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Abstract Objectives To undertake a systematic review to assess the accuracy of fetal MRI in diagnosis of non-CNS congenital anomalies of the fetal body in comparison with antenatal ultrasound when correlated to postnatal diagnosis. Methods Searches were conducted from electronic databases, key journals and reference lists for eligible papers. Inclusion criteria was original research studies comparing the diagnostic results of antenatal ultrasound, fetal MRI and final postnatal diagnosis via imaging, surgery or post-mortem testing. Studies of CNS anomalies were excluded. Studies were assessed for risk of bias by two reviewers working independently and data was then extracted by a single reviewer. Results 12 studies were included with a total of 361 eligible patients who underwent USS and MRI and had a postnatal diagnosis. USS alone had a diagnostic accuracy of 60.6% whereas MRI had an improved diagnostic accuracy of 86.4%. The overall odds ratio was 0.86 (CI 0.202–1.519 and p-value

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. 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, obstetric 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 patients 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 births. 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. DISCUSSION AND 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 Background Noninvasive prenatal testing (NIPT) is widely used to screen for fetal aneuploidies. However, there are few reports of using NIPT for screening chromosomal microduplications and microdeletions. This study aimed to investigate the application efficiency of NIPT for detecting chromosomal microduplications. Methods Four cases of copy number gains on the long arm of chromosome 17 (17q12) were detected using NIPT and further confirmed using copy number variation (CNV) analysis based on chromosome microarray analysis (CMA). Results The prenatal diagnosis CMA results of the three cases showed that the microduplications in 17q12 (ranging from 1.5 to 1.9 Mb) were consistent with the NIPT results. The karyotypic analysis excluded other possible unbalanced rearrangements. The positive predictive value of NIPT for detecting chromosomal 17q12 microduplication was 75.0%. Conclusions NIPT has a good screening effect on 17q12 syndrome through prenatal diagnosis, therefore it could be considered for screening fetal CNV during the second trimester. With the clinical application of NIPT, invasive prenatal diagnoses could be effectively reduced while also improving the detection rate of fetal CNV.

Fetal anomalies, characterized by structural or functional abnormalities occurring during intrauterine life, pose a significant medical challenge, with a notable prevalence, affecting approximately 2–3% of live births and 20% of spontaneous miscarriages. This study aims to identify the genetic cause of ultrasound anomalies through clinical exome sequencing (CES) analysis. The focus is on utilizing CES analysis in a trio setting, involving the fetuses and both parents. To achieve this objective, prenatal trio clinical exome sequencing was conducted in 51 fetuseses exhibiting ultrasound anomalies with previously negative results from chromosomal microarray (CMA) analysis. The study revealed pathogenic variants in 24% of the analyzed cases (12 out of 51). It is worth noting that the findings include de novo variants in 50% of cases and the transmission of causative variants from asymptomatic parents in 50% of cases. Trio clinical exome sequencing stands out as a crucial tool in advancing prenatal diagnostics, surpassing the effectiveness of relying solely on chromosomal microarray analysis. This underscores its potential to become a routine diagnostic standard in prenatal care, particularly for cases involving ultrasound anomalies.

Abstract 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.

Amniocentesis is one of the known and accessible methods for prenatal diagnosis, which is performed for various reasons during pregnancy. The present study was performed to determine the most common reasons for amniocentesis to detect aneuploidy. This retrospective cohort study was performed on the records of 635 pregnant women who underwent amniocentesis guided by high-resolution ultrasound during 2010-2019 at Yas Hospital of Tehran University of Medical Sciences, Tehran, Iran. The study evaluated the indications for amniocentesis in order to investigate the relationship between each of these indications and fetal aneuploidy results. All participants were evaluated for genetic study results. The prevalence of aneuploidy was 8.2% and abnormal screening test was the most common reason for performing amniocentesis (68% of cases). Also, abnormal ultrasound results had the strongest correlation with the possibility of genetic abnormalities in the current pregnancy. Therefore, amniocentesis is highly recommended for women with indications, especially in cases of abnormal ultrasound results.

Abstract Background Chromosomal microarray analysis (CMA) has emerged as a critical instrument in prenatal diagnostic procedures, notably in assessing congenital heart diseases (CHD). Nonetheless, current research focuses solely on CHD, overlooking the necessity for thorough comparative investigations encompassing fetuses with varied structural abnormalities or those without apparent structural anomalies. Objective This study sought to assess the relation of single nucleotide polymorphism-based chromosomal microarray analysis (SNP-based CMA) in identifying the underlying causes of fetal cardiac ultrasound abnormalities. Methods A total of 2092 pregnant women who underwent prenatal diagnosis from 2017 to 2022 were included in the study and divided into four groups based on the presence of ultrasound structural abnormalities and the specific type of abnormality. The results of the SNP-Array test conducted on amniotic fluid samples from these groups were analyzed. Results Findings from the study revealed that the non-isolated CHD group exhibited the highest incidence of aneuploidy, overall chromosomal abnormalities, and trisomy 18, demonstrating statistically significant differences from the other groups (p 0.05). The occurrence rates of 22q11.2 and 15q11.2 were also not statistically different between the isolated CHD group and the non-isolated congenital heart defect group (p > 0.05). Conclusion SNP-based CMA enhances the capacity to detect abnormal CNVs in CHD fetuses, offering valuable insights for diagnosing chromosomal etiology and facilitating genetic counseling. This research contributes to the broader understanding of the utility of SNP-based CMA in the context of fetal cardiac ultrasound abnormalities.

Here, we report a case of a congenital peribronchial myofibroblastic tumor (CPMT). A 34-year-old primigravida was referred to our hospital at 31 gestation weeks because of suspected congenital pulmonary airway malformation (CPAM). Fetal ultrasonography showed a mass measuring 4.6 × 4.0 × 3.9 cm with mixed high and low echogenicity in the left lung, which was associated with microvascular blood flow in the tumor. Fetal magnetic resonance imaging (MRI) revealed a low-intensity left lobe lung lesion on a T2-weighted image. These findings suggested that the mass was a CPAM with atypical hypointense findings on MRI T2-weighted images or a rare primary pulmonary tumor, such as a CPMT. Unfortunately, the fetus died in utero at 34 gestation weeks due to cardiovascular failure, which could have resulted from direct encasement of the great vessels or cardiac compression due to rapid tumor growth. The autopsy findings confirmed the diagnosis of CPMT. Primary pulmonary tumors, such as CPMT, are extremely rare lung diseases that develop in utero. These tumors often rapidly grow during pregnancy, resulting in intrauterine fetal death. However, if the patient survives surgical mass resection, the prognosis is good. Given the adverse outcomes observed in our case, careful fetal monitoring is required in case of suspected CPMT during the third trimester of pregnancy. Moreover, in case the well-being of the fetus cannot be assured, immediate delivery should be considered, even in the preterm period, followed by surgery.

Digital PCR is a powerful method for absolute nucleic acid quantification and is widely used in the absolute quantification of viral copy numbers, tumor marker detection, and prenatal diagnosis. However, for most of the existing droplet-based dPCR systems, the droplet generation, PCR reaction, and droplet detection are performed separately using different instruments. Making digital PCR both easy to use and practical by integrating the qPCR workflow into a superior all-in-one walkaway solution is one of the core ideas. A new innovative and integrated digital droplet PCR platform was developed that utilizes cutting-edge microfluidics to integrate dPCR workflows onto a single consumable chip. This makes previously complex workflows fast and simple; the whole process of droplet generation, PCR amplification, and droplet detection is completed on one chip, which meets the clinical requirement of "sample in, result out". It provides high multiplexing capabilities and strong sensitivity while all measurements were within the 95% confidence interval. This study is the first validation of the DropXpert S6 system and focuses primarily on verifying its reliability, repeatability, and consistency. In addition, the accuracy, detection limit, linearity, and precision of the system were evaluated after sample collection. Among them, the accuracy assessment by calculating the absolute bias of each target gene yielded a range from -0.1 to 0.08, all within ±0.5 logarithmic orders of magnitude; the LOB for the assay was set at 0, and the LoD value calculated using probit curves is MR4.7 (0.002%); the linearity evaluation showed that the R2 value of the BCR-ABL was 0.9996, and the R2 value of the ABL metrics calculated using the ERM standard was 0.9999; and the precision evaluation showed that all samples had a CV of less than 4% for intra-day, inter-day, and interinstrument variation. The CV of inter-batch variation was less than 7%. The total CV was less than 5%. The results of the study demonstrate that dd-PCR can be applied to molecular detection and the clinical evaluation of CML patients and provide more precise personal treatment guidance, and its reproducibility predicts the future development of a wide range of clinical applications. [ABSTRACT FROM AUTHOR]

