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Introduction: This study aims to investigate non‐invasive electrocardiography as a method for the detection of congenital heart disease (CHD) with the help of artificial intelligence. Material and methods: An artificial neural network was trained for the identification of CHD using non‐invasively obtained fetal electrocardiograms. With the help of a Bayesian updating rule, multiple electrocardiographs were used to increase the algorithm's performance. Results: Using 122 measurements containing 65 healthy and 57 CHD cases, the accuracy, sensitivity, and specificity were found to be 71%, 63%, and 77%, respectively. The sensitivity was however 75% and 69% for CHD cases requiring an intervention in the neonatal period and first year of life, respectively. Furthermore, a positive effect of measurement length on the detection performance was observed, reaching optimal performance when using 14 electrocardiography segments (37.5 min) or more. A small negative trend between gestational age and accuracy was found. Conclusions: The proposed method combining recent advances in obtaining non‐invasive fetal electrocardiography with artificial intelligence for the automatic detection of CHD achieved a detection rate of 63% for all CHD and 75% for critical CHD. This feasibility study shows that detection rates of CHD might improve by using electrocardiography‐based screening complementary to the standard ultrasound‐based screening. More research is required to improve performance and determine the benefits to clinical practice. [ABSTRACT FROM AUTHOR]

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

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

The objective of the present study was to demonstrate the blood flow velocities, blood flow rate (BFR; bpm) with the accurate ratio of both systolic and diastolic velocities points (S/D) in addition to Doppler indices (resistive and pulsatility index [RI and PI]) in both fetal [fetal heart (FH), fetal abdominal aorta (Ab. A), and umbilical artery (UM.A)] and maternal [Middle uterine artery (MU.A)] sides during the last month of gestation. Ten Zaraibi (Egyptian Nubian) goats weighing 40-50kg and aged from 5–7 years were examined twice per month till reached the last month of pregnancy. Then all females were examined every 5 days starting from day -35 till day -1 before kidding.The pregnant goats were examined by ultrasonic and Doppler indices were recorded with Doppler scanning (7.5 -12 MHz, with colored and spectral graph to form the perfect wave to assess Doppler measurements). The obtained data were analyzed using analysis of variance. Results indicated that on the fetal side; the maximum point of velocity (MSV; cm/sec) in the FH and BFRwere elevated from day -35 till day -10 with a slight decline at days -5 and -1 at the peripartum period (P < 0.05), while FH.PI and S/D ratio declined till day -1(P < 0.05). In addition, the fetal Ab. A, and UM.A PI, RI, and S/D ratio declined from day -35 till day -1 at the peripartum period with a significant increase in the peak systolic velocity (PSV) and BFR(P < 0.05). However, non-significant changes in the end diastolic velocity (EDV) were detected. On the maternal side, the MU.A PI and S/D declined from day -35 till day -1 with an elevation of both PSV and BFRat the same time points (P < 0.05). In conclusion, the Doppler evaluation of fetal and maternal blood flow vessels is important to give complete information that directly affects the health status of the mother and fetus. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to investigate the feasibility of visualizing and quantifying the normal pattern of vortex formation in the left ventricle (LV) and right ventricle (RV) of the fetal heart during diastole using vector flow mapping (VFM). Methods: A total of 36 healthy fetuses in the second trimester (mean gestational age: 23 weeks, 2 days; range: 22–24 weeks) were enrolled in the study. Color Doppler signals were recorded in the four-chamber view to observe the phase of the diastolic vortices in the LV and RV. The vortex area and circulation were measured, and parameters such as intraventricular pressure difference (IVPD), intraventricular pressure gradient (IVPG), and average energy loss (EL_AVG) were evaluated at different diastolic phases, including isovolumic relaxation (D1), early diastole (D2), and late diastole (D3). Results: Healthy second-trimester fetal vortex formations were observed in both the LV and RV at the end of diastole, with the vortices rotating in a clockwise direction towards the outflow tract. There were no significant differences in vortex area and circulation between the two ventricles (p > 0.05). However, significant differences were found in IVPD, IVPG, and EL_AVG among the diastolic phases (D1, D2, and D3) (p < 0.05). Trends in IVPD, IVPG, and EL_AVG during diastole (D1-D2-D3) revealed increasing IVPD and EL_AVG values, as well as decreasing IVPG values. Furthermore, during D3, the RV exhibited significantly higher IVPD, IVPG, and EL_AVG compared to the LV (p > 0.05). Conclusion: VFM is a valuable technique for analyzing the formation of vortices in the left and right ventricles during fetal diastole. The application of VFM technology has the potential to enhance the assessment of fetal cardiac parameters. [ABSTRACT FROM AUTHOR]

