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Deep learning algorithms have demonstrated remarkable potential in clinical diagnostics, particularly in the field of medical imaging. In this study, we investigated the application of deep learning models in early detection of fetal kidney anomalies. To provide an enhanced interpretation of those models' predictions, we proposed an adapted two-class representation and developed a multi-class model interpretation approach for problems with more than two labels and variable hierarchical grouping of labels. Additionally, we employed the explainable AI (XAI) visualization tools Grad-CAM and HiResCAM, to gain insights into model predictions and identify reasons for misclassifications. The study dataset consisted of 969 ultrasound images from unique patients; 646 control images and 323 cases of kidney anomalies, including 259 cases of unilateral urinary tract dilation and 64 cases of unilateral multicystic dysplastic kidney. The best performing model achieved a cross-validated area under the ROC curve of 91.28% ± 0.52%, with an overall accuracy of 84.03% ± 0.76%, sensitivity of 77.39% ± 1.99%, and specificity of 87.35% ± 1.28%. Our findings emphasize the potential of deep learning models in predicting kidney anomalies from limited prenatal ultrasound imagery. The proposed adaptations in model representation and interpretation represent a novel solution to multi-class prediction problems. [ABSTRACT FROM AUTHOR]

18p deletion syndrome constitutes one of the most frequent autosomal terminal deletion syndromes, affecting one in 50,000 live births. The syndrome has un-specific clinical features which vary significantly between patients and may overlap with other genetic conditions. Its prenatal description is extremely rare as the fetal phenotype is often not present during pregnancy. Trisomy 8p Syndrome is characterized by heterogenous phenotype, with the most frequent components to be cardiac malformation, developmental and intellectual delay. Its prenatal diagnosis is very rare due to the unspecific sonographic features of the affected fetuses. We present a very rare case of a fetus with multiple anomalies diagnosed during the second trimester whose genomic analysis revealed a 18p Deletion and 8p trisomy Syndrome. This is the first case where this combination of DNA mutations has been described prenatally and the second case in general. The presentation of this case, as well as the detailed review of all described cases, aim to expand the existing knowledge regarding this rare condition facilitating its diagnosis in the future. [ABSTRACT FROM AUTHOR]

Large-scale copy number variants (CNVs) are structural alterations in the genome that involve the duplication or deletion of DNA segments, contributing to genetic diversity and playing a crucial role in the evolution and development of various diseases and disorders, as they can lead to the dosage imbalance of one or more genes. Massively parallel sequencing (MPS) has revolutionized the field of genetic analysis and contributed significantly to routine clinical diagnosis and screening. It offers a precise method for detecting CNVs with exceptional accuracy. In this context, a non-invasive prenatal test (NIPT) based on the sequencing of cell-free DNA (cfDNA) from pregnant women's plasma using a low-coverage whole genome MPS (WGS) approach represents a valuable source for population studies. Here, we analyzed genomic data of 12,732 pregnant women from the Slovak (9,230), Czech (1,583), and Hungarian (1,919) populations. We identified 5,062 CNVs ranging from 200 kbp and described their basic characteristics and differences between the subject populations. Our results suggest that re-analysis of sequencing data from routine WGS assays has the potential to obtain large-scale CNV population frequencies, which are not well known and may provide valuable information to support the classification and interpretation of this type of genetic variation. Furthermore, this could contribute to expanding knowledge about the central European genome without investing in additional laboratory work, as NIPTs are a relatively widely used screening method. [ABSTRACT FROM AUTHOR]

This study had two main objectives. Firstly, we conducted a thorough literature review on the prenatal diagnosis of abdominal congenital arteriovenous fistulas (CAVFs) involving the abdominal aorta and hepatic arteries. Secondly, we aimed to provide detailed descriptions of eight additional cases diagnosed at our medical center and assess the outcome of this anomaly for informed counseling. We conducted a systematic search of online databases using specific keywords like "outcome", "ultrasound", "intrahepatic fistulae", and "fetal venous anomalies", focusing on studies published between 1998 and 2023. We selected 10 relevant articles and analyzed 13 cases. Additionally, we conducted a five-year prospective study in two referral centers, identifying eight CAVF cases with an incidence rate of 0.16%. Among the 21 cases evaluated, 11 resulted in live births, all of which received treatment. However, four cases (36.3%) had poor postnatal outcomes and neonatal demise due to heart failure. Prenatal signs of poor fetal hemodynamics, including cardiomegaly or hydrops, were observed in 52.3% of cases, regardless of outcome. Our findings highlight the rarity of this vascular malformation and emphasize the importance of effective treatment to avoid unfavorable outcomes. The long-term effectiveness of prenatal treatment or postnatal embolization remains uncertain, with liver transplantation being considered the most reliable treatment option. [ABSTRACT FROM AUTHOR]

NKAP mutations are associated with Hackmann‐Di Donato‐type X‐linked syndromic intellectual developmental disorder (MRXSHD, MIM: #301039). Here, we elucidate the potential prenatal manifestation of NKAP mutation‐associated disorder for the first time, alongside revealing the relationship between NKAP mutations and congenital heart defect (CHD) in the Chinese population. An NKAP mutation (NM_024528.4: c.988C>T, p.Arg330Cys) was identified in two foetuses presenting with CHD. Subsequent mechanistic exploration revealed a marked downregulation of NKAP transcription within HEK293T cells transfected with NKAP p.R330C. However, no significant change was observed at the protein level. Moreover, the mutation led to a dysregulation in the transcription of genes associated with cardiac morphogenesis, such as DHRS3, DNAH11 and JAG1. Additionally, our research determined that NKAP p.R330C affected Nkap protein intra‐nuclear distribution, and binding with Hdac3. Summarily, our study strengthens NKAP mutations as a cause of CHD and prompts the reclassification of NKAP p.R330C as likely pathogenic, thereby establishing a prospective prenatal phenotypic spectrum that provides new insight into the prenatal diagnosis of CHD. Our findings also provide evidence of NKAP p.R330C pathogenicity and demonstrate the potential mechanism by which p.R330C dysregulates cardiac developmental gene transcription by altering Nkap intra‐nuclear distribution and obstructing the interaction between Nkap and Hdac3, thereby leading to CHD. [ABSTRACT FROM AUTHOR]

Background: Maldevelopment of the fetal bowel can result in the rare condition of intestinal atresia, which results in congenital bowel obstruction. This report describes a case of prenatal diagnosis of fetal ileal atresia at 22 weeks' gestation. Case Report: Here, we present a 24-year old woman who was 22 weeks into her first pregnancy when she underwent routine fetal ultrasound. She was diagnosed with gestational diabetes mellitus. Her body mass index was normal and she had normal weight gain. The ultrasonographic examination performed revealed a hyperechoic bowel and a small dilatation of the bowel. The couple was counselled for possible intestinal atresia and its postnatal implications. At 33 weeks of gestation, polyhydramnios appeared, and the intestinal distension was much more pronounced, with hyperechoic debris in the intestinal lumen (succus-entericus). After birth, surgery was performed and we concluded the patient had type II atresia, which was surgically treated. Conclusions: This report has highlighted the importance of antenatal ultrasound in detecting fetal abnormalities, and has shown that rare conditions such as intestinal atresia can be accurately diagnosed and successfully managed. Surgical correction, if implemented promptly after stabilizing the general condition, can have a relatively good prognosis. Coexisting fetal ileal atresia and gestational diabetes mellitus are rare occurrences, which can make each condition even more difficult to treat. [ABSTRACT FROM AUTHOR]

Various soft markers can be detected in the ultrasonography of foetuses, which can be related to chromosomal abnormalities and increases the risk of abnormalities, or they can be considered as normal variations that can disappear due to the pregnancy progress. There are different tools to detect chromosomal abnormalities like conventional karyotyping, chromosomal microarray analysis (CMA), single nucleotide polymorphism (SNP) array, non-invasive prenatal test (NIPT), and non-invasive prenatal screening (NIPS). Therefore, in the present study, we aim to assess the accuracy of ultrasonic soft markers in the diagnosis of chromosomal abnormalities such as chromosomal structural abnormalities, aneuploidy, and triploidy, especially Trisomy 21 and Trisomy 18. A systemic literature search was performed using PubMed, Scopus, Google Scholar, and Web of Science. We gathered all articles published before August 2023. We selected English studies such as retrospective and cross-sectional ones that assessed the relationship between ultrasonic soft markers and foetal chromosomal abnormalities. A total of 10 articles with 18,580 cases were included in our systematic review article that assessed the foetal abnormalities and aneuploidies by using conventional karyotyping, SNP array, CMA, and NIPT (or NIPS). Trisomy 21, Trisomy 18, and chromosomal structural abnormalities were the most common abnormalities related to ultrasonic soft markers by karyotyping; however, Trisomy 13, 47, XXY, 45, X, and mosaic chromosomal abnormalities were other abnormalities detected. Results by CMA showed Trisomy 21 and Trisomy 18 as the most common abnormalities in the foetuses also with ultrasonic soft markers, and other abnormalities were pathogenic copy-number variations, Turner (XO), polyploidy, 22q11.2deletion, and Trisomy13, respectively. It was discovered that there is a greater possibility of having pathogenic copy number variations (CNVs) in the groups with multiple ultrasonic soft markers, while foetuses with ultrasonic soft markers have a decreased prevalence of CMA abnormality compared to those who had significant abnormalities or abnormal nuchal translucency. Trisomy 21 was the only abnormality found by NIPT in the groups with 1 and 2 soft markers, while groups with multiple soft markers were all normal. By using SNP array, it was identified that the rate of chromosomal abnormalities such as aneuploidy and triploidy, LOH, and CNVs was lower in the group with a single ultrasonic soft marker compared to the group with structural abnormalities in multiple systems. Trisomy 21, Trisomy 18, and chromosomal structural abnormalities were the most common chromosomal abnormalities that ultrasound soft markers could diagnose. Therefore, it is recommended to employ soft markers besides CMA, SNP array, and NIPS (or NIPT) for greater accuracy in detecting foetus abnormalities. [ABSTRACT FROM AUTHOR]