Introduction: In October 2020, rapid prenatal exome sequencing (pES) was introduced into routine National Health Service (NHS) care in England, requiring the coordination of care from specialist genetics, fetal medicine (FM) and laboratory services. This mixed methods study explored the experiences of professionals involved in delivering the pES service during the first 2 years of its delivery in the NHS. Methods: A survey (n = 159) and semi-structured interviews (n = 63) with healthcare professionals, including clinical geneticists, FM specialists, and clinical scientists (interviews only) were used to address: 1) Views on the pES service; 2) Capacity and resources involved in offering pES; 3) Awareness, knowledge, and educational needs; and 4) Ambitions and goals for the future. Results: Overall, professionals were positive about the pES service with 77% rating it as Good or Excellent. A number of benefits were reported, including the increased opportunity for receiving actionable results for parental decision-making, improving equity of access to genomic tests and fostering close relationships between FM and genetics departments. Nonetheless, there was evidence that the shift to offering pES in a clinical setting had brought some challenges, such as additional clinic time, administrative processes, perceived lack of autonomy in decision-making regarding pES eligibility and difficulty engaging with peripheral maternity units. Concerns were also raised about the lack of confidence and gaps in genomics knowledge amongst non-genetics professionals - especially midwives. However, the findings also highlighted value in both FM, obstetric and genetics professionals benefiting from further training with a focus on recognising and managing prenatally diagnosed genetic conditions. Conclusion: Healthcare professionals are enthusiastic about the benefits of pES, and through multi-collaborative working, have developed relationships that have contributed to effective communication across specialisms. Although limitations on resources and variation in knowledge about pES have impacted service delivery, professionals were hopeful that improvements to infrastructure and the upskilling of all professionals involved in the pathway would optimise the benefits of pES for both parents and professionals. [ABSTRACT FROM AUTHOR]

Background: Chromosomal abnormalities are the main cause of birth defects in newborns. Since the inception of noninvasive prenatal testing (NIPT) technology, it has primarily been applied to the detection of common trisomy (T21, T18, T13). However, the application of NIPT in microdeletion and microduplication detection is still controversial. Methods: This study retrospectively analyzed the data of 68,588 cases that underwent NIPT at Ganzhou Maternal and Child Health Hospital in China. These data were used to evaluate the performance of NIPT in fetal chromosome microdeletion/microduplication detection and to investigate the key factors affecting the NIPT performance. Results: A total of 281 cases (0.41%) had positive NIPT results with copy number variants (CNVs), of which 161 were validated by karyotyping and chromosome microarray analysis (CMA). Among the 161 cases, 92 were confirmed as true positives through karyotyping or CMA, including 61 microdeletion cases and 31 microduplication cases, resulting in a positive predictive value (PPV) of 57.14%. Improvements in library construction methods increased the fraction of cell-free fetal DNA (cffDNA) from 13.76% to 18.44%, leading to a significant improvement in the detection rate (0.47% vs. 0.15%) and PPV (59.86% vs. 28.57%) of NIPT for CNVs. Conclusion: This study proved the robust performance of NIPT for fetal chromosome microdeletion/microduplication detection. In addition, the cffDNA fraction is a key factor influencing NIPT, with increased cffDNA fraction improving the performance of NIPT. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the efficacy of α-thalassemia gene testing as a part of an antenatal intervention program over a 10-year period. Methods: All patients underwent α-thalassemia gene testing, which included the analysis of three types of deletions and mutations. Rare α-thalassemia gene testing was performed using Sanger sequencing, multiplex ligation-dependent probe amplification, and sequencing techniques. Prenatal diagnosis was performed in high-risk couples using chorionic villus sampling or amniocentesis. Results: From 2010 to 2019, among the 91,852 patients examined, α-thalassemia mutations were identified in 41.78% of patients. The most frequent α0 gene mutation was--SEA, followed by--THAI. Two rare α0 -thalassemia gene mutations at --32.8 and --230, were also observed. A total of 2,235 high-risk couples were identified, of which 562 were affected, including three with the--SEA/--THAI genotype and one with the--SEA/--230 genotype. Additionally, prenatal diagnosis revealed four cases of fetal anemia and/or mild edema, along with two cases of severe fetal edema. Chromosome and gene chip results were normal. Thalassemia gene testing showed an αCSα/αCSα genotype in four patients with anemia and/or mild edema, while two patients with severe fetal edema had one--SEA/αCSα genotype and one--SEA/--GX genotype. Using the cut-off points of 74.6 fL and 24.4 pg as criteria for identifying α0 -thalassemia carriers and HbH disease, the detection rate of missed diagnoses in high-risk couples is consistent with national guidelines for standards, potentially saving 10,217,700 ¥. Conclusion: Routine molecular testing for α-thalassemia in high-risk prenatal populations effectively prevented severe α-thalassemia births. Despite the high cost, the cutoff points proposed by this study suggest that implementing screening using a new parameter has the potential to reduce current expenses. [ABSTRACT FROM AUTHOR]

Objectives: Congenital diaphragmatic hernia (CDH) is defined as organ protrusion from the abdominal to the thoracic cavity. The Hadlock formula is the most commonly used tool for calculating estimated fetal weight (EFW). The anatomical nature of CDH usually leads to underestimation of the abdominal circumference, resulting in underestimation of fetal weight. Accurate weight estimation is essential before birth for counselling, preparation before surgery and ECMO. The research is made to compare the accuracy of Hadlock's formula and Faschingbauer's formula for fetal weight estimation in CDH fetuses population. Methods: In our study, we investigated differences between EFW and actual birthweight in 42 fetuses with CDH as compared to 80 healthy matched controls. EFW was calculated using the Hadlock formula and a recently introduced formula described by Faschingbauer et al., which was tailored for fetuses with CDH. Additionally, both of the formulas were adjusted for the interval between the ultrasound and delivery for both of the groups. Results: The majority of hernias were left-sided (92.8% vs. 7.2%). EFW adjusted for the interval between the ultrasound and delivery had the highest correlation with the actual birthweight in both, study group and controls. We compared the results for both tools and found the Hadlock formula to predict birthweight in CDH children with a 7.8 ± 5.5% error as compared to 7.9 ± 6.5% error for the Faschingbauer's formula. Conclusions: The Hadlock formula adjusted for the interval between the ultrasound and delivery is a more precise method of calculating EFW in fetuses with CDH. Routine biometry scan using Hadlock's formula remains reliable for predicting birthweight. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the potential connections between marginal cord insertion during the first trimester and furcate cord insertion later in pregnancy. Methods: This is a prospective study of screening data on the cord insertion site in 3178 singleton pregnancies. The cord insertion site was examined in two stages. The first stage was screening for the cord insertion site between 10–13 weeks of gestation, the purpose is to determine the category of umbilical cord insertion. The second stage, performed at 22–28 weeks of gestation, was to follow up on the relationship between the cord insertion site and the placenta and to identify any changes in the category of umbilical cord insertion. This was performed to diagnose or exclude furcate cord insertion by identifying whether the umbilical cord trunk separated or branched before it reached the placenta. Factors influencing progression to furcate cord insertion and perinatal complications were assessed. Results: Fourteen cases (0.44%) with progression to furcate cord insertion, all of which showed marginal cord insertion on ultrasound in the first trimester (p < 0.001). without progression to furcate cord insertion, there were no changes in the category of umbilical cord insertion in 3050 cases (96.40%) compared to the early pregnancy. 114 cases (3.60%) with changes in the category of umbilical cord insertion that was not consistent with furcate cord insertion. A total of 14 cases progressed to furcate cord insertion, all showed the cord insertion site were in close proximity, and 11 (78.57%) cases showed a low insertion site (p < 0.001). Regarding the choice of mode of delivery, elective caesarean delivery was done in 8/14 (57.14%). The incidences of spontaneous vaginal delivery were 5/14 (35.71%) (p < 0.001). One (7.14%) case of progression to furcate cord insertion due to haematoma at the root of the umbilical cord ended with an emergency caesarean section. In terms of perinatal complications, marginal cord insertion that progressed to furcate cord insertion had higher incidences of SGA infants, abnormal placental morphology, retention of the placenta, and cord-related adverse pregnancy outcomes than not progressed to furcate cord insertion (p < 0.05). Conclusions: Marginal cord insertion in the first trimester has the potential to progress to furcate cord insertion. We suggest that ultrasound-diagnosed marginal cord insertion in the first trimester should be watched carefully in the second trimester, which is clinically useful to accurately determine the category of cord insertion and to improve the rate of prenatal diagnosis of furcate cord insertion. [ABSTRACT FROM AUTHOR]