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

HDlive Flow demonstrates three-dimensional (3D) cardiovascular structures with greater depth perception and dimension using a light source to create favorable lighting and shadowing effects. The supplemental usefulness of this technique for evaluation of the normal fetal heart and diagnosis of congenital heart anomaly in the second and third trimesters of pregnancy has been described. The potential advantages of HDlive Flow for the diagnosis of congenital heart anomaly need to be explored in the first trimester of pregnancy. In this pictorial essay, we present our experiences of the use of HDlive Flow to diagnose congenital heart anomalies in the first trimester of pregnancy. [ABSTRACT FROM AUTHOR]

Background: Pregnant patients are at high risk of maternal and fetal complications from Coronavirus Disease 2019 (COVID-19) infections. The COVID-19 pandemic prompted a surge in the development and repurposing of therapies for the SARS-CoV-2 virus. Evidence is sparse on the efficacy and safety of these therapies in pregnant patients. Our objective was to describe adverse events (AEs) to COVID-19 therapeutics in pregnant patients. Methods: This was a case series of AEs reported to the FDA ACMT COVID-19 ToxIC (FACT) Pharmacovigilance Project between November 23, 2020, and June 28, 2022. FACT is an ongoing toxicosurveillance project at 17 sites to proactively identify and report AEs associated with COVID-19 therapeutics. Abstracted information includes demographics, case narratives, exposure details, clinical information, pregnancy details, treatments, and outcomes. Results: Forty-six COVID-19-positive pregnant patients who developed AEs following COVID-19 therapeutics were reported to the FACT Pharmacovigilance Project over 19 months. The most reported medications were remdesivir in 22 patients (47.8%) and casirivimab/imdevimab in 8 patients (17.4%). Four patients (8.7%) had life-threatening clinical manifestation, and 16 patients (34.8%) required intervention to prevent permanent damage. The most common maternal and fetal events were elevated serum alanine aminotransferase (26.1%) and non-reassuring fetal heart patterns (20.0%), respectively. Conclusions: This case series reports AEs of elevated serum alanine aminotransferase, maternal bradycardia, maternal hypothermia, non-reassuring fetal heart patterns, and emergent or unplanned cesarean sections following administration of several COVID-19 therapeutics. This study was not designed to definitely identify causation, and further study is needed to evaluate the causal role of these therapeutics in AEs affecting pregnant COVID-19 patients. [ABSTRACT FROM AUTHOR]

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]

Ketamine, a noncompetitive N-methyl D-aspartate (NMDA) receptor antagonist, is widely used in pediatric clinical practice. The neuroprotective and neurotoxic effects of ketamine on brain neurons during development remain controversial. The reason may be related to the different concentrations of ketamine used in practice and the small range of concentrations used in previous studies. In this study, cultured hippocampal neurons were treated with ketamine in a wide range of concentrations to comprehensively observe the effects of different concentrations of ketamine on neurons. We demonstrated that low concentrations of ketamine (10 μM, 100 μM and 1000 μM) promoted neuronal survival (p < 0.05) and reduced neuronal apoptosis (p < 0.05) compared with those of the control group. High concentrations of ketamine (2000 μM, 2500 μM and 3000 μM) reduced neuronal survival (p < 0.05) and promoted neuronal apoptosis (p < 0.05). The p38 MAPK inhibitor SB203580 reduced neuronal apoptosis induced by high concentrations of ketamine (2500 μM) (p < 0.05). Our findings indicate that ketamine exerts a dual effect on the apoptosis of primary cultured fetal rat hippocampal neurons in vitro and that the neurotoxic effects of ketamine are related to activation of the p38 MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

The fetal pulmonary circulation represents less than 25% of the fetal cardiac output. In comparison with the pulmonary arteries, studies on pulmonary veins are few and limited, and many questions remain to be answered. The literature reports that pulmonary veins play an important role in regulating vascular flow, forming an active segment of the pulmonary circulation. The development of more sophisticated ultrasonography technology has allowed the investigation of the extraparenchymal pulmonary veins and their waveform. The recognition of the pulmonary vein anatomy in echocardiography is important for the diagnosis of anomalous pulmonary venous connections, with a significant impact on prognosis. On the other hand, the identification of the normal pulmonary vein waveform seems to be a reliable way to study left heart function, with potential applicability in fetal and maternal pathology. Thus, the goal of this narrative review was to provide a clinically oriented perspective of the available literature on this topic. [ABSTRACT FROM AUTHOR]

