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Objective: To evaluate the clinical features and perinatal outcomes of antenatally diagnosed fetuses with omphalocele and gastroschisis. Material and Methods: This was a retrospective, single-center, cohort study of prenatally diagnosed fetuses with omphalocele and gastroschisis followed-up and delivered at a university hospital. Demographic, pregnancy, birth and perinatal outcomes were compared between gastroschisis and omphalocele. Results: A total of 75 fetuses with omphalocele and 21 cases with gastroschisis were evaluated. The mean maternal age of women carrying a fetus with omphalocele was significantly higher than the women with gastroschisis (p=0.001). Associated structural anomalies were found in 53.3% and 4.7% of fetuses with omphalocele and gastroschisis, respectively (p<0.001). The rate of chromosomal anomaly was 8.3% in pregnancies with omphalocele. In liveborn pregnancies, the mean gestational age at delivery and birth weight did not differ between the study groups. Time to postoperative oral intake, duration of parenteral nutrition and length of hospital stay were significantly longer in babies with gastroschisis than omphalocele (p<0.01). Rates of termination, intrauterine, neonatal and infant death of fetuses with omphalocele were 25.3%, 6.7%, 10.7% and 2.7% respectively. Time to postoperative oral intake, duration of parenteral nutrition and duration of hospitalization were significantly longer in babies with complex compared to simple gastroschisis (p<0.01). Survival rates were 95.2%, 82.9% and 20% in fetuses with gastroschisis, isolated and non-isolated omphalocele, respectively. Conclusion: Associated structural and chromosomal anomalies were significantly more common in fetuses with omphalocele compared to those with gastroschisis. Prognosis of fetuses with omphalocele depended on the associated structural and chromosomal anomalies, whereas bowel compromise was the main determining factor in gastroschisis. [ABSTRACT FROM AUTHOR]

Backgroud: A systematic analysis was conducted to investigate the molecular etiology of fetal cleft lip and/or palate (CL/P) and the association between various types of CL/P and copy number variations (CNVs), as well as their impact on birth outcomes. Methods: In this retrospective study conducted between January 2016 and July 2022, a cohort of pregnancies diagnosed with fetal CL/P was enrolled and comprehensive clinical data for all cases were extracted from our medical record database, including demographic data about the pregnancies, ultrasound findings, results of Chromosomal microarray (CMA), as well as relevant pregnant and perinatal outcomes. Results: Among the 358 cases, 32 clinically significant variants in 29 (8.1%) fetuses with CL/P were detected by CMA. In 338 singleton pregnancies, the diagnostic yield of CMA in the context of CL/P fetuses was determined to be 7.7% (26/338). CP cases exhibited a relatively higher prevalence of pathogenic/likely pathogenic CNVs at a rate of 25% (3/12), followed by CLP cases at 8.0% (23/288). Notably, the CL group did not demonstrate any pathogenic/likely pathogenic CNV findings among the examined cases (0/38). The diagnostic rate of clinically significant variants was notably higher in the non-isolated CL/P group than in the isolated CL/P group (11/33, 33.3% vs. 15/305, 4.9%, p < 0.001). Within the remaining 20 twin pregnancies, three clinically significant variants (15%) were observed. Conclusions: This study provides powerful evidence supporting the efficacy of CMA as a valuable tool for facilitating the prenatal genetic diagnosis of fetal CL/P. The presence of CP and CLP in fetal cases demonstrated a relatively higher incidence of pathogenic/likely pathogenic CNVs. Moreover, when these cases were accompanied by additional ultrasound abnormalities, the likelihood of identifying diagnostic CNVs significantly increased. Conversely, cases of CL alone might not be associated with positive CNVs. The present data may significantly enhance prenatal diagnosis accuracy and facilitate informed genetic counseling for cases of fetal CL/P. [ABSTRACT FROM AUTHOR]

