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Prediction of fetal growth restriction (FGR) and small of gestational age (SGA) infants by using various ultrasound cardiac parameters in a logistic regression model. In this retrospective study we obtained standardized ultrasound images of 357 fetuses between the 20th and 39th week of gestation, 99 of these fetuses were between the 3rd and 10th growth percentile, 61 smaller than 3rd percentile and 197- appropriate for gestational age over the 10th percentile (control group). Several cardiac parameters were studied. The cardiothoracic ratio and sphericity of the ventricles was calculated. A binary logistic regression model was developed for prediction of growth restriction using the cardiac and biometric parameters. There were noticeable differences between the control and study group in the sphericity of the right ventricle (p = 0.000), left and right longitudinal ventricle length (pright = 0.000, pleft = 0.000), left ventricle transverse length (p = 0.000), heart diameter (p = 0.002), heart circumference (p = 0.000), heart area (p = 0.000), and thoracic diameter limited by the ribs (p = 0.002). There was no difference of the cardiothoracic ratio between groups. The logistic regression model achieved a prediction rate of 79.4 % with a sensitivity of 74.5 % and specificity of 83.2 %. The heart of growth restricted infants is characterized by a more globular right ventricle, shorter ventricle length and smaller thorax diameter. These parameters could improve prediction of FGR and SGA. [ABSTRACT FROM AUTHOR]

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

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]

• 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]

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The objective of this work was to investigate the application of 2D Time-of-Flight (TOF) magnetic resonance angiography (MRA) to observe the placental vasculature at both 1.5 T and 3 T. Fifteen appropriate for gestational age (AGA) (GA: 29.7 ± 3.4 weeks; GA range: 23 and 6/7 weeks to 36 and 2/7 weeks) and eleven patients with an abnormal singleton pregnancy (GA: 31.4 ± 4.4 weeks; GA range: 24 weeks to 35 and 2/7 weeks) were recruited in the study. Three AGA patients were scanned twice at different gestational ages. Patients were scanned either at 3 T or 1.5 T using both T 2 -HASTE and 2D TOF to image the entire placental vasculature. The umbilical, chorionic vessels, stem vessels, arcuate arteries, radial arteries, and spiral arteries were shown in most of the subjects. Hyrtl's anastomosis was found in two subjects in the 1.5 T data. The uterine arteries were observed in more than half of the subjects. For those patients scanned twice, the same spiral arteries were identified in both scans. 2D TOF is a technique that can be applied in studying the fetal-placental vasculature at both 1.5 T and 3 T. • The placental vasculature can be visualized using 2D TOF MRA at both 1.5 T and 3 T. • The spiral artery could be reproducibly identified at different gestational ages by MRA. • Hyrtl's Anastomosis can be identified in MRA. [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]

Elevated circulating progesterone (P4) concentrations in the first week after conception have been associated with accelerated post-hatching conceptus elongation. However, the consequences, if any, on the development of the fetus are unknown. The objective of this study was to determine the relationship between early circulating P4 and fetal and placental morphometric characteristics at 42 days of gestation. A previously validated model of asynchronous embryo transfer (ET), known to alter uterine exposure to P4, was used in 107 heifers divided in two replicates (replicate 1: n = 51, replicate 2: n = 56). Heifers were randomly assigned to one of the two following groups: those receiving a Day 7 embryo on Day 7 of the cycle (synchronous; ET_D7, n = 49) and those transferred a Day 7 embryo on Day 9 of the cycle (asynchronous; ET_D9, n = 58). The synchronization protocol was started two days earlier for heifers in the ET_D9 group such that ET was done on the same day for both groups. P4 concentrations were determined from Day 3 after estrus to the day of ET. Pregnant heifers were slaughtered at Day 42 of gestation for fetal and placental morphometric measurements. The effects of the group, replicate, fetal sex, and interactions between these variables on fetal and placental characteristics were determined by ANOVA, while Pearson correlation was employed to assess the linear relationship between P4 concentrations two days before and on the day of ET on the fetal parameters. The uteri of heifers in the ET_D9 group were exposed to higher concentrations (P < 0.0001) of P4 from four days before ET, than heifers in the ET_D7 group. Both group and fetal sex variables impacted on fetal crown-rump length (CRL) (group: P < 0.0001, sex: P = 0.001) and fetal weight (group: P = 0.006, sex: P = 0.003). Fetal sex influenced the amniotic sac area (P = 0.003) and amniotic sac weight (P = 0.004); while the group affected the number of cotyledons (P = 0.0009), and the fetal heart weight (P = 0.018). All these parameters were larger in the ET_D9 group compared with ET_D7, and in males compared with females. There was a positive correlation between P4 concentrations two days before ET and fetal weight and CRL, for each sex or considering all fetuses (R2 ∼0.4, p < 0.05). In conclusion, bovine embryos transferred into a uterus primed with higher P4 concentrations underwent enhanced development reflected in higher weight and size at the beginning of the fetal period. • An optimal embryo-maternal interaction is mainly driven by progesterone (P4). • Asynchronous embryo transfer (ET) primes the uterus with high P4 concentrations. • This model accelerates conceptus elongation but the effect on the fetus was unknown. • We found a positive correlation between P4 before ET and fetal size at 42 days. • P4 concentrations early in gestation regulate conceptus and fetal development. [ABSTRACT FROM AUTHOR]

Background: Image-domain motion correction of black-blood contrast T2-weighted fetal cardiovascular magnetic resonance imaging (CMR) using slice-to-volume registration (SVR) provides high-resolution three-dimensional (3D) images of the fetal heart providing excellent 3D visualisation of vascular anomalies [1]. However, 3D segmentation of these datasets, important for both clinical reporting and the application of advanced analysis techniques is currently a time-consuming process requiring manual input with potential for inter-user variability. Methods: In this work, we present novel 3D fetal CMR population-averaged atlases of normal and abnormal fetal cardiovascular anatomy. The atlases are created using motion-corrected 3D reconstructed volumes of 86 third trimester fetuses (gestational age range 29-34 weeks) including: 28 healthy controls, 20 cases with postnatally confirmed neonatal coarctation of the aorta (CoA) and 38 vascular rings (21 right aortic arch (RAA), 17 double aortic arch (DAA)). We used only high image quality datasets with isolated anomalies and without any other deviations in the cardiovascular anatomy.In addition, we implemented and evaluated atlas-guided registration and deep learning (UNETR) methods for automated 3D multi-label segmentation of fetal cardiac vessels. We used images from CoA, RAA and DAA cohorts including: 42 cases for training (14 from each cohort), 3 for validation and 6 for testing. In addition, the potential limitations of the network were investigated on unseen datasets including 3 early gestational age (22 weeks) and 3 low SNR cases. Results: We created four atlases representing the average anatomy of the normal fetal heart, postnatally confirmed neonatal CoA, RAA and DAA. Visual inspection was undertaken to verify expected anatomy per subgroup. The results of the multi-label cardiac vessel UNETR segmentation showed 100 % per-vessel detection rate for both normal and abnormal aortic arch anatomy. Conclusions: This work introduces the first set of 3D black-blood T2-weighted CMR atlases of normal and abnormal fetal cardiovascular anatomy including detailed segmentation of the major cardiovascular structures. Additionally, we demonstrated the general feasibility of using deep learning for multi-label vessel segmentation of 3D fetal CMR images. [ABSTRACT FROM AUTHOR]