Introduction: Myocardial bridges (MB) are congenital anomalies of hearts observed as muscle fibers covering epicardial branches of the coronary artery. The left anterior descending artery (LAD) was found to be commonly showing myocardial bridges (MBs). Clinically, MBs were claimed to cause varied symptomatology. The data on the morphology and prevalence of MBs in fetuses was limited, despite the commonly accepted congenital origin. Material and methods: Fetal hearts obtained from 37 fetuses from the donation program were used. The hearts were dissected out from the thorax by standard dissection procedure. The pericardium and epicardium were dissected. The coronary arteries were delineated, and MBs were observed and noted. The coronary artery segment having MBs, its distance from the ostium as well as the direction and length of the MBs were studied. Results: The MBs were observed in 20 out of 37 fetal hearts studied over the left anterior descending, right coronary, posterior interventricular and circumflex arteries. The mid or distal part of the coronary arteries frequently exhibited MBs. The mean length of the MB was 4.2 mm, with MBs being situated about 1.5 cm away from the coronary ostium. The oblique pattern of MB was more frequently noted. Conclusion: The morphology and prevalence of fetal MBs showed common occurrence in the LAD artery, with a predominant oblique morphological pattern. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Do spontaneously conceived (SC) fetuses from subfertile couples show the same signs of cardiac remodeling as those observed after IVF treatments? SUMMARY ANSWER As opposed to fetuses from IVF, SC fetuses from subfertile couples do not show cardiac remodeling and present a similar cardiac structure and function to those of SC fetuses from fertile couples. WHAT IS KNOWN ALREADY Subjects conceived by IVF present signs of cardiac remodeling and suboptimal function in utero and during childhood, including larger atria, more globular and thicker ventricles, reduced longitudinal motion, and impaired relaxation as compared to SC individuals from fertile couples. There are no previous publications investigating the independent cardiac programming effects of infertility in SC fetuses from subfertile couples (with time-to-pregnancy (TTP) over 12 months). STUDY DESIGN, SIZE, DURATION A prospective cohort study of 289 singleton pregnancies exposed and not exposed to subfertility recruited from 2019 to 2021, including 96 SC pregnancies from fertile couples (TTP under 12 months), 97 SC from subfertile couples (TTP over 12 months), and 96 from IVF after fresh embryo transfer. Fetal echocardiography was performed in all pregnancies. Epidemiological data and perinatal outcomes were collected in all pregnancies. The overall attrition rate was 15.7%. PARTICIPANTS/MATERIALS, SETTING, METHODS SC from subfertile couples and IVF pregnancies were identified as eligible at pregnancy diagnosis, and eligible SC pregnancies from fertile couples who attended our maternal-fetal unit were invited to participate at third trimester, being matched to the other groups by maternal age. Fetal echocardiography was performed at 29–34 weeks of pregnancy to assess cardiac structure and function, and results were adjusted by parental age, maternal smoking status, child's birth order, birthweight centile, gestational age, and estimated fetal weight at scan. MAIN RESULTS AND THE ROLE OF CHANCE Parental age, ethnicity, BMI, and smoking exposure, median gestational age and estimated fetal weight were similar in all study groups. There were no significant differences in infertility duration or etiology between the subfertile and the IVF populations (TTP: subfertile median 35 months (interquartile range 20–48) versus IVF: 47 (25–61); P -value = 0.051). While both fertile and subfertile SC groups presented similar fetal cardiac results, IVF fetuses showed larger atria (right atria-to-heart ratio: IVF mean 18.9% (SD 3.4) versus subfertile 17.8% (3.5) versus fertile 17.6% (3.3); adjusted P -value < 0.001), more globular ventricles (right ventricular sphericity index: IVF 1.56 (0.25) versus subfertile 1.72 (0.26) versus fertile 1.72 (0.26); <0.001), and thicker myocardial walls (relative wall thickness: IVF 0.86 (0.22) versus subfertile 0.64 (0.13) versus fertile 0.64 (0.18); <0.001). Whereas SC fetuses from fertile and subfertile couples had preserved cardiac function, IVF fetuses showed signs of suboptimal systolic and diastolic function, with reduced tricuspid ring displacement (IVF 7.26 mm (1.07) versus subfertile 8.04 mm (1.18) versus fertile 7.89 mm (1.51); <0.001) and increased left myocardial performance index (IVF 0.49 (0.08) versus subfertile 0.45 (0.09) versus fertile 0.45 (0.10); <0.001). A sub-analysis including only unexplained infertility cases in subfertile SC and IVF groups showed similar results. LIMITATIONS, REASONS FOR CAUTION The fetal cardiac changes reported here are subclinical, and most of the cardiovascular parameters were within normal ranges. Although echocardiographic changes are recognized as potential cardiovascular risk factors, their association with long-term cardiovascular disease remains to be demonstrated. WIDER IMPLICATIONS OF THE FINDINGS Subfertility per se does not seem to be associated to fetal cardiac remodeling, which has been previously described in IVF fetuses. Future studies are warranted to further investigate other factors related to the observed fetal cardiac changes associated with ART. STUDY FUNDING/COMPETING INTEREST(S) This project has been partially funded with support from the Erasmus + Programme of the European Union (Framework Agreement number: 2013-0040). This publication reflects the views only of the author, and the Commission cannot be held responsible for any use, which may be made of the information contained therein. Additionally, the research leading to these results has received funding from 'la Caixa' Foundation under grant agreement LCF/PR/GN18/10310003, the Instituto de Salud Carlos III (PI15/00130, PI16/00861, PI17/00675, PI18/00073, INT21/00027)—co-funded by the European Union, Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK) and AGAUR 2017 SGR grant no 1531. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Chorangioma is a rare non-trophoblastic benign vascular neoplasm originating from the primitive chorionic mesenchyme. Usually asymptomatic, it affects approximately 1% of female fetuses. We present the case of a giant placental chorangioma (GPC) in a preterm male pregnancy coexisting with a maternal neuroendocrine carcinoma. A 30-week primigravida was admitted to the Obstetrics and Gynecology Clinic of the Targu-Mures Emergency Clinical Hospital, with abdominal discomfort, and an emergency C-section was performed for fetal congestive heart failure. Medical history revealed an advanced-stage rectal neuroendocrine carcinoma. At 20th gestational week, a well-vascularized placental mass was diagnosed. A 1500g premature male fetus was delivered. Histopathologically, the placental mass revealed an unencapsulated but well-circumscribed tumor with lobular architecture composed of congested vascular capillaries and thinwalled vessels. Diagnosis of giant placental chorangioma (GPC) was rendered. GPC is a challenging condition typically occurring in hypertensive or diabetic primigravidas with female fetuses. Antenatal management is suggested at an early stage for a desirable perinatal outcome. [ABSTRACT FROM AUTHOR]