Background: For women in the first trimester, amniocentesis or chorionic villus sampling is recommended for screening. Machine learning has shown increased accuracy over time and finds numerous applications in enhancing decision-making, patient care, and service quality in nursing and midwifery. This study aims to develop an optimal learning model utilizing machine learning techniques, particularly neural networks, to predict chromosomal abnormalities and evaluate their predictive efficacy. Methods/ design: This cross-sectional study will be conducted in midwifery clinics in Mashhad, Iran in 2024. The data will be collected from 350 pregnant women in the high-risk group who underwent screening tests in the first trimester (between 11-14 weeks) of pregnancy. Information collected includes maternal age, BMI, smoking habits, history of trisomy 21 and other chromosomal disorders, CRL and NT levels, PAPP-A and B-HCG levels, presence of insulin-dependent diabetes, and whether the pregnancy resulted from IVF. The study follows up with the women during their clinic visits and tracks the results of amniocentesis. Sampling is based on Convenience Sampling, and data is gathered using a checklist of characteristics and screening/amniocentesis results. After preprocessing, feature extraction is conducted to identify and predict relevant features. The model is trained and evaluated using K-fold cross-validation. Discussion: There is a growing interest in utilizing artificial intelligence methods, like machine learning and deep learning, in nursing and midwifery. This underscores the critical necessity for nurses and midwives to be well-versed in artificial intelligence methods and their healthcare applications. It can be beneficial to develop a machine learning model, specifically focusing on neural networks, for predicting chromosomal abnormalities. Ethical code: IR.MUMS.NURSE.REC. 1402.134 Plain English Summary: Approximately 3% of newborns are affected by congenital abnormalities and genetic diseases, leading to disability and death. Among live births, around 3000 cases of Down syndrome (trisomy 21) can be expected based on the country's birth rate. Pregnant women carrying fetuses with Down syndrome face an increased risk of pregnancy complications. Artificial intelligence methods, such as machine learning and deep learning, are being used in nursing and midwifery to improve decision-making, patient care, and research. Nurses need to actively participate in the development and implementation of AI-based decision support systems. Additionally, nurses and midwives should play a key role in evaluating the effectiveness of artificial intelligence-based technologies in professional practice. [ABSTRACT FROM AUTHOR]

Purpose: The identification and prognosis of the agenesis of the corpus callosum (ACC) for prenatal consultation are complex and currently unclear. This study aims to explore the correlated genetic mutations of prenatal ACC. Methods: We retrospectively analyzed 114 prenatal cases of ACC. All cases (n = 114) were subjected to chromosomal microarray analysis (CMA), and 66 CMA-negative cases underwent prenatal exome sequencing (pES) for further analysis. Results: CMA was diagnosed positively in 15/114 (13.2%) cases and pES was diagnosed positively in 24/66 (36.4%) CMA-negative cases. The detection rate of genetic causes between complete and partial ACCs was not significantly different (P > 0.05). Between isolated and non-isolated (other anomalies present) ACCs, the diagnostic rate of pES in non-isolated cases was significantly higher (P < 0.001), while CMA results did not differ (P > 0.05). The diagnostic rate of CMA was significantly increased in cases combined with intracranial and extracranial malformations (P = 0.014), while no CMA positivity was detected in cases combined with only intracranial malformations. Conclusion: For fetuses with prenatal ACC, further pES analysis should be recommended after negative CMA results. Chromosome abnormalities are less likely to occur when ACC with only intracranial malformations combined. [ABSTRACT FROM AUTHOR]

Noninvasive prenatal testing (NIPT) has become widely available in recent years. While initially used to screen for trisomies 21, 18, and 13, the test has expanded to include a range of other conditions and will likely expand further. This paper addresses the ethical issues that arise from one particularly controversial potential use of NIPT: screening for adult‐onset conditions (AOCs). We report data from our quantitative survey of Australian NIPT users' views on the ethical issues raised by NIPT for AOCs. The survey ascertained support for NIPT for several traits and conditions including AOCs. Participants were then asked about their level of concern around implications of screening for AOCs for the future child and parent(s). Descriptive and comparative data analyses were conducted. In total, 109 respondents were included in data analysis. The majority of respondents expressed support for NIPT screening for preventable (70.9%) and nonpreventable AOCs (80.8%). Most respondents indicated concern around potential harmful impacts associated with NIPT for AOCs, including the psychological impact on the future child and on the parent(s). Despite this, the majority of participants thought that continuation of a pregnancy known to be predisposed to an AOC is ethically acceptable. The implications of these data are critically discussed and used to inform the normative claim that prospective parents should be given access to NIPT for AOCs. The study contributes to a body of research debating the ethical acceptability and regulation of various applications of NIPT as screening panels expand. [ABSTRACT FROM AUTHOR]