The rapid advancement of deep neural networks (DNNs) has significantly transformed various sectors, demonstrating unparalleled proficiency in managing intricate tasks in multiple domains. This progress holds promising implications for fetal monitoring systems, particularly in leveraging artificial intelligence (AI) to enhance the detection of abnormalities through cardiotocography (CTG). Understanding the evolving role of AI in obstetrics and gynecology, and its potential to revolutionize clinical practices, is crucial. This paper provides a comprehensive review of the integration of computerized cardiotocography and its associated technologies, coupled with a detailed analysis of the latest developments in machine learning (ML) and deep learning (DL) within the realm of CTG research over recent years. It further explores additional tools for fetal heart monitoring, such as fetal cardiotocography, and delves into the implications of these advancements. Moreover, the study outlines prospective research avenues, discusses innovative AI approaches to overcome existing challenges, and envisages the transformative impact of AI on the future of antepartum and intrapartum care, paving the way for a new era of automated fetal monitoring. • Discusses AI, ML, and DL advancements in fetal heart monitoring, focusing on CTG. • Highlights the subjective nature of traditional CTG and need for standards. • Emphasizes AI's role in improving CTG analysis for accurate, objective diagnostics. • Reviews literature to pinpoint future research avenues for enhancing AI in CTG. • Stresses the importance of transparent AI for better clinical decision support. [ABSTRACT FROM AUTHOR]

The fetal electrocardiogram (FECG) provides an important way for clinicians to assess fetal health and to monitor pregnancy conditions. Although FECG can be captured through abdominal electrocardiogram (AECG) recordings from pregnant women, it often receives interference from maternal cardiac activity and other external sources. Particularly, as the high-amplitude maternal electrocardiogram (MECG) typically obscures the waveform of the FECG, isolating FECG from the AECG signals is challenging. Nevertheless, the differences in frequency patterns between MECG and FECG suggest a potential way for reconstructing FECG by combining the frequency and amplitude information. To this end, we proposed a novel method for separating FECG signals from the AECG via the time–frequency representation. We designed an encoder–decoder architecture based hierarchical multiscale-aware network to capture features embedded in both the time and frequency domains. Equipped with a holistic attention-aware module (HAA), the model extracts and consolidates fetal heart activity-related features in the time–frequency domain. Further introducingan attention gate module (AG) to emphasize key features during encoder-to-decoder transmission, the model enhances the quality and efficiency of FECG extraction without any redundancy in high-quality feature mapping. The model was trained using a hybrid time-domain and frequency-domain loss function and validated on two public databases. Excellent performances, such as an average Pearson correlation coefficient of 0.85 for estimating the quality of FECG signals, were observed demonstrating its excellent performance and providing a promising non-invasive method for monitoring fetal health. These findings indicate that the proposed method effectively captures the amplitude differences between fetal and maternal heartbeats across various frequency components within the AECG, leading to the extraction of high-quality FECG signals. • We modified the main text according to reviewers' suggestions and comments. • We had a very careful proof-reading over the whole texts and corrected the grammar errors and refined some expressions. • We added additional experimental results to verify the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Fetal echocardiography has become a recommended investigation during pregnancy routine examination in the second semester of fetal development. The heart structures are now sufficiently developed to detect any indication of a possible congenital heart disease. However, the inspection of the key components is not as straightforward for the less experienced young obstetricians. Moreover, a background automatic check of the presence of the main elements could be helpful in speeding up the overall assessment during the periodic pregnancy control. In this respect, the current paper proposes the support of a deep learning model towards the semantic segmentation of eleven key structures that need to be identified within the second trimester fetal heart scans. [ABSTRACT FROM AUTHOR]

Can an artificial intelligence embryo selection assistant predict the incidence of first-trimester spontaneous abortion using static images of IVF embryos? In a blind, retrospective study, a cohort of 172 blastocysts from IVF cases with single embryo transfer and a positive biochemical pregnancy test was ranked retrospectively by the artificial intelligence morphometric algorithm ERICA. Making use of static embryo images from a light microscope, each blastocyst was assigned to one of four possible groups (optimal, good, fair or poor), and linear regression was used to correlate the results with the presence or absence of a normal fetal heart beat as an indicator of ongoing pregnancy or spontaneous abortion, respectively. Additional analyses included modelling for recipient age and chromosomal status established by preimplantation genetic testing for aneuploidy (PGT-A). Embryos classified as optimal/good had a lower incidence of spontaneous abortion (16.1%) compared with embryos classified as fair/poor (25%; OR = 0.46, P = 0.005). The incidence of spontaneous abortion in chromosomally normal embryos (determined by PGT-A) was 13.3% for optimal/good embryos and 20.0% for fair/poor embryos, although the difference was not significant (P = 0.531). There was a significant association between embryo rank and recipient age (P = 0.018), in that the incidence of spontaneous abortion was unexpectedly lower in older recipients (21.3% for age ≤35 years, 17.9% for age 36–38 years, 16.4% for age ≥39 years; OR = 0.354, P = 0.0181). Overall, these results support correlation between risk of spontaneous abortion and embryo rank as determined by artificial intelligence; classification accuracy was calculated to be 67.4%. This preliminary study suggests that artificial intelligence (ERICA), which was designed as a ranking system to assist with embryo transfer decisions and ploidy prediction, may also be useful to provide information for couples on the risk of spontaneous abortion. Future work will include a larger sample size and karyotyping of miscarried pregnancy tissue. [ABSTRACT FROM AUTHOR]

Porcine reproductive and respiratory syndrome (PRRS) is one of the costliest diseases to pork producers worldwide. We tested samples from the pregnant gilt model (PGM) to better understand the fetal response to in-utero PRRS virus (PRRSV) infection. Our goal was to identify critical tissues and genes associated with fetal resilience or susceptibility. Pregnant gilts (N=22) were infected with PRRSV on day 86 of gestation. At 21 days post maternal infection, the gilts and fetuses were euthanized, and fetal tissues collected. Fetuses were characterized for PRRS viral load in fetal serum and thymus, and preservation status (viable or meconium stained: VIA or MEC). Fetuses (N=10 per group) were compared: uninfected (UNIF; <1 log/µL PRRSV RNA), resilient (HV_VIA, >5 log virus/µL but viable), and susceptible (HV_MEC, >5 log virus/µL with MEC). Gene expression in fetal heart, kidney, and liver was investigated using NanoString transcriptomics. Gene categories investigated were hypothesized to be involved in fetal response to PRRSV infection: renin- angiotensin-aldosterone, inflammatory, transporter and metabolic systems. Following PRRSV infection, CCL5 increased expression in heart and kidney, and ACE2 decreased expression in kidney, each associated with fetal PRRS susceptibility. Liver revealed the most significant differential gene expression: CXCL10 decreased and IL10 increased indicative of immune suppression. Increased liver gene expression indicated potential associations with fetal PRRS susceptibility on several systems including blood pressure regulation (AGTR1), energy metabolism (SLC16A1 and SLC16A7), tissue specific responses (KL) and growth modulation (TGFB1). Overall, analyses of non-lymphoid tissues provided clues to mechanisms of fetal compromise following maternal PRRSV infection. [Display omitted] • Fetal response to late gestation PRRSV infection is dependent on viral load and preservation status. • Infection alters gene expression associated with blood pressure, glucose transport, sodium homeostasis and immune response. • Gene expression changes associated with fetal susceptibility were prominent in fetal liver, followed by kidney and heart. [ABSTRACT FROM AUTHOR]