Background: Accurate prenatal diagnosis of cleft lip and palate is essential to discuss severity prediction, perform appropriate parental counseling, and, at last, establish long-term treatment planning. The aim of this systematic review was to analyze the accuracy of various imaging techniques for the prenatal diagnosis of cleft lip and palate, assess the pregnancy phase for orofacial clefts diagnosis, and study the different cleft types in terms of diagnostic methods, timing, and predictability. Methods: A search of the PubMed, EMBASE, Scopus, and Web of Science databases was conducted to identify potentially relevant studies published until January 2024. The quality of the selected articles was assessed using the Newcastle–Ottawa scale for methodological quality assessment of cohort studies and the QUADAS-2 scale for diagnostic test studies. Results: A total of 18 studies met the eligibility criteria and were included in the review. The findings of this review indicate that the majority of studies showed improved diagnostic accuracy when supplementary techniques, such as 3D ultrasound or magnetic resonance imaging, were added to 2D ultrasound. Conclusions: The implementation of magnetic resonance imaging as a standard procedure could significantly improve the precision of diagnosing cleft lip and palate. Therefore, the diagnostic technique used will play a crucial role in the accuracy of the diagnosis. [ABSTRACT FROM AUTHOR]

Background: Contemporary diagnostic methods aimed at assessing neonatal outcomes predominantly rely on the medical history of pregnant women. Ideally, universal biomarkers indicating an increased risk of delivering infants in poor clinical condition, with a heightened likelihood of requiring hospitalization in a Neonatal Intensive Care Unit (NICU), would be beneficial for appropriately stratifying pregnant women into a high-risk category. Our study evaluated whether biochemical and ultrasonographical markers universally used in first-trimester screenings for non-heritable chromosomal aberrations could serve this purpose. Methods: This study encompassed 1164 patients who underwent first-trimester screening, including patient history, ultrasound examinations, and biochemical tests for pregnancy-associated plasma protein-A (PAPP-A) and the free beta-HCG subunit (fbHCG), from January 2019 to December 2021. The research concentrated on the correlation between these prenatal test results and neonatal outcomes, particularly Apgar scores, umbilical blood pH levels, and the necessity for NICU admission. Results: In our cohort, neonates scoring lower than 8 on the Apgar scale at birth exhibited lower concentrations of PAPP-A in the first trimester, both in raw and normalized values (PAPP-A MoM 0.93 vs. 1.027, p = 0.032). We also observed a higher pulsatility index in the venous duct in the first trimester in full-term neonates born with <8 points on the Apgar scale. Additionally, newborns born with an umbilical blood pH < 7.2 had lower normalized first-trimester PAPP-A concentrations (0.69 vs. 1.01 MoM, p = 0.04). We also noted that neonates requiring NICU hospitalization post-delivery had lower first-trimester bHCG concentrations (0.93 MoM vs. 1.11 MoM, p = 0.03). However, none of the correlations in our study translated into a robust prognostic ability for predicting dichotomous outcomes. All areas under the curve achieved a value < 0.7. Conclusions: Low concentrations of PAPP-A and free bHCG subunit in the first trimester may be associated with poorer clinical and biochemical conditions in neonates post-delivery. However, the relationship is weak and has limited predictive capability. Further research evaluating these relationships is necessary for the appropriate stratification of pregnant women into high-risk categories for neonatological complications. [ABSTRACT FROM AUTHOR]

Background: Congenital toxoplasmosis (CT) can be accompanied by serious organ manifestations, particularly retinochoroiditis, and may occur throughout life. We aimed to monitor long-term ocular prognosis in a large French cohort of patients with CT and its changes over time in the context of mandatory prenatal screening (since 1992) and incidence decrease since 2008. Methods: Patients with CT diagnosed between 1987 and 2021 were prospectively included and followed for up to 35 years. The effect of the period of conception on the risk of first retinochoroiditis has been tested using a flexible extension of the Cox model. Incidence rates of retinochoroiditis were estimated. Results: A total of 646 infected live born children were followed for a median of 12 years (range, 0.5-35); 187 patients (29%) had at least 1 ocular lesion (first at a median age of 5 years; range, 0-26 years) with peaks at 7 and 12 years. Early maternal infection and the presence of nonocular signs at birth were associated with a higher risk of retinochoroiditis, whereas delayed diagnosis of CT (after birth versus before or at birth) was associated with a lower risk (13% decrease for each additional month after birth; P = .01). A period effect for the risk of developing retinochoroiditis in patients born after 2008 was not detected. Conclusions: Despite prenatal screening and prolonged perinatal treatment, retinochoroiditis is not a rare event in French patients with CT and can occur well into adulthood, with peak incidences at 7 and 12 years of age. It rarely causes severe damage but warrants regular follow-up into adulthood. [ABSTRACT FROM AUTHOR]

Conjoined twins have an estimated prevalence between one in 50,000 and one in 1,00,000 births. Prenatal two- and threedimensional (2D and 3D) real-time ultrasonography is the most reliable method for establishing a prenatal diagnosis and detecting associated anomalies. Recent improvements in ultrasonography have made early diagnosis of conjoined fetuses in the first trimester possible. Most cases of conjoined twins occur in monochorionic monoamniotic pregnancies, making sonographic identification of distinct placentae and/or intervening amniotic membrane(s) a criterion to exclude fetal conjunction. There are two opposing pathogenetic theories, supporting fission vs fusion of embryos in the early first trimester. In very rare cases of diamniotic monochorionic conjoined twins, a distinct pathogenetic mechanism of conjoined twinning, similar to that of body stalk anomaly may exist. Prenatal diagnosis of conjoined fetuses is essential for further management. Parents need detailed counseling in order to decide among various management options--(1) pregnancy continuation and scheduled neonatal surgery, (2) termination of pregnancy, and (3) multifetal pregnancy reduction or selective fetocide in cases of high-order multifetal pregnancies with a component of conjoined fetuses. Pre- and postnatal management is challenging, and an interdisciplinary medical team involving obstetricians, neonatologists, pediatric surgeons, and anesthetists should carefully approach and assist parents in their decisions. In special cases, additional consultation by specialized centers in other countries may be needed. Furthermore, adequate psychosocial support should be offered, and palliative care services should be available in selected cases. [ABSTRACT FROM AUTHOR]

Skeletal dysplasias are a heterogeneous group of bone growth disorders resulting in abnormal shape and/or size of the skeleton involving bone and cartilage structures. The current classification is based upon either descriptive findings or the presumed pathogenesis of the disease. The classification system most commonly used is the International Nomenclature and Classification of Constitutional Disorders of Bone. There are now over 33 osteochondrodysplasias groups and 3 genetically determined dysostoses. The prevalence of skeletal dysplasias identified at birth is approximately 2.4/10,000 births. The overall frequency of skeletal dysplasias among perinatal deaths is approximately 9.1/1000. While more than 200 different skeletal dysplasias have been described, the number that can be recognized by ultrasound in the antenatal period is far fewer. The antenatal diagnosis of skeletal dysplasia can be difficult. The challenge involves not only accurately identifying the fetus affected with an abnormal skeleton but also accurately diagnosing the skeletal abnormality and predicting the fetal outcome. The majority of skeletal dysplasias are diagnosed after the first trimester. Approximately 50% will be diagnosed prior to 24 weeks. The accurate antenatal diagnosis of skeletal dysplasias is good at 60--65%, with approximately 19% being missed diagnosed, in 21% the diagnosis was imprecise. Ultrasound can be a valuable tool not only in identifying the potentially affected fetus but also in counseling the parents regarding the potential outcome and options for pregnancy management. [ABSTRACT FROM AUTHOR]