Fetal chromosomal abnormalities are the main cause of adverse pregnancy outcomes and are the focus of invasive prenatal diagnosis. Recent studies have demonstrated that various techniques have distinct advantages. Achieving high-resolution and effective prenatal chromosomal abnormality diagnosis requires a multi-technology integration strategy. Based on retrospective samples from a single center, we propose that integrating CNVseq and karyotype analysis is an effective strategy for prenatal diagnosis of chromosomal abnormalities. In this study, 13.80% of the pregnant women (347/2514) were found to have likely pathogenic or pathogenic fetal chromosomal abnormalities using this integrated approach. Among these cases, 53.89% (187/347) had consistent chromosomal abnormalities detected by both CNV-seq and karyotyping analysis, while 19.02% (66/347) and 27.09% (94/347) of cases were diagnosed solely by CNV-seq or karyotyping, respectively. Fetal chromosomal abnormalities were identified in 18.39% of samples with abnormal ultrasound, which was significantly higher than the percentage found in samples with normal ultrasound (p < 0.001). Samples with multiple ultrasound abnormalities and single-indicator ultrasound abnormalities such as nasal bone dysplasia, renal dysplasia, or echogenic fetal bowel also had higher rates of chromosomal abnormalities (p < 0.05) compared to normal samples. Analyzing samples with Trio family data (N = 521) revealed that about 94% of variants of uncertain significance were inherited from parents and were nonpathogenic. Overall, integrating CNV-seq and karyotype analysis is an effective strategy for prenatal diagnosis of chromosomal abnormalities. This study provides valuable insights for correlating prenatal screening indicators with chromosomal abnormalities. [ABSTRACT FROM AUTHOR]

L1 syndrome, a neurological disorder with an X‐linked inheritance pattern, mainly results from mutations occurring in the L1 cell adhesion molecule (L1CAM) gene. The L1CAM molecule, belonging to the immunoglobulin (Ig) superfamily of neurocyte adhesion molecules, plays a pivotal role in facilitating intercellular signal transmission across membranes and is indispensable for proper neuronal development and function. This study identified a rare missense variant (c.1759G>C; p.G587R) in the L1CAM gene within a male fetus presenting with hydrocephalus. Due to a lack of functional analysis, the significance of the L1CAM mutation c.1759G>C (p.G587R) remains unknown. We aimed to perform further verification for its pathogenicity. Blood samples were obtained from the proband and his parents for trio clinical exome sequencing and mutation analysis. Expression level analysis was conducted using western blot techniques. Immunofluorescence was employed to investigate L1CAM subcellular localization, while cell aggregation and cell scratch assays were utilized to assess protein function. The study showed that the mutation (c.1759G>C; p.G587R) affected posttranslational glycosylation modification and induced alterations in the subcellular localization of L1‐G587R in the cells. It resulted in the diminished expression of L1CAM on the cell surface and accumulation in the endoplasmic reticulum. The p.G587R altered the function of L1CAM protein and reduced homophilic adhesion capacity of proteins, leading to impaired adhesion and migration of proteins between cells. Our findings provide first biological evidence for the association between the missense mutation (c.1759G>c; p.G587R) in the L1CAM gene and L1 syndrome, confirming the pathogenicity of this missense mutation. Significance statement: This study identified a rare missense variant (c.1759G>C; p.G587R) in the L1CAM gene within a male fetus presenting with hydrocephalus. Due to a lack of functional analysis, the significance of the L1CAM mutation C.1759G>C (p.G587R) remains unknown according to the ACMG. Variants of uncertain significance cannot perform diagnosed prenatal, so further verification of their pathogenicity is required. Functional analysis at the cellular level in our experiment demonstrated that mutation affected posttranslational glycosylation modifications of L1CAM, altering its subcellular localization and thus affecting the function of protein. Our findings provide first biological evidence for the association between the missense mutation (c.1759G>C; p.G587R) in L1CAM and L1 syndrome, confirming the pathogenicity of this missense mutation. [ABSTRACT FROM AUTHOR]

Introduction: Objective: Prenatal detection of congenital heart disease (CHD) using fetal echocardiography (FE) helps in early diagnosis leading to prompt management and treatment. FE provides a highly accurate non-invasive modality to improve the survival or quality of life of CHD patients. The aim of this study was to evaluate the antenatal detection of CHD by FE and compare it with the results of postnatal echocardiography. Methods: A prospective cohort study of pregnant women referred to a tertiary center Imam-Reza Hospital, Mashhad, Iran, for performing FE in the hands of an experienced pediatric cardiologist between 2012 and 2021. Cardiac echocardiography was performed by GE Vivid 7 color Doppler and Mindray Resona 7 color Doppler with convex probe 5-7 megahertz during late first trimester or early second trimester and after birth until 2 months later. Data were analyzed using SPSS and MedCalc software, and agreement was assessed using kappa. Results: Out of 261 studied fetuses, 101 normal cases were detected in full agreement with postnatal echo diagnosis. Acceptable diagnosis was found for septal defects; VSDs were highly statistically detected (sensitivity= 90%, specificity= 93%). Complex CHDs were found to be the most accurate prenatal diagnosis. Right arch anomalies, aortic stenosis, hypoplastic left heart syndrome and cardiac masses were perfectly acceptable, but detection of coarctation of the aorta faced with over-diagnosis. Prenatally diagnosed arrhythmias without structural defects, mostly premature beats, shifted to normal postnatal echo. Conclusion: FE is a safe and sensitive modality in prenatal diagnosis of CHDs. The study showed the effectiveness accuracy of early first trimester; also complete detection in both sides of the defect spectrum. [ABSTRACT FROM AUTHOR]

Multiple congenital contractures (MCC) due to fetal akinesia manifest across a broad spectrum of diseases, ranging from mild distal arthrogryposis to lethal fetal akinesia deformation sequence. We hereby present a series of 26 fetuses displaying severe MCC phenotypes from 18 families and describe detailed prenatal ultrasound findings, postmortem clinical evaluations, and genetic investigations. Most common prenatal findings were abnormal facial profile (65%), central nervous system abnormalities (62%), polyhydramnios (50%), increased nuchal translucency (50%), and fetal hydrops (35%). Postmortem examinations unveiled additional anomalies including facial dysmorphisms, dysplastic skeletal changes, ichthyosis, multiple pterygia, and myopathy, allowing preliminary diagnosis of particular Mendelian disorders in multiple patients. Evaluation of the parents revealed maternal grip myotonia in one family. By exome sequencing and targeted testing, we identified causative variants in ACTC1, CHST14, COG6, DMPK, DOK7, HSPG2, KLHL7, KLHL40, KIAA1109, NEB, PSAT1, RAPSN, USP14, and WASHC5 in 15 families, and one patient with a plausible diagnosis associated with biallelic NEB variants. Three patients received a dual diagnosis. Pathogenic alterations in newly discovered genes or in previously known genes recently linked to new MCC phenotypes were observed in 44% of the cohort. Our results provide new insights into the clinical and molecular landscape of lethal MCC phenotypes. [ABSTRACT FROM AUTHOR]

