It is well recognized that diabetes in pregnancy confers an increased risk of fetal anomalies compared with pregnancies without diabetes. The congenital anomaly rate nears the background population in pregnancies that achieve adequate periconception glycemic control. Appropriate diagnosis of anomalies is critical for improving outcomes and allows for the possibility for pregnancy interruption, if desired. There are multiple proposed workflows tailored to detect structural anomalies in pregnancies affected by diabetes. In this chapter, we describe the ability of prenatal ultrasound to detect congenital anomalies associated with diabetes in pregnancy.

To assess the natural history of conotruncal anomalies (CTA) diagnosed by early fetal echocardiography, focusing on lesion progression and genetic findings. A secondary aim was to develop nomograms for great arteries at 12 + 0 to 15+6weeks to assess whether early measurements could help identify fetuses at risk of CTA progression. A retrospective cohort study of fetuses diagnosed with CTA before 16weeks' were identified between 2018 and 2024. Only cases with postnatal or postmortem confirmation were included. Progression was defined as a morphological change requiring revision of the initial diagnosis. Genetic testing was offered. Measurements of aortic and pulmonary artery diameters were collected in normal fetuses. Of 152 cases of CTA diagnosed before 16weeks, 101 met the inclusion criteria. Pregnancy termination was chosen in 31 of these cases. Among 70 ongoing pregnancies, intrauterine demise and postnatal death occurred in 4 cases. Lesion progression was observed in 28.6% of cases. Early great-artery biometry differed between progressing and non-progressing phenotypes. Genetic abnormalities were detected in 13 cases, including 8 non-isolated and 5 isolated cases. CTA diagnosed before 16weeks of gestation are dynamic conditions, with one in four showing antenatal progression. Early assessment of great-artery diameters may help identify cases at higher risk of progression.

To measure embryonic nuchal translucency (NT) thickness and ductus venosus (DV) blood flow indices using transvaginal two-dimensional sonography and Doppler ultrasound at 8-10 + 6weeks. Transvaginal scans were performed for 149 normal and three abnormal embryos (trisomy 18 with ventricular septal defect (VSD), tricuspid insufficiency (TR), and intrauterine fetal death with trisomy 21) at 8-10 + 6weeks. NT thickness, S wave (cm/s), D wave (cm/s), "a" wave (cm/s), S/a, pulsatility index (PI), and resistance index (RI) of DV were measured, and reference values for each parameter were determined. NT, S, D, S/a, PI, and RI increased linearly with advancing gestation (p < 0.01). The 'a' (mean, 5.55cm/s; SD, 1.8cm/s) value was constant at 8-10 + 6weeks of gestation. There were significant linear correlations between NT, S, D, S/a, PI, and RI, and crown-rump length (CRL) (p < 0.01). The "a" value remained unchanged with increasing CRL during this period. NT thickness (2.8mm) in the trisomy 18 patient with VSD was high at 10 + 6weeks, and reversed "a" wave was evident in the patient with TR at 10 + 1weeks. In a fetus with intrauterine fetal death with trisomy 21 at 11weeks and 6days, NT thickness was 2.1mm, and reversed DV flow was noted at 9weeks and 6days. Our results provide reference values for NT thickness and DV flow parameters, which may advance our understanding of embryonic growth and promote earlier prenatal diagnosis of chromosome abnormalities and/or cardiac anomalies before 11weeks.