Triploidy and monosomy X (Turner syndrome) are the two most common chromosomal anomalies at conception. Their prevalence decreases with increasing gestational age (GA), and they are relatively rare at birth. These genetic conditions can be prenatally or postnatally detected by karyotyping [chromosome analysis of fetal cells collected by chorionic villous sampling (CVS) or amniocentesis or blood lymphocytes]. Triploidy is caused by a complete extra set of chromosomes (the presence of 69 chromosomes). If the extra set of chromosomes is maternal in origin, the disease is called digynic triploidy, while if the extra set of chromosomes is paternal in origin, the disease is called diandric triploidy. Triploidy is lethal, most affected embryos are miscarried; however, some individuals survive a few hours or days after birth. Turner syndrome is an aneuploidy (monosomy X) in which only one chromosome X is present, and the other sex chromosome is either absent or abnormal. Severe forms of Turner syndrome present major fetal anomalies, including fetal hydrops and usually progress to early fetal demise (the lethal Turner phenotype). Postnatally, Turner syndrome presents as a form of primary ovarian insufficiency, determined by a gonadic digenesis (not by agenesis). Both triploidy and Turner syndrome must be taken in consideration if sonography reveals minor or major abnormalities in the first or second trimester of pregnancy. Active screening in the general pregnant population is not justified for these conditions alone. Both conditions can be diagnosed prenatally in individual cases. [ABSTRACT FROM AUTHOR]

We report a case of fetal nasal chondromesenchymal hamartoma (NCMH) first noted on prenatal ultrasound at 34 weeks. A solid‐cystic mass which predominantly hyperechoicgenic and relatively clear margin, was located on the left nasal cavity and pharynx, with anterior extension and moderate blood flow. Further follow‐up ultrasound examination depicted an enlargement of the tumor. Fetal magnetic resonance imaging (MRI) showed an inhomogeneous signal lesion involving the ethmoid sinuses, nasal cavity, and pharynx. The infant, delivered via cesarean section at 37 + 5 weeks, required urgent neonatology intervention due to respiratory difficulties. Neonatal MRI and computer tomography were subsequently performed at 1 day after birth. Surgical excision occurred at 7 days, confirming NCMH via histological examination. Awareness of this entity, is essential to avoid potentially harmful therapies, especially in prenatal period. Considered NCMH in diagnosis when fetal nasal masses presenting with predominantly high‐level echo, well‐defined margins and moderate vascularity. [ABSTRACT FROM AUTHOR]

This study represents our second investigation into NIPT, involving a more extensive patient cohort with a specific emphasis on the high-risk group. The high-risk group was subsequently divided into two further groups to compare confirmed cases versus unconfirmed via direct methods. The methodology encompassed the analysis of 1400 consecutive cases from a single genetic center in western Romania, where NIPT was used to assess the risk of specific fetal chromosomal abnormalities. All high-risk cases underwent validation through direct analysis of fetal cells obtained via invasive methods, including chorionic villus sampling and amniocentesis. The confirmation process utilized QF-PCR, karyotyping, and SNP-Array methods customized to each case. Results: A high risk of aneuploidy at NIPT was identified in 36 out of 1400 (2.57%) cases and confirmed in 28 cases. The study also detected an increased risk for copy number variations (CNVs) in 1% of cases, confirmed in two instances involving one large microdeletion and one large microduplication. Trisomy 21 was the exclusive anomaly where NIPT confirmed all cases with identified risk. High-risk NIPT results which were not validated by invasive methods, were classified as false positives; parents in these cases determined to continue the pregnancy. In conclusion, NIPT can serve as a screening method for all pregnancies; however, in high-risk cases, an invasive confirmation test is strongly recommended. [ABSTRACT FROM AUTHOR]

Congenital anomalies of the kidney and urinary tract are collectively one of the most commonly diagnosed antenatal conditions. Clinicians have several tools available to diagnose anomalies, including imaging, biomarkers, family history and genetic studies. In certain cases, antenatal interventions such as vesico-amniotic shunting may be considered to improve postnatal outcomes. Congenital kidney anomalies detected antenatally can vary in clinical significance from almost no impact postnatally to significant morbidity and perinatal mortality. Prognosis broadly depends on kidney size, structure and amount of amniotic fluid, alongside genetics and family history, and progression on subsequent scans. It is important to counsel parents appropriately using a parent-focused and personalised approach. The use of a multidisciplinary team should always be considered. [ABSTRACT FROM AUTHOR]

Due to recent news coverage of noninvasive prenatal testing (NIPT) technology, in combination with an increase in political rhetoric around women's reproductive health and choice, I explore how language is used for promotional materials of the top 10 NIPT brands in the U.S. and convey dominant/hegemonic messages of comfort, confidence, and trustworthiness despite concerns about NIPT technology. A reflexive thematic analysis showed patterns of reliance on discourses on motherhood, parenting, and reproduction to advertise products and, conversely, a lack of the "full picture" of prenatal testing on company websites. From these results, we can gather that the potential interpretation of the website language could have more significant implications, like the premature termination of pregnancies, the increased chance of depression, and over-reliance on health information listed on the Internet. Ultimately, the language on NIPT company websites may influence decision-making and reinforce the more "powerful" messages that could potentially harm women. [ABSTRACT FROM AUTHOR]

Adverse prenatal diagnoses, regardless of the women's choice of continuing the pregnancy or terminating it, can impact a women's psychological and psychosocial wellbeing. Supportive interventions during this time are important. However, understanding what is deemed useful and best practice is complex and multifaceted. To understand the need for support during this time, the authors undertook a research study where 12 women were interviewed. The women spoke about feeling pressured by time in making a decision regarding their pregnancy option and having limited psychoeducation and support provided. They also spoke about post-traumatic growth in their grief experience. To assist health professionals, the authors have addressed the following areas in the study's findings and discussion sections: the lack of appropriate information delivery skills of the professionals, the need for an assessment of each woman's unique needs, the need for appropriate referrals to be given, and the need for appropriate follow-ups of the women. The SARF (Skills, Assessment, Referral, and Follow-up) model, presented in this article as a synthesis of this research, has the potential to inform the development of clinical services and social work practice to support women's care following adverse prenatal diagnosis. IMPLICATIONS Psychosocial assessments are vital in providing good quality care to women after a poor prenatal diagnosis. The model can provide guidance to ensure that psychosocial assessments and explorations of values are undertaken before referring women to follow-up services. Given social workers' experience in providing psychosocial assessments and their recommendations, social work clinicians should be utilised in health settings to their full scope of practice. [ABSTRACT FROM AUTHOR]

Spinal dysraphisms are amenable to diagnosis in utero. The prognosis and the neonatal management of these conditions differ significantly depending on their types, mainly on the distinction between open and closed defects. A detailed evaluation not only of the fetal spine, but also of the brain, skull, and lower limbs is essential in allowing for the right diagnosis. In this article, recommendations from the Fetal Task Force of the European Society of Paediatric Radiology (ESPR) and the European Society of Neuroradiology (ESNR) Pediatric Neuroradiology Committee will be presented. The aim of this paper is to review the imaging features of the normal and abnormal fetal spinal cord, to clarify the prenatal classification of congenital spinal cord anomalies and to provide guidance in their reporting. [ABSTRACT FROM AUTHOR]

Background: Despite recent advances in prenatal genetic diagnosis, medical geneticists still face considerable difficulty in interpreting the clinical outcome of copy‐number‐variant duplications and defining the mechanisms underlying the formation of certain chromosomal rearrangements. Optical genome mapping (OGM) is an emerging cytogenomic tool with proved ability to identify the full spectrum of cytogenetic aberrations. Methods: Here, we report on the use of OGM in a prenatal diagnosis setting. Detailed breakpoint mapping was used to determine the relative orientations of triplicated and duplicated segments in two unrelated foetuses harbouring chromosomal aberrations: a de novo 15q23q24.2 triplication and a paternally inherited 13q14.2 duplication that overlapped partially with the RB1 gene. Results: OGM enabled us to suggest a plausible mechanism for the triplication and confirmed that the RB1 duplication was direct oriented and in tandem. This enabled us to predict the pathogenic consequences, refine the prognosis and adapt the follow‐up and familial screening appropriately. Conclusion: Along with an increase in diagnostic rates, OGM can rapidly highlight genotype–phenotype correlations, improve genetic counselling and significantly influence prenatal management. [ABSTRACT FROM AUTHOR]

Background: To explore the clinical application value of pre‐conception expanded carrier screening (PECS) in the Chinese Han ethnicity population of childbearing age. Methods: The results of genetic testing of infertile parents who underwent PECS in the Reproductive Medicine Center of the Second Affiliated Hospital of Zhengzhou University, China, from September 2019 to December 2021, were retrospectively analyzed. The carrier rate of single gene disease, the detection rate of high‐risk parents, and the clinical outcome of high‐risk parents were statistically analyzed. Results: A total of 1372 Chinese Han ethnicity patients underwent PECS, among which 458 patients underwent the extended 108‐gene test, their overall carrier rate was 31.7%, and the detection rate of high‐risk parents was 0.3%. The highest carrier rates were SLC22A (2.4%), ATP7B (2.4%), MMACHC (2.2%), PAH (1.8%), GALC (1.8%), MLC1 (1.3%), UNC13D (1.1%), CAPN3 (1.1%), and PKHD1 (1.1%). There were 488 women with fragile X syndrome—FMR1 gene detection, and 6 patients (1.2%) had FMR1 gene mutation. A total of 426 patients were screened for spinal muscular atrophy—SMN1, and the carrier rate was 3.5%, and the detection rate of parents' co‐carrier was 0.5%. Conclusion: Monogenic recessive hereditary diseases had a high carrier rate in the population. Pre‐pregnancy screening could provide good prenatal and postnatal care guidance for patients and preimplantation genetic testing for monogenic/single gene disorders (PGT‐M) and prenatal diagnosis could provide more precise reproductive choices for high‐risk parents. [ABSTRACT FROM AUTHOR]

