groups associated with pregnancy loss were HLHS and variants (aOR, 3.0 (95% CI, 1.7–5.3)), other single ventricles (aOR, 2.4 (95% CI, 1.1–4.9)) and other (aOR, 0.1 (95% CI, 0–0.97)). Time‐to‐pregnancy‐loss analysis demonstrated a steeper survival curve for cases with an additional fetal diagnosis, indicating a higher rate of pregnancy loss compared to cases with isolated CHD (P < 0.0001). Conclusions: The risk of pregnancy loss is higher in cases with major fetal CHD compared with the general population and varies according to CHD type and presence of additional fetal diagnoses. Improved understanding of the incidence, risk factors and timing of pregnancy loss in CHD cases should inform patient counseling, antenatal surveillance and delivery planning. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. A video abstract of this article is available online here. [ABSTRACT FROM AUTHOR]

The extraction of Fetal Electrocardiogram (FECG) during labor or prenatal phases of pregnancy holds significant importance for early prediction of heart abnormalities. The accuracy of the extracted FECG is crucial for effective diagnosis, but the presence of external noises, particularly from the Maternal ECG (MECG), poses a major challenge in obtaining precise information. To address this issue in biomedical data processing, the study employs Finite Impulse Response (FIR) filters using an array multiplier. One notable challenge encountered in this process is the interference caused by external noises, leading to higher delay and power dissipation. In response, a modified High-Performance Multiplier (HPM) based modified booth multiplier is thoroughly reviewed and validated. This modification aims to enhance overall performance and enable high-speed operations in filtering the FECG signals. The effectiveness of these modified multipliers is assessed using ECG signal information collected from the MIT-BIH Arrhythmia Database, comprising 120 samples. In addition to noise filtering, the study explores the validation of Multiple-Input Multiple-Output Orthogonal Frequency Division Multiplexing (MIMO-OFDM) transceivers. These transceivers play a crucial role in ensuring the effective transmission of the extracted FECG signals. The research reveals a significant reduction, up to 80.4%, in both area and power dissipation during simulations conducted in Xilinx ISE 9.1 and Cadence Virtuoso. This achievement highlights the potential for improved efficiency and reliability in the processing and transmission of FECG signals, paving the way for advancements in early detection of fetal heart abnormalities. [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]

Introduction: Ventriculomegaly (VM) is a fetal brain malformation which may present independently (isolated form) or in association with different cerebral malformations, genetic syndromes or other pathologies (non-isolated form). Methods: This paper aims to study the effect of ventriculomegaly on the internal tridimensional architecture of fetal brains by way of Klingler's dissection. Ventriculomegaly was diagnosed using fetal ultrasonography during pregnancy and subsequently confirmed by necropsy. Taking into consideration the diameter of the lateral ventricle (measured at the level of the atrium), the brains were divided into two groups:moderate ventriculomegaly (with atrial diameter between 13 and 15 mm) and severe ventriculomegaly (with atrial diameter above 15 mm). Results and discussion: The results of each dissection were described and illustrated, then compared with age-matched reference brains. In the pathological brains, fascicles in direct contact with the enlarged ventricles were found to be thinner and displaced inferiorly, the opening of the uncinate fasciculus was wider, the fornix was no longer in contact with the corpus callosum and the convexity of the corpus callosumwas inverted. We have studied the prevalence of neurodevelopmental delay in children born with ventriculomegaly in the literature and discovered that a normal developmental outcome was found in over 90% of the mild VM cases, approximately 75% of the moderate and 60% in severe VM, with the correlated neurological impairments ranging from attention deficits to psychiatric disorders. [ABSTRACT FROM AUTHOR]