Purpose: To establish a reliable nomogram model to predict the risk of major adverse pregnancy outcomes in pregnant women with adenomyosis, and to provide a reference tool for the hierarchical management and the prenatal examination of pregnant women. Methods: We collected the clinical data of pregnant women with adenomyosis who were treated in the First Affiliated Hospital of Chongqing Medical University, the Women and Children's Hospital of Chongqing Medical University, and Yubei District People's Hospital of Chongqing from January 2014 to June 2020. They were divided into the training cohort and the validation cohort, respectively. In the training cohort, we screened out risk factors associated with major adverse pregnancy outcomes and established a model, which was subsequently validated. Results: In the training cohort, we found that previous parity, natural conception or not, type of adenomyosis, with or without endometriosis, history of infertility or adverse pregnancy outcomes, and history of uterine body surgery were associated with major adverse pregnancy outcomes of pregnant women with adenomyosis, and based on these factors, a nomogram model was constructed. The calibration curves of the model were well fitted in both the training and validation cohorts. The receiver-operating characteristic curve (ROC curve) showed that the area under the curve (AUC) was 0.873 and 0.851 in the training and validation cohorts, respectively. The optimal risk threshold of the model was 0.22, and this threshold can be applied to risk stratification of pregnant women. Conclusion: The nomogram model established in this study can reliably predict the risk of major APO in pregnant women with AD. [ABSTRACT FROM AUTHOR]

Technological advancements before and after delivery have greatly altered the counseling of pregnant patients facing a fetal diagnosis of severe oligohydramnios or anhydramnios secondary to congenital anomalies of the kidneys and urinary tract. Once considered a nearly uniformly lethal abnormality, long-term survival may now be possible secondary to prenatal innovations aimed restoring the amniotic fluid volume and the availability of more advanced neonatal dialysis techniques. However, these available therapies are far from perfect. The procedures are onerous for pregnant patients without a guarantee of success, and families must prepare themselves for the complex life-long medical care that will be necessary for surviving individuals. Multidisciplinary counseling is imperative to help pregnant individuals understand the complexity of these conditions and assist them in exercising their right to informed decision-making. Moreover, as with any developing field of medicine, providers must contend with ethical questions related to the treatment options, including questions regarding patient-hood, distributive justice, and the blurred lines between research, innovation, and standard care. These ethical questions are best addressed in a multidisciplinary fashion with consideration of multiple points of view from various subspecialties. Only by seeing the entirety of the picture can we hope to best counsel patients about these highly complex situations and help navigate the most appropriate care path. [ABSTRACT FROM AUTHOR]

To report the outcome of fetuses with a prenatal diagnosis of congenital lung malformation (CLM) diagnosed on ultrasound by performing a comprehensive assessment of these outcomes through a systematic review and meta-analysis. CLMs are a heterogeneous group of anomalies that involve the lung parenchyma and its bronchovascular structures. Their presentation and evolution are variable, from entirely asymptomatic lesions with sonographic regression in utero to hydropic fetuses requiring fetal therapy, intrauterine death or neonatal morbidity. A systematic review was conducted in Medline, Embase and Cochrane databases including studies on fetuses with CLM diagnosed prenatally in order to report the in-utero natural history of these lesions. Thirty-nine studies (2,638 fetuses) were included in the final review. Regression/reduction in size of the lung lesion during pregnancy was reported in 31 % of cases, while its increase in 8.5 % of cases. Intra-uterine death complicated 1.5 % of pregnancies with fetal CLM, while neonatal and perinatal death were 2.2 and 3 %, respectively. Neonatal morbidity occurred in 20.6 % of newborns with CLM; 46 % had surgery, mainly elective. In fetuses with CLM and hydrops, fetal/perinatal loss occurred in 42 %. Assessment of the role of fetal therapy in improving the outcomes of pregnancies complicated by CLM was hampered by the small number of included cases and heterogeneity of type of interventions. Fetuses with CLM prenatally diagnosed have a generally favorable outcome. Conversely, there is a low quality of evidence on the actual role of fetal therapy in improving the outcome of fetuses presenting with these anomalies. [ABSTRACT FROM AUTHOR]

With the availability of Next Generation Sequencing (NGS) diagnosis of genetic disorders has improved significantly. Its use is also applicable to ascertain diagnosis and management in a perinatal setting. The study aims to detect the genetic aetiology of various congenital structural and functional defects using NGS technology in the reproductive cohort at a tertiary centre. The secondary objective is to address challenges in the interpretation of variants. This was a retrospective study of couples who underwent exome sequencing (Mono-testing proband only or Duo-testing parents only or Trio-testing proband and parents) for suspected single gene disorders between years 2020–2022 at a tertiary care perinatal center in the South India. American College of Medical Genetics (ACMG) guidelines were followed to classify the pathogenicity of the variants identified by exome sequencing. The overall diagnostic yield as defined by pathogenic/likely pathogenic variants obtained was (23/43) 53.4 %. The individual subsets have the following diagnostic yield viz., Mono 5/6 (83 %); Carrier 16/32 (50 %); Trio 2/5 (40 %). Diagnostic yield was significantly higher in consanguineous couples. However, miscarriage history, and organ system involvement did not have a significant effect on the diagnostic yield. Prenatal diagnosis was offered for seven patients based on the exome result. One fetus was confirmed with a compound heterozygous pathogenic variant. Diagnostic yield of exome sequencing in our cohort was 53 %. The detection of pathogenic variants was maximum in those cases undergoing Mono exome sequencing. In places where there is a high prevalence of consanguinity and endogamy, NGS may be offered as first line test in the context of prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Decisional conflict and regret about prenatal genetic screening and diagnostic tests may have important consequences in the current pregnancy and for future reproductive decisions. Identifying mechanisms that reduce conflict associated with the decision to use or decline these options is necessary for optimal patient counseling. We conducted a cluster-randomized controlled trial of a shared decision-making tool (NEST) at the beginning of prenatal care. Enrolled patients completed follow-up surveys at the time of testing (QTT) and in the second–third trimester (QFF), including the Decision Conflict Scale (DCS). Total DCS scores were analyzed using a multivariate linear mixed-effect model. Of the total number of participants (n=502) enrolled, 449 completed the QTT and QFF surveys. The mean age of participants was 31.6±3.8, with most parous at the time of study participation (n=321; 71.7 %). Both the NEST (the intervention) and control groups had lower median total DCS scores at QFF (NEST 13.3 [1.7, 25.0] vs. control 16.7 [1.7, 25.0]; p=0.24) compared to QTT (NEST 20.8 [5.0, 25.0] vs. control 18.3 [3.3, 26.7]; p=0.89). Participants exposed to NEST had lower decisional conflict at QFF compared to control (β −3.889; [CI −7.341, −0.437]; p=0.027). Using a shared decision-making tool at the start of prenatal care decreased decisional conflict regarding prenatal genetic testing. Such interventions have the potential to provide an important form of decision-making support for patients facing the unique type of complex and preference-based choices about the use of prenatal genetic tests. [ABSTRACT FROM AUTHOR]

Background: Caring for parents continuing pregnancy after learning about a severe life-limiting condition in their unborn is challenging. Most existing studies focus on affected families, whereas research on the subjective experience of care professionals is scarce. Aim: We aimed to (1) explore experiences and needs of involved care professionals, (2) obtain information about existing care structures, and (3) identify requirements for a structured perinatal palliative care program. Design: Grounded Theory study using theoretical sampling. Data was collected by semi-structured interviews and analyzed following the principles of grounded theory coding and situational analysis. Setting: A total of 18 professionals from 12 different services in Munich and surroundings participated in the study: 8 physicians, 3 midwives, 2 nurses, 1 each pregnancy counselor, grief counselor, chaplain, clinical psychologist, and undertaker. Results: Several organizations provide support for affected parents, but inter-institutional communication is scarce. Due to the lack of a dedicated perinatal palliative care program, professionals make immense and partly unpaid efforts to support concerned parents. Providers experience "collateral beauty" in their work despite all the suffering and grief. This includes the development of a humble attitude and feelings of gratitude toward life, the feeling of having a meaningful task and professional as well as personal growth. Requirements for a structured perinatal palliative care program include: fostering peer support, ensuring regular supervision, and enhancing interdisciplinary exchange. Conclusions: Perinatal palliative care demands a high level of personal engagement but is experienced as highly rewarding by care professionals. [ABSTRACT FROM AUTHOR]