Posterior fossa abnormalities include, Dandy-Walker malformation (DWM), mega cisterna magna (MCM), Blake's pouch cyst (BPC), isolated vermian hypoplasia (VH). They are congenital central nervous system (CNS) malformations which considered the second most common anomalies in fetuses following the cardiac malformations. It is associated with high rates of morbidity and mortality which can affect the neuro- developmental function with lifelong sequelae. The purpose of this study was to identify the different types of posterior fossa abnormalities in our population, to assess the outcomes associated with different types of posterior fossa abnormalities such as neurologic development, in National guard hospital, Riyadh, Saudi Arabia, from 2017 to 2021 A retrospective cohort study conducted between January 2017 and December 2021 in king Abdulaziz medical city, Riyadh, Saudi Arabia. Included all fetuses diagnosed with posterior fossa malformations during antenatal ultrasound. Posterior fossa abnormalities were defined on the basis of a proposed: morphological approach includes: Dandy-Walker malformation (DWM), Mega cisterna magna (MCM), Blake's pouch cyst (BPC), Isolated vermian hypoplasia (VH). We identified 65 posterior fossa anomalies in the NGHA – Riyadh, Saudi Arabia between 2017-2021 The annual incidence rates were 2.64, 2.48, 4.41, 8.75, and 1.71 per 1000 anatomy scans for 2017, 2018, 2019, 2020, and 2021, respectively. Infants with DWM appeared to have a higher proportion of associated central nervous system (CNS) abnormalities (70.4% vs. 39.5%; p-value=.014) and seizures than others (45% vs. 17.9%; p-value=.041). Among the 65 patients with the posterior fossa anomalies, approximately over one third of their mothers have consanguineous marriages that increases risk for congenital malformations and autosomal recessive diseases. Antenatal karyotyping was done for 21 of the cases. There were 5 cases with abnormal result (4 cases with Trisomy 18 and 1 case of Trisomy 13). Postnatally, WES or WGS were done for 17 infants, and 12 had an abnormal result. Among the 12 patients, two infants had abnormal karyotypes, one had Trisomy 18, and the other had a heterozygous likely pathogenic deletion within the cytogenic band 2q.23.1(147940954_148024399) which was not previously known to cause posterior fossa anomaly. The rest have a single gene mutation causing CNS abnormalities. The most common PFA is MCM and DWM. The autosomal recessive pathogenic mutation is the major cause of genetic disease in Saudi patients diagnosed with PFA. [ABSTRACT FROM AUTHOR]

• Fetal phonocardiography suitable for FHR estimation. • Automatic filter selection increase FHR estimation success rate. • Both Hilbert autocorrelation and cyclic repetition frequency algorithm provide reliable FHR estimation even in poor quality fPCG recordings. Fetal phonocardiography (fPCG) is a passive and non-invasive technique for measuring fetal heart rate. Due to the presence of external and internal noises, filtering is mandatory to obtain clinically usable signals from fPCG recordings. Frequency characteristics of the fPCG signal recorded from the mother's abdomen change with fetal parameters like gestation week, fetal position, etc. This makes the choice of filter frequencies challenging and unproductive. Therefore, our aim is to develop automatic filter selection based on fetal heart sounds characteristics. This work presents algorithms for the automatic filter selection based on fPCG signal characteristics. The automatic filter selection algorithms are coupled with fetal heart rate estimation algorithms based on Hilbert-autocorrelation and cyclic repetition frequency. Three performance measures are determined to test the algorithms: accuracy, reliability, and success rate. The automatic filter selection show significant improvement in success rate when compared with manually selected fixed frequency band filters. The success rate improves from 79% to 93% for Hilbert-autocorrelation based algorithm and 71% to 90% for cyclic repetition frequency-based algorithm. Automated filter selection could enable robust automated estimation of fetal heart rate from fPCG recordings across variety of clinical settings. [ABSTRACT FROM AUTHOR]

Background: Knowledge about extracardiac anomalies (ECA) in fetal congenital heart disease (CHD) can improve our understanding of the developmental origins of various outcomes in these infants. The prevalence and spectrum of ECA, including structural brain anomalies (SBA), on magnetic resonance imaging (MRI) in fetuses with different types of CHD and at different gestational ages, is unknown.Objectives: The purpose of this study was to evaluate ECA rates and types on MRI in fetuses with different types of CHD and across gestation.Methods: A total of 429 consecutive fetuses with CHD and MRI between 17 and 38 gestational weeks were evaluated. ECA and SBA rates were assessed for each type of CHD and classified by gestational age (<25 or ≥25 weeks) at MRI.Results: Of all 429 fetuses with CHD, 243 (56.6%) had ECA on MRI, and 109 (25.4%) had SBA. Among the 191 fetuses with normal genetic testing results, the ECA rate was 54.5% and the SBA rate 19.4%. Besides SBA, extrafetal (21.2%) and urogenital anomalies (10.7%) were the most prevalent ECA on MRI in all types of CHD. Predominant SBA were anomalies of hindbrain-midbrain (11.0% of all CHD), dorsal prosencephalon (10.0%) development, and abnormal cerebrospinal fluid spaces (10.5%). There was no difference in the prevalence or pattern of ECA between early (<25 weeks; 45.7%) and late (≥25 weeks; 54.3%) fetal MRI.Conclusions: ECA and SBA rates on fetal MRI are high across all types of CHD studied, and ECA as well as SBA are already present from midgestation onward. [ABSTRACT FROM AUTHOR]

After gestational exposure, BBOP inhibits phosphorylation of AKT1, AKT2, ERK1/2, thus possibly down-regulating fetal Leydig cell (FLC) gene expression and leading to the reduction its proteins, thereby resulting in decrease in INSL3 and testosterone (T) production. [Display omitted] • Bis(2-butoxyethyl) phthalate disrupts fetal Leydig cell development. • Bis(2-butoxyethyl) phthalate lowers testosterone production in fetal testis. • Bis(2-butoxyethyl) phthalate increases Leydig cell number. • Bis(2-butoxyethyl) phthalate inhibits the phosphorylation of AKT1, AKT2, and ERK1/2 signaling in fetal testis. Phthalates are plasticizers widely found in the environment. They are potential endocrine disruptors. Bis(2-butoxyethyl) phthalate (BBOP) is a unique phthalate that contains oxygen atoms in the carbon backbone. Little is known about its reproductive and developmental toxicity. The objective of this study was to determine the effect of BBOP on fetal Leydig cell development after in utero exposure to rats. Sprague Dawley pregnant dams were randomly allocated into 6 groups, and were gavaged with BBOP (0, 10, 100, 250, 500, and 1000 mg/kg body weight/day) from gestational day (GD) 14–21. Seven of the 8 dams in the 1000 mg/kg BBOP group died before giving birth. Twelve of the 20 dams in the 500 mg/kg BBOP group had whole litter loss. BBOP significantly reduced the body weight of dams and male offspring and serum testosterone level and anogenital distance of male fetus on GD 21 at 500 mg/kg. BBOP markedly increased fetal Leydig cell proliferation and number at 500 mg/kg while inducing their abnormal aggregation at 250 and 500 mg/kg. BBOP down-regulated the expression of Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Cyp17a1, Hsd17b3, Insl3 , and Nr5a1 at various doses while up-regulating the expression of Sertoli cell gene Fshr and Sox9. The phosphorylation of AKT1, AKT2, and ERK1/2 was also markedly reduced by BBOP. In conclusion, BBOP in utero exposure can disrupt fetal Leydig cell development, possibly via the mechanism that may include inhibiting the phosphorylation of AKT1, AKT2, and ERK1/2. [ABSTRACT FROM AUTHOR]