A key feature of the fetal period is the rapid emergence of organised patterns of spontaneous brain activity. However, characterising this process in utero using functional MRI is inherently challenging and requires analytical methods which can capture the constituent developmental transformations. Here, we introduce a novel analytical framework, termed "maturational networks" (matnets), that achieves this by modelling functional networks as an emerging property of the developing brain. Compared to standard network analysis methods that assume consistent patterns of connectivity across development, our method incorporates age-related changes in connectivity directly into network estimation. We test its performance in a large neonatal sample, finding that the matnets approach characterises adult-like features of functional network architecture with a greater specificity than a standard group-ICA approach; for example, our approach is able to identify a nearly complete default mode network. In the in-utero brain, matnets enables us to reveal the richness of emerging functional connections and the hierarchy of their maturational relationships with remarkable anatomical specificity. We show that the associative areas play a central role within prenatal functional architecture, therefore indicating that functional connections of high-level associative areas start emerging prior to exposure to the extra-utero environment. An analytical framework termed "maturational networks" (matnets) is applied to MRI data from 144 fetuses in utero, characterising emerging functional connectivity in the fetal brain and revealing that human functional connections of high-level associative areas emerge prior to extra-utero environment exposure [ABSTRACT FROM AUTHOR]

Background: Rapid delivery is important in cases of umbilical cord prolapse to prevent hypoxic injury to the fetus/neonate. However, the optimal decision-to-delivery interval remains controversial. Objective: The aim of the study was to investigate the association between the decision-to-delivery interval in women with umbilical cord prolapse, stratified by fetal heart rate pattern at diagnosis, and neonatal outcome. Study design: The database of a tertiary medical center was retrospectively searched for all cases of intrapartum cord prolapse between 2008 and 2021. The cohort was divided into three groups according to findings on the fetal heart tracing at diagnosis: 1) bradycardia; 2) decelerations without bradycardia; and 3) reassuring heart rate. The primary outcome measure was fetal acidosis. The correlation between cord blood indices and decision-to-delivery interval was analyzed using Spearman's rank correlation coefficient. Results: Of the total 103,917 deliveries performed during the study period, 130 (0.13%) were complicated by intrapartum umbilical cord prolapse. Division by fetal heart tracing yielded 22 women (16.92%) in group 1, 41 (31.53%) in group 2, and 67 (51.53%) in group 3. The median decision-to-delivery interval was 11.0 min (IQR 9.0–15.0); the interval was more than 20 min in 4 cases. The median cord arterial blood pH was 7.28 (IQR 7.24–7.32); pH was less than 7.2 in 4 neonates. There was no correlation of cord arterial pH with decision-to-delivery interval (Spearman's Ρ = − 0.113; Ρ = 0.368) or with fetal heart rate pattern (Spearman's Ρ =.425; Ρ =.079, Ρ = −.205; Ρ =.336, Ρ = −.324; Ρ =.122 for groups 1–3, respectively). Conclusion: Intrapartum umbilical cord prolapse is a relatively rare obstetric emergency with an overall favorable neonatal outcome if managed in a timely manner, regardless of the immediately preceding fetal heart rate. In a clinical setting which includes a high obstetric volume and a rapid, protocol-based, response, there is apparently no significant correlation between decision-to-delivery interval and cord arterial cord pH. [ABSTRACT FROM AUTHOR]

Recent advances in functional magnetic resonance imaging (fMRI) have helped elucidate previously inaccessible trajectories of early-life prenatal and neonatal brain development. To date, the interpretation of fetal-neonatal fMRI data has relied on linear analytic models, akin to adult neuroimaging data. However, unlike the adult brain, the fetal and newborn brain develops extraordinarily rapidly, far outpacing any other brain development period across the life span. Consequently, conventional linear computational models may not adequately capture these accelerated and complex neurodevelopmental trajectories during this critical period of brain development along the prenatal-neonatal continuum. To obtain a nuanced understanding of fetal-neonatal brain development, including nonlinear growth, for the first time, we developed quantitative, systems-wide representations of brain activity in a large sample (>500) of fetuses, preterm, and full-term neonates using an unsupervised deep generative model called variational autoencoder (VAE), a model previously shown to be superior to linear models in representing complex resting-state data in healthy adults. Here, we demonstrated that nonlinear brain features, that is, latent variables, derived with the VAE pretrained on rsfMRI of human adults, carried important individual neural signatures, leading to improved representation of prenatal-neonatal brain maturational patterns and more accurate and stable age prediction in the neonate cohort compared to linear models. Using the VAE decoder, we also revealed distinct functional brain networks spanning the sensory and default mode networks. Using the VAE, we are able to reliably capture and quantify complex, nonlinear fetal-neonatal functional neural connectivity. This will lay the critical foundation for detailed mapping of healthy and aberrant functional brain signatures that have their origins in fetal life. [ABSTRACT FROM AUTHOR]