ABSTRACT Background Pregnancy is a critical period for safeguarding maternal and foetal health, often involving diagnostic and screening methods to detect risks early. These decisions impact not only the foetus (e.g. abortion) but also the mother (e.g. anxiety, depression), the partner (e.g. family conflict), and society. The prenatal period is especially complex due to the physical, psychological, and social changes it entails. This study aims to explore in depth the psychological and social experiences of women who were informed of a potential foetal anomaly during pregnancy but ultimately gave birth to healthy babies. Rather than focusing solely on the diagnostic process, the study sought to understand how women internally managed the uncertainty and emotional burden. Method This qualitative study used a phenomenological approach and interviewed 18 women who were informed of a potential foetal anomaly but gave birth to healthy babies. A total of 151 pages of transcribed data were thematically analysed using Maxqda software. Findings Six themes emerged: confronting anomaly suspicion, the socio-psychological state of the pregnant woman, reactions from family and partner, process management, difficulties encountered, and emotions during childbirth. Participants reported significant emotional impact upon learning of a possible foetal anomaly, followed by socio-psychological challenges after the diagnosis. Conclusion The findings demonstrate that prenatal anomaly diagnoses affect women on multiple levels, transcending the clinical domain. Holistic prenatal care that acknowledges emotional, social, and cultural dimensions – alongside medical needs – is essential for supporting women during these experiences.

MRPS22-related mitochondrial disease (MIM#611719) is a rare autosomal recessive disorder caused by defects in the mitochondrial ribosomal protein S22, a component of the small mitoribosomal subunit essential for mitochondrial translation. Of the few reported cases, most present antenatally with a severe phenotype, conveying a poor prognosis. We describe a fetus with severe antenatal-onset MRPS22-related mitochondrial disease and the use of multi-omics in the molecular diagnosis. A primigravida underwent termination of pregnancy following identification of multiple congenital anomalies (hydrops fetalis, microcephaly, corpus callosal agenesis, periventricular cysts and cardiac hypertrophy) on ultrasound at 20 + 2 weeks' gestation, confirmed on fetal magnetic resonance imaging. Trio genome sequencing revealed compound heterozygous variants in MRPS22 (NM_020191.4: c.509G>A; p.(Arg170His) and c.565C>G; p.(Arg189Gly)). Rapid proteomic analysis demonstrated destabilisation of the small mitoribosomal subunit and combined reduction of OXPHOS complexes, supporting the pathogenicity of the variants. This case consolidates the antenatal phenotype of severe MRPS22-related disease and highlights the importance of considering mitochondrial disease in the differential diagnosis of congenital anomalies, especially hydrops fetalis and corpus callosum anomalies. This study provides evidence for the utility of multi-omic approaches (trio genome sequencing, proteomics) in confirming variant pathogenicity following pregnancy loss, enabling accurate diagnosis, and informing reproductive counselling for affected families.

According to the classification of the International Society for the Study of Vascular Anomalies (ISSVA), vascular anom- alies include a wide range of pathologies classified as vascular tumors or vascular malformations. This classification, last updated in 2018, is intended to explain the biological basis of vascular anomalies and help doctors in their treatment. In vascular tumors, proliferative changes in endothelial cells are observed, while vascular malformations are mainly struc- tural vascular anomalies. Vascular malformations are an extensive group of malformations of the arterial, venous, and lymphatic systems, both isolated and in combination with each other. Radiological examination plays a key role in the treatment of children with these diseases. This clinical example describes the stages of diagnosis and treatment of a child with arteriovenous malformation of the soft tissues of the back of the neck.

Objectives: Primary hyperoxaluria type III (PH3) causes kidney stones in children and adults. Gas chromatography/mass spectrometry (GC/MS)-based metabolomics has been applied to study patients with primary hyperoxaluria types I and II, 2,8-dihydroxyadenine lithiasis, and xanthinuria types I to III. This study was performed to verify the usefulness of this technique for the diagnosis of PH3. Specifically, we evaluated an 8-month-old infant with recurrent kidney stones. Methods: GC/MS-based metabolomics was performed on spot urine samples using initial urease pretreatment without fractionation. Results: Metabolomics revealed increased levels of 2,4-dihydroxyglutarate and 4-hydroxyglutamate. No simultaneous elevations of these two critical biomarkers were observed in other patients, except for one case of PH3 confirmed by the identification of HOGA1 mutations. A moderate increase in 4-hydroxyglutamate has been observed only in cases of primary hyperammonemia, in which analytes such as orotate, uridine, glutamine, or proline, but not 2,4-dihydroxyglutarate, are biomarkers, thus distinguishing PH3 from primary hyperammonemia. Conclusions: GC/MS-based urine metabolomics enables the rapid screening and chemical diagnosis of PH3 and other congenital anomalies that cause urolithiasis. This technique can also be used to monitor disease progression, as patients with PH3 benefit from long-term follow-up, particularly when transitioning from childhood to adulthood. The timely identification of patients with hereditary urolithiasis is crucial. To address this, a discussion was had about the current diagnostic criteria.

