Fetal Congenital Heart Disease Research Articles

Dynamic sequential cross-sectional scanning increases detection rate of congenital heart disease in sonographers: a prenatal ultrasound training program

BackgroundPrenatal ultrasound is the preferred modality for diagnosing fetal congenital heart disease. Given issues of physician proficiency and hospital distribution, we propose a dynamic sequential cross-sectional scanning (SCS) to explore the feasibility of cardiac screening by sonographers with less than 5 years of experience in ultrasound.Materials and methodsTwenty residents were randomly divided into two groups, receiving training in the American Institute of Ultrasound in Medicine (AIUM) fetal echocardiography and the SCS method. According to the needs of training, the professional staff developed the theoretical knowledge question bank, the CHD ultrasonic video disease bank, and the assessment scale. Trainees completed the pre-training examination, theory and skill operation training, and post-training assessment. For the two groups, the theoretical knowledge, skill operation and disease diagnosis were analyzed statistically before and after training.ResultsAfter training, the trainees in both groups had significantly improved knowledge and diagnostic abilities, their diagnostic thinking about CHD was clear, and they could identify major or even all structural abnormalities and make a definite diagnosis. In terms of skill operation, both groups could complete all required scanning within the specified time. The scanning time of the SCS group was significantly lower than that of the AIUM group, and the effect of the receptor site in the AIUM group was significantly higher than that in the SCS group.ConclusionSCS can be used as a new rapid fetal cardiac scanning method and try to popularize among echocardiographer.

The Role of Collaboration in Prenatal Congenital Heart Disease Diagnosis: A Comparison of Maternal-Fetal Medicine Specialist and Pediatric Cardiologist Performance.

This study compared the accuracy of prenatal congenital heart disease (CHD) diagnosed by maternal-fetal medicine specialists (MFMs) and pediatric cardiologists (PCs), using postnatal cardiac findings as the reference standard. This retrospective analysis at Siriraj Hospital, Bangkok, Thailand, involved 125 pregnancies with fetal CHD diagnosed by MFMs and evaluated by PCs later. Prenatal CHD diagnoses by either MFM or PC were compared with postnatal diagnoses obtained through echocardiography, cardiac surgery/catheterization, or autopsy. Diagnostic accuracy was classified as (A) correct diagnosis, (B) minor differences not impacting clinical management or outcomes, or (C) major differences affecting prognosis or treatment. Cardiac sonography by MFM achieved diagnostic accuracies of 73.6% (A), 16% (B), and 10.4% (C), while fetal echocardiography by PC resulted in accuracies of 72% (A), 20% (B), and 8% (C). No statistically significant differences were found between MFM and PC in each category (P = .375-.832). The MFMs' accuracy was highest for tetralogy of Fallot (94.4%; 95% CI, 72.7-99.9%) and lowest for right atrial isomerism (71.4%; 95% CI, 29-96.3%) and pulmonary atresia with ventricular septal defect (57.1%; 95% CI, 18.4-90.1%). MFMs and PCs demonstrated high and comparable accuracy in prenatal CHD diagnosis. Although PCs tended to outperform MFMs in cases where misdiagnosis could significantly impact neonatal care and outcomes, MFMs can effectively perform primary screening for fetal CHD in all pregnancies. Collaboration with PCs remains essential when fetal CHD is suspected, particularly in complex cases.