Background:: Intra-uterine fetal death (IUFD) is the term used to describe the death of a foetus that is >24 weeks gestational age and/or >500 g in weight. The intricate process of fetal mortality involves the mother, the fetus, and the placenta; therefore these issues should be handled together Methods: This study was carried out in the Department of Gynaecology, GMC Jammu in collaboration with Department of Pathology w.e.f March 2021 to October 2021. A total of 114 patients with intra-uterine fetal deaths diagnosed either through ultrasound reports or on clinical examination by absence of fetal heart sound were included in the study. The study comprised placentas from all cases of intrauterine fetal deaths with gestational ages greater than 28 weeks that were received in the histopathology section of the hospital. Results: Majority of IUFD patients accounting for (73.7%) had (28-36) weeks of gestational age. In majority of patients, the cause of IUFD was maternal (68.4%). PIH etiology was present in (55.1%), maternal anemia was evident in 21.7%, GDM was found in 11.5% patients. Majority of patients had calcification (54.4%), followed by 37.7% with infarct finding. Perivillous fibrin was present in 65.8%, followed by syncytial knots (46.5%), intervillous haemorrhage (43.9%). Conclusion: The morphology of the placenta can be further studied comprehensively to learn more about pregnancy anomalies, so that an optimal strategy can be developed concerning pregnancy management and risk assessment and even preventing IUFD in subsequent pregnancies. [ABSTRACT FROM AUTHOR]

With the development of computer technology and neural networks, artificial intelligence (AI) has become sufficiently mature to assist in various technical and medical tasks, including the prenatal diagnosis of congenital heart disease (CHD). Moreover, the AI-based approach to solving this challenge has provided new ideas, concepts, and techniques. This review focuses on fetal CHD and conventional methods of its diagnostics, highlights the main achievements and particular techniques of AI application to CHD diagnostics, and discusses their advantages, drawbacks, and ways of further improvement regarding CHD and other heart disease. [ABSTRACT FROM AUTHOR]