Abdominal compartment syndrome (ACS) is a rare complication of extracorporeal membrane oxygenation (ECMO) and is associated with high morbidity and mortality. Despite being the treatment of choice for ACS, decompressive laparotomy (DL) has been a matter of debate in children supported with ECMO due to high bleeding risk and presumed futility. We report the first neonatal DL for ACS while on ECMO following congenital diaphragmatic hernia (CDH) repair. Given its excellent outcomes, our case challenges current literature and supports prompt bedside laparotomy to treat ACS on neonatal ECMO. [ABSTRACT FROM AUTHOR]

Purpose: Fetal karyotyping is commonly used to detect chromosomal abnormalities in high-risk pregnancies. Our study is intended to evaluate the results of fetal karyotyping performed in our laboratory for six years and to determine the frequency of chromosomal abnormalities, thus revealing their clinical significance. Materials and Methods: The cytogenetic results of 661 prenatal samples with an indication for invasive prenatal procedures (amniocentesis, cordocentesis) who had a chromosome analysis and FISH testing between February 2013 and March 2019 were analyzed in our study. Results: A total of 72 (10.8%) abnormal fetal karyotypes were observed in the study group. Trisomy 21 was the most common numerical aberration (29%, n = 23), followed by trisomy 18 (16%, n = 13), trisomy 13 (2.6%, n = 2), triploid (2.6%, n = 2), sex chromosome aneuploidies (5.2%, n = 4), and rare mosaic autosomal aneuploidies (2.6%, n = 2). Inversions (16%, n = 13), inherited translocations (7.8%, n = 6), unbalanced/de novo translocations (6.5%, n = 5), d eletions (5.2%, n = 4), additional chromosomes (1.3%, n = 1), isochromosomes (1.3%, n = 1), and derivative chromosomes (1.3%, n = 1) were identified as structural abnormalities. Of the 18 cases that underwent FISH testing, trisomy 18 was detected in 1 case and tetrasomy 12p was detected in 1 case. Conclusion: Fetal karyotyping is still an effective and valuable method in the diagnosis of fetal anomalies and provision of effective genetic counseling. In addition, fetal karyotyping should be supported by complementary methods and advanced technologies for accurate and rapid prenatal genetic diagnosis. [ABSTRACT FROM AUTHOR]

To report the prevalence of coarctation of the aorta (CoA) in fetuses with single left superior vena cava (SL-SVC) and to evaluate changes in echocardiographic measurements. Additionally, to report the prevalence of associated malformations. Retrospective observational study of fetuses diagnosed with SL-SVC between 2012 and 2021 at a tertiary fetal cardiology unit. In fetuses without intracardiac abnormalities, Z-scores of the ventricles, great arteries, and Doppler flow patterns are reported. We identified 47 fetuses with SL-SVC of which 8/47 (17%) had abnormal intracardiac anatomy. One fetus was lost to follow-up. Of those with normal intracardiac anatomy and postnatal follow-up (38), karyotype abnormalities were confirmed in 2/38 (5%) and ECA in 8/38 (21%). 33/38 were live-born. None developed CoA postnatally. Paired analysis of Z-scores between early and late scans of 24 fetuses showed that diameters of the right heart structures and Doppler flows of tricuspid valve increased significantly during pregnancy, while the left heart structures and flow patterns did not change. The median risk of CoA did not change between the early and the late scan. We did not observe CoA in this cohort. A degree of ventricular asymmetry was present, but this was due to right heart dominance rather than hypoplasia of left heart structures. This likely reflects redistribution of blood and does not appear to confer increased risk of CoA. Predictive models of the postnatal development of CoA which set the dimensions of right and left heart structures in relation might not be applicable in this situation. [ABSTRACT FROM AUTHOR]

Objective: Harlequin ichthyosis (MIM 242500) is a rare autosomal recessive skin disorder caused by a congenital disorder of epidermal keratinization and associated with a mutation in the ABCA12 gene of chromosome 2q35. We report a case of a fetus at 25 weeks of gestation with harlequin ichthyosis and a deletion of chromosome 15q11.2-q12. Case(s): The results of an ultrasound examination at 13 weeks 2 days and 18 weeks of pregnancy showed no pathology. Two previous male children were presumably born with harlequin ichthyosis (genetic diagnosis was not performed due to unavailability at that time) and died on the first day of life. Analysis of amniotic fluid using SNP - array technology at 23 weeks revealed a deletion of 15q11.2-q12. Subsequent ultrasound examination at 25 weeks of pregnancy showed signs of harlequin ichthyosis, including an abnormal flat facial profile, a constantly open large mouth, and a large number of inclusions in the amniotic fluid. Considering the family history, a diagnosis of harlequin ichthyosis was made, leading the family to decide to terminate the pregnancy. A male child was born, weighing 800 g, with a typical harlequin ichthyosis phenotype, and died 2 hours after birth. Conclusion: In case of a suspicion of this disease in a family, prenatal diagnosis of harlequin ichthyosis can be carried out by prenatal chromosomal microarray analysis using tissue obtained from chorionic villus sampling, amniocentesis or cordocentesis in the early terms of pregnancy. Ultrasound signs of the disease typically manifest after 24 weeks of pregnancy. [ABSTRACT FROM AUTHOR]

Key Clinical Message: An encephalocele is a congenital malformation characterized by protrusion of the intracranial contents through a cranial defect. We report that a fetus of a pregnant mother who had two consecutive pregnancies with ultrasound‐detected encephalocele carried compound heterozygous variants in B3GALNT2 NM_152490.5:c.[1423C > T (p.Gln475Ter)]; [261‐2A > G] of maternal and paternal origins, respectively, as confirmed by exome sequencing followed by Sanger sequencing validation. The present case implies that mutations in B3GALNT2, a well‐known dystroglycanopathy causative gene, may result in a phenotype of neural tube defect, providing new insights into the clinical spectrum of B3GALNT2‐related disorders. Our study may contribute to prenatal screening/diagnosis and genetic counseling of congenital brain malformations. [ABSTRACT FROM AUTHOR]

Introduction Twin-twin transfusion syndrome (TTTS) is a typical complication of monochorionic twin pregnancies (MCTP). Placental vessels that communicate in the chorionic plate between donor and recipient, are responsible for the imbalance of blood flow. Circulatory imbalance causes hypovolemia in donor and hypervolemia in recipient fetus. In a typical case, recipient fetus develops polyhydramnios, weight gain, cardiomegaly and hydrops fetalis. In contrast, donor fetus develops oligohydramnios and fetal growth restriction. Aim The objective of this review is to evaluate in detail the main diagnostic aspects and add other important data for diagnosis of TTTS. Scientific bases The main diagnostic event for this condition is based on the ultrasonographic discovery of oligohydramnios-polyhydramnios sequence. Other useful elements for diagnosis, staging and prognosis are fetal urinary bladder visualization, urinary bladder volumen measurements, edema of subcutaneous and/or generalized tissue edema, Doppler flow velocity waves and cardiac evaluation. Conclusion Considerations regarding diagnosis of TTTS make it possible to emphasize that role of physicians treating patients with MCTP is to identify ultrasound sequence of oligohydramnios-polyhydramnios. Other ultrasonographic fetal data as fetal urinary bladder visualization, urinary bladder volumen measurements, edema of subcutaneous and/or generalized tissue edema, Doppler flow velocity waves and cardiac evaluation; may help diagnosis, staging and prognosis of TTTS. It is their responsibility to accurately assess severity, therapeutic possibilities and prognosis. Key Points The role of physicians treating patients with MCTP, regarding diagnosis of TTTS, must be to identify ultrasound sequence of oligohydramnios–polyhydramnios. Other ultrasonographic fetal data may help diagnosis, staging, and prognosis of TTTS as follows: fetal urinary bladder visualization, urinary bladder volume measurements, edema of subcutaneous and/or generalized tissue edema, Doppler flow velocity waves, and cardiac evaluation. It is physicians' responsibility to accurately assess severity, therapeutic possibilities, and prognosis of patients with MCTP and diagnosis of TTTS. [ABSTRACT FROM AUTHOR]