Background: The protein kinase domain containing cytoplasmic (PKDCC) gene (OMIM#618821) is associated with bone development. Biallelic variants in the PKDCC gene can cause rhizomelic limb shortening with dysmorphic features. Case Report: A fetus was found to be rhizomelic limb shortening at 16 weeks of gestation and amniocentesis was performed at 19 weeks of gestation. Genomic DNA extracted from the amniotic fluid was subjected to chromosomal microarray analysis (CMA), and Trio‐total whole‐exome sequencing (Trio‐WES). Sanger sequencing was used to verify the candidate pathogenic variants. CMA was normal, while Trio‐WES identified two compound heterozygous variants in the PKDCC gene, namely c.417_c.423delCGGCGCG insTCATGGGCTCAGTACAC(p.G140fs*35) and c.345G>A (p.W115*,379). Then the fetus was aborted and the development of its bone cells were compared with that of a normal fetus of similar gestational age by histopathological examination. Clinical findings of the fetus were shortening humerus and femur, synophrys, much hair on the side face, simian line on the right palm, etc. Histopathological examination showed that the affected fetus had increased proliferative chondrocytes, widened proliferative bands, and delayed bone mineralization. Conclusions: We reported a prenatal case of rhizomelic shortening of limbs caused by compound heterozygous variants in the PKDCC gene, which emphasized the important role of Trio‐WES for diagnosis of skeletal dysplasia in fetuses. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the outcomes and demographics of encephalocele patients who were born and received treatment in our neonatal ICU and conduct a PRISMA literature review. Methods: An Institutional Review Board (IRB)-approved retrospective cohort study was undertaken to investigate the results of treating encephalocele patients at Jackson Memorial Hospital (JMH) from 1998 to 2022. The study focused on assessing outcomes and the impact of maternal socioeconomic factors, such as religion, age, and education, along with the timing of diagnosis, in connection with a systematic review. Results: A total of 20 encephalocele patients were identified (13 females and 7 males), with 15 having available medical records for review. Most of these cases involved occipital encephaloceles (73.3%). Maternal ages at the time of delivery ranged from 15 to 42 years, with a mean age of 27.3 years. The average gestational age at birth was 37 weeks. Ten cases had a prenatal diagnosis documented, occurring between 12 and 24.5 weeks of gestation. Three of the surviving patients had records of prenatal counseling that included discussions about termination. No infections were reported. Among the 15 cases, 11 patients (73.3%) were alive at the last follow-up, with a mean age at follow-up of 4.12 years, ranging from 6 weeks to 15 years post-birth. Hydrocephalus was noted in 26.7%. Only 1 mother had completed high school. Most mothers were either on Medicaid (9 patients) or uninsured (3 patients), with only 3 having commercial insurance. Religious affiliations varied among the mothers, with 14 out of 15 identifying with a particular religion. The systematic review identified 22 articles from various countries, with 11 articles meeting the inclusion criteria for qualitative analysis. These articles revealed potential maternal risk factors for encephaloceles, including low-nutrient diets, inadequate folic acid intake, young maternal age, advanced maternal age, low socioeconomic status, and limited educational attainment. Conclusions: In the twenty-first century, there is a positive trend in the survival rates of children born with encephalocele. However, maternal factors such as low socioeconomic status and limited educational attainment remain prominent, affecting their ability to access timely prenatal care and impacting follow-up medical care for these children. [ABSTRACT FROM AUTHOR]

Objectives: To compare 5-year survival rate and morbidity in children with spina bifida, transposition of great arteries (TGA), congenital diaphragmatic hernia (CDH) or gastroschisis diagnosed prenatally with those diagnosed postnatally. Methods: Population-based registers' data were linked to hospital and mortality databases. Results: Children whose anomaly was diagnosed prenatally (n = 1088) had a lower mean gestational age than those diagnosed postnatally (n = 1698) ranging from 8 days for CDH to 4 days for TGA. Children with CDH had the highest infant mortality rate with a significant difference (p < 0.001) between those prenatally (359/1,000 births) and postnatally (116/1,000) diagnosed. For all four anomalies, the median length of hospital stay was significantly greater in children with a prenatal diagnosis than those postnatally diagnosed. Children with prenatally diagnosed spina bifida (79% vs 60%; p = 0.002) were more likely to have surgery in the first week of life, with an indication that this also occurred in children with CDH (79% vs 69%; p = 0.06). Conclusions: Our findings do not show improved outcomes for prenatally diagnosed infants. For conditions where prenatal diagnoses were associated with greater mortality and morbidity, the findings might be attributed to increased detection of more severe anomalies. The increased mortality and morbidity in those diagnosed prenatally may be related to the lower mean gestational age (GA) at birth, leading to insufficient surfactant for respiratory effort. This is especially important for these four groups of children as they have to undergo anaesthesia and surgery shortly after birth. Appropriate prenatal counselling about the time and mode of delivery is needed. Significance: What is already known on this subject?: Prenatal detection of congenital anomalies has become more common with improvements in technology and increased accuracy of detection. Previous findings on the effect of timing of diagnoses on newborn outcomes are limited and conflicting. What this study adds?: Our findings do not show better outcomes for prenatally diagnosed infants with spina bifida, transposition of great arteries, congenital diaphragmatic hernia or gastroschisis. More severe anomalies may be more likely to be prenatally detected. Appropriate prenatal counselling about the time and mode of delivery is needed. [ABSTRACT FROM AUTHOR]

Since the summer of 2022, statutory health insurance in Germany reimburses the costs of using non-invasive prenatal testing (NIPT), a new technology used in prenatal testing, in 'justified individual cases'. Analysing moments in the long debate on NIPT in Germany through the framework of bioconstitutionalism and with pragmatic lenses helps us to understand how and why this comparatively unique reimbursement decision became a reasonable and moral one. Conflicts and conversations in these moments reveal two competing definitions and visions of human life relating to measures deemed desirable and legitimate to protect that life. Actors articulating a liberal bioconstitutional vision framed NIPT as a biomedical technology that could protect the lives of foetuses and enable women to exercise their right to know without putting their pregnancy at risk. Actors foregrounding a societal bioconstitutional vision framed NIPT as a selective technology and spoke in the name of all those lives that would be affected by the direct and indirect consequences of NIPT. When public health care authorities endorsed NIPT as a biomedical technology to be reimbursed in individual cases, they sought to reconcile elements of both visions. The case of Germany shows that enduring controversies on reproductive technologies can put constraints on what state authorities are allowed to do. It also suggests that moral controversies on reproductive technologies and the salience of private markets of reproductive care might be the two sides of the same coin. [ABSTRACT FROM AUTHOR]

This is a single tertiary population-based study conducted at a center in southwest Romania. We retrospectively compared data obtained in two periods: January 2008–December 2013 and January 2018–December 2023. The global incidence of the transposition of great arteries in terminated cases, in addition to those resulting in live-born pregnancies, remained almost constant. The live-birth incidence decreased. The median gestational age at diagnosis decreased from 29.3 gestational weeks (mean 25.4) to 13.4 weeks (mean 17.2). The second trimester and the overall detection rate in the prenatal period did not significantly change, but the increase was statistically significant in the first trimester. The proportion of terminated pregnancies in fetuses diagnosed with the transposition of great arteries significantly increased (14.28% to 75%, p = 0.019). [ABSTRACT FROM AUTHOR]