Fetal MRI has been increasingly used in diagnosis and assessment of congenital anomalies and conditions by providing detailed structural information. However, such information is only part of the whole landscape of these genetic disorders. Given that genetic disorders are associated with significant morbidity and mortality in infants, multidisciplinary team management is essential for perinatal management and parental counseling. In the past two decades, there are advances in both fetal MRI and genetic testing for prenatal diagnosis of genetic disorders. This narrative review consolidates the current literature and aims to provide a systematic overview of fetal MRI applications in genetic disorders affecting the central nervous system, craniofacial structures, skeletal system, lungs, and urinary system. Understanding embryological and genetic basis as well as imaging phenotypes of genetic disorders are important in improving perinatal diagnosis and management.

Complex Lymphatic Anomalies: A Comprehensive Review of Imaging Features and Diagnostic Considerations.

In recent years, Non-Invasive Prenatal Testing (NIPT) has been introduced as a promising screening test for Trisomies 21, 13, 18 and Monosomy X. This test quantifies the number of these chromosomes in fetal cells found in maternal blood. It is not considered diagnostic since there is a low percentage of false positive and false negative results. Additionally, to date, it is limited to 4 aneuploidies and does not cover other chromosomal aberrations. Therefore, its clinical benefit is debated in cases of increased nuchal translucency (NT) and the management of these cases should be determined. Herein, we present three cases in which an early anomaly scan led to the diagnosis of significant anomalies in fetuses with an increased NT and a normal NIPT. Genetic testing detected genetic aberrations in two of the three cases, including Monosomy X, which was missed by NIPT. In light of these cases and the existing literature, there is a high diagnostic yield for performing an early anomaly scan, as early as possible, and completing genetic investigation in fetuses with increased NT, despite a normal NIPT. In cases of increased NT, relying solely on a normal NIPT result is expected to lead to underdiagnosis of genetic and anatomic abnormalities.