Background: The Fetal Blood Sample (FBS) is used as an indicator of fetal acidosis during labor. Its place is discussed through the lack of randomized trials, as well as the limitations related to the technical procedure. An alternative could be the Fetal Scalp Stimulation (FSS).Aim: Our objective was to describe the FSS diagnostic value to predict fetal wellbeing defined from FBS.Methods: The FSS consisted in a digital scalp stimulation for 15 s. Test was negative when an acceleration and/or a normal variability were elicited in the 2 min following. FSS was performed before each FBS which was classified as normal when pH was > 7.25. The diagnostic value was assessed by sensibility, specificity, positive and negative predictive values.Findings: 148 women were included in our center from February to December 2019. Of the 191 FBS procedures, when accelerations were elicited sensibility was 58,3 (36.8-77.1), specificity was 67,5 (59.3-75), positive predictive value was 20,9 (12.5-32.9) and negative predictive value was 91.7 % (95 %CI, 85-95.5).Discussion: FBS is considered as the gold standard in our study which could be discussed as it is abandoned in some countries because of its questioned reliability and the lack of controlled randomized trials.Conclusion: This study suggests that FSS could be an interesting alternative adjunctive test to perform in the first instance as it seems to be reliable, non-invasive and easy to perform in order to limit FBS only to absence of acceleration after FSS. [ABSTRACT FROM AUTHOR]

Fetal cardiac ultrasound is a valuable tool for screening fetal cardiac health during pregnancy. Ultrasound standard section testing is an essential part of fetal heart ultrasound diagnosis. Due to the many scattered and partially similar anatomical structures in standard ultrasound views of the fetal heart, the results strongly depend on the clinical experience and knowledge of the sonographer. To improve detection efficiency and reduce misdiagnosis and omission, we propose a single-stage fetal cardiac ultrasound standard plane detection model (FCUM) based on multitask learning and a hybrid attention mechanism to assist sonographers in diagnosis. The feature fusion pyramids of the backbone and detection networks of this model are each embedded with a hybrid attention mechanism module of our design, which enables the multitasking network to extract shared features more accurately and efficiently and improves the accuracy of the detection and classification networks. We designed a classification module for multilayer residual network feature fusion that leads to better classification and faster convergence time. We conducted comprehensive experiments on a dataset of fetal cardiac ultrasound images acquired with several types of devices and in different geographic regions. The experimental results show that our model outperforms baseline models such as YOLOv8 and ResNet-50 in terms of detection precision and classification accuracy. [ABSTRACT FROM AUTHOR]

• GDM induced fetal myocardial injury. • A total of 462 DE-mRNAs were present in heart tissues of GDM offspring. • DE-mRNAs mainly regulate immunity, redox reactions, and cellular communication. • ATP5me alleviates high glucose-induced myocardial injury in vitro. Gestational diabetes mellitus (GDM) is associated with adverse myocardial remodeling and impaired cardiac function of fetus. Nevertheless, specific molecular mechanisms underlying type 1 GDM-induced fetal myocardial injury remain unknown. Therefore, this study proposes to identify possible molecular mechanisms using RNA-seq. A rat type 1 GDM model was developed using streptozotocin (STZ) (25 and 50 mg/kg), and weight and glucose tolerance of maternal and offspring were evaluated. Changes in markers of myocardial injury and oxidative stress identified by ELISA and biochemical kits in offspring hearts. Identification of differentially expressed mRNAs (DE-mRNAs) associated with myocardial injury in type 1 GDM offspring using RNA-seq. Proliferation, apoptosis, and oxidative stress were assessed in high glucose-induced H9C2 cells after exogenously modulating ATP Synthase Membrane Subunit E (ATP5me). Maternal weight, glucose and glucose tolerance, and fetal weight and heart weight were reduced in the type 1 GDM model, especially in 50 mg/kg STZ-induced. Increased of creatine kinase-MB (CK-MB), cardiac troponin T (cTnT), hypersensitive C-reactive protein (hs-CRP), reactive oxygen species (ROS) and malondialdehyde (MDA) and decreased of superoxide dismutase (SOD) were observed in type 1 GDM offspring hearts. type 1 GDM offspring hearts exhibited disorganized cardiomyocytes with enlarged gaps, broken myocardial fibers, erythrocyte accumulation and inflammatory infiltration. RNA-seq identified 462 DE-mRNAs in type 1 GDM offspring hearts, which mainly regulate immunity, redox reactions, and cellular communication. Atp5me was under-expressed in type 1 GDM offspring hearts, and high glucose decreased Atp5me expression in H9C2 cells. Overexpressing Atp5me alleviated high glucose-induced decrease in proliferation, mitochondrial membrane potential, BCL2 and SOD, and increase in apoptosis, MDA, ROS, c-Caspase-3, and BAX in H9C2 cells. This study first demonstrated that ATP5me attenuated type 1 GDM-induced fetal myocardial injury. This provides a possible molecular mechanism for the treatment of type 1 GDM-induced fetal myocardial injury. [ABSTRACT FROM AUTHOR]

Fetal brain extraction from magnetic resonance (MR) images is of great importance for both clinical applications and neuroscience studies. However, it is a challenging task, especially when dealing with twins, which are commonly existing in pregnancy. Currently, there is no brain extraction method dedicated to twins, raising significant demand to develop an effective twin fetal brain extraction method. To this end, we propose the first twin fetal brain extraction framework, which possesses three novel features. First, to narrow down the region of interest and preserve structural information between the two brains in twin fetal MR images, we take advantage of an advanced object detector to locate all the brains in twin fetal MR images at once. Second, we propose a Twin Fetal Brain Extraction Network (TFBE-Net) to further suppress insignificant features for segmenting brain regions. Finally, we propose a Two-step Training Strategy (TTS) to learn correlation features of the single fetal brain for further improving the performance of TFBE-Net. We validate the proposed framework on a twin fetal brain dataset. The experiments show that our framework achieves promising performance on both quantitative and qualitative evaluations, and outperforms state-of-the-art methods for fetal brain extraction. • We propose a novel Twin Fetal Brain Extraction Network to extract the fetal brains of twins. • We elaborate a new training strategy to learn the correlation features between the singleton and twins. • We employ an object detector to simultaneously locate all fetal brains from the maternal tissues. • Our framework outperforms SOTA methods on clinical fetal MRI dataset of twins. [ABSTRACT FROM AUTHOR]

Introduction: There is a strong association between gestational obesity and fetal cardiac dysfunction, while the exact mechanisms remain largely unknown. The purpose of this study was to investigate the role of exosomes from maternal visceral adipose tissue in abnormal embryonic development in obese pregnancy.Methods: Female C57BL/6J obese mice were induced by a high-fat diet (containing 60% fat). Fetal cardiac function and morphology were examined by echocardiography and histology. The placenta was extracted for histological examination. miRNA expression in exosomes from the visceral adipose tissue was profiled by RNA-seq. Gene expression of inflammatory factors was analyzed by qPCR.Results: In the obese pregnant mice, there were obvious inflammation and lipid droplets in the placenta. And the fetal cardiac function in obese pregnancy was also compromised. Moreover, injection of the visceral adipose tissue exosomes from the obese mice significantly decreased the fetal cardiac function in the normal lean pregnant mice. Mechanistically, the decreased expression of miR-19b might be responsible for the enhanced inflammation in the placenta.Discussion: Exosomes derived from visceral adipose tissue in obese mice contribute to fetal heart dysfunction, at least partially via affecting the function of the placenta. [ABSTRACT FROM AUTHOR]