Bio Inspired Technological Performance in Color Doppler Ultrasonography and Echocardiography for Enhanced Diagnostic Precision in Fetal Congenital Heart Disease

The aim of this experiment is to investigate the bioinspired diagnostic performance of color Doppler ultrasound (CDUS) and two-dimensional (2D) echocardiography (ECG) for fetal congenital heart disease (FCHD). The research subjects were 33 expectant mothers with a diagnosis of FCHD at Xiangyang No. 1 People's Hospital between January 2017 and January 2021. The accuracy, sensitivity, and specificity of the two detection techniques were computed to ascertain and compare the diagnostic efficiency after CDUS and ECG examinations of all pregnant women. According to the findings, the prenatal CDUS detection rate was 92.61% higher than the 2D ECG detection rate (64.32%). The CDUS had an accuracy of 93.94%, sensitivity of 93.55%, and specificity of 100%, detecting 29 true positives, 0 false positives, 2 false negatives, and 2 true negatives. At 84.85% accuracy, 88.89% sensitivity, and 80% specificity, the 2D ECG identified 16 true positives, 3 false positives, 2 false positives, and 12 true negatives. There was a statistically significant (P < 0.05) difference between the accuracy, sensitivity, and specificity of 2D ECG and CDUS. In summary, CDUS was more effective than 2D ECG in diagnosing prenatal FCHD, and it also had a lower rate of missed and incorrect diagnoses.

Impact of isolated fetal congenital heart disease on pregnancy and perinatal outcomes.

The aim of the present study was to evaluate the obstetric complications associated with isolated fetal congenital heart disease (CHD) by comparing pregnancies with and without this condition. In this retrospective matched comparative study at Siriraj Hospital, Thailand, we included 233 postnatally confirmed fetal CHD cases and 466 unaffected fetuses. Controls were selected at a 2:1 ratio, ensuring that they matched the cases in terms of maternal age, parity, and history of preterm deliveries. Fetal CHD was significantly associated with an increased risk of spontaneous preterm labor (30% vs 9.7%; adjusted odds ratio [aOR] 2.42; 95% confidence interval [CI]: 1.35-4.36; P = 0.003), delivery before 34 gestational weeks (11.6% vs 0.6%; aOR 12.33; 95% CI: 3.32-45.78; P < 0.001), and pre-eclampsia (11.6% vs 2.8%; aOR 2.19; 95% CI: 1.01-4.76; P = 0.047). Newborns with CHD were significantly more likely to be small for gestational age (10.7% vs 5.2%; aOR 2.09; 95% CI: 1.11-3.94; P = 0.022). Intriguingly, a prenatal diagnosis of CHD was associated with a reduced risk of preterm delivery in affected pregnancies (P = 0.002). Pregnancies affected by isolated fetal CHD demonstrated a higher propensity for several adverse outcomes. These findings underscore the importance of prenatal CHD detection and tailored perinatal care to potentially improve both pregnancy outcomes and neonatal health.

Study on ultrasound diagnosis and pathological anatomy of fetal complex congenital heart disease in the first trimester.

To assess the feasibility of using the stereo-microscope to identify the pathological anatomy of the congenital heart diseases in the first trimester. Fifteen fetuses of 8-12 weeks aborted due to prevent miscarriage failure and 42 fetuses of 11-14 weeks with congenital heart diseases were included in the study, we dissected their hearts through a stereo-microscope, then compared with the prenatal ultrasonographic diagnosis. Using stereomicroscopy, the positive view of the heart and the great arteries, the long axis view of the aortic arch, the inflow tract view of the bottom heart, the semilunar valve view of the bottom heart, and the transverse section of the ventricle were showed contented and obtained satisfactory images, but the structure of atrioventricular valve and venous system had a lower rate of display. The characteristic pathological changes of cardiac inflow and outflow tract can be obtained by dissecting the heart sequential under the stereo-microscopy. However it is often difficult to obtain satisfactory pathological sections for pulmonary venous abnormalities and Ebstein anomaly.