Introduction: The corpus callosum is one of the five main cerebral commissures. It is key to combining sensory and motor functions. Its structure can be pathological (dysgenesis) or completely absent (agenesis). The corpus callosum dys- or agenesis is a rare disease (1:4000 live births), but it can have serious mental effects. Methods: In our study, we processed the data of 64 pregnant women. They attended a prenatal diagnostic center and genetic counseling from 2005 to 2019 at the Department of Obstetrics and Gynecology at Semmelweis University. Results: The pregnancies had the following outcomes: 52 ended in delivery, 1 in spontaneous abortion, and 11 in termination of pregnancy (TOP) cases (n = 64). The average time of detection with imaging tests was 25.24 gestational weeks. In 16 cases, prenatal magnetic resonance imaging (MRI) was performed. If the abnormality was detected before the 20th week, a genetic test was performed on an amniotic fluid sample obtained from a genetic amniocentesis. Karyotyping and cytogenetic tests were performed in 15 of the investigated cases. Karyotyping gave normal results in three cases (46,XX or XY). In one of these cases, postnatally chromosomal microarray (CMA) was later performed, which confirmed Aicardi syndrome (3q21.3–21.1 microdeletion). In one case, postnatally, the test found Wiedemann–Rautenstrauch syndrome. In other cases, it found X ring, Di George syndrome, 46,XY,del(13q)(q13q22) and 46,XX,del(5p)(p13) (Cri-du-chat syndrome). Edwards syndrome was diagnosed in six cases, and Patau syndrome in one case. Conclusions: We found that corpus callosum abnormalities are often linked to chromosomal problems. We recommend that a cytogenetic test be performed in all cases to rule out inherited diseases. Also, the long-term outcome does not just depend on the disease's severity and the associated other conditions, and hence proper follow-up and early development are also key. For this reason, close teamwork between neonatology, developmental neurology, and pediatric surgery is vital. [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]

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]

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: 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: 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]

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]

This study was to evaluate the performance of noninvasive prenatal testing (NIPT) in detecting fetal chromosome disorders in pregnant women. Methods: From October 1st, 2017, to December 31th, 2022, a total of 15,304 plasma cell free DNA-NIPT samples were collected for fetal chromosome disorders screening. The results of NIPT were validated by confirmatory invasive testing or clinical outcome follow-up. Further, NIPT performance between low-risk and high-risk groups, as well as singleton pregnancy and twin pregnancy groups was compared. Besides, analysis of 111 false-positive cases was performed. Results: Totally, NIPT was performed on 15,086 eligible venous blood samples, of which 179 (1.19%) showed positive NIPT results and 68 were further validated to be true positive samples via confirmatory invasive testing or follow-up of clinical outcomes. For common chromosome aneuploidies, sex chromosome abnormalities (SCA) and other chromosomal aneuploidies, the detection sensitivities of NIPT were all 100%, the specificities were 99.87%, 99.70%, and 99.68% and the positive predictive values (PPVs) were 65.45%, 31.82%, and 10.91%, respectively. No statistically significant variance in detection performance was observed among 2987 high-risk and 12,099 low-risk subjects, as well as singleton and twin pregnancy subjects. The concentration of cell-free fetal DNA of 111 false-positive cases ranged from 5.5% to 33.7%, which was higher than the minimum requirement of NIPT. Conclusion: With stringent protocol, NIPT shows high sensitivity and specificity for detecting fetal chromosome disorders in a large-scale clinical service, helping improving overall pregnancy management. [ABSTRACT FROM AUTHOR]

Background: Copy number variation (CNV) of X chromosome can lead to a variety of neonatal abnormalities, especially for male fetuses. In recent years, due to the high sensitivity and high specificity of NIPS, its application has gradually expanded from chromosome aneuploidy to CNV. Few prenatal cases involving the detection of Xq duplication and deletion by NIPS have been reported, but it is of great significance for genetic counseling. Case presentation: A 36-year-old woman was referred for prenatal diagnosis and genetic counseling at 17 weeks of gestation because of abnormal result of noninvasive prenatal screening (NIPS). Multiple congenital malformations, hydrocephalus, and enlarged gallbladder were observed by prenatal ultrasound. Amniocentesis revealed the karyotype of the fetus as 46, XN, add(X) (p22.2) and the result of chromosomal microarray analysis was arr[hg19] Xq27.1q28(138,506,454–154896094) × 2 and arr[hg19] Xp22.33p22.32(168,551–5,616,964) × 1. CNV-seq showed that the mother shares a 16.42 Mb duplication in the Xq27.1-q28 region and a 2.97 Mb deletion in the Xp22.33-p22.32 region. After genetic counseling, the couple chose to terminate the pregnancy. Conclusion: The combination of NIPS and CMA would be of values in detection of subchromosomal duplications and/or deletions at fetal stage. The detection of X chromosome aberration in a male fetus should give suspicion of the possibility of maternal inheritance. [ABSTRACT FROM AUTHOR]