The Congenital Diaphragmatic Hernia Study Group (CDHSG) is an international consortium of medical centers actively collecting and voluntarily contributing data pertaining to live born congenital diaphragmatic hernia (CDH) patients born and/or managed at their institutions. These data are aggregated to construct a comprehensive registry that participating centers can access to address specific clinical inquiries and track patient outcomes. Since its establishment in 1995, 147 centers have taken part in this initiative, including 53 centers from 17 countries outside the United States, with 95 current active centers across the globe. The registry has amassed data on over 14,000 children, resulting in the creation of over 75 manuscripts based on registry data to date. International, multicenter consortia enable health care professionals managing uncommon, complex, and diverse diseases to formulate evidence-based hypotheses and draw meaningful and generalizable conclusions for clinical inquiries. This review will explore the formation and structure of the CDHSG and its registry, outlining their functions, center participation, and the evolution of data collection. Additionally, we will provide an overview of the evidence generated by the CDHSG, with a particular emphasis on contributions post-2014, and look ahead to the future directions the study group will take in addressing CDH. [ABSTRACT FROM AUTHOR]

Background: The objective of our study to analyze the data of the prenatal diagnosis of congenital malformations at the maternity and reproductive health hospital "Les Orangers" in Rabat and to identify the main anomalies detected, their percentage and their short-term outcome. Methods: This is a cross-sectional study conducted at the maternity and reproductive health hospital "Les Orangers" in Rabat, Morocco. The data was collected and reported on pre-established sheets and on the register of malformations of the hospital. Results: A total of 245 cases of congenital malformations comprising 470 types of congenital malformations were recorded out of a total of 43,923 births over a period of five and a half years, giving a prevalence of 5.58 per thousand. Prenatal diagnosis was made in a third of cases (33%), essentially during the 2nd-3rd trimester of pregnancy. The anomalies revealed by this antenatal diagnosis were dominated by urinary malformations in 70% and central nervous system anomalies in 67%, followed by other types of congenital anomalies in less than 40% of cases, while genetic problems were detected in 2.5%; this rate is underestimated since chromosomal abnormalities sometimes appear as syndromes, so that in some diseases, genetic changes are not separated from other abnormalities, and since more than half (50.7%) of cases presenting polymalformative syndromes not survived 77% of cases i.e. (48.5% of deaths and 28.5% of FDIU) and an etiological study was not carried out. Conclusion: Antenatal ultrasound allows early detection and monitoring of the evolution of congenital malformations, and thus the possibility of ensuring early and adequate management of these anomalies from birth. In our context, it is necessary to develop a prenatal screening program for congenital anomalies and a network of reference centers for the management of these anomalies in order to improve their prognosis. [ABSTRACT FROM AUTHOR]

Introduction. Anophthalmia and microphthalmia are orbito-facial developmental disorders characterized by deficient growth and impaired visual capability [1]. These rare disorders may be unilateral or bilateral. Congenital anophthalmia is the complete absence of the eye [2,3]. The prevalence of both conditions is estimated at 0.2-3 per 10,000 births [4]. We report a case of congenital bilateral anophthalmia that was undetected during follow-up but diagnosed after birth. Case Description. 24-year-old Bahraini female, who is not a known case of any medical illnesses, primigravida at 39+6 weeks of gestation gave birth to a live male baby via vacuum extraction delivery due to recurrent variable decelerations and poor maternal effort. On physical examination, bilateral anophthalmia was immediately observed. No other anomalies were detected. The investigations ordered were MRI brain and orbit, which showed: Absence of bilateral eye globes-features of bilateral anophthalmia. We advised the parents the baby will need socket expansion/conformer placement to maintain facial symmetry and cosmetic outcome with neurocognitive and development assessment every 2 months as well as speech and language evaluation. Conclusion. Although many probable factors leading to anophthalmia are suggested, many cases arise idiopathically. Due to the nature of the defect, oftentimes prenatal diagnosis with routine scans is challenging. Therefore, more research into probable causes will prompt the healthcare professional to use more sensitive studies to detect the anomaly prenatally to potentially reduce the psychological and financial impact on the parents. [ABSTRACT FROM AUTHOR]

There is some evidence that in twin reversed arterial perfusion sequence, intervention at early gestational age could prevent a spontaneous death of the pump twin, achieving a better global survival. To review the perinatal outcomes of early intervention in pregnancies complicated by twin reversed arterial perfusion (TRAP) sequence. A comprehensive search from inception to December 2022 was conducted on databases including MEDLINE, EMBASE, Cochrane Library and LILACS. All studies that reported intervention in twin or triplet pregnancy complicated with TRAP sequence at 12 + 0 to 16 + 6 weeks of gestation were eligible. A descriptive and bivariate analysis was performed. Out of the 222 full-text articles, 44 studies reporting 108 cases of early intervention in TRAP sequence were included. A successful procedure was achieved in 105 (95.5 %) interventions: 89 (94.7 %) among twin pregnancies and 16(100 %) among triplet pregnancies. An overall livebirth rate was achieved in 75 patients (70.8 %): intrafetal laser group 55 (73.3 %), radiofrequency 10 (76.9 %) and endoscopic laser 3 (75.0 %). The median gestational age at delivery was 38 + 0 (37 + 4 – 39 + 4) weeks. The median treatment–delivery interval was 23 + 2 (IQR, 21 + 0–25 + 6) weeks. The most frequent adverse outcomes reported were preterm labor in 7 (13.7 %) patients. There were no severe adverse maternal outcomes. Early intervention with intrafetal laser and radiofrequency in TRAP sequence achieves a livebirth rate of the pump twin of about 75 %. [ABSTRACT FROM AUTHOR]

• The risk of vertical transmission is higher in primary compared to non-primary infection, but there are no differences in terms of long-term sequelae once congenital infection has been established. • Ultrasound is the primary imaging modality to evaluate fetuses with congenital CMV infection. However, the positive predictive value of ultrasound is poor in the absence of confirmed fetal infection with amniocentesis. • MRI should be used to detect anomalies not easily identified by ultrasound and should be recommended in all pregnant women with positive amniocentesis at 28–32 weeks of gestation. • Early gestational age at maternal infection is one of the main determinants of post-natal adverse outcome in fetuses with congenital CMV infection. • Maternal therapy with high dose valacyclovir (2 g every 6 h, 8 g/day) can reduce the risk of vertical transmission, the symptomatic status and other adverse outcomes associated with congenital CMV infection, while HIG is not recommended. Although the clinical work-up of CMV in pregnancy has gradually become more accurate, counseling for CMV is still challenging. Despite the potential feasibility of universal prenatal serological screening, its introduction in prenatal diagnosis continues to raise concerns related to its real cost-effectiveness. Contextually, anticipating the confirmation of fetal infection earlier in pregnancy is one of the most pressing issues to reduce the parental psychological burden. Amniocentesis is still the gold standard and recent data have demonstrated that it could be performed before 20 weeks of gestation, provided that at least 8 weeks have elapsed from the presumed date of maternal seroconversion. New approaches, such as chorionic villus sampling (CVS) and virome DNA, even if not yet validated as confirmation of fetal infection, have been studied alternatively to amniocentesis to reduce the time-interval from maternal seroconversion and the amniocentesis results. Risk stratification for sensorineural hearing loss (SNHL) and long-term sequelae should be provided according to the prognostic predictors. Nevertheless, in the era of valacyclovir, maternal high-dose therapy, mainly for first trimester infections, can reduce the risk of vertical transmission and increase the likelihood of asymptomatic newborns, but it is still unclear whether valacyclovir continues to exert a beneficial effect on fetuses with positive amniocentesis. This review provides updated evidence-based key counseling points with GRADE recommendations. [ABSTRACT FROM AUTHOR]