Aim: This study aims to investigate the effects of maternal asthma on fetal cardiac functions. Methods: The study was planned with 30 pregnant women who presented to a tertiary health center and were diagnosed with asthma and 60 healthy controls with similar gestational ages. The fetal echocardiographic assessment was assessed between 33 and 35 weeks of gestation with pulsed‐wave Doppler (PW), M‐mode, and tissue Doppler imaging (TDI). Fetal cardiac functions were compared between maternal asthma and the control group. Cardiac functions were assessed according to the duration of maternal asthma diagnosis, as well. Results: Early diastolic function parameters, tricuspid E wave (p =.001), and tricuspid E/A ratio (p =.005) were significantly lower in the group with maternal asthma. Tricuspid annular plane systolic excursion (TAPSE) and measurements of mitral annular plane systolic excursion (MAPSE) values were statistically lower in the study group than in the control group; p =.010 and p =.012, respectively. Parameters assessed with TDI (E′, A′, S′, E/E′, and MPI′ of tricuspid valves) and global cardiac function parameters assessed with PW like myocardial performance index (MPI) and left cardiac output (LCO) were similar between groups (p >.05). Although, MPI did not change between groups, and the isovolumetric relaxation time (IVRT) value was prolonged in maternal asthma cases (p =.025). Conclusion: We found that maternal asthma disease causes alteration in fetal diastolic and early systolic cardiac functions, but the global fetal cardiac function does not change. Diastolic heart function values also varied with the duration of maternal asthma. Prospective studies are needed to compare fetal cardiac functions with additional patient groups according to disease severity and type of medical treatment. [ABSTRACT FROM AUTHOR]

Although the ductal anomalous origin of the pulmonary artery (DOPA) constitutes a rare heart anomaly, this malformation has a high mortality rate due to the rapid development of pulmonary hypertension(PTH) and right heart failure. Case Presentation: We report a case of DOPA, in which ductus arteriosus originated from the left pulmonary artery. This article summarizes the embryogenesis, clinical manifestations, complications and prognosis, diagnosis and experience, and treatment strategies of DOPA. The most fundamental sonographic finding was the lack of confluence at the bifurcation of the main pulmonary artery. Scanning upper mediastinum views is essential for the diagnosis. In addition, three‐dimensional echocardiography with high‐definition flow imaging and spatio‐temporal image correlation technique facilitates the identification of the anomalous origin of the pulmonary artery. It should be considered a complementary modality in fetal cardiac examinations. Although rare, DOPA can be diagnosed prenatally, usually at the three‐vessel view (3VV). The early diagnosis of DOPA thus can prevent the potentially devastating effects of PHT and right heart failure. [ABSTRACT FROM AUTHOR]