Fetal Cardiovascular Magnetic Resonance Feature Tracking Myocardial Strain Analysis in Congenital Heart Disease

BackgroundCardiovascular magnetic resonance (CMR) is an emerging imaging modality for assessing anatomy and function of the fetal heart in congenital heart disease (CHD). This study aimed to evaluate myocardial strain using fetal CMR feature tracking (FT) in different subtypes of CHD. MethodsFetal CMR FT analysis was retrospectively performed on four-chamber cine images acquired with Doppler US gating at 3 Tesla. Left ventricular (LV) global longitudinal strain (GLS), LV global radial strain (GRS), LV global longitudinal systolic strain rate (SR), and right ventricular (RV) GLS were quantified using a dedicated software optimized for fetal strain analysis. Analysis was performed in normal fetuses and different CHD subtypes (d-Transposition of the great arteries (dTGA), hypoplastic left heart syndrome (HLHS), coarctation of the aorta (CoA), tetralogy of Fallot (TOF), RV-dominant atrioventricular septal defect (AVSD), and critical pulmonary stenosis or atresia (PS/PA)). Analyses of variance (ANOVA) with Tukey post-hoc test was used for group comparisons. ResultsA total of 60 fetuses were analyzed (8/60 (13%) without CHD, 52/60 (87%) with CHD). Myocardial strain was successfully assessed in 113/120 ventricles (94%). Compared to controls, LV GLS was significantly reduced in fetuses with HLHS (-18.6±2.7% vs. -6.2±5.6%; p<0.001) and RV-dominant AVSD (-18.6±2.7% vs. -7.7±5.0%; p=0.003) and higher in fetuses with CoA (-18.6±2.7% vs. -25.0±4.3%; p=0.038). LV GRS was significantly reduced in fetuses with HLHS (25.7±7.5% vs. 11.4±9.7%; p=0.024). Compared to controls, RV GRS was significantly reduced in fetuses with PS/PA (-16.1±2.8% vs. -8.3±4.2%; p=0.007). Across all strain parameters, no significant differences were present between controls and fetuses diagnosed with dTGA and TOF. ConclusionsFetal myocardial strain assessment with CMR FT in CHD is feasible. Distinct differences are present between various types of CHD, suggesting potential implications for clinical decision-making and prognostication in fetal CHD.

Potential candidate maternal serum miRNAs for the diagnosis of fetal congenital heart disease.

Congenital heart disease (CHD) is one of the most significant birth defects leading to infant mortality worldwide. Circulating microRNAs (miRNAs) are emerging as novel biomarkers for the detection of cardiovascular diseases. In this study, we aimed to investigate the role of maternal serum miRNAs expression as biomarkers in the diagnosis and prediction of children with CHD. High-throughput sequencing of peripheral blood from pregnant women with abnormal and normal fetal hearts identified 1939 differentially expressed miRNAs, the first 11 of which were selected as predictive biomarkers of CHD. The expression of miRNAs in more clinical samples was then quantitatively verified by reverse transcriptase polymerase chain reaction and the correlation between abnormal miRNAs and CHD was analyzed. Two miRNAs (hsa-miR-3195 and hsa-miR-122-5p) were found to be significantly down-regulated in pregnant women with fetal CHD. By further bioinformatics analysis, we predicted that hsa-miR-3195 and hsa-miR-122-5p could induce CHD by influencing biometabolic processes. hsa-miR-3195 and hsa-miR-122-5p may serve as novel non-invasive biomarkers for prenatal detection of fetal CHD.

Maternal Vascular Malperfusion and Anatomic Cord Abnormalities Are Prevalent in Pregnancies With Fetal Congenital Heart Disease.

Impairments in the maternal-fetal environment are associated with adverse postnatal outcomes among infants with congenital heart disease. Therefore, we sought to investigate placental anomalies as they related to various forms of fetal congenital heart disease (FCHD). We reviewed the placental pathology in singleton pregnancies with and without FCHD. FCHD was divided into separate categories (transposition physiology, obstructive left, obstructive right, biventricular without obstruction, and others). Exclusion criteria included other prenatally known structural malformations and/or aneuploidy. The significance threshold was set at p<0.05 or False Discovery rate q<0.05 when multiple tests were performed. The cohort included 215 FCHD and 122 non-FCHD placentas. FCHD placentas showed increased rates of maternal vascular malperfusion (24% vs. 5%, q<0.001) and cord anomalies (27% vs. 1%, q<0.001). Placentas with fetal TGA demonstrated a lower rate of hypoplasia when compared with other FCHD types (1/39 vs. 51/176, Fisher's exact p=0.015). Placental maternal vascular malperfusion is increased in FCHD. The prevalence of vascular malperfusion did not differ by FCHD type, indicating that CHD type does not predict the likelihood of placental vascular dysfunction. Further investigation of the placental-fetal heart axis in FCHD is warranted given the importance of placental health.