Objective: To determine the diagnostic accuracy of prenatal ultrasound in detecting coarctation of the aorta (CoA). Methods: An individual participant data meta‐analysis was performed to report on the strength of association and diagnostic accuracy of different ultrasound signs in detecting CoA prenatally. MEDLINE, EMBASE and CINAHL were searched for studies published between January 2000 and November 2021. Inclusion criteria were fetuses with suspected isolated CoA, defined as ventricular and/or great vessel disproportion with right dominance on ultrasound assessment. Individual participant‐level data were obtained by two leading teams. PRISMA‐IPD and PRISMA‐DTA guidelines were used for extracting data, and the QUADAS‐2 tool was used for assessing quality and applicability. The reference standard was CoA, defined as narrowing of the aortic arch, diagnosed after birth. The most commonly evaluated parameters on ultrasound, both in B‐mode and on Doppler, constituted the index test. Summary estimates of sensitivity, specificity, diagnostic odds ratio (DOR) and likelihood ratios were computed using the hierarchical summary receiver‐operating‐characteristics model. Results: The initial search yielded 72 studies, of which 25 met the inclusion criteria. Seventeen studies (640 fetuses) were included. On random‐effects logistic regression analysis, tricuspid valve/mitral valve diameter ratio > 1.4 and > 1.6, aortic isthmus/arterial duct diameter ratio < 0.7, hypoplastic aortic arch (all P < 0.001), aortic isthmus diameter Z‐score of < −2 in the sagittal (P = 0.003) and three‐vessel‐and‐trachea (P < 0.001) views, pulmonary artery/ascending aorta diameter ratio > 1.4 (P = 0.048) and bidirectional flow at the foramen ovale (P = 0.012) were independently associated with CoA. Redundant foramen ovale was inversely associated with CoA (P = 0.037). Regarding diagnostic accuracy, tricuspid valve/mitral valve diameter ratio > 1.4 had a sensitivity of 72.6% (95% CI, 48.2–88.3%), specificity of 65.4% (95% CI, 46.9–80.2%) and DOR of 5.02 (95% CI, 1.82–13.9). The sensitivity and specificity values were, respectively, 75.0% (95% CI, 61.1–86.0%) and 39.7% (95% CI, 27.0–53.4%) for pulmonary artery/ascending aorta diameter ratio > 1.4, 47.8% (95% CI, 14.6–83.0%) and 87.6% (95% CI, 27.3–99.3%) for aortic isthmus diameter Z‐score of < –2 in the sagittal view and 74.1% (95% CI, 58.0–85.6%) and 62.0% (95% CI, 41.6–78.9%) for aortic isthmus diameter Z‐score of < –2 in the three‐vessel‐and‐trachea view. Hypoplastic aortic arch had a sensitivity of 70.0% (95% CI, 42.0–88.6%), specificity of 91.3% (95% CI, 78.6–96.8%) and DOR of 24.9 (95% CI, 6.18–100). The diagnostic yield of prenatal ultrasound in detecting CoA did not change significantly when considering multiple categorical parameters. Five of the 11 evaluated continuous parameters were independently associated with CoA (all P < 0.001) but all had low‐to‐moderate diagnostic yield. Conclusions: Several prenatal ultrasound parameters are associated with an increased risk for postnatal CoA. However, diagnostic accuracy is only moderate, even when combinations of parameters are considered. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To compare the performance of two‐dimensional ultrasound (2D‐US), three‐dimensional ultrasound (3D‐US) and magnetic resonance imaging (MRI) at 36 weeks' gestation in predicting the delivery of a large‐for‐gestational‐age (LGA) neonate, defined as birth weight ≥ 95th percentile, in patients at high and low risk for macrosomia. Methods: This was a secondary analysis of a prospective observational study conducted between January 2017 and February 2019. Women with a singleton pregnancy at 36 weeks' gestation underwent 2D‐US, 3D‐US and MRI within 15 min for estimation of fetal weight. Weight estimations and birth weight were plotted on a growth curve to obtain percentiles for comparison. Participants were considered high risk if they had at least one of the following risk factors: diabetes mellitus, estimated fetal weight ≥ 90th percentile at the routine third‐trimester ultrasound examination, obesity (prepregnancy body mass index ≥ 30 kg/m2) or excessive weight gain during pregnancy. The outcome was the diagnostic performance of each modality in the prediction of birth weight ≥ 95th percentile, expressed as the area under the receiver‐operating‐characteristics curve (AUC), sensitivity, specificity and positive and negative predictive values. Results: A total of 965 women were included, of whom 533 (55.23%) were high risk and 432 (44.77%) were low risk. In the low‐risk group, the AUCs for birth weight ≥ 95th percentile were 0.982 for MRI, 0.964 for 2D‐US and 0.962 for 3D‐US; pairwise comparisons were non‐significant. In the high‐risk group, the AUCs were 0.959 for MRI, 0.909 for 2D‐US and 0.894 for 3D‐US. A statistically significant difference was noted between MRI and both 2D‐US (P = 0.002) and 3D‐US (P = 0.002), but not between 2D‐US and 3D‐US (P = 0.503). In the high‐risk group, MRI had the highest sensitivity (65.79%) compared with 2D‐US (36.84%, P = 0.002) and 3D‐US (21.05%, P < 0.001), whereas 3D‐US had the highest specificity (98.99%) compared with 2D‐US (96.77%, P = 0.005) and MRI (96.97%, P = 0.004). Conclusions: At 36 weeks' gestation, MRI has better performance compared with 2D‐US and 3D‐US in predicting birth weight ≥ 95th percentile in patients at high risk for macrosomia, whereas the performance of 2D‐US and 3D‐US is comparable. For low‐risk patients, the three modalities perform similarly. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Cervical and oropharyngeal teratomas are rare forms of congenital tumors. External compression of the respiratory tract is the major complication. Due to their high mortality, it is very important to establish prenatal diagnosis using ultrasound and fetal magnetic resonance imaging to plan airway management at birth and its eventual resection. If respiratory obstruction due to the tumor is suspected, an EXIT procedure is performed. We describe a case of a cervical teratoma and another of an oropharyngeal teratoma, along with their imaging studio and a literature review. [ABSTRACT FROM AUTHOR]

A single-center retrospective study of G-band karyotyping and chromosomal microarray analysis (CMA) for the invasive prenatal diagnosis of 6159 fetuses with ultrasound abnormalities was conducted. This study aimed to investigate the incidence rates of chromosomal abnormalities and pregnancy outcomes and postpartum clinical manifestations by long-term follow-up and to explore the correlation between different types of prenatal ultrasound abnormalities and pathogenic chromosomal abnormalities. The overall incidence of pathogenic chromosomal aberrations in fetuses with ultrasound abnormalities was 7.58% (467/6159), which comprised 41.7% (195/467) with chromosome number abnormalities, 57.6% (269/467) with pathogenic copy-number variations (pCNVs), and 0.64% (3/467) with uniparental disomy (UPD). In addition, 1.72% (106/6159) with likely pathogenic copy-number variations (lpCNVs) and 3.04% (187/6159) with variants of unknown significance (VOUS) were detected by CMA. Ultrasound abnormalities were categorized into structural anomalies and soft marker anomalies. The incidence rate of pathogenic and likely pathogenic chromosomal abnormalities was significantly higher among fetuses with structural anomalies than soft markers (11.13% vs 7.59%, p < 0.01). We retrospectively analyzed the prenatal genetic outcomes for a large cohort of fetuses with different types of ultrasound abnormalities. The present study showed that the chromosomal abnormality rate and clinical outcomes of fetuses with different types of ultrasound abnormalities varied greatly. Our data have important implications for prenatal genetic counseling for fetuses with different types of ultrasound abnormalities. [ABSTRACT FROM AUTHOR]

More than 290 million people worldwide, and almost 2 million people in the United States, are infected with hepatitis B virus, which can lead to chronic hepatitis B, a vaccine-preventable communicable disease. The prevalence of chronic hepatitis B infection in pregnancy is estimated to be 0.7% to 0.9% in the United States, with >25,000 infants born annually at risk for chronic infection due to perinatal transmission. Given the burden of disease associated with chronic hepatitis B infection, recent national guidance has expanded both the indications for screening for hepatitis B infection and immunity and the indications for vaccination. The purpose of this document is to aid clinicians caring for pregnant patients in screening for hepatitis B infection and immunity status, discuss the perinatal risks of hepatitis B infection in pregnancy, determine whether treatment is indicated for maternal or perinatal indications, and recommend hepatitis B vaccination among susceptible patients. The following are the Society for Maternal-Fetal Medicine recommendations: (1) we recommend triple-panel testing (hepatitis B surface antigen screening, antibody to hepatitis B surface antigen, and total antibody to hepatitis B core antigen) at the initial prenatal visit if not previously documented or known to have been performed (GRADE 1C); (2) we recommend universal hepatitis B surface antigen screening alone at the initial prenatal care visit for all pregnancies where there has been a previously documented negative triple-panel test (GRADE 1B); (3) we recommend that individuals with unknown hepatitis B surface antigen screening status be tested on any presentation for care in pregnancy; we also recommend that those with clinical hepatitis or those with risk factors for acute hepatitis B infection be tested at the time of admission to a birthing facility when delivery is anticipated (GRADE 1B); (4) we do not recommend altering routine intrapartum care in individuals chronically infected with hepatitis B; administration of neonatal immunoprophylaxis is standard of care in these situations (GRADE 1B); (5) we do not recommend cesarean delivery for the sole indication of reducing perinatal hepatitis B virus transmission (GRADE 1B); (6) we recommend that individuals with HBV infection can breastfeed as long as the infant has received immunoprophylaxis at birth (GRADE 1C); (7) we suggest individuals with hepatitis B infection who desire invasive testing may have the procedure performed after an informed discussion on risks and benefits in the context of shared decision-making and in the context of how testing will affect clinical care (GRADE 2C); (8) in individuals with hepatitis viral loads >200,000 IU/mL (>5.3 log 10 IU/mL), we recommend antiretroviral therapy with tenofovir (tenofovir alafenamide at 25 mg daily or tenofovir disoproxil fumarate at 300 mg daily) in the third trimester (initiated at 28–32 weeks of gestation) as an adjunctive strategy to immunoprophylaxis to reduce perinatal transmission (GRADE 1B); (9) we recommend administering hepatitis B vaccine and hepatitis B immunoglobin within 12 hours of birth to all newborns of hepatitis B surface antigen–positive pregnant patients or those with unknown or undocumented hepatitis B surface antigen status, regardless of whether antiviral therapy has been given during the pregnancy to the pregnant patient (GRADE 1B); and (10) we recommend hepatitis B vaccination in pregnancy for all individuals without serologic evidence of immunity or documented history of vaccination (GRADE 1C). [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study is to examine the diagnosis types and rates of patients with central nervous system (CNS) anomalies detected in the prenatal period between 2021-2022 in our perinatology clinic and to contribute to the literature. Materials and Methods: Our study included 191 patients with CNS anomaly and whose pregnancy results were reached. Demographic characteristics of the patients, additional detected anomalies, fetal Magnetic Resonance Imaging (MRI) and genetic results, o bstetric and neonatal results were evaluated if requested. Results: Neural tube defects (NTD) were found most frequently at 75.3%, and among these, acrania was found most frequently at 27.2%. While 74.3% of the detected CNS anomalies were isolated anomalies, it was found that 5.2% were accompanied by additional CNS anomalies and 21.9% were accompanied by additional extracranial anomalies. Abnormal karyotype was obtained in 12.1% of the pa tients who wanted to have a prenatal diagnosis test. It was found that 11% of the patients requested fetal MRI and ventriculomegaly was the most common fetal MRI indication. While the pregnancies of 56.5% of the patients were terminated, 37.7% of them gave live bir ths. The rate of surgical intervention in live-born babies with CNS anomalies was found to be 56.9%. A total mortality rate of 43% was found in live-born babies. Conclusion: Since CNS anomalies are associated with serious morbidity and mortality; Prenatal diagnosis is very important so that families can be offered a pregnancy termination option and those who will continue to be pregnant should be informed about the treatment and rehabilitation processes of their babies. [ABSTRACT FROM AUTHOR]