Chronic intrauterine hypoxia is a significant pregnancy complication impacting fetal heart growth, metabolism, and mitochondrial function, contributing to cardiovascular programming of the offspring. PGC1α (peroxisome proliferator-activated receptor γ co-activator 1α) is the master regulator of mitochondrial biogenesis. We investigated the effects of hypoxia on PGC1α expression following exposure at different gestational ages. Time-mated pregnant guinea pigs were exposed to normoxia (NMX, 21% O2) or hypoxia (HPX, 10.5% O2) at either 25-day (early-onset) or 50-day (late-onset) gestation, and all fetuses were extracted at term (term = ~65-day gestation). Expression of nuclear PGC1α, sirtuin 1 (SIRT1), AMP-activated protein kinase (AMPK), and mitochondrial sirtuin 3 (SIRT3) was measured, along with SIRT3 activity and mitochondrial acetylation of heart ventricles of male and female fetuses. Early-onset hypoxia increased (P<0.05) fetal cardiac nuclear PGC1α and had no effect on mitochondrial acetylation of either growth-restricted males or females. Late-onset hypoxia had either no effect or decreased (P<0.05) PCC1α expression in males and females, respectively, but increased (P<0.05) mitochondrial acetylation in both sexes. Hypoxia had variable effects on expression of SIRT1, AMPK, SIRT3, and SIRT3 activity depending on the sex. The capacity of the fetal heart to respond to hypoxia differs depending on the gestational age of exposure and sex of the fetus. Further, the effects of late-onset hypoxia on fetal heart function impose a greater risk to male than female fetuses, which has implications toward cardiovascular programming effects of the offspring. [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. [ABSTRACT FROM AUTHOR]

Objectives: Fully effective intrapartum cardiotocographic (CTG) fetal heart monitoring is still missing. Visual analysis is far from credibility. Additional, computerized analysis techniques were proposed however they did not substantially decrease possible risks of fetal asphyxia. In twin pregnancies the problem is even more complicated. Our goal is to find the most valuable parameters in intrapartum CTG surveillance in twins, based on actual FIGO criteria. Material and methods: Study included 58 women in labor who had been admitted to Delivery Department of tertiary care hospital with twin pregnancy in a period of one year. The features of the CTG (e.g., baseline, oscillation, decelerations, brady- or tachycardia) were grouped to create three variables that were closest to the FIGO CTG scale. All three groups were compared according to neonatal status (Apgar score at 5 min ≥ 7 or < 7; pH value in umbilical artery ≥ 7.20, < 7.20 or < 7.10 and BE (base excess) > or ≤ –12). Fetal status and its acid — base equilibrium was compared either with long term variability (LTV), short term variability (STV), or percentage of the signal loss. Results: Out of 58 twin pregnancies, a total of 116 babies were born. One baby was born dead. From this group, 11 deliveries were natural births and 47 deliveries were C-sections. None of the analyzed features (pH, BE, Apgar, CTG features except tracing length, CTG FIGO categories) were statistically different between groups of singleton and twin pregnancies, except percentage of C-sections. No differences were found either for STV or LTV and fetal status.org CTG categories. Conclusions: Prior to cardiotocographic tracing of twins during labor, ultrasound examination should be mandatory. Considerable loss of signal in CTG tracing in twins should provoke ultrasonographic confirmation of the fetal status. [ABSTRACT FROM AUTHOR]

Increasing evidence shows that maternal hyperglycemia inhibits cardiomyocyte (CM) proliferation and promotes cell apoptosis during fetal heart development, which leads to cardiac dysplasia. Accumulating evidence suggests that the overexpression of miR-21 in CMs has a protective role in cardiac function. Therefore, we investigated whether miR-21 can rescue CM injury caused by high glucose. First, we performed biological function analysis of miR-21-5p overexpression in H9c2 cells treated with high glucose. We found that the proliferation of H9c2 cells treated with high glucose decreased significantly and was rescued after overexpression of miR-21-5p. CCK-8 and EdU incorporation assays were performed to assess cell proliferation. The cell proliferation of the miR-21-5p mimic transfection group was improved compared with that of the NC mimic group (* p < 0.05, miR-21-5p mimics vs. NC mimics) when the proliferation of H9c2 cells was reduced by high glucose (**** p < 0.0001, high glucose (HG) vs. normal glucose (NG)). Then, we verified the targeted and negative regulation of miR-21-5p on Rhob using a dual-luciferase activity assay and RT-qPCR, respectively. We further demonstrated that miR-21-5p regulates Rhob to rescue the inhibition of CM proliferation induced by high glucose. The CCK-8 results showed that the cell proliferation of the siRNA-Rhob group was higher than that of the NC mimic group (*** p < 0.001) and that of the cotransfection group with Up-Rhob plasmids and miR-21-5p mimics was lower than that of the miR-21-5p mimic group (* p < 0.05). Conclusion: Overexpression of miR-21-5p rescues the inhibition of high glucose-induced CM proliferation through regulation of Rhob. [ABSTRACT FROM AUTHOR]