To investigate the incidence of pathogenic recurrent CNVs in fetuses with different referral indications and review the intrauterine phenotypic features of each CNV. A total of 7,078 amniotic fluid samples were collected for chromosome microarray analysis (CMA) and cases carrying pathogenic recurrent CNVs were further studied. The highest incidence of pathogenic recurrent CNVs was 2.25 % in fetal ultrasound anomalies (FUA) group. Moreover, regardless of other indications, pregnant women with advanced maternal age have a lower incidence compared with whom less than 35 years old (p<0.05). In total 1.17 % (83/7,078) samples carried pathogenic recurrent CNVs: 20 cases with 22q11.2 recurrent region (12 microdeletion and eight microduplication), 11 with 1q21.1 (five microdeletion and six microduplication) and 16p13.11 (four microdeletion and seven microduplication), 10 with 15q11.2 recurrent microdeletion, seven with Xp22.31 recurrent microdeletion and 16p11.2 (three microdeletion and four microduplication), four with 7q11.23 (two microdeletion and two microduplication), three with 17p11.2 (three microdeletion), 17p12 (two microdeletion and one microduplication) and 17q12 (two microdeletion and one microduplication). The rest ones were rare in this study. Pathogenic recurrent CNVs are more likely to be identified in FUA group. Pregnant women with advanced maternal age have a lower incidence of pathogenic recurrent CNVs. The profile of pathogenic recurrent CNVs between prenatal and postnatal is different, especially in 22q11.2, 1q21.1, 15q13.3 recurrent region and 15q11.2 deletion. [ABSTRACT FROM AUTHOR]

A rare congenital condition known as fetal megacystis, characterized by an unusual enlargement of the fetal urinary bladder, exhibits a distinctive keyhole appearance. This anomaly was identified during a routine prenatal ultrasound of a male fetus at 21 weeks gestational age. The degree of fetal megacystis can vary, often exceeding the normal bladder measurement of 7-8 mm during the first trimester. The atypical configuration of the bladder and urethra, leading to a narrowed and elongated shape, imparts the keyhole appearance to the bladder. While the exact etiology remains uncertain, it is believed to be associated with various factors, including genetic disorders and urinary tract obstruction. This condition can profoundly affect the health and development of the affected fetus, potentially resulting in renal dysfunction, urinary tract infections, and organ damage. Other congenital anomalies, such as those involving the kidneys, lungs, or skeletal system, may also be linked to this condition. The management and treatment approach is contingent upon several factors, including the severity of the condition, the presence of associated anomalies, and the patient's gestational age. Close monitoring through regular ultrasound examinations may be recommended in milder cases to track the condition's progression. Interventions such as fetal urinary bladder catheter implantation or neurosurgical procedures may be viable options in more severe instances. [ABSTRACT FROM AUTHOR]

Rapid improvements in the field of prenatal medicine have been achieved due to the technological advancement of ultrasonography that has allowed recognition of various ultrasonographic findings and their combination with biochemical results and demographic characteristics in order to estimate a final individual risk for a chromosomal anomaly of the fetus and analysis of short fragments of fetal DNA released into the mother's bloodstream through a natural process of cell death. Invasive testing still remains the main clinically available diagnostic modality for the definite diagnosis of both chromosomal anomalies and many single-gene disorders. Amniocentesis is performed between 15 and 20 weeks of pregnancy to obtain fetal cells for genetic testing. This method is performed almost in the middle of pregnancy, and waiting for the results of the analysis may indicate termination of pregnancy in the second trimester. Chorionic villus sampling (CVS), usually performed between 11+0 and 13+6 weeks of gestation, is one of the invasive diagnostic methods used to diagnose chromosomal, genetic, and metabolic diseases in the embryonic period. Invasive procedures such as CVS and amniocentesis still remain the only definitive diagnostic tests for aneuploidy in pregnancy. CVS, as an invasive procedure carried out with experienced physicians in specialist centers, is not associated with a significant increase in fetal loss rate, with a risk rate below 0.5%, and the possible background risk for miscarriage is significantly higher in the presence of fetal anomaly and abnormal karyotype. Ultrasound-guided transabdominal (TA) CVS is a useful outdoor procedure and is considered the method of choice for fetal sampling and accurate early prenatal diagnosis. [ABSTRACT FROM AUTHOR]

The phenotypes of Xp22.33 or Yp11.32 microdeletions comprising the short-stature homeobox (SHOX