Periodontal disease is very common in pregnant women. Paraprobiotics are a subset of probiotics. They can be defined as inactivated microbial cells providing health benefits to the host and are considered particularly safe. The aim of this study was to compare the periodontal health of pregnant women and puerperae after 6 months of home use of paraprobiotics. A total of 30 pregnant women were enrolled and divided into two groups: the test group, who had to use a paraprobiotic-based toothpaste (Biorepair Peribioma Pro, Coswell S.p.A., Funo di Argelato, BO, Italy) and mousse (Mousse Mouthwash Biorepair Peribioma, Coswell S.p.A.) twice a day, and the control group, who had to use only the paraprobiotic-based toothpaste. The time frames of the study were: 1 month (T1), 3 months (T2) and 6 months (T3), and data were collected during pregnancy and in the period immediately following delivery. The following indices were evaluated at T0, T1, T2 and T3: clinical attachment loss (CAL), probing pocket depth (PPD), bleeding on probing (BOP), plaque control record (PCR), modified marginal gingival index (mMGI), papillary marginal gingival index (PMGI) and recessions (R). All data were subjected to statistical analysis. PCR decreased significantly from T0 to T1 in the control group and from T0 to T2 and from T0 to T3 in the test group. BOP tended to decrease in both groups, but a significant reduction was observed only in the test group. CAL, PPD, PMGI and mMGI tended to decrease gradually in both groups without significant differences between or within groups. The combination of the paraprobiotic-based toothpaste and the paraprobiotic-based mousse significantly reduced BoP and plaque control over time, although there were no significant differences with the use of the paraprobiotic-based toothpaste alone. In addition, the combination of the two products promoted a trend towards the better stabilization of recessions. [ABSTRACT FROM AUTHOR]

The article discusses the definition and diagnosis of vasa previa, a condition where fetal blood vessels are exposed and unprotected over the cervix. The author argues against the commonly used definition of vasa previa as vessels within 2 cm of the internal os, stating that this definition is not supported by data and can be dangerous. They propose that any unprotected fetal vessels within a radius of 5 cm of the internal os should be defined as vasa previa. The author emphasizes the importance of providing accurate information and involving patients in the decision-making process to ensure their autonomy and informed consent. [Extracted from the article]

This article discusses the prenatal diagnosis of a rare combination of ocular abnormalities: bilateral congenital cataracts with strabismus. Congenital cataracts are a progressive condition that can lead to vision loss, and they can be caused by disruptions in the development of the lens during gestation. Strabismus is a vision disorder characterized by misalignment of the eyes. The article explains that these conditions can be diagnosed through prenatal ultrasound, and early diagnosis and treatment are crucial for optimal visual outcomes. The article also mentions the importance of genetic testing and a multidisciplinary approach involving pediatric ophthalmology and genetic counseling. [Extracted from the article]

Central nervous system (CNS) malformations encompass diverse congenital anomalies impacting brain and spinal cord development, profoundly affecting neurological function. They arise from disruptions in embryonic neural tube formation, neuronal migration, and cortical organization. This abstract provides a comprehensive overview of CNS malformations, covering classification, etiology, clinical manifestations, and diagnostic challenges. CNS malformations fall into distinct groups: neural tube defects (e.g., anencephaly, spina bifida), resulting from incomplete neural tube closure; malformations of cortical development (e.g., lissencephaly, polymicrogyria), featuring irregularities in cortical folding; and anomalies affecting structures like the corpus callosum, cerebellum, and CNS vasculature, alongside conditions such as hydrocephalus and Chiari malformations. Genetic factors, including mutations in LIS1, DCX, and RELN, contribute significantly, while environmental factors like maternal folic acid deficiency also play a role. Some malformations occur in genetic syndromes (e.g., tuberous sclerosis, neurofibromatosis). Clinical presentations vary, with neural tube defects typically presenting severe deficits at birth, while cortical malformations manifest as intellectual disabilities, seizures, and motor deficits. Hydrocephalus elevates intracranial pressure, and Chiari malformations cause headaches and neurological symptoms. Diagnosis necessitates a multidisciplinary approach involving clinical evaluation, neuroimaging, genetic testing, and histopathological analysis. Prenatal diagnosis via ultrasound and magnetic resonance imaging is crucial for planning interventions, while postnatal diagnosis relies on clinical and imaging findings. Understanding CNS malformations is vital for early detection, intervention, and comprehensive care provision. Advances in genetics and neuroimaging offer hope for improved outcomes and better quality of life for affected individuals. [ABSTRACT FROM AUTHOR]

Hydrocephalus is a heterogeneous disorder of cerebrospinal fluid (CSF) flow that leads to abnormal enlargement of the brain ventricles. The prevalence of infant hydrocephalus is approximately one case per 1,000 births. Hydrocephalus occurs due to an imbalance between the production and the absorption of CSF. The causes of hydrocephalus secondary to CSF overproduction are papilloma of the choroid plexus and rarely diffuse hyperplasia of the villi. All the other hydrocephalus forms are secondary to obstruction to normal CSF reabsorption and are also known as obstructive hydrocephalus. According to the location of obstruction, obstructive hydrocephalus can be defined as communicating, when caused by extraventricular obstruction of the CSF flow or decreased resorption of CSF distal to the fourth ventricle in the cisterns of the base or in the subarachnoid spaces, or as not communicating, in case of intraventricular obstruction to fluid flow. There is a third category, common in preterm infants, called external hydrocephalus which is secondary to delayed development of arachnoid function. Hydrocephalus leads to an increase in intraventricular pressure because of the lack of the mechanism regulating the homeostasis of the CSF flow. Increased intraventricular pressure is responsible for the clinical symptoms in affected child. Clinical presentation varies with age. In the neonatal period, prolonged or frequent apneic or bradycardic events, increasing head circumference, presence of sunsetting eyes or upward gaze palsy, evidence of full or tense anterior/posterior fontanelle, and splayed cranial sutures are signs of increased intracranial pressure. In infants, the most common signs are progressive macrocephaly, irritability, nausea/vomiting, headache, gait changes, and regression of developmental milestones. The extent of brain damage depends on the cause that led to hydrocephalus, the patient's age, and the rapidity of onset. The surgical treatment modalities consist of endoscopic ventriculostomy of the third ventricle and ventriculoperitoneal or ventriculoatrial CSF shunt. [ABSTRACT FROM AUTHOR]

ABSTRACT Prenatal genetic testing is to determine the possibility of the fetus having a genetic aberration or birth defect. Prenatal screening consists of serum analytes screening with or without nuchal translucency (NT) scanning or with cell‐free DNA (CfDNA) screening. Prenatal screening is recommended for all pregnant women regardless of the duration of pregnancy and maternal age or baseline risk. It is not advisable to screen with serum analytes and CfDNA concurrently to avoid discordant results. In developed countries, prenatal testing has been a part of routine antenatal care for a long time with adopting newer methods of screening and testing. In Bhutan, since the integration of the Safe Motherhood Program into primary healthcare in 1994, there has been an unprecedented improvement in obstetric care services. Almost all pregnant women attend antenatal and postnatal care, and 98.5% of deliveries are attended by trained health workers. The maternal mortality has reduced to 53 in 2023 from 770 per 100,000 live births in 1984 and the neonatal dealth has reduced to 15.2 per 1000 live births in 2023. However, despite improvements in the care of pregnant women, many babies are detected with congenital anomalies, syndromes, and birth defects during the postnatal period. Bhutan, being an underdeveloped country, could not initiate any form of prenatal testing program except for the anatomical scanning performed at 18–22 weeks of gestation. Early ultrasound dating scans, limited anomaly scanning, and growth scanning are offered to all pregnant women. There is a need to start centralized prenatal testing services in Bhutan to provide a comprehensive package of obstetric care to pregnant women. In addition, legal rights for parents to terminate severely deformed fetuses or severe genetic diseases before 24 weeks of pregnancy need to be established.