[Display omitted] [ABSTRACT FROM AUTHOR]

Background Fetal growth restriction (FGR), defined as an estimated fetal weight (EFW)<10th percentile, is associated with an increased risk for adverse fetal and neonatal outcome. Early antenatal diagnosis is important and remains challenging. Deformation changes in the fetal myocardium are early signs of myocardial dysfunction. These changes can be measured using two-dimensional speckle tracking echocardiography (2D-STE) to predict impaired placental function in the growth restricted fetus. Aim To review the literature on fetal heart deformation values measured with 2D-STE, in fetuses with an EFW< 10th centile and appropriate for gestational age (AGA) fetuses, and to compare the results in both groups. Methods The EMBASE, Medline, and Cochrane databases were searched from inception until April 2020. Observational studies on evaluating the cardiac deformation values longitudinal strain, strain rate, and/or global dyssynchrony of both ventricles in FGR, using 2D-STE, were included. Methodological quality was assessed using the Newcastle-Ottowa risk of bias scale. Results Four studies met the inclusion criteria. The mean gestational age (GA) varied from 30 to 38 weeks in the FGR group and 20 to 40 weeks in AGA fetuses. The number of included FGR fetuses (with or without Doppler abnormalities), varied from 30 to 50. Longitudinal strain in FGR fetuses was described as comparable (n = 2), increased (n = 1) and>95th percentile (n = 1) compared to AGA fetuses. Strain rate was measured in two studies. One reported an increased strain rate, another showed comparable strain rate. Two studies addressed global left ventricle (LV) and right ventricle (RV) dyssynchrony. Dyssynchrony was increased in FGR compared to AGA fetuses. Conclusion The currently published data is limited and heterogeneous concerning GA and Doppler profiles. The data presentation and the interpretation thereof make qualitative comparisons impossible. Large prospective longitudinal cohort studies looking at the value of deformation measurements of the fetal heart in FGR and AGA fetuses are needed to assess the clinical significance of deformation values measured with 2D-STE. [ABSTRACT FROM AUTHOR]

• No previous work utilized a Chebyshev filter and wavelet analysis to extract FECG. • Only two AECG signals are required for the FECG extraction. • The proposed extraction method conserves the fetal QRS complex. • The proposed method can be adjusted based on the power levels of the signals. Monitoring the heartbeat of the fetus during pregnancy is a vital part in determining their health. Current fetal heart monitoring techniques lack the accuracy in fetal heart rate monitoring and features acquisition, resulting in diagnostic medical issues. The demand for a reliable method of non-invasive fetal heart monitoring is of high importance. Electrocardiogram (ECG) is a method of monitoring the electrical activity produced by the heart. The extraction of the fetal ECG (FECG) from the abdominal ECG (AECG) is challenging since both ECGs of the mother and the baby share similar frequency components, adding to the fact that the signals are corrupted by white noise. This paper presents a method of FECG extraction by eliminating all other signals using AECG. The algorithm is based on attenuating the maternal ECG (MECG) by filtering and wavelet analysis to find the locations of the FECG, and thus isolating them based on their locations. Two signals of AECG collected at different locations on the abdomens are used. The ECG data used contains MECG of a power of five to ten times that of the FECG. The FECG signals were successfully isolated from the AECG using the proposed method through which the QRS complex of the heartbeat was conserved, and heart rate was calculated. The fetal heart rate was 135 bpm and the instantaneous heart rate was 131.58 bpm. The heart rate of the mother was at 90 bpm with an instantaneous heart rate of 81.9 bpm. The proposed method is promising for FECG extraction since it relies on filtering and wavelet analysis of two abdominal signals for the algorithm. The method implemented is easily adjusted based on the power levels of signals, giving it great ease of adaptation to changing signals in different biosignals applications. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to determine the reference ranges for filling time (FT) and systolic-to-diastolic time index (SDI) of the left ventricle (LV) by using spectral Doppler, and FT' and SDI' of the LV, right ventricle, and interventricular septum (IVS) by using tissue Doppler of the fetal heart.Study Design: This prospective and cross-sectional study included 360 low-risk singleton pregnancies between 20 and 36 + 6 weeks of gestation. The SDI/SDI' is the sum of the ejection time, isovolumic contraction time, and isovolumic relaxation time (IRT) divided by the FT. We measured FT/FT' from the beginning of the opening click of the E wave of the mitral valve to the closing click of the A wave of the mitral valve. We used regression analysis to obtain the best-fit model polynomial equation for the parameters. Additionally, we assessed intra- and inter-observer reproducibility by using concordance correlation coefficient (CCC).Results: There was a weak correlation among FT LV (r = 0.31, p < 0.0001), SDI LV (r = -0.23, p < 0.0001), and gestational age (GA). Additionally, there was a very weak positive correlation among FT' RV (r = 0.09, p = 0.0001), FT' LV (r = 0.07, p < 0.0001), FT' IVS (r = 0,08, p < 0.0001), and GA. In contrast, there was a very weak negative correlation among SDI' LV (r=-0.09, p < 0.0001), SDI' IVS (r=-0.05, p < 0.0021), and GA. There was no significative correlation between SDI' RV (r=-0.06, p < 0.081) and GA. Poor/very poor intra- and inter-observer reliability was observed for all the parameters (CCC = 0.19-0.79), whereas moderate intra- and inter-observer agreement was observed for all parameters (CCC = 0.37-0.72).Conclusions: The reference ranges for FT and SDI were determined by using spectral and tissue Doppler of the fetal heart and showed a poor reproducibility. [ABSTRACT FROM AUTHOR]

Objective: To determine the cardiotocograph (CTG) changes in women with symptomatic COVID-19 infection.Study Design: 12 anonymised CTG traces from 2 hospitals in Spain were retrospectively analysed by 2 independent assessors. CTG parameters were studied based on fetal pathophysiological responses to inflammation and hypoxia that would be expected based on the pathogenesis of COVID-19 patients. Correlation was made with perinatal outcomes (Apgar score at 5 min and umbilical cord pH).Results: All fetuses showed an increased baseline FHR > 10 percent compared to the initial recording, in addition to absence of accelerations. 10 out of 12 CTG traces (83.3 percent) demonstrated late or prolonged decelerations and 7 out of 12 fetuses (58.3 percent) showed absence of cycling. Not a single case of sinusoidal pattern was observed. ZigZag pattern was found in 4 CTG traces (33 percent). Excessive uterine activity was observed in all CTG traces where uterine activity was monitored (10 out of 12). Apgar scores at 5 min were normal (>7) and absence of metabolic acidosis was found in the umbilical cord arterial pH (pH > 7.0) in the cases that were available (11 and 9, respectively).Conclusion: Fetuses of COVID-19 patients showed a raised baseline FHR (>10 percent), loss of accelerations, late decelerations, ZigZag pattern and absence of cycling probably due to the effects of maternal pyrexia, maternal inflammatory response and the "cytokine storm". However, the perinatal outcomes appear to be favourable. Therefore, healthcare providers should optimise the maternal environment first to rectify the reactive CTG changes instead of performing an urgent operative intervention. [ABSTRACT FROM AUTHOR]