Background: Abnormalities of the fetal cardiovascular system caused by fetal growth restriction (FGR) may lead to adverse outcomes. The fetal cardiac function assessment is of great significance for treatment selection and prognostic evaluation of fetuses with FGR. Objective: This study aimed to explore the value of fetal HQ analysis based on speckle tracking imaging (STI) to evaluate the global and regional cardiac function of fetuses with early‐onset or late‐onset FGR. Methods: From June 2020 to November 2022, 30 pregnant women with early‐onset FGR (21–38 gestational weeks) and 30 pregnant women with late‐onset FGR (21–38 gestational weeks) in the Department of Ultrasound, Shandong Maternal and Child Health Hospital were enrolled. Also, 60 healthy volunteer pregnant women were enrolled as two control groups according to the principle of matching gestational weeks (21–38 gestational weeks). The fetal cardiac functions, including fetal cardiac global spherical index (GSI), left ventricular ejection fraction (LVEF), fractional area change (FAC) of both ventricles, global longitudinal strain (GLS) of both ventricles, 24‐segmental fractional shortening (FS), 24‐segmental end‐diastolic ventricular diameter (EDD), and 24‐segmental spherical index (SI), were assessed using fetal HQ. The standard biological values of fetuses and Doppler blood flow parameters of fetuses and mothers were measured. The estimated fetal weight (EFW) measured by the last prenatal ultrasound was calculated, and the weights of newborns were followed up. Results: Among early FGR, late FGR and total control group, significant differences were found in global cardiac indexes of right ventricle (RV), left ventricle (LV) and GSI. For the segmental cardiac indexes, there are significant differences in three groups except parameter of LVSI. Compared with the control group at the same gestational week, the Doppler indexes including MCAPI and CPR in both the early‐onset FGR group and the late‐onset FGR group were significantly different. The intra‐ and inter‐observer correlation coefficients of RV FAC, LV FAC, RV GLS, and LV GLS were good. Further, the intra‐ and inter‐observer variability in FAC and GLS was small, as analyzed using the Bland–Altman scatter plot. Conclusions: Fetal HQ software based on STI showed that FGR affected the global and segmental cardiac function of both ventricles. FGR no matter early‐onset or late‐onset altered Doppler indexes significantly. The FAC and the GLS had satisfactory repeatability in evaluating fetal cardiac function. [ABSTRACT FROM AUTHOR]

Comprehensive detailed characterization of new mouse models can be challenging due to the individual focus involved in developing these models. Often models are engineered to test a specific hypothesis in a limited number of tissues, stages, and/or other contexts. Whether or not the model produces the desired phenotypes, phenotyping beyond the desired context can be extremely work intensive and these studies are often not undertaken. However, the general information resulting from broader phenotyping can be invaluable to the wider scientific community. The International Mouse Phenotyping Consortium (IMPC) and its subsidiaries, like the Knockout Mouse Project (KOMP), has made great strides in streamlining this process. In particular, the use of microCT has been an invaluable resource in examining internal organ systems throughout fetal/developmental stages. Here, we provide several novel vignettes demonstrating the utility of microCT in uncovering cardiac phenotypes both based on human disease correlations and those that are unpredicted. [ABSTRACT FROM AUTHOR]

Introduction: Maternal anti-Ro/SSA antibodies can cause fetal atrioventricular blocks (AVB). This pilot study aims to apply previously published echocardiographic reference ranges of the fetal atrioventricular (AV) intervals in the setting of anti-Ro/SSA antibody-positive pregnancies in order to exclude a 1° AVB. Materials and Methods: Between January 2018 and September 2022, we included all women with known anti-Ro/SSA antibodies followed up at the prenatal ultrasound department of the University Hospital of Bern. AV intervals were serially measured by two previously reported methods and plotted against previously created reference ranges. Results: We included 23 pregnancies from 17 anti-Ro/SSA antibody-positive women with connective tissue diseases. 443 AV interval measurements were recorded between 16+3 and 38+4 weeks of gestation. 14 (3.2%) AV-intervals measured >150 ms, none measured >170 ms and 8 (1.8%) were found to be >95th percentile. In none of the pregnancies, serial AV-prolongations were noted. The postnatal electrocardiograms demonstrated normal sinus rhythm without AVB in all children. Conclusion: AV intervals of pregnancies followed up for anti-Ro/SSA antibodies without neonatal AVB lie within our published polynomial reference ranges. While diagnosing a 1° AVB remains controversial, more data are needed to prove that our reference ranges are helpful exclude a 1° AVB. [ABSTRACT FROM AUTHOR]