Parent and healthcare professional experiences of critical congenital heart disease in New Zealand to advance health equity

BackgroundHigher odds of survival have been reported in European infants compared to Indigenous Māori and Pasifika infants with critical congenital heart disease in New Zealand. We therefore aimed to understand how to mitigate this disparity by investigating the parent and healthcare professional experiences’ of critical congenital heart disease healthcare in New Zealand.MethodsA prospective qualitative study utilising semi-structured interviews was conducted on a cohort of purposefully sampled parents and health professionals with experience of critical congenital heart disease healthcare in New Zealand. Parents were recruited after a fetal critical congenital heart disease diagnosis and offered two interviews at least three months apart, whilst multidisciplinary fetal and cardiosurgical health professionals were interviewed once. Interviews were recorded and transcribed verbatim before coding, categorization and qualitative analysis.ResultsDuring 2022 and 2023, 45 people participated in 57 interviews (25 parents: 19 mothers, 6 fathers; Indigenous Māori, n = 5; Pasifika, n = 6; Asian, n = 4; European, n = 10; and 20 healthcare professionals: European n = 17). The three lessons learned from participants were: (1) Minoritized groups experience disparate healthcare quality; (2) healthcare systems are under-resourced to provide equitable support for the differential needs of grieving parents; and (3) healthcare systems could engage minoritized families more optimally in shared decision-making.ConclusionsAccording to the experiences of parents and healthcare professionals, persisting inequities in CCHD healthcare quality occur by ethnic group, with the New Zealand healthcare system privileging European families. The concepts from this study could be translated by healthcare leaders, policymakers, and professionals into evidence-based healthcare system improvements to enhance experiences for non-European families more broadly.

Assisted reproductive technology and the risk of fetal congenital heart disease: insights from a tertiary-care referral center

PurposeTo investigate whether congenital heart diseases exhibit higher rates in pregnancies achieved through assisted reproductive technology (ART) compared to natural conception.MethodsIn this retrospective cohort study, multinomial logistic regression was employed to analyze the relationship between categories of congenital heart diseases and three conception groups (IVF, ICSI, and natural pregnancies). The main outcome measures are risks of congenital heart disease categories in IVF and ICSI groups using the natural group as reference. We selected fetuses referred for fetal echocardiography to IRCCS Policlinico Sant’Orsola, Bologna, between January 2005 and November 2023, diagnosed with congenital heart diseases.ResultsWe categorized the congenital heart diseases into six groups based on anatomical and embryological criteria. The estimated risk of left ventricular outflow tract, valvular, conotruncal, and atrioventricular septal defects was lower in the IVF group compared to natural conception. The estimated risk of valvular and atrioventricular septal defects was lower in the ICSI group vs natural. Conversely, the risk for right heart anomalies was higher both in the IVF and ICSI groups compared to natural conception. Heart rhythm diseases were more frequent in IVF pregnancies. When comparing ART methods, valvular defects, conotruncal defects, and right heart anomalies were more frequently observed in the ICSI group, while atrioventricular septal defects were more common in the IVF group.ConclusionSignificant differences were found in the occurrence of congenital heart diseases in pregnancies conceived through IVF and ICSI, versus those conceived naturally, underscoring the importance of further studying the underlying mechanisms of these associations.

Advanced magnetic resonance imaging in human placenta: insights into fetal growth restriction and congenital heart disease.