Objective: To compare the fetal cardiac functions in preeclampsia and control group, and determine whether the severity or amount of proteinuria affects fetal cardiac functions. Methods: This prospective case–control study involves 48 pregnant women with preeclampsia and 48 healthy women. Pulsed wave Doppler, M‐mode, and tissue Doppler imaging were used to measure the cardiac function between the 32 and 34 gestational weeks in each group. All Doppler indices and cardiac function parameters were also compared in subgroups with mild and severe preeclampsia and between subgroups with proteinuria >3 g/24 hours and <3 g/24 hours. Results: Decreased diastolic function (decreased E, A, E′, and A′ values in mitral/tricuspid valves and increased isovolumetric relaxation time) and decreased systolic functions (decreased mitral and tricuspid annular plane systolic excursion and S′ value in mitral/tricuspid valves) were detected in the preeclampsia group. Decreased tricuspid E value in severe preeclampsia compared with mild preeclampsia was shown in the present study. Conclusion: Preeclampsia may cause changes in systolic and diastolic functions in the fetal heart. Subclinical functional changes of these fetuses can be detected earlier and more sensitively with the help of tissue Doppler imaging. Biventricular diastolic functional changes are more prominent in preeclamptic cases with proteinuria >3 g/24 hours. [ABSTRACT FROM AUTHOR]

ObjectiveTo describe outcomes associated with monoclonal antibody use in pregnant persons with mild-to-moderate coronavirus disease 2019 (COVID-19).MethodsWe present a retrospective case series of pregnant patients who received anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibody infusions at a single center from April 1, 2021, through October 16, 2021. Pregnant patients who had a positive SARS-CoV-2 polymerase chain reaction (PCR) test result and mild-to-moderate COVID-19 symptoms were eligible for monoclonal antibody infusion. Exclusion criteria for administration included need for supplemental oxygen, hospitalization due to COVID-19, and positive SARS-CoV-2 PCR test result more than 7 days before screening. All patients received either bamlanivimab plus etesevimab or casirivimab plus imdevimab based on availability and dosing instructions of the product and emerging resistance patterns in the community.ResultsDuring the study period, monoclonal antibody infusions were administered to 450 individuals at our institution, of whom 15 were pregnant. Of the 15 pregnant persons receiving monoclonal antibody, six (40%) had full-vaccination status at the time of infusion. Two individuals (13%, CI 0-31%) experienced systemic reactions during the infusion, both resulting in temporary changes in the fetal heart rate tracing that recovered with maternal and intrauterine resuscitative efforts. One patient delivered after infusion for worsening maternal and fetal status; the remainder of the patients did not require admission for COVID-19.ConclusionIn this case series, pregnant persons who received anti-SARS-CoV-2 monoclonal antibody infusions had generally favorable outcomes.

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.

Background: Congenital heart disease occurs in approximately 1 in 100 cases. Although sibling occurrence is high (3–9%), the causative genes for this disease are still being elucidated. PLD1 (Phospholipase D1) is a recently discovered gene; however, few case reports have been published on it. In this report, we describe a case of triplicate fetal congenital heart disease that was diagnosed as a PDL1 mutation. Our objective is to explore the clinical manifestations of PLD1 mutations in this particular case. Case presentation: A 32-year-old Japanese woman (gravida, para 0) was introduced since fetus four chamber view was not clear and was diagnosed with ductus arteriosus-dependent left ventricular single ventricle and pulmonary atresia at 21 weeks and 1 day of gestation during her first pregnancy. Artificial abortion using Gemeprost was performed at 21 weeks and 5 days of gestation. The second pregnancy was diagnosed as pulmonary atresia with intact ventricular septum with cardiomegaly, a cardiothoracic area ratio of more than 35%, and a circulatory shunt at 13 weeks and 3 days of gestation. Subsequently, intrauterine fetal death was confirmed at 14 weeks and 3 days of gestation. Regarding the third pregnancy, fetal ultrasonography at 11 weeks and 5 days of gestation showed mild fetal hydrops and moderate tricuspid valve regurgitation. At 16 weeks and 5 days of gestation, the fetus was suspected to have a left ventricular-type single ventricle, trace right ventricle, pulmonary atresia with intact ventricular septum, or cardiomyopathy. Cardiac function gradually declined at 26 weeks of gestation, and intrauterine fetal death was confirmed at 27 weeks and 5 days of gestation. The fourth pregnancy resulted in a normal heart with good progression and no abnormal baby. We submitted the first and second fetuses' umbilical cord, third fetus' placenta, and the fourth fetus' blood to genetic testing using whole exome analysis with next generation sequencing. Genetic analysis identified hemizygous PLD1 mutations in the first, second, and third fetuses. The fourth fetus was heterozygous. In addition, the parents were heterozygous for PLD1. This case is based on three consecutive cases of homozygosity for the PLD1 gene in the sibling cases and the fetuses with recurrent right ventricular valve dysplasia. This will elucidate the cause of recurrent congenital heart disease and intrauterine fetal death and may serve as an indicator for screening the next fetus. To date, homozygous mutations in PLD1 that repeat three times in a row are not reported, only up to two times. The novelty of this report is that it was repeated three times, followed by a heterozygous live birth. Conclusions: This report is consistent with previous reports that mutations in PLD1 cause right ventricular valve dysplasia. However, there have been few case reports of PLD1 mutations, and we hope that this report will contribute to elucidate the causes of congenital heart disease, especially right ventricular valve dysplasia, and that the accumulation of such information will provide more detailed information on PLD1 mutations in heart disease. [ABSTRACT FROM AUTHOR]