Prenatal diagnosis of critical congenital heart disease (CCHD) has improved over time, and previous studies have identified CCHD subtype and socioeconomic status as factors influencing rates of prenatal diagnosis. Our objective of this single-center study was to compare prenatal diagnosis rates of newborns with CCHD admitted for cardiac intervention from the COVID-19 pandemic period (March 2020 to March 2021) to the pre-pandemic period and identify factors associated with the lack of CCHD prenatal diagnosis. The overall rate of CCHD and rates of the various CCHD diagnoses were calculated and compared with historical data collection periods (2009–2012 and 2013–2016). Compared with the 2009–2012 pre-pandemic period, patients had 2.17 times higher odds of having a prenatal diagnosis of CCHD during the pandemic period controlling for lesion type (aOR = 2.17, 95% CI 1.36–3.48, p = 0.001). Single ventricle lesions (aOR 6.74 [4.64–9.80], p < 0.001) and outflow tract anomalies (aOR 2.20 [1.56–3.12], p < 0.001) had the highest odds of prenatal diagnosis compared with the remaining lesions. Patients with outflow tract anomalies had higher odds for prenatal detection in the pandemic period compared with during the 2009–2012 pre-pandemic period (aOR 2.01 [1.06–3.78], p = 0.031). In conclusion, prenatal detection of CCHD among newborns presenting for cardiac intervention appeared to have improved during the pandemic period. [ABSTRACT FROM AUTHOR]

Congenitally corrected transposition of the great arteries (ccTGA) is a rare malformation with diverse morphology. We assessed features of fetuses with ccTGA and evaluated neonatal and pediatric outcomes. This was a retrospective review of fetuses with ccTGA at Birmingham Women's and Children's Hospital born from 2005 to 2019. Of thirty-six fetuses identified, six had unavailable prenatal data, one was postnatally diagnosed with isomerism and 29 fetuses were evaluated. ccTGA without associated cardiac lesions was found in 28% (8/29), ccTGA with significant VSD in 31% (9/29), ccTGA with pulmonary obstruction in 24% (7/29) and ccTGA with complex anomalies in 17% (5/29). Tricuspid regurgitation (TR) was observed in 17% (5/29) and heart block (HB) in 10% (3/29) prenatally. Six, that is 21% underwent genetic testing of which one was abnormal. Five extra-cardiac anomalies were reported prenatally and postnatally. Pregnancy was discontinued in five, of which two had moderate TR. There were thirty-one liveborn. Coarctation of the aorta was found in five postnatally but not suspected prenatally. In one, pulmonary stenosis was underestimated; otherwise, prenatal morphology was confirmed. Cardiac interventions were performed in 77% (24/31) liveborn with 39% (12/31) undergoing neonatal intervention. Overall, 6/31 liveborn died including all three with prenatal heart block and one with TR. Estimated survival for all liveborn at 1, 5 and 10 years was 87% (95% CI 76–100%), 83% (95% CI 72–98%) and 80% (95% CI 66–96%) respectively. Accurate prenatal diagnosis of ccTGA is critical for counseling. Early outcomes are favorable with 77% of liveborn undergoing surgery. Fetuses with prenatal diagnosis of complex associated abnormalities, HB and TR appear to do less well. [ABSTRACT FROM AUTHOR]

Objective: Craniorachischisis is a rare and severe variant of neural tube defects (NTDs). It occurs in 0.51 of every 10,000 pregnancies. There is no reported etiology for this fetal abnormality. Material and methods: Over 13 years data was obtained retrospectively. Fetuses diagnosed to have craniorachischisis whose definite diagnoses were clarified by necroscopy were enrolled in the study. Results: We present six cases diagnosed with Craniorachischisis in our clinic in the last 13 years, whose definitive diagnosis was clarified by necroscopy. Craniorachischisis is still a vital anomaly because it is a severe anomaly itself and the rate of accompanying other abnormalities is high. Fully elucidating the cause can also be a guide for others. Conclusion: Craniorachischisis can be diagnosed in the first trimester. The vertebral column should especially be examined in patients diagnosed with exencephaly. The heart, extremities, and thoracic-abdomen should be carefully examined when craniorachischisis is diagnosed. The rate of other anomalies accompanying is high. In future research, if the cause of craniorachischisis is understood, it will provide an understanding of the cause of other accompanying this anomaly. [ABSTRACT FROM AUTHOR]

Mosaicism for autosomal trisomy is uncommon in clinical practice. However, despite its rarity among both prenatally and postnatally diagnoses, there are a large number of characterized and published cases. Surprisingly, in contrast to regular trisomies, no attempts at systematic analyses of mosaic carriers' demographics were undertaken. This is the first study aimed to address this gap. For that, we have screened more than eight hundred publications on mosaic trisomies, reviewing data including gender and clinical status of mosaic carriers, maternal age and reproductive history. In total, 596 publications were eligible for analysis, containing data on 948 prenatal diagnoses, including true fetal mosaicism (TFM) and confined placental mosaicism (CPM), and on 318 cases of postnatally detected mosaicism (PNM). No difference was found in maternal age between normal pregnancy outcomes with appropriate birth weight and those with intrauterine growth restriction. Unexpectedly, a higher proportion of advanced maternal ages (AMA) was found in normal outcomes compared to abnormal ones (abnormal fetus or newborn) and fetal losses, 73% vs. 56% and 50%, p = 0.0015 and p = 0.0011, correspondingly. Another intriguing finding was a higher AMA proportion in mosaic carriers with concomitant uniparental disomy (UPD) for chromosomes 7, 14, 15, and 16 compared to carriers with biparental disomy (BPD) (72% vs. 58%, 92% vs. 55%, 87% vs. 78%, and 65% vs. 24%, correspondingly); overall figures were 78% vs. 48%, p = 0.0026. Analysis of reproductive histories showed a very poor reporting but almost two-fold higher rate of mothers reporting a previous fetal loss from PNM cohort (in which almost all patients were clinically abnormal) compared to mothers from the TFM and CPM cohorts (with a large proportion of normal outcomes), 30% vs. 16%, p = 0.0072. The occurrence of a previous pregnancy with a chromosome abnormality was 1 in 13 in the prenatal cohort and 1 in 16 in the postnatal cohort, which are five-fold higher compared to published studies on non-mosaic trisomies. We consider the data obtained in this study to be preliminary despite the magnitude of the literature reviewed since reporting of detailed data was mostly poor, and therefore, the studied cohorts do not represent "big data". Nevertheless, the information obtained is useful both for clinical genetic counseling and for modeling further studies. [ABSTRACT FROM AUTHOR]

Celocentesis is a new sampling tool for prenatal diagnosis available from 7 weeks in case of couples at risk for genetic diseases. In this study, we reported the feasibility of earlier prenatal diagnosis by celocentesis in four cases of cystic fibrosis and one case of cystic fibrosis and β-thalassemia co-inherited in the same fetus. Celomic fluids were aspired from the celomic cavity between 8+2 and 9+3 weeks of gestation and fetal cells were picked up by micromanipulator. Maternal DNA contamination was tested and target regions of fetal DNA containing parental pathogenetic variants of CFTR and HBB genes were amplified and sequenced. Four of the five fetuses resulted as being affected by cystic fibrosis and, in all cases, the women decided to interrupt the pregnancy. In the other case, the fetus presented a healthy carrier of cystic fibrosis. The results were confirmed in three cases on placental tissue. In one case, no abortive tissue was obtained. In the last case, the woman refused the prenatal diagnosis to confirm the celocentesis data; the pregnancy is ongoing without complications. This procedure provides prenatal diagnosis of monogenic diseases at least four weeks earlier than traditional procedures, reducing the anxiety of patients and providing the option for medical termination of the affected fetus at 8–10 weeks of gestation, which is less traumatic and safer than surgical termination in the second trimester. [ABSTRACT FROM AUTHOR]

• Prenatal diagnosis is an important issue in cases like pelvic kidney because early detection can give the opportunity for anatomic and genetic screening for related anomalies. • Pelvic kidneys could be diagnosed in the early prenatal period. • Postnatal follow-up should be performed closely for the assessment of renal functions. Evaluation of demographic characteristics and postnatal outcomes of patients with suspected fetal pelvic kidney diagnosis followed in a tertiary center. This retrospective study was conducted in Ankara Bilkent City Hospital perinatology clinic between 2020–2023. Demographic features, prenatal ultrasound findings, and postnatal outcomes were reported. Pelvic kidney localization was on the left in 11(55 %) patients, on the right in 7(35 %), and bilateral in 2(10 %) patients in prenatal ultrasonography. The gender of the 12(60 %) fetuses were male and 8(40 %) of them were female. The pelvic kidney was an isolated finding in 8(40 %) fetuses, additional findings were present in the remaining 12(60 %) fetuses. Pelvic kidney was confirmed postnatally by ultrasound in all 18 fetuses. However two cases with prenatal ultrasound findings resulted in intrauterine fetal demise and the final diagnosis could not be confirmed as the parents refused autopsia. Cases were divided into 3 groups according to postnatal follow-up duration as 0–12 months (n = 7), 12–24 months (n = 7) and 24–44 months (n = 4). Atrial septal defect was the most common accompanying abnormality in the postnatal period (n = 4). Smaller kidney size (n = 7), vesicoureteral reflux (n = 3), and impaired renal function (n = 3) were the most common postnatal complications. Pelvic kidney can be diagnosed in fetal abnormality screening ultrasound and postnatal follow-up should be performed closely for the assessment of renal functions. [ABSTRACT FROM AUTHOR]