Placental function plays a crucial role in fetal development, as it serves as the primary interface for delivery of nutrients and oxygen from the mother to fetus. Magnetic resonance imaging (MRI) has significantly improved our ability to visualize and understand the placenta's complex structure and function. This review provides an up-to-date examination of the most common and novel placental MRI techniques. It will also discuss the clinical applications of MRI in diagnosing and monitoring placental insufficiency, as well as its implications for fetal growth restriction (FGR) and congenital heart disease (CHD). Ongoing research using multi-parametric MRI techniques aims to develop novel biomarkers and uncover the relationships between placental parameters and pre-onset diseased states, ultimately contributing to better maternal and fetal health outcomes, which is essential to better guide clinical judgement.

DNA methylation of the Lamin A/C gene is associated with congenital heart disease.

Prior studies report associations of maternal serum Lamin A, encoded by the LMNA gene, with fetal congenital heart disease (CHD). It is unknown whether DNA methylation (DNAm) of cytosine-phosphate-guanine (CpG) sites in LMNA impacts the CHD susceptibility. We investigated the associations of LMNA DNAm with CHD using publicly available data of CHD cases (n = 197) and controls (n = 134) from the Gene Expression Omnibus repository. Peripheral blood DNAm was measured using Illumina 850 K BeadChip for cases and 450 K BeadChip for controls. We tested 31 LMNA CpGs to identify differences in DNAm between cases and controls using linear regression correcting for multiple testing with false discovery rate (FDR). In a case-only analysis, we tested the variations in LMNA DNAm between CHD subtypes. To identify the consistency of DNAm across tissue types we compared peripheral blood (n = 197) and heart tissue DNAm (n = 20) in CHD cases. After adjusting for age, sex, and cell types there were significant differences in 17 of the 31 LMNA CpGs between CHD cases and controls (FDR p ≤ .05). We identified lower DNAm of cg09820673 at 3' UTR for hypoplastic left heart syndrome compared to other CHD subtypes. Three CpGs exhibited uniform DNAm in blood and heart tissues in cases. Eleven CpGs showed changes in the same direction in blood and heart tissues in cases compared to controls. We identify statistically significant differences in LMNA DNAm between CHD cases and controls. Future studies should investigate the role of maternal LMNA DNAm in CHD development.

Delivery room and early postnatal management of neonates with congenital heart disease.

Advancements in prenatal detection have improved postnatal outcomes for patients with congenital heart disease (CHD). Detailed diagnosis during pregnancy allows for preparation for the delivery and immediate postnatal care for the newborns with CHD. Most CHDs do not result in hemodynamic instability at the time of birth and can be stabilized following the guidelines of the neonatal resuscitation program (NRP). Critical CHD that requires intervention immediately after birth is recommended to be delivered in facilities where immediate neonatal and cardiology care can be provided. Postnatal stabilization and resuscitation for these defects warrant deviation from the standardized NRP. For neonatal providers, knowing the diagnosis of fetal CHD allows for preparation for the anticipated instability in the delivery room. Prenatal detection fosters collaboration between fetal cardiology, cardiology specialists, obstetrics, and neonatology, improving outcomes for neonates with critical CHD.

Interaction between clinicians and artificial intelligence to detect fetal atrioventricular septal defects on ultrasound: how can we optimize collaborative performance?