Purpose: 17q12 copy number variants (CNVs) have variable presentations and incomplete penetrance, challenging prenatal counseling and management. This study aims to investigate the intrauterine phenotype. Methods: We included 48 fetuses diagnosed with 17q12 microdeletion or microduplication by chromosomal microarray analysis. Results: For 17q12 deletion, renal anomalies were found in 35 fetuses (35/37, 94.6 %), with hyperechogenic kidneys (HEK, 28/37, 75.7 %) and multicystic dysplastic kidneys (17/37, 45.9 %) being the most common findings. Duodenal obstruction (DO) was most frequently combined in 17q12 duplication fetuses. In addition, cardiac abnormalities were the first reported prenatal phenotype in 17q12 duplication fetuses. Conclusion: Our study shows that HEK and DO are the most predominant presentations of 17q12 deletion and duplication, respectively, and cardiac structural abnormalities may be associated with the latter. Although 17q12 CNVs have incomplete penetrance and variable expressivity and may be mainly involved in neurodevelopmental disorders, their short-term prognosis appears positive.

ObjectiveThe recurrent 1q21.1 microdeletion syndrome is an autosomal dominant disorder and is characterized by dysmorphic facial features, microcephaly, developmental delay, and congenital defects. However, most studies on the distal deletions in the 1q21.1 region were diagnosed postnatally. This study aimed to provide a better understanding of the ultrasound and molecular findings of fetuses with recurrent 1q21.1 microdeletions in prenatal diagnosis.MethodsIn this retrospective study, we reported 21 cases with the recurrent 1q21.1 microdeletion syndrome diagnosed at our prenatal diagnostic center from January 2016 to January 2023. The clinical data were reviewed for these cases, including the maternal demographics, indications for invasive testing, ultrasound findings, CMA results, and pregnancy outcomes.ResultsIn the study, a total of 21 cases with recurrent 1q21.1 microdeletions were diagnosed prenatally by CMA. Fifteen cases were described with ultrasound indications, and the most common findings are as follows: increased nuchal translucency (NT) (26.7%), intrauterine growth retardation (IUGR) (26.7%), congenital heart defects (CHD) (20%), and congenital anomalies of the kidney and urinary tract (CAKUT) (13.3%). All the cases with the distal 1q21.1 deletions contain the common minimal region (located between BP3 and BP4) and eight OMIM genes. Parental studies to determine the inheritance of the deletion were performed for eight cases, and half of the cases were inherited from one of the parents. Pregnancy outcomes were available for nine cases; eight (88.9%) pregnancies were determined to be terminated and one (11.1%) was full-term delivery.ConclusionTo our knowledge, this is the largest study to find that fetuses with recurrent 1q21.1 microdeletions were closely associated with increased NT, CHD, IUGR, and CAKUT. In addition, ours is the first study to report that cerebral ventriculomegaly might be associated with recurrent 1q21.1 microdeletions. More comprehensive studies are needed for a better understanding of the prenatal phenotype–genotype relationship of the recurrent 1q21.1 microdeletion syndrome in future.

ObjectiveThis study aims to analyze the value of prenatal ultrasound in the screening, diagnosis, and treatment of double aortic arch (DAA) malformations.MethodsA retrospective analysis was conducted on 31 fetal cases with double aortic arch anomalies over a 12-year period from June 1, 2011 to June 1, 2023. The assessment included combined measurements of fetal tracheal internal diameter Z-score and DAA pinch angle, along with ultrasonographic findings, associated anomalies, genetic abnormalities, postnatal CTA images, and long-term postnatal outcomes.ResultsOf the 31 fetal double aortic arch cases, 15 were right aortic arch dominant, 2 were left aortic arch dominant, and 14 had a balanced double arch. Genetic testing was performed on 19 cases, revealing abnormalities in 2 cases, including one Turner syndrome, and one carrier of ichthyosis gene with heterozygous deletion. Out of the total cases, 29 were delivered, and 2 cases were terminated. Prenatal diagnosis accurately identified 29 cases (29/31, 93.5%), which was confirmed by postnatal pathological anatomy, echocardiography, surgery or CTA. Fetal tracheal internal diameter Z-scores were significantly smaller in the symptomatic group than in the asymptomatic group (−1.27 ± 0.49 vs −0.68 ± 0.60, P = 0.018). The area under the curve was 0.776 (95% confidence interval, 0.593–0.960) using a tracheal internal diameter z-score cutoff of −0.73 with a sensitivity of 90% and specificity of 64.7%. The double arch pinch angle was significantly smaller in the symptomatic group than in the asymptomatic group [52.50° (38.25° to 59.00°) vs 60.00° (53.50° to 70.50°), P = 0.035]. The area under the curve was 0.744 (95% confidence interval, 0.554–0.935), and the sensitivity for determining the presence or absence of symptoms was 90% when the cutoff value was 62.5°, with a specificity of 47.1%. Fifteen cases opted for surgery with favorable surgical outcome.ConclusionPrenatal echocardiography demonstrates good diagnostic efficacy for fetal double aortic arch. It is also essential to detect the presence of other underlying intra- and extracardiac malformations and genetic abnormalities. There is a significant difference in prenatal tracheal internal diameter Z-scores and double arch pinch angle between asymptomatic and symptomatic DAA infants. Symptomatic infants require early surgery, while asymptomatic infants should be monitored.

Neural tube defects (NTDs) are severe congenital anomalies that result from the failure of early neural tube closure during fetal neurogenesis. They are the most common and severe congenital malformations of the central nervous system. Identifying reliable prenatal diagnostic ultrasound and molecular markers that can predict NTDs is of paramount importance. Early diagnosis of NTDs allows embryonic treatment and prevention strategies, which are crucial for reducing the disability rate associated with these malformations, reducing the burden on individuals and on society. The purpose of this comprehensive review was to summarize the ultrasound biomarkers between 11 and 13 weeks of gestation and the molecular biomarkers used in the diagnosis of NTDs, providing additional insights into early screening for NTDs.

This study aimed to assess the efficiency of CNV-seq and WES in detecting genetic cause of congenital heart disease (CHDs) in prenatal diagnoses and to compare CNV detection rate between isolated and non-isolated CHD cases. We conducted a retrospective study of 118 Chinese fetuses diagnosed with CHD by prenatal ultrasound. Participants underwent CNV-seq and, if necessary, WES to detect chromosomal and single nucleotide variations. The overall detection rate for pathogenic or likely pathogenic chromosomal abnormalities was 16.9%, including 7.6% aneuploidies and 9.3% pathogenic/likely pathogenic copy number variations (CNVs), predominantly 22q11.2 deletion syndrome (54.4%). The sensitivity and specificity of CNV-Seq for detecting P/Lp CNVs were 95% and 100%, respectively. CNV-Seq offered a 6.7% improvement in detecting chromosomal abnormalities over karyotyping. WES further identified significant single nucleotide and small indel variations contributing to CHD in genes such as TMEM67, PLD1, ANKRD11, and PNKP, enhancing diagnostic yield by 14.8% in cases negative for CNVs. Non-isolated CHD cases exhibited higher rates of detectable chromosomal abnormalities compared to isolated cases (32.4% vs. 9.9%, p = 0.005), underlining the genetic complexity of these conditions. The combined use of CNV-seq and WES provides a comprehensive approach to prenatal genetic testing for CHDs, unveiling significant genetic cause that could impact clinical management and parental decision-making. This study supports the integration of these advanced genomic technologies in routine prenatal diagnostics to increase detection diagnostic yields of causal genetic variants associated with CHDs.

Cell-free fetal DNA (cffDNA) screening is a valuable tool in clinical practice for detecting chromosomal abnormalities and autosomal dominant (AD) conditions. This study introduces a novel proof-of-concept assay designed for autosomal recessive (AR) cffDNA screening, focusing on cases involving the NPC1 gene. We aim to illustrate the significant benefits of AR cffDNA screening in managing high-risk pregnancies, specifically where biallelic pathogenic variants in NPC1 cause Niemann–Pick disease, type C1 (NPC), a disorder marked by progressive neurodegeneration. Three participants for this study were recruited and gave consent to a hospital in Saudi Arabia. These participants were either carriers of NPC or had a first- or second-degree relative affected by the disorder. No specific criteria were set for the age of the participants. All were between 15 and 18 weeks of gestation. Using amplicon-based next-generation sequencing (NGS), we analyzed the zygosity and variants in cffDNA extracted from maternal peripheral blood. After amplicon NGS, analysis was completed by a custom data analysis pipeline that included in-house-built data processing scripts and commonly used software packages. Importantly, the results were not disclosed to the patients. Our findings showed that in all three cases, AR cffDNA screening results were consistent with standard invasive diagnostic testing. This screening method offers several advantages: it provides critical information to families earlier in the pregnancy compared to invasive diagnostic tests, and it helps to alleviate parental anxiety. Moreover, this non-invasive method can determine pregnancy status in the first trimester for known familial variants. Future research may extend this approach to screen for known disease-causing variants in common AR conditions.