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

Aim Methods Results Conclusion We aimed to investigate fetal cardiac output (CO) in pregnancies with preterm premature rupture of membranes (PPROM) and its relationship with umbilical cord pH.This was a prospective study in total 90 pregnancies at 24–37 weeks gestation including 42 pregnancies with PPROM and 48 that healthy controls. Fetal cardiac function including combined, left and right CO z‐scores were compared. The neonates in the PPROM group were separated with umbilical cord pH above and below 7.25, and cardiac output was compared between groups.In PPROM group, CCO z‐score, left cardiac output (LCO) z‐score, and right cardiac output (RCO) were significantly lower compared to healthy pregnancies (p = .036, p = .001, p = .032, respectively), while RCO z‐score showed no significant differences between the two groups. The aortic annulus and pulmonary artery annulus z‐scores were measured smaller in the PPROM group (p = .000 and p = .001, respectively). In PPROM group, the fetal LCO z‐score was significantly lower in neonates with an umbilical cord pH of 7.25 or less (p = .048).This study provides evidence that fetal CCO is lower in PPROM compared with healthy pregnancies. Reduced LCO z‐scores may be useful for predicting adverse neonatal outcomes in pregnancies with PPROM. [ABSTRACT FROM AUTHOR]

In recent years, attention has significantly increased to the problem of the constant growth of diseases and deformities of the dental system. Despite the fact that modern diagnostic methods are being introduced, unfortunately, there is an increase in the prevalence rate every year. The strategy of orthodontic treatment of dental deformities and the choice of orthodontic devices in patients of different ages depends on the etiological and pathogenetic components of pathologies of a particular dental apparatus. In addition, the correct choice of an orthodontic device depends on the condition of the patient's oral cavity (gastrointestinal tract), the capabilities of the orthodontic laboratory and the professional abilities of the orthodontist. Currently, many fundamental aspects of prevention in the process of orthodontic treatment have not yet found their full solution. There is no data on the use of deep fluoridation in orthodontics. During orthodontic treatment, the issues of evaluating the effectiveness of tooth enamel resistance and remineralizing agents using Cappa are not sufficiently disclosed. Therefore, the improvement of preventive measures in the process of orthodontic treatment is an urgent task. It is known from a number of scientific publications that the development of dental anomalies and deformations is considered polyetiological. Including general etiological factors: low birth weight, pregnancy and birth defects, fetal development delay, nervous system disorders, infection with various diseases in infancy, dietary disorders, raxian strains: local etiological factors - negative changes in the motor activity of the jaws as a result of bad habits, improper nutrition. treatment of baby teeth, premature loss of baby teeth, untimely elimination of defects in dentistry. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the agreement between visual and automatic methods in assessing the adequacy of fetal cardiac views obtained during second trimester ultrasonographic examination. In a prospective observational study frames of the four-chamber view left and right outflow tracts, and three-vessel trachea view were obtained from 120 consecutive singleton low-risk women undergoing second trimester ultrasound at 19–23 weeks of gestation. For each frame, the quality assessment was performed by an expert sonographer and by an artificial intelligence software (Heartassist™). The Cohen's κ coefficient was used to evaluate the agreement rates between both techniques. The number and percentage of images considered adequate visually by the expert or with Heartassist™ were similar with a percentage >87 % for all the cardiac views considered. The Cohen's κ coefficient values were for the four-chamber view 0.827 (95 % CI 0.662–0.992), 0.814 (95 % CI 0.638–0.990) for left ventricle outflow tract, 0.838 (95 % CI 0.683–0.992) and three vessel trachea view 0.866 (95 % CI 0.717–0.999), indicating a good agreement between the two techniques. Heartassist™ allows to obtain the automatic evaluation of fetal cardiac views, reached the same accuracy of expert visual assessment and has the potential to be applied in the evaluation of fetal heart during second trimester ultrasonographic screening of fetal anomalies. [ABSTRACT FROM AUTHOR]