Artificial intelligence (AI) has shown promise in improving the performance of fetal ultrasound screening in detecting congenital heart disease (CHD). The effect of giving AI advice to human operators has not been studied in this context. Giving additional information about AI model workings, such as confidence scores for AI predictions, may be a way of further improving performance. Our aims were to investigate whether AI advice improved overall diagnostic accuracy (using a single CHD lesion as an exemplar), and to determine what, if any, additional information given to clinicians optimized the overall performance of the clinician-AI team. An AI model was trained to classify a single fetal CHD lesion (atrioventricular septal defect (AVSD)), using a retrospective cohort of 121 130 cardiac four-chamber images extracted from 173 ultrasound scan videos (98 with normal hearts, 75 with AVSD); a ResNet50 model architecture was used. Temperature scaling of model prediction probability was performed on a validation set, and gradient-weighted class activation maps (grad-CAMs) produced. Ten clinicians (two consultant fetal cardiologists, three trainees in pediatric cardiology and five fetal cardiac sonographers) were recruited from a center of fetal cardiology to participate. Each participant was shown 2000 fetal four-chamber images in a random order (1000 normal and 1000 AVSD). The dataset comprised 500 images, each shown in four conditions: (1) image alone without AI output; (2) image with binary AI classification; (3) image with AI model confidence; and (4) image with grad-CAM image overlays. The clinicians were asked to classify each image as normal or AVSD. A total of 20 000 image classifications were recorded from 10 clinicians. The AI model alone achieved an accuracy of 0.798 (95% CI, 0.760-0.832), a sensitivity of 0.868 (95% CI, 0.834-0.902) and a specificity of 0.728 (95% CI, 0.702-0.754), and the clinicians without AI achieved an accuracy of 0.844 (95% CI, 0.834-0.854), a sensitivity of 0.827 (95% CI, 0.795-0.858) and a specificity of 0.861 (95% CI, 0.828-0.895). Showing a binary (normal or AVSD) AI model output resulted in significant improvement in accuracy to 0.865 (P < 0.001). This effect was seen in both experienced and less-experienced participants. Giving incorrect AI advice resulted in a significant deterioration in overall accuracy, from 0.761 to 0.693 (P < 0.001), which was driven by an increase in both Type-I and Type-II errors by the clinicians. This effect was worsened by showing model confidence (accuracy, 0.649; P < 0.001) or grad-CAM (accuracy, 0.644; P < 0.001). AI has the potential to improve performance when used in collaboration with clinicians, even if the model performance does not reach expert level. Giving additional information about model workings such as model confidence and class activation map image overlays did not improve overall performance, and actually worsened performance for images for which the AI model was incorrect. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

SPReCHD: Four-Chamber Semantic Parsing Network for Recognizing Fetal Congenital Heart Disease in Medical Metaverse.

Echocardiography is essential for evaluating cardiac anatomy and function during early recognition and screening for congenital heart disease (CHD), a widespread and complex congenital malformation. However, fetal CHD recognition still faces many difficulties due to instinctive fetal movements, artifacts in ultrasound images, and distinctive fetal cardiac structures. These factors hinder capturing robust and discriminative representations from ultrasound images, resulting in CHD's low prenatal detection rate. Hence, we propose a multi-scale gated axial-transformer network (MSGATNet) to capture fetal four-chamber semantic information. Then, we propose a SPReCHD: four-chamber semantic parsing network for recognizing fetal CHD in the clinical treatment of the medical metaverse, integrating MSGATNet to segment and locate four-chamber arbitrary contours, further capturing distinguished representations for the fetal heart. Comprehensive experiments indicate that our SPReCHD is sufficient in recognizing fetal CHD, achieving a precision of 95.92%, a recall of 94%, an accuracy of 95%, and a F1 score of 94.95% on the test set, dramatically improving the fetal CHD's prenatal detection rate.

Comparison of Different Ultrasonic Screening Methods and Analysis of High Risk Factors for Fetal Cardiac Malformation in Second Trimester of Pregnancy.