Prenatal exome sequencing for the diagnosis of fetal anomalies was implemented nationally in England in October 2020 by the National Health Service Genomic Medicine Service. To evaluate the new prenatal exome sequencing service to provide evidence that will inform improvements to quality of care and equity of access for parents having prenatal tests. Our theoretically driven, multi-site, convergent parallel mixed-methods study design combined qualitative analyses of the service, stakeholder perspectives and ethical considerations with quantitative analyses of staff experiences, clinical outcomes and cost-effectiveness. Our final data set included interviews with parents offered prenatal exome sequencing (n = 48) and professionals (n = 63), surveys with professionals (n = 159) and data from prenatal exome sequencing testing referrals between October 2021 and June 2022 (413 referrals and 241 prenatal exome sequencing tests) linked to National Congenital Anomaly and Rare Disease Registration Service data and the Maternity Services Data Set. The study had oversight from a Steering Group and a Patient and Public Involvement Advisory Group. The Patient and Public Involvement Advisory Group contributed to study design, developing study materials and interpreting findings. Parents and professionals welcomed the introduction of a national prenatal exome sequencing service. Parents need emotional support across the testing journey, including follow-up care. A newly developed prenatal sequencing animation increased self-reported and objective knowledge of prenatal exome sequencing. Good communication and close working between genetics, fetal medicine and laboratory teams has supported successful implementation. Challenges for service delivery included increased administrative time and gaps in genomics education, particularly for midwives and fetal medicine clinicians. Local implementation varied in leadership, staffing and approaches to multidisciplinary team working. Ethical issues centred on barriers for equity of access and the intersecting timelines of prenatal exome sequencing testing and termination of pregnancy laws. Between October 2021 and June 2022, the diagnostic yield for prenatal exome sequencing was 35% (85/241) with a median turnaround time of 15 days to the final report. For 85 women who had a diagnosis, 40% had a termination of pregnancy, 18% had a stillbirth and 42% had a live birth. For women with a no findings result, 18% had a termination of pregnancy, 5% had a stillbirth and 78% had a live birth. The median gestational age at termination was 26 weeks. Total National Health Service costs for the 413 cases in the study period, with the most common staffing model, was £962,727 (£775,454 to £1,204,027, 95% credibility interval), or £2331 per case referred and £3592 per case that proceeded with testing. Our parent interview sample lacked diversity, with most being White/White British and educated to degree level or above. Details on prenatal exome sequencing service pathways from smaller units have not been captured. Assessment of variation in outcomes was restricted by the relatively small sample size of prenatal exome sequencing tests in the study period. This is the first study to explore the implementation of the national prenatal exome sequencing service in England. Our findings will inform the evolving prenatal exome sequencing service to ensure equity of access, high standards of care and benefits for all parents. Future research should include gathering the views and experiences from parents from diverse backgrounds, evaluating the prenatal sequencing animation in clinical practice and building on EXPRESS to identify and agree optimal care pathways that will ensure equity of access for all parents. This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme as award number NIHR127829.

7. A patient's personal account of navigating a Mullerian Anomaly diagnosis

This paper highlights a communal fault detection and isolation framework integrating a convolutional neural network (CNN) with a finite-state machine (FSM). The proposed concepts ensure state-based controlled discriminate pattern recognition and enable the diagnosis of different anomalies in the mobile robot in a multi-robot environment. The framework processes the time-series sensor data through the convolution layer upon experiencing different types of fault and governs different states based on fault diagnosis and recovery. The proposed concept has been validated using a Python 3.11 and Webot environment featuring the shrimp robot in a multi-robot arena. The model obtained an accuracy of 97% in identifying and classifying faults, enabling automated recovery of faulty robots in the multi-robot environment. Experiments conducted on different simulators demonstrate that effective fault management can be achieved with low training loss.

Conventional anomaly diagnosis methods often treat process faults and model drift as distinct, independent issues: anomalous behavior is attributed to process problems, whereas drift is seen as a secondary concern. This traditional perspective neglects the fact that, when a fault is detected, the first diagnosis that must be provided regards the source of the observed deviation: a process fault or a model malfunction. In this context, the present study tackles this fundamental diagnosis problem, proposing that effective anomaly diagnosis should distinguish process faults from model inadequacies originating from operational changes. To address this challenge, the Nearest Normal Value (NNV) contribution analysis technique was developed to quantify individual variable contributions through counterfactual analysis. Unlike conventional diagnostic methods that rely on static references, the NNV technique provides contribution profiles that characterize the operational state dynamically. The methodology was validated using three distinct datasets, including actual operational data from an oil production system. On real data, the normalized dispersion index (S) decreased from 0.92 to 0.58 during a documented fault (37% change), whereas it changed from 0.76 to 0.63 during an operating mode shift (17% change), showing, thus, distinct contribution signatures for faults versus drift-related regime changes. The findings suggest that incorporating the proposed approach into anomaly diagnosis systems could reduce false alarms and improve diagnostic accuracy in dynamic industrial environments where operating conditions evolve over time.

A detailed description of prenatal ultrasound signs of congenital renal cystic dysplasia (CRCD) is reported. Molecular investigations identified the c.179G>T, p.(Gly60Val) "de novo" variant in a heterozygous state in the RAP1B gene. This is a missense variant not described in the literature. Predictive tools suggest a pathogenic role for this mutation and a likely association with the clinical phenotype.