• Fetuses with isolated choroid plexus cyst is related to chromosome abnormalities and pathogenic or likely pathogenic copy number variants (CNVs). • There is a possibility of residual risk when providing NIPT. To evaluate the the diagnostic yield of chromosomal microarray analysis (CMA) in fetuses with isolated CPC (iCPC). A total of 315 fetuses with iCPC (iCPC group) and 364 fetuses without abnormal ultrasound findings (control group) were recruited between July 2014 to March 2018. The overall diagnostic yield of chromosomal abnormalities by CMA and karyotyping in iCPC group was up to 4.1 %, higher than 1.4 % in the control group, p < 0.05. The detection rate of pathogenic or likely pathogenic copy number variants (CNVs) with clinical significance by CMA in iCPC group (1.3 %) was higher than in control group (0 %), p < 0.05. According to the type of chromosome abnormalities, the missed diagnosis rate of non-invasive prenatal testing (NIPT) was 1.6 % in our study. The presence of iCPC on ultrasound examination suggests a potential indication for genetic counseling. Karyotyping and chromosomal microarray analysis may be considered for fetuses with iCPC. It is important to be aware of the limitations of non-invasive prenatal testing, as there is a possibility of residual risk. [ABSTRACT FROM AUTHOR]

This article discusses a case study involving the prenatal detection and neonatal surgical resection of a giant aneurysm in the left atrial appendage of a fetus. The study highlights the feasibility of prenatal diagnosis and emphasizes the importance of timely assessment and treatment in the early postpartum period. The use of multimodal imaging is also emphasized for accurate characterization of the appendage and optimal surgical planning. The article concludes by noting that giant aneurysms in the left atrial appendage are rare and potentially associated with thromboembolism. [Extracted from the article]

Placental development is a complex process which sets the stage for normal fetal development. Any variation/disruption occurring during the initial stages of placental formation leads to placental malfunction causing increased maternal–fetal morbidity and mortality. The succenturiate lobe is a structural variation of the placenta that usually appears as a distinct lobe from the main placental mass. Succenturiate lobe is a rare placental anomaly, with high risk of fetal distress, hemorrhage, abruptio placentae and even fetal death because the vessels of this succenturiate lobe are vulnerable to both compression and laceration. Prenatal imaging diagnosis of this pathology improves the fetal prognosis through more careful surveillance and, in case of complications such as abruptio placentae, by shortening the time-to-decision making in favor of cesarean delivery. We present the case of a 27-year-old patient, without risk factors for placental abnormalities, diagnosed antenatally with succenturiate placenta, who presented at 34 weeks of pregnancy for abruptio placentae. [ABSTRACT FROM AUTHOR]

Aim To develop a non-invasive prenatal test for beta-hemoglobinopathies based on analyzing maternal plasma by using next generation sequencing. Methods We applied next generation sequencing (NGS) of maternal plasma to the non-invasive prenatal testing (NIPT) of autosomal recessive diseases, sickle cell disease and beta-thalassemia. Using the Illumina MiSeq, we sequenced plasma libraries obtained via a Twist Bioscience probe capture panel covering 4 Kb of chromosome 11, including the beta-globin (HBB) gene and >450 genomic single-nucleotide polymorphisms (SNPs) used to estimate the fetal fraction (FF). The FF is estimated by counting paternally transmitted allelic sequence reads present in the plasma but absent in the mother. We inferred fetal betaglobin genotypes by comparing the observed mutation (Mut) and reference (Ref ) read ratios to those expected for the three possible fetal genotypes (Mut/Mut; Mut/Ref; Ref/ Ref ), based on the FF. Results We bioinformatically enriched the FF by excluding reads over a specified length via in-silico size selection (ISS), favoring the shorter fetal reads, which increased fetal genotype prediction accuracy. Finally, we determined the parental HBB haplotypes, which allowed us to use the read ratios observed at linked SNPs to help predict the fetal genotype at the mutation site(s). We determined HBB haplotypes via Oxford Nanopore MinION sequencing of a 2.2 kb amplicon and aligned these sequences using Soft Genetics' NextGENe LR software. Conclusion The combined use of ISS and HBB haplotypes enabled us to correctly predict fetal genotypes in cases where the prediction based on variant read ratios alone was incorrect. [ABSTRACT FROM AUTHOR]

Objective: To analyze the value of prenatal ultrasound and molecular testing in diagnosing fetal skeletal dysplasia (SD). Methods: Clinical data, prenatal ultrasound data, and molecular results of pregnant women with fetal SD were collected in the ultrasound department of our clinic from May 2019 to December 2021. Results: A total of 40 pregnant women with fetal SD were included, with 82.5% exhibiting short limb deformity, followed by 25.0% with central nervous system malformations, 17.50% with facial malformations, 15% with cardiac malformations, and 12.5% with urinary system malformations. The genetic testing positive rate was 70.0% (28/40), with 92.8% (26/28) being single‐gene disorders due to mutations in FGFR3, COL1A1, COL1A2, EVC2, FLNB, LBR, and TRPV4 genes. The most common SD subtypes were osteogenesis imperfecta (OI), thanatophoric dysplasia (TD), and achondroplasia (ACH). The gestational age (GA) at initial diagnosis for TD, OI, and ACH was 16.6, 20.9, and 28.3 weeks, respectively (p < 0.05), with no significant difference in femoral shortening between the three groups (p > 0.05). Of the OI cases, 5 out of 12 had a family history. Conclusion: Short limb deformity is the most prevalent phenotype of SD. When fetal SD is suspected, detailed ultrasound screening should be conducted, combined with GA at initial diagnosis, family history, and molecular evidence, to facilitate more accurate diagnosis and enhance prenatal counseling and perinatal management. [ABSTRACT FROM AUTHOR]

Hereditary Hemorrhagic Telangiectasia (HHT), commonly known as Osler–Weber–Rendu disease, is an autosomal dominant multisystemic vascular disease associated with approximately 70% of cases of pulmonary arteriovenous malformations (PAVMs). Prenatal cases of PAVMs typically present with pulmonary vein dilatation on ultrasonography. This study presents a prenatal diagnosis of PAVMs with enlarged right pulmonary vein, cardiomegaly, cystic‐appearing areas in the right lung and subsequent confirmation of Osler–Weber–Rendu syndrome using autopsy and whole exom sequencing. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to develop a sonographic technique using two-dimensional (2D) markers for detecting isolated fetal cleft palate (no cleft lip) and to evaluate the ability of 2D and three-dimensional (3D) sonography to image the normal and abnormal palate. Methods: Seventy-three fetuses with a high risk of cleft palate at 12-39 weeks of gestation were referred for specialist ultrasound. A detailed evaluation of the palate was performed through 2D ultrasound, which revealed the appearance of the palatine line in the sagittal plane; the palate and alveolar ridge in the coronal plane of the fetal face; the horizontal plate of the palatine bone in the axial maxillary plane; and the soft palate in the transverse plane of the cavum pharyngis. Subsequently, 3D ultrasound imaging of the palate was performed in all fetuses. Antenatal diagnoses were compared with postnatal findings or autopsy findings. Results: Visualization of 2D markers was accomplished in all fetuses, and 3D assessment was achieved in 97% of fetuses. Cleft palate was suspected in 16 cases (21.9%), among which 14 were suspected on the basis of both 2D and 3D evaluation, and two were suspected only on the basis of 3D evaluation. A normal palate was observed in 57 fetuses (78.1%). The mean gestational age was 27 weeks (range of 12 weeks to 39 weeks). All 16 fetuses with suspected cleft palate were confirmed by postnatal or autopsy findings, no false-positives were observed, and one case with a bifid uvula was missed among 57 fetuses with a presumed normal palate. Conclusions: The fetal palate can be evaluated with 2D markers and 3D sonography. The detection of isolated cleft palate is more sensitive when 2D markers are present in all four planes. [ABSTRACT FROM AUTHOR]