Double outlet right ventricle (DORV) is a malformation of the fetal heart in utero that affects the ventricular chambers. It usually presents with a displacement of the aorta and more than half the circumference of both arterial valves in the right ventricle. A peculiar characteristic is given by an interventricular septal defect (VSD), which allows communication between the left ventricle and the right with consequent mixing of oxygenated and non-oxygenated blood inside the cavities. A crucial question in assessing the degree of severity of functional dysfunction concerns the percentage of oxygenated blood that is ejected into the primary circulation via the aorta, a result that depends on the details of the vortex flow pattern within the two ventricular chambers. This study analyzes a complete DORV case through the use of numerical simulations that allow to identify the concentrations of oxygenated and non-oxygenated blood passing through this geometry. Results show that the VSD presents a significant impact on the fluid dynamic performance of the two ventricles. The analysis of blood concentration allowed to quantify the presence of oxygenated blood ejected into the pulmonary artery and of non-oxygenated blood into the aortic artery. The analysis of this specific case aims to demonstrate how the fluid dynamics analysis of this rare malformation, properly coupled with imaging technology, can provide information that could not be obtained otherwise and that are relevant for a careful clinical management including timely therapeutic intervention. [ABSTRACT FROM AUTHOR]

Hypoplastic left heart syndrome (HLHS) is characterized by underdevelopment of the left-sided heart structures. The prenatal diagnosis of this congenital heart disease is crucial because a newborn with undiagnosed HLHS often presents with clinical signs of low cardiac output once the ductus arteriosus begins to close. With that in mind, the aim of this article was to perform a nonsystematic review focusing on the key ultrasound features that can be used in the prenatal diagnosis of HLHS. Severe forms of HLHS are characterized by a markedly abnormal four-chamber view of the fetal heart (small left atrium, hypoplastic left ventricle, or abnormal mitral valve). The left ventricular outflow tract view allows the degree of hypoplasia in the tract to be evaluated and the diameter of the ascending aorta to be measured. The Z-scores are intended to aid in the diagnosis and follow-up of HLHS. In mild forms of HLHS, a right ventricle/left ventricle length ratio > 1.28 was the strongest predictor of a univentricular outcome. [ABSTRACT FROM AUTHOR]

This study aimed to compare fetal myocardial performance index (MPI) between fetuses of pregnant women with gestational diabetes mellitus (GDM) and healthy controls and to evaluate the relationship between MPI and maternal glucose levels. This was a prospective study of 90 pregnant women, including 50 pregnancies with GDM (27 pregnancies with insulin‐regulated GDM and 23 pregnancies with diet‐regulated GDM) and 40 healthy controls. Isovolumetric contraction time (ICT) + isovolumetric relaxation time (IRT)/ejection time (ET) were used to calculate the MPI (MPI = [ICT + IRT]/ET). Fetal MPI, PR interval, E/A ratio, maternal plasma glucose levels on the day of MPI measurement, and neonatal outcomes were compared. The fetal left‐MPI was significantly higher in the GDM group than healthy controls (0.43 ± 0.04 vs. 0.40 ± 0.06, p = 0.007). The best cut‐off level for MPI was >0.41 to predict adverse perinatal outcomes (sensitivity: 70%, specificity: 68%, area under the curve: 0.715, 95% confidence interval: 0.5143–0.8205, p < 0.001). The fetal MPI values showed no correlation with maternal plasma fasting, postprandial glucose, and hemoglobin A1c (HbA1c) levels. Reduced E/A ratio, higher neonatal intensive care unit admissions, and the need for cesarean delivery were detected in the GDM group. Fetal MPI is impaired in women with GDM, and the need for insulin therapy is associated with higher MPI values and adverse neonatal outcomes. Fetal MPI can help detect fetuses with potential adverse outcome risks, owing to impaired fetal cardiac function. [ABSTRACT FROM AUTHOR]

In this study, we propose a simple, cost-effective, and sensitive high-performance liquid chromatography with both detection techniques such as diode-array detection and fluorescence detection (HPLC-DAD-FLD) for the determination of nesfatin-1 in fetal bovine serum samples. The limit of detection (LOD) and limit of quantification (LOQ) for nesfatin-1 were set at satisfactory values in the range 0.22–0.35 mg mL−1 and in the range 0.67–1.05 mg mL−1, respectively (at two different wavelengths (DAD) and at four different wavelengths (FLD)). Analyte concentrations were determined as the average value from fetal bovine serum matrix samples. The preliminary results show that the SPE procedure on Isolute Si-TsOH (SCX-3) could be used for further nesfatin-1 analyses in human serum samples. Both the SPE technique, chromatographic analysis with gradient elution mode and detection technique are fast and convenient. [ABSTRACT FROM AUTHOR]

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]