Prenatal diagnosis and postnatal outcomes of a rare venous anomaly: prominent azygos vein with an uninterrupted inferior vena cava.

Piriform sinus fistula (PSF) is a rare congenital anomaly derived from the third or fourth pharyngeal pouch. However, its developmental mechanisms remain poorly understood owing to the absence of suitable animal models. Cotton rats (Sigmodon hispidus) spontaneously develop PSF, providing a unique opportunity to investigate its anatomical origin and postnatal remodeling. In this study, we performed a three-dimensional reconstruction of serial histological sections from two inbred strains, HIS/Mz with third-pouch-derived PSF and HIS/Hiph with fourth-pouch-derived PSF. The third-pouch PSF opened dorsally at the base of the piriform sinus and terminated outside the thyroid gland, whereas the fourth-pouch PSF opened ventrally at the apex and extended into the thyroid parenchyma. Focusing on the fourth-pouch PSF in the HIS/Hiph, we further identified progressive epithelial stratification and age-dependent inflammation leading to suppurative thyroiditis. This remodeling was accompanied by marked alterations in epithelial marker expression, including a shift from Nkx2-1+/CK8+/UEA-I- to p63+/CK5+/UEA-I+ cell populations. Together, these features resemble the known characteristics of ultimobranchial body remnants and highlight the dynamic inflammation-associated transformation of the PSF epithelium. Collectively, our findings establish the cotton rat as a biologically informative experimental animal model for elucidating the developmental origin and pathological progression of PSF. This study provides new insights that may improve understanding, diagnosis, and clinical management of congenital cervical anomalies in humans.

Purpose: This study evaluates the role of coronary computed tomography (CT) angiography in diagnosis and management of coronary artery anomalies and explores demographic variations.Materials and Methods: A retrospective analysis of 2,786 patients undergoing Coronary CT angiography from November 2018 to October 2023 identified 53 cases (21 females, 32 males) of coronary artery anomalies. Anomalies were classified by origin, course, and structure. Imaging was performed using a dual-source CT scanner. Results: Coronary artery anomaly prevalence was 1.82%. The most common anomaly was a high take-off origin of the right coronary artery (41.5%). Left main anomalies were more frequent in males, while malignant courses occurred only in females (19%). Additional findings included coronary stenosis and diverticula. Coronary CT angiography provided critical 3D visualization for preoperative planning and revealed gender-specific differences, emphasizing the need for tailored approaches. Conclusion: Coronary CT angiography is an indispensable tool for diagnosing and characterizing coronary artery anomalies. Its non-invasive imaging allows for detailed preoperative evaluation, improving clinical and surgical outcomes. This study underscores the importance of addressing demographic variations and highlights the need for standardized protocols and further multicenter research.

Background: Vascular anomalies (VAs), including hemangiomas and vascular malformations, present a significant diagnostic challenge due to their high prevalence, complex classification (nearly 100 subtypes), and visual mimicry. Current Multimodal Large Language Models (MLLMs) struggle in this specialized domain, often failing to capture fine-grained visual features or lacking evidence-based reasoning. To address these limitations, we introduce HevaDx, an agentic diagnostic system that explicitly decouples visual perception from clinical reasoning. Methods: Leveraging a newly constructed large-scale dataset of VA patients, HevaDx employs a lightweight visual specialist for precise feature extraction and a reasoning specialist equipped with Retrieval-Augmented Generation (RAG) for therapeutic planning. This cooperative architecture mitigates the "reasoning gap" observed in end-to-end models by grounding decisions in up-to-date clinical guidelines. Results: Experimental results demonstrate that HevaDx achieves high performance with a top-3 diagnostic accuracy of 94.8% and a treatment recommendation accuracy of 83.3%. Conclusions: By bridging visual precision with transparent, verifiable logic, HevaDx offers a reliable framework for AI-assisted management of vascular anomalies.

Mesonephric duct anomalies in unilateral multicystic dysplastic kidney: A two-center retrospective study.