Objectives: To explore the image characteristics and main types of abnormal branching of fetal pulmonary artery in prenatal echocardiography. Material and methods: A retrospective analysis of 41 cases diagnosed with abnormal branching of fetal pulmonary artery by prenatal echocardiography was made. The image characteristics of the abnormalities, their combination with intra- or extra-cardiac malformations and chromosomal anomalies were analyzed. Results: The results of prenatal echocardiography showed that, among the 41 cases: 1) 4 cases were with anomalous origin of single pulmonary artery, 8 cases with pulmonary artery agenesis, 9 cases with pulmonary artery sling; 20 cases with crossed pulmonary arteries; 2) 11 cases were complicated with intracardiac malformations and 10 with extracardiac malformations; 3) only 7 case underwent chromosomal examination and 1 tested abnormal; 4) pregnancy outcomes: 25 fetuses were born and their abnormalities confirmed by echocardiography (MRI or surgery) to be consistent with prenatal ultrasound diagnosis; 16 cases had their pregnancy terminated due to their combination with other severe malformations, which were confirmed by pathological anatomy after induced abortion. Conclusions: Prenatal echocardiography can provide detailed images for the diagnosis of abnormal branching of fetal pulmonary artery, which can be complicated by intra- and extracardiac malformations and chromosomal anomalies and should be alerted. [ABSTRACT FROM AUTHOR]

Background: This study's aim was to determine whether diminished oocyte reserve (DOR) increases the risk of having a fetus with trisomy 13, 18, or 21 at 10 weeks as evaluated by non-invasive prenatal testing (NIPT) and to evaluate the confounding effect of advanced age. Methods: NIPT was undertaken in all pregnancies conceived through natural treatment or assisted reproductive technology that reached 10 weeks from conception with a viable fetus from one infertility center. Data were stratified according to serum anti-Mullerian hormone (AMH) < 1 ng/mL and ≥1 ng/mL. Results: No woman < 39 or with AMH ≥ 1 ng/mL showed trisomy 13, 18, or 21 by NIPT. Only women ≥ age 39 with DOR had one of these trisomies. Conclusions: Hopefully these data, coupled with other factors, e.g., etiology of infertility, age, insurance, or financial circumstances, and personal views of pregnancy termination, will aid patients with DOR when choosing treatment options, including natural conception, IVF-ET, IVF with pre-implantation genetic testing for aneuploidy, or transfer of fertilized donor eggs. [ABSTRACT FROM AUTHOR]

Background: In addition to the potential for multiple pregnancies, natural conception occurring in preimplantation genetic testing (PGT) increases undesired genetic risk. Some studies showed that a dichorionic diamniotic twin pregnancy after a single blastocyst transfer could be caused by embryo splitting or concurrent spontaneous conception. Case: We describe a patient undergoing PGT who had a dichorionic diamniotic twin pregnancy after single blastocyst transfer in a natural cycle. In this case, we recommended to determine genetic status of the twins by prenatal diagnosis. The results showed that karyotype, chromosome copy number variation, and parental ACAT1 variation of the twins were all normal and similar. To investigate the origin of pregnancy, we used the genotype data of single‐nucleotide polymorphisms typical of genome‐wide association studies. Dizygotic twins were inferred by robust estimation of kinship coefficients, which confirmed the occurrence of a spontaneous conception. Conclusions: This case strengthens the importance of genetic counseling to inform couples with reproductive genetic risk, such as those who undergo PGT, that intercourse should be avoided, especially in natural transfer cycles. Moreover, prenatal diagnosis remains essential and is strongly recommended to avoid genetic risks. [ABSTRACT FROM AUTHOR]

Although there are numerous benefits to diagnostic prenatal testing, such as fetal exome sequencing, there are also consequences, including the possibility of receiving variants of uncertain significance or identifying secondary findings. In this study, we utilized a survey‐based discrete choice experiment to elicit the preferences of pregnant people in Northern California for hypothetical prenatal genomic tests. Pregnant individuals were invited to complete the survey through advertisements on social media. Five test attributes were studied: likelihood of getting a result, time taken to receive results, who explains results, reporting of uncertain results, and reporting of secondary findings. The survey also gathered information about the participants' demographics, current and past pregnancies, and tolerance of uncertainty using the IUS‐12 scale. Participants were eligible if they were female, currently 24 or more weeks pregnant, and able to read/write enough English or Spanish to complete an online survey. Overall, participants (n = 56) preferred the option of having a prenatal test over not having a prenatal test (p < 0.01) and had substantially higher preferences for tests with the highest likelihood of getting a result (p < 0.01). There were also positive preferences for tests that reported secondary findings (p = 0.01) and those where results were returned by a genetic specialist (vs. their prenatal provider) (p = 0.04). These findings can be used to guide conversations between pregnant individuals and genetics specialists, such as genetic counselors, as they weigh the pros and cons of diagnostic prenatal testing options. [ABSTRACT FROM AUTHOR]

Genetic counseling (GC) following abnormal Down syndrome (DS) screening tests aims to ensure learning of complex medical concepts and discussion of counselees' personal desires. Pre‐GC use of electronic learning tools (e‐learning tools) can facilitate GC sessions by allowing more time for dialogue rather than learning medical and genetic concepts, enabling greater focus on the counselee's decisional, psychological, and personal needs. Few studies have investigated such tools for DS screening tests and those who have focused on screening uptake rather than abnormal results and implications. This study evaluated prenatal GC outcomes following implementation of an e‐learning tool utilizing an educational animated movie for couples of varied ethnic backgrounds in northern Israel, with abnormal DS screening tests. E‐learning tool impact was assessed as knowledge level, informed choices, satisfaction with the intervention and GC process, the state of anxiety and duration of the GC meeting. The 321 study participants were randomized to three groups: animation movie, booklet, and control. All participants had been asked to complete pre‐ and post‐counseling questionnaires. Outcome scores were compared between the research groups. Results showed increased knowledge level in general among participants in the animation group; among minority participants, the highest knowledge level was in the animation group. Anxiety levels and informed choices were not statistically different among the groups. However, watching the animation, Jewish ethnicity, good level of genetic literacy, and academic degree were significant predictors of informed choice, and those who watched the animation were three times more likely to make an informed choice than the control group. Our findings suggest that this e‐learning tool is efficient and acceptable for the general population. Special attention is needed for minorities with lower genetic literacy and education. [ABSTRACT FROM AUTHOR]

Shwachman Diamond Syndrome (SDS) is a multi-system disease characterized by exocrine pancreatic insufficiency with malabsorption, infantile neutropenia and aplastic anemia. Life-threatening complications include progression to acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), critical deep-tissue infections and asphyxiating thoracic dystrophy. In most patients, SDS results from biallelic pathogenic variants in the SBDS gene, different combinations of which contribute to heterogenous clinical presentations. Null variants are not well tolerated, supporting the theory that the loss of SBDS expression is likely lethal in both mice and humans. A novel complex genotype (SBDS:c.[242C>G;258+2T>C];[460-1G>A]/WFS1:c.[2327A>T];[1371G>T]) was detected in a family with recurrent neonatal deaths. A female neonate died three hours after birth with hemolytic anemia, and a male neonate with severe anemia, thrombocytopenia and neutropenia succumbed on day 40 after Staphylococcus epidermidis infection. A subsequent review of the literature focused on fatal complications, complex SBDS genotypes and/or unusual clinical presentations and disclosed rare cases, of which some had unexpected combinations of genetic and clinical findings. The impact of pathogenic variants and associated phenotypes is discussed in the context of data sharing towards expanding scientific expert networks, consolidating knowledge and advancing an understanding of novel underlying genotypes and complex phenotypes, facilitating informed clinical decisions and disease management. [ABSTRACT FROM AUTHOR]