Aim: To develop gestational age-based reference ranges for the modified Doppler myocardial performance index (Mod MPI) and to examine the maternal characteristics that affect this measurement.Methods: This was a cross-sectional study, comprised of 1021 healthy pregnancies between 20+0 to 35+6 weeks' gestation. They were all undergoing ultrasound examination in Cairo Fetal Medicine Unit (CAIFM) in Cairo University, Egypt from 1st April 2017 till 1st April 2019. Mod MPI was obtained used method described by Friedman et al. (2003). Median and SD models were fitted between Mod MPI and gestational age. The distributions of Mod MPI Z-scores were examined in relation to maternal characteristics RESULTS: The normal Mod MPI in second and third trimester (20 + 1 to 35 + 6 weeks' gestation) was 0.408 ± 0.08. Mod MPI was not affected by maternal age, body mass index (BMI) or parity (p value 0.5, 0.6 and 0.2 respectively).Conclusion: This study established normal reference ranges for Mod MPI according to gestational age and generated a graph with 5th,10th, 90th and 95th centiles. Maternal characteristics as age, BMI or parity do not affect value of Mod MPI. [ABSTRACT FROM AUTHOR]

Establishment of the maturational patterns of the fetal left and right ventricle strain and strain rate by two-dimensional speckle tracking echocardiography is a prerequisite for its routine clinical adaptation in pregnancy. The aim of this study is to review systematically current literature on the development of left and right ventricle strain and strain rate derived by speckle tracking during gestation. EMBASE, Medline and Central were searched, from inception to October 2019, for observational studies of singletons in uncomplicated, non-anomalous pregnancies, measuring global longitudinal strain and strain rate with 2D speckle tracking echocardiography in the fetal heart during gestation. 23 Studies met the inclusion criteria. The gestational age of the included fetuses varied from 12 to 42 weeks. Four studies used a longitudinal study design, with few consecutive measurements at varying gestational ages. 19 Studies performed either cross sectional or both longitudinal and cross sectional measurements. The ultrasound devices and speckle tracking algorithm software used, varied. Strain and strain rate during gestation increased, decreased or remained stable in the left and right fetal ventricle with increasing gestation. Due to considerable variation in the included gestational ages measured and inconsistency in the direction of strain and strain rate development, a meta-analysis could not be performed. Contradictory results concerning the development of strain and strain rate during gestation were shown, probably due to suboptimal study designs and varying algorithms and ultrasound devices used. A large longitudinal cohort study is needed to obtain reference values for fetal cardiac deformation in the uncomplicated, singleton pregnancy. [ABSTRACT FROM AUTHOR]

• Mdx quadriceps and heart but not diaphragm have low tissue carnitine. • mOctn2 protein is reduced in mdx quadriceps, heart and diaphragm. • mOctn1 and mOctn2 mRNA by qRT-PCR are upregulated in mdx quadriceps. • mOctn2 and mOctn3 mRNA by qRT-PCR are upregulated in mdx heart. • No upregulation of mOctn1,-2 or-3 mRNA in mdx diaphragm. Carnitine is essential for long-chain fatty acid oxidation in muscle and heart. Tissue stores are regulated by organic cation/Cn transporter plasmalemmal Octn2. We previously demonstrated low carnitine in quadriceps/gluteus and heart of adult mdx mice. We studied protein and mRNA expression of Octn2, mitochondrial Octn1 and peroxisomal Octn3 in adult male C57BL/10ScSn-DMD mdx /J quadriceps, heart, and diaphragm compared to C57BL/10SnJ mice. We demonstrated reduction in mOctn2 expression on Western blot and similar expression of mOctn1 and mOctn3 in mdx quadriceps, heart and diaphragm. There was a significant upregulation of mOctn1 and mOctn2 mRNA by qRT-PCR in mdx quadriceps and of mOctn2 and mOctn3 mRNA in mdx heart. We showed upregulation of mdx mOctn1 and mOctn3 mRNA but no increase in protein expression. Dystrophin deficiency likely disrupts Octn2 expression decreasing muscle carnitine uptake thus contributing to membranotoxic long-chain acyl-CoAs with sarcolemmal and organellar membrane oxidative injury providing a treatment rationale for early L-carnitine in DMD. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to review our institution's experience with fetal cardiac rhabdomyoma, and to document the prenatal genetic testing for tuberous sclerosis complex (TSC) and clinical outcome of the affected pregnancies.Study Design: During a four-year period, patients with fetal cardiac rhabdomyoma were detected by echocardiography in the second trimester of pregnancy. Molecular genetic analysis was conducted on fetuses to screen for variants of TSC1/TSC2 genes. We reviewed medical records of these affected pregnancies, including maternal demographics, sonographic findings, genotyping results and pregnancy outcomes.Results: Eleven cases with fetal cardiac rhabdomyoma were studied during the study period. A pathogenic variant of TSC1/TSC2 genes was detected in all cases, including two with an inherited variant and nine with a de novo variant. Out of these eleven cases diagnosed prenatally, eight pregnancies were terminated and three continued till term.Conclusions: Cardiac rhabdomyoma is the prenatal sign of TSC. A molecular investigation of TSC1/TSC2 genes should be recommended for fetuses with a rhabdomyoma and the parents, and the prognostic counselling should include TSC and its consequences. [ABSTRACT FROM AUTHOR]

Congenital heart defects are a leading cause of neonatal morbidity and mortality. Accurate prenatal diagnosis of congenital heart defects can reduce morbidity and mortality by improving prenatal care, facilitating predelivery pediatric cardiology consultation, and directing delivery to facilities with resources to manage the complex medical and surgical needs of newborns with congenital heart defects. Unfortunately, less than one half of congenital heart defect cases are detected prenatally, resulting in lost opportunities for counseling, shared decision-making, and delivery at an appropriate facility. Quality improvement initiatives to improve prenatal congenital heart defects detection depend on the ability to measure the rate of detection at the level of providers, facilities, or populations, but no standard metric exists for measuring the detection of congenital heart defects at any level. The need for such a metric was recognized at a Cooperative Workshop held at the 2016 Annual Meeting of the Society for Maternal-Fetal Medicine, which recommended the development of a quality metric to assess the rate of prenatal detection of clinically significant congenital heart defects. In this paper, we propose potential quality metrics to measure prenatal detection of critical congenital heart defects, defined as defects with a high rate of morbidity or mortality or that require surgery or tertiary follow-up. One metric is based on a retrospective approach, assessing whether postnatally diagnosed congenital heart defects had been identified prenatally. Other metrics are based on a prospective approach, assessing the sensitivity and specificity of prenatal diagnosis of congenital heart defects by comparing prenatal ultrasound findings with newborn findings. Potential applications, limitations, challenges, barriers, and value for both approaches are discussed. We conclude that future development of these metrics will depend on an expansion of the International Classification of Diseases system to include specific codes that distinguish fetal congenital heart defects from newborn congenital heart defects and on the development of record systems that facilitate the linkage of fetal records (in the maternal chart) with newborn records. [ABSTRACT FROM AUTHOR]