Current study aims to compare the application of two-dimensional (2D) color doppler ultrasound (CDU) and four-dimensional (4D) ultrasound spatiotemporal image correlation (STIC) in fetal congenital heart disease in the second trimester of pregnancy and to analyze the high risk factors of the disease. From August 2019 to July 2021, 135 second-trimester patients with highly suspected congenital heart malformations were selected who underwent prenatal screening at South Taihu Hospital Affiliated to Huzhou University. 2D-CDU, 4D STIC, and postnatal examination were completed in all patients. 2D-CDU, 4D STIC and 2D-CDU combined with 4D STIC were used to detect fetal cardiac malformations and classify cardiac malformations. The sensitivity, specificity, positive predictive value, negative predictive value and coincidence rate of 2D-CDU, 4D STIC and 2D-CDU combined with 4D STIC were compared. The results of 2D-CDU, 4D STIC and 2D-CDU combined with 4D STIC screening were analyzed for consistency using the results of postpartum diagnosis as the gold standard. Moreover, effects of maternal gestational factors on fetal cardiac malformations by univariate and multivariate analysis. 2D-CDU combined with 4D STIC showed significantly higher section display number than 2D-CDU or 4D STIC in the view of ductal arch, aortic arch, and aortic short-axis. A total of 45 cases of fetal congenital heart malformation were detected in 135 patients in the second trimester, 40, 38 or 42 cases were detected by 2D-CDU, 4D STIC or 2D-CDU combined with 4D STIC, respectively. The sensitivity, specificity, positive predictive value, negative predictive value and coincidence rate of 2D-CDU combined with 4D ultrasound in congenital heart malformation screening were higher than those of 2D-CDU or 4D STIC. Kappa agreement analysis showed that the diagnostic results of 4D STIC and 2D-CDU combined with 4D ultrasound in fetuses with suspected congenital heart malformation were in excellent agreement (κ > 0.75), while 2D-CDU was in good agreement with postpartum diagnosis (κ < 0.75). Univariate and multivariate regression analysis revealed that maternal age ≥ 35, drinking during pregnancy, and history of adverse pregnancy and childbirth were all independent risk factors for fetal cardiac malformations, while folic acid supplementation was an independent protective factor for fetal cardiac malformations. 2D-CDU combined with 4D echocardiography may be superior to single 2D-CDU or 4D STIC in the screening of fetal congenital heart malformation in the second trimester. In order to reduce the incidence of fetal heart anomalies, we should strengthen the screening of pregnancy anomalies in high-risk pregnant women and control the risk factors.

Is there an increased risk of genetic abnormalities in fetuses with congenital heart disease in the setting of growth restriction?

To determine if the presence of fetal growth restriction (FGR) is associated with an increased risk of genetic abnormalities in the setting of congenital heart disease (CHD). This was a retrospective cohort study involving pregnancies that met the following criteria: (i) prenatal diagnosis of CHD, (ii) singleton live-birth, and (iii) genetic testing was performed either pre- or postnatally. Genetic results were reviewed by a clinical geneticist for updated variant classification. Fetal growth was stratified as appropriate for gestational age (AGA) or FGR. Of the total of 445 fetuses that met the study criteria, 325 (73.0%) were AGA and 120 (27.0%) were FGR. Genetic abnormalities were detected in 131 (29.4%) pregnancies. There was a higher rate of genetic abnormalities (36.7% vs. 26.8%, p=0.04), which was driven by aneuploidies (20.8% vs. 8.9%, p=0.0006) in the FGR population. Early onset growth restriction was associated with a higher rate of genetic abnormalities (44.5% vs. 25.9%, p=0.03). The rate of genetic abnormalities was significantly higher in the shunt category as compared to remainder of the cardiac anomalies (62.5% in shunt lesions vs. 24.7%, p<0.00001). The rates of FGR (40.9% vs. 21.4%, p<0.0001) and genetic abnormalities (52% vs. 20.4%, p<0.0001) were significantly higher in the presence of extra-cardiac anomalies (ECA). The presence of FGR in fetal CHD population was associated with underlying genetic abnormalities, specifically aneuploidies. Patients should be appropriately counseled regarding the higher likelihood of a genetic condition in the presence of FGR, early onset FGR, shunt lesions and ECA.