Background: Intrauterine growth restriction (IUGR) exerts a negative impact on developing cardiomyocytes and emerging evidence suggests activation of oxidative stress pathways plays a key role in this altered development. Here, we provided pregnant guinea pig sows with PQQ, an aromatic tricyclic o-quinone that functions as a redox cofactor antioxidant, during the last half of gestation as a potential antioxidant intervention for IUGR-associated cardiomyopathy. Methods: Pregnant guinea pig sows were randomly assigned to receive PQQ or placebo at mid gestation and fetuses were identified as spontaneous IUGR (spIUGR) or normal growth (NG) near term yielding four cohorts: NG ± PQQ and spIUGR ± PQQ. Cross sections of fetal left and right ventricles were prepared and cardiomyocyte number, collagen deposition, proliferation (Ki67) and apoptosis (TUNEL) were analyzed. Results: Cardiomyocyte endowment was reduced in spIUGR fetal hearts when compared to NG; however, PQQ exerted a positive effect on cardiomyocyte number in spIUGR hearts. Cardiomyocytes undergoing proliferation and apoptosis were more common in spIUGR ventricles when compared with NG animals, which was significantly reduced with PQQ supplementation. Similarly, collagen deposition was increased in spIUGR ventricles and was partially rescued in PQQ-treated spIUGR animals. Conclusion: The negative influence of spIUGR on cardiomyocyte number, apoptosis, and collagen deposition during parturition can be suppressed by antenatal administration of PQQ to pregnant sows. These data identify a novel therapeutic intervention for irreversible spIUGR-associated cardiomyopathy. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to assess the ascending and descending aorta area measurements by three-dimensional (3D) ultrasound using spatiotemporal image correlation (STIC) in the rendering mode comparing these measurements with pregestational diabetic mothers and assessing the reproducibility of the method. Methods: We carried out a retrospective cross-sectional study with 58 normal and nine fetuses from pregestational diabetic mothers between 20 and 33 + 6 weeks of gestation. Fetal heart volumes were acquired at the level of four-chamber view to obtain the reconstructed planes for the ascending and descending aorta areas in the rendering mode. Linear regression was performed to assess the correlation between the fetal aorta areas and gestational age (GA). To assess the intra- and interobserver reproducibility, we used the concordance correlation coefficient (CCC). Results: The mean ascending and descending aorta areas were 0.12 (0.02–0.48) and 0.11 (0.04–0.39) cm2 in normal fetuses, respectively. There was a moderate positive correlation between GA and ascending aorta area measurements (0.005676*GA – 0.01283; r = 0.53, P < 0.0001) and strong positive correlation between GA and descending aorta area (0.01095*GA – 0.1581; r = 0.68, P < 0.0001). We observed a weak intra- and interobserver reproducibility with CCC ranging from 0.05 to 0.91. The mean difference in the ascending and descending aorta area measurements of normal and fetuses of pregestational diabetic mothers was −0.03 cm2 (P = 0.276) and −0.03 cm2 (P = 0.231), respectively. Conclusion: The fetal ascending and descending aorta area measurements obtained by 3D ultrasound using STIC in the rendering mode increased with GA in normal fetuses. The method showed weak intra- and interobserver reproducibility.