There is no established transplacental treatment for heart failure (HF) in utero , and no animal models or experimental systems of fetal HF have been established. This study aimed to investigate the effect of maternal tadalafil administration on fetal cardiovascular function and uteroplacental circulation in a murine model of fetal HF. We first used an ultra-high-frequency ultrasound imaging system in utero and demonstrated that Hey2 −/− embryos had worsening right ventricular hypoplasia and marked left ventricular (LV) dilatation as gestation progressed. In both ventricles, fractional shortening (FS) and the E/A ratio were significantly lower in Hey2 −/− embryos than in wild-type embryos, indicating that the embryos can be used as a murine model of fetal HF. Subsequently, we evaluated the effect of tadalafil treatment (0.04 or 0.08 mg/ml; T0.04 or T0.08 groups, respectively) on fetoplacental circulation in Hey2 −/− embryos. LV FS was significantly higher in the T0.04 group than in control (P < 0.01), whereas LV dilation, mitral E/A ratio, and umbilical artery resistance index were not significantly different among all groups. The thinness of the LV compacted layer did not differ between the T0.04 and vehicle-treated Hey2 −/− embryos. A phenotype comprising marked dilatation and reduced FS of the left ventricles was identified in Hey2 −/− embryos, suggesting these embryos as a murine model of fetal HF. In addition, maternal administration of tadalafil improved LV systolic function without altering LV morphological abnormalities in Hey2 −/− embryos. Our findings suggest that tadalafil is a potential agent to treat impaired fetal ventricular systolic function. • Hey2 knockout embryos can be used as a murine model of fetal heart failure. • Tadalafil improved fetal left ventricular systolic function in Hey2 knockout embryos. • Tadalafil is a potential agent to treat impaired fetal ventricular systolic function. • Ultra-high-frequency ultrasound imaging is useful for assessing fetal heart failure. [ABSTRACT FROM AUTHOR]

Background: Maturity of the autonomic nervous system (ANS) is of paramount importance for fetal adaptation to extrauterine life and for early neurological development. Markers of ANS maturity, such as electrophysiological heart rate parameters, are of interest as tools to determine prenatal fetal maturity. The available technology, fetal magnetocardiography is expensive and not suitable for clinical use. Detection of fetal electrocardiographic signals using traditional ECG leads on the maternal abdomen may be brought to the bedside, but is technically challenging. Our group has recently developed an innovative system consisting of a standard ECG with external leads applied on the maternal abdomen coupled with a software that extracts the fetal heart signal from the maternal noise.Objective: To validate the use of this innovative non-invasive system to detect fetal ECG (fECG) and its ability to detect changes in electrophysiological fetal cardiac parameters associated with ANS maturation.Study Design: we recruited 50 pregnant women between 24 and 41 weeks and they received non-invasive recording of fECG.Results: fECG was measurable at all gestational ages. Fetal heart rate variability (RR interval) and other associated parameters, such as low and high frequency increased with gestational age, particularly up to the 31st week.Conclusions: This study shows that non-invasive fECG is feasible throughout a broad range of gestational ages and allows detecting electrophysiological parameters of the fetal heart that may be used a surrogate of ANS maturity. Technological implementation of this system and its further exploitation may generate new tool to estimate fetal maturity. [ABSTRACT FROM AUTHOR]

The present study aimed to compare two methods of prostaglandin-induced abortion in mares by determining blood markers (progesterone, estradiol-17β, alpha-fetoprotein, 13,14-dihydro-15-keto-prostaglandin-F2α (PGFM)), B-mode ultrasonographic parameters, and time until loss of fetal heartbeat. It was hypothesized that intrauterine infusion of cloprostenol results in earlier fetal compromise than intramuscular administration. Ovarian structures (number and sizes of follicles and corpora lutea area), fetal heartbeat, and fetal mobility of thirteen singleton pregnancies were assessed daily by transrectal ultrasonography until induction of pregnancy termination (60 ± 2 days of gestation). Mares received 500 μg of cloprostenol intramuscularly every 12 h (IM, n = 7) or once transcervically (TC, n = 6). After initial cloprostenol administration, ultrasonographic examinations were repeated at 6-h intervals until loss of fetal heartbeat was detected. Plasma progesterone, estradiol-17β, and alpha-fetoprotein were assessed for five days before and after pregnancy loss. In addition, plasma PGFM concentrations were assessed immediately before cloprostenol administration (0 min), and then 15, 30, and 45 min, and 1, 2, 3, 4, 6, 12 h after administration. Data were analyzed using the MIXED procedure with repeated measures in SAS. Significance was set at P < 0.05. All mares lost their pregnancies within 48 h after initial cloprostenol administration, with no difference in time to pregnancy loss. There were significant effects of time starting by 12 h post-induction of pregnancy termination but there was no time by group interaction for progesterone concentrations. Estradiol-17β and alpha-fetoprotein concentrations were not altered upon impending abortion. Concentrations of PGFM increased significantly by 2 h after cloprostenol administration, but there were no differences between groups. No time effects or time by group interaction for fetal mobility and heartbeat was detected. Expectedly, the number and area of corpora lutea decreased significantly after cloprostenol administration with no significant differences between groups. In conclusion, intrauterine administration of cloprostenol was not different from repeated systemic administration to terminate the pregnancy. Both models for early fetal loss were equivalent for the endpoints assessed herein. The present study provides evidence that transcervical cloprostenol administration technique is repeatable in different settings and results in negligible side effects. While systemic administration results in colic-like signs and may result in severe reaction. • Hormonal and ultrasonographic parameters did not change upon impending abortion for the two models. • There were no side effects observed following the intrauterine administration of cloprostenol. • All mares displayed minor side effects, and one mare had a strong adverse reaction to systemic cloprostenol administration. • All mares lost their pregnancies by 48 h after first cloprostenol injection and had similar times to fetal heart beat loss. [ABSTRACT FROM AUTHOR]

Uterine contractions in labor result in a 60% reduction in uteroplacental perfusion, causing transient fetal and placental hypoxia. A healthy term fetus with a normally developed placenta is able to accommodate this transient hypoxia by activation of the peripheral chemoreflex, resulting in a reduction in oxygen consumption and a centralization of oxygenated blood to critical organs, namely the heart, brain, and adrenals. Providing there is adequate time for placental and fetal reperfusion between contractions, these fetuses will be able to withstand prolonged periods of intermittent hypoxia and avoid severe hypoxic injury. However, there exists a cohort of fetuses in whom abnormal placental development in the first half of pregnancy results in failure of endovascular invasion of the spiral arteries by the cytotrophoblastic cells and inadequate placental angiogenesis. This produces a high-resistance, low-flow circulation predisposing to hypoperfusion, hypoxia, reperfusion injury, and oxidative stress within the placenta. Furthermore, this renders the placenta susceptible to fluctuations and reduction in uteroplacental perfusion in response to external compression and stimuli (as occurs in labor), further reducing fetal capillary perfusion, placing the fetus at risk of inadequate gas/nutrient exchange. This placental dysfunction predisposes the fetus to intrapartum fetal compromise. In the absence of a rare catastrophic event, intrapartum fetal compromise occurs as a gradual process when there is an inability of the fetal heart to respond to the peripheral chemoreflex to maintain cardiac output. This may arise as a consequence of placental dysfunction reducing pre-labor myocardial glycogen stores necessary for anaerobic metabolism or due to an inadequate placental perfusion between contractions to restore fetal oxygen and nutrient exchange. If the hypoxic insult is severe enough and long enough, profound multiorgan injury and even death may occur. This review provides a detailed synopsis of the events that can result in placental dysfunction, how this may predispose to intrapartum fetal hypoxia, and what protective mechanisms are in place to avoid hypoxic injury. [ABSTRACT FROM AUTHOR]