Efficiency of copy number variation sequencing combined with karyotyping in fetuses with congenital heart disease and the following outcomes

BackgroundBoth copy number variant-sequencing (CNV-seq) and karyotype analysis have been used as powerful tools in the genetic aetiology of fetuses with congenital heart diseases (CHD). However, CNV-seq brings clinicians more confusions to interpret the detection results related to CHD with or without extracardiac abnormalities. Hence, we conducted this study to investigate the clinical value of CNV-seq in fetuses with CHD.ResultsA total of 167 patients with fetal CHD including 36 single CHD (sCHD), 41 compound CHD (cCHD) and 90 non-isolated CHD (niCHD) were recruited into the study. 28 cases (16.77%, 28/167) were revealed with chromosomal abnormalities at the level of karyotype. The pathogenic detection rate (DR) of CNV-seq (23.17%, 19/82) was higher than that of karyotyping (15.85%, 13/82) in 82 cases by CNV-seq and karyotyping simultaneously. The DR of pathogenic copy number variations (PCNVs) (31.43%) was higher in niCHD subgroup than that in sCHD and cCHD (9.52% and 23.08%). Conotruncal defect (CTD) was one of the most common heart malformations with the highest DR of PCNVs (50%) in 7 categories of CHD. In terms of all the pregnancy outcomes, 67 (40.12%) cases were terminated and 100 (59.88%) cases were live neonates. Only two among 34 cases with a pathogenic genetic result chose to continue the pregnancy.ConclusionsCNV-seq combined with karyotyping is a reliable and accurate prenatal technique for identifying pathogenic chromosomal abnormalities associated with fetal CHD with or without extracardiac abnormalities, which can assist clinicians to perform detailed genetic counselling with regard to the etiology and related outcomes of CHD.

Interdependence of placenta and fetal cardiac development.

The placenta and fetal heart undergo development concurrently during early pregnancy, and, while human studies have reported associations between placental abnormalities and congenital heart disease (CHD), the nature of this relationship remains incompletely understood. Evidence from animal studies suggests a plausible cause and effect connection between placental abnormalities and fetal CHD. Biomechanical models demonstrate the influence of mechanical forces on cardiac development, whereas genetic models highlight the role of confined placental mutations that can cause some forms of CHD. Similar definitive studies in humans are lacking; however, placental pathologies such as maternal and fetal vascular malperfusion and chronic deciduitis are frequently observed in pregnancies complicated by CHD. Moreover, maternal conditions such as diabetes and pre-eclampsia, which affect placental function, are associated with increased risk of CHD in offspring. Bridging the gap between animal models and human studies is crucial to understanding how placental abnormalities may contribute to human fetal CHD. The next steps will require new methodologies and multidisciplinary approaches combining innovative imaging modalities, comprehensive genomic testing, and histopathology. These studies may eventually lead to preventative strategies for some forms of CHD by targeting placental influences on fetal heart development.

The combination of deep learning and pseudo-MS image improves the applicability of metabolomics to congenital heart defect prenatal screening

To investigate the metabolic alterations in maternal individuals with fetal congenital heart disease (FCHD), establish the FCHD diagnostic models, and assess the performance of these models, we recruited two batches of pregnant women. By metabolomics analysis using Ultra High-performance Liquid Chromatography-Mass/Mass (UPLC-MS/MS), a total of 36 significantly altered metabolites (VIP >1.0) were identified between FCHD and non-FCHD groups. Two logistic regression models and four support vector machine (SVM) models exhibited strong performance and clinical utility in the training set (area under the curve (AUC) = 1.00). The convolutional neural network (CNN) model also demonstrated commendable performance and clinical utility (AUC = 0.89 in the training set). Notably, in the validation set, the performance of the CNN model (AUC = 0.66, precision = 0.714) exhibited better robustness than the six models above (AUC≤0.50). In conclusion, the CNN model based on pseudo-MS images holds promise for real-world and clinical applications due to its better repeatability.