Background: Airborne pollution particles have been shown to translocate from the mother's lung to the fetal circulation, but their distribution and internal placental-fetal tissue load remain poorly explored. Here, we investigated the placental-fetal load and distribution of diesel engine exhaust particles during gestation under controlled exposure conditions using a pregnant rabbit model. Pregnant dams were exposed by nose-only inhalation to either clean air (controls) or diluted and filtered diesel engine exhaust (1 mg/m3) for 2 h/day, 5 days/week, from gestational day (GD) 3 to GD27. At GD28, placental and fetal tissues (i.e., heart, kidney, liver, lung and gonads) were collected for biometry and to study the presence of carbon particles (CPs) using white light generation by carbonaceous particles under femtosecond pulsed laser illumination. Results: CPs were detected in the placenta, fetal heart, kidney, liver, lung and gonads in significantly higher amounts in exposed rabbits compared with controls. Through multiple factor analysis, we were able to discriminate the diesel engine exposed pregnant rabbits from the control group taking all variables related to fetoplacental biometry and CP load into consideration. Our findings did not reveal a sex effect, yet a potential interaction effect might be present between exposure and fetal sex. Conclusions: The results confirmed the translocation of maternally inhaled CPs from diesel engine exhaust to the placenta which could be detected in fetal organs during late-stage pregnancy. The exposed can be clearly discriminated from the control group with respect to fetoplacental biometry and CP load. The differential particle load in the fetal organs may contribute to the effects on fetoplacental biometry and to the malprogramming of the fetal phenotype with long-term effects later in life. [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]

Clinically serious congenital heart valve defects arise from improper growth and remodeling of endocardial cushions into leaflets. Genetic mutations have been extensively studied but explain less than 20% of cases. Mechanical forces generated by beating hearts drive valve development, but how these forces collectively determine valve growth and remodeling remains incompletely understood. Here, we decouple the influence of those forces on valve size and shape, and study the role of YAP pathway in determining the size and shape. The low oscillatory shear stress promotes YAP nuclear translocation in valvular endothelial cells (VEC), while the high unidirectional shear stress restricts YAP in cytoplasm. The hydrostatic compressive stress activated YAP in valvular interstitial cells (VIC), whereas the tensile stress deactivated YAP. YAP activation by small molecules promoted VIC proliferation and increased valve size. Whereas YAP inhibition enhanced the expression of cell-cell adhesions in VEC and affected valve shape. Finally, left atrial ligation was performed in chick embryonic hearts to manipulate the shear and hydrostatic stress in vivo. The restricted flow in the left ventricle induced a globular and hypoplastic left atrioventricular (AV) valves with an inhibited YAP expression. By contrast, the right AV valves with sustained YAP expression grew and elongated normally. This study establishes a simple yet elegant mechanobiological system by which transduction of local stresses regulates valve growth and remodeling. This system guides leaflets to grow into proper sizes and shapes with the ventricular development, without the need of a genetically prescribed timing mechanism. [ABSTRACT FROM AUTHOR]

Fetal acidemia is a common final pathway to fetal death, and in many cases, to fetal central nervous system injury. However, certain fetal pathophysiological processes are associated with significant category II or category III fetal heart rate changes before the development of or in the absence of fetal acidemia. The most frequent of these processes include fetal infection and/or inflammation, anemia, fetal congenital heart disease, and fetal central nervous system injury. In the presence of significant category II or category III fetal heart rate patterns, clinicians should consider the possibility of the aforementioned fetal processes depending on the clinical circumstances. The common characteristic of these pathophysiological processes is that their associated fetal heart rate patterns are linked to increased adverse neonatal outcomes despite the absence of acidemia at birth. Therefore, in these cases, the fetal heart rate patterns may provide more insight about the fetal condition and pathophysiology than the acid–base status at birth. In addition, as successful timing of intrapartum interventions on the basis of evolution of fetal heart rate patterns aims to prevent fetal acidemia, it may not be logical to continue to use the fetal acid–base status at birth as the gold standard outcome to determine the predictive ability of category II or III fetal heart rate patterns. A more reasonable approach may be to use the umbilical cord blood acid–base status at birth as the gold standard for determining the appropriateness of the timing of our interventions. [ABSTRACT FROM AUTHOR]