• It is suggested that the etiology of sporadic Congenital Heart Disease (CHD) co-occurring with Neurodevelopmental Disorders (NDD) may be attributed to genetic variations. Consequently, this review summarizes the regulatory roles of relevant gene families, including the T-box transcription factor (TBX) family, GATA-binding protein (GATA) family, Notch receptor (NOTCH) family, and NK2 homeobox (NKX2) family, in diseases where sporadic CHD co-occurs with NDD. • Employing CiteSpace, a clustering analysis was conducted on 1656 articles related to CHD and NDD. The results reveal that the GATA and NKX2 gene families play a pivotal role in the genetic research of diseases associated with sporadic CHD co-occurring with NDD. • This article provides an overview of the current application status of gene detection techniques in exploring the shared molecular mechanisms of CHD co-occurring with NDD-related diseases. During embryonic development, the cardiovascular system and the central nervous system exhibit a coordinated developmental process through intricate interactions. Congenital heart disease (CHD) refers to structural or functional abnormalities that occur during embryonic or prenatal heart development and is the most common congenital disorder. One of the most common complications in CHD patients is neurodevelopmental disorders (NDD). However, the specific mechanisms, connections, and precise ways in which CHD co-occurs with NDD remain unclear. According to relevant research, both genetic and non-genetic factors are significant contributors to the co-occurrence of sporadic CHD and NDD. Genetic variations, such as chromosomal abnormalities and gene mutations, play a role in the susceptibility to both CHD and NDD. Further research should aim to identify common molecular mechanisms that underlie the co-occurrence of CHD and NDD, possibly originating from shared genetic mutations or shared gene regulation. Therefore, this review article summarizes the current advances in the genetics of CHD co-occurring with NDD, elucidating the application of relevant gene detection techniques. This is done with the aim of exploring the genetic regulatory mechanisms of CHD co-occurring with NDD at the gene level and promoting research and treatment of developmental disorders related to the cardiovascular and central nervous systems. [ABSTRACT FROM AUTHOR]

Diuron is a phenylurea herbicide widely used in the agricultural industry. In recent years, the risk of infertility and developmental defects has increased due to exposure to environmental pollutants. In this study, we investigated the toxicity of diuron in fetal mouse testes using three-dimensional organ cultures. Fetal testes derived from embryonic day (E) 14.5 were cultured with 200 µM diuron for 5 days. The results revealed that diuron did not impair fetal germ cell proliferation or the expression levels of germ cell markers such as Ddx4, Dazl, Oct 4, Nanog, Plzf, and TRA 98. Similarly, the gene or protein expression of the Sertoli cell markers Sox9 and Wt1 in diuron-exposed fetal testes did not change after 5 days of culture. In contrast, diuron increased fetal Leydig cell markers (FLC), Cyp11a1, Cyp17a1, Thbs2, and Pdgf α, and decreased adult Leydig cell (ALC) markers, Sult1e1, Hsd173, Ptgds, and Vcam1. However, 3-βHSD, an FLC and ALC marker, was consistently maintained upon exposure to diuron in fetal testes compared to non-treated groups. In conclusion, our study demonstrates that diuron negatively impacts Fetal Leydig cell development, although it does not affect germ and Sertoli cells. • Germ cell and Sertoli cell proliferation were not affected by Diuron in in vitro cultured testes. • No significant difference in gene and protein expression of Germ cell and Sertoli cell marker by Diuron. • Diuron increased the expression of Fetal Leydig cells marker in in vitro cultured testes. • Diuron suppressed the expression of Adult Leydig cell marker in in vitro cultured testes. [ABSTRACT FROM AUTHOR]

The morphology knowledge is essential for clinical, diagnostic and surgical practice in medicine. However, it is a great challenge teaching this science in an integrated curriculum, since it has the need of active methods associated with technology, in a total impaired workload. Therefore, this work described an educational design of multiple practice stations in order to teach morphology of the cardiovascular system in the undergraduate medical education. This activity was conducted in the Multicampi School of Medical Sciences of Federal University of Rio Grande do Norte (UFRN) in Caicó/Brazil. Four anatomy stations and four embryology and histology stations of heart and blood vessels were drawn up. Anatomy stations approached cardiac cycle and cardiac valves (1 A); mediastinum and pericardium (2 A); internal morphology and heart conduction system (3 A) and external morphology of heart (4 A). Whereas embryology and histology stations approached embryogenesis of the heart (1B); cardiac microanatomy and fetal circulation (2B); and vascular microanatomy (3B;4B). All the stations emphasized cognitive and psychomotor fields associated with clinical correlations to active application of morphology knowledge. The multiple stations were considered as an organized, productive, enlightening and riveting alternative to medical students and teaching staff. This innovative experience integrated and energized the three areas of morphological sciences, resignifying the teaching and learning of cardiovascular system morphology. [ABSTRACT FROM AUTHOR]

Cardiomyocytes are highly metabolic cells responsible for generating the contractile force in the heart. During fetal development and regeneration, these cells actively divide but lose their proliferative activity in adulthood. The mechanisms that coordinate their metabolism and proliferation are not fully understood. Here, we study the role of the transcription factor NFYa in developing mouse hearts. Loss of NFYa alters cardiomyocyte composition, causing a decrease in immature regenerative cells and an increase in trabecular and mature cardiomyocytes, as identified by spatial and single-cell transcriptome analyses. NFYa -deleted cardiomyocytes exhibited reduced proliferation and impaired mitochondrial metabolism, leading to cardiac growth defects and embryonic death. NFYa, interacting with cofactor SP2, activates genes linking metabolism and proliferation at the transcription level. Our study identifies a nodal role of NFYa in regulating prenatal cardiac growth and a previously unrecognized transcriptional control mechanism of heart metabolism, highlighting the importance of mitochondrial metabolism during heart development and regeneration. [Display omitted] • Deleting NFYa in cardiomyocytes results in cardiac noncompaction and embryonic death • Fetal cardiomyocyte subtypes identified by multi-modal single-cell transcriptomics • NFYa deletion alters cardiomyocyte composition and mitochondrial metabolism • NFYa, working with SP2, activates metabolic gene transcription In this study, Cui et al. identified a critical role of the nuclear transcription factor Y in regulating mitochondrial metabolism and proliferation in heart muscle cells of the developing mouse heart. [ABSTRACT FROM AUTHOR]

[Display omitted] • In anthropoid pregnancy, vertical posture of the torso may normally be associated with a head-down position of the fetus. • This may have caused fetal physiologic craniovascular hypertension and the progressive growth of the anthropoid brain. • The current report opens a perspective for research on fetal postural cranial hemodynamics. Evolutionary cerebrovascular consequences of upside-down postural verticality of the anthropoid fetus have been largely overlooked in the literature. This working hypothesis-based report provides a literature interpretation from an aspect that the rapid evolution of the human brain has been promoted by fetal head-down position due to maternal upright and semi-upright posture. Habitual vertical torso posture is a feature not only of humans, but also of monkeys and non-human apes that spend considerable time in a sitting position. Consequently, the head-down position of the fetus may have caused physiological craniovascular hypertension that stimulated expansion of the intracranial vessels and acted as an epigenetic physiological stress, which enhanced neurogenesis and eventually, along with other selective pressures, led to the progressive growth of the anthropoid brain and its organization. This article collaterally opens a new insight into the conundrum of high cephalopelvic proportions (i.e., the tight fit between the pelvic birth canal and fetal head) in phylogenetically distant lineages of monkeys, lesser apes, and humans. Low cephalopelvic proportions in non-human great apes could be accounted for by their energetically efficient horizontal nest-sleeping and consequently by their larger body mass compared to monkeys and lesser apes that sleep upright. One can further hypothesize that brain size varies in anthropoids according to the degree of exposure of the fetus to postural verticality. The supporting evidence for this postulation includes a finding that in fossil hominins cerebral blood flow rate increased faster than brain volume. This testable hypothesis opens a perspective for research on fetal postural cerebral hemodynamics. [ABSTRACT FROM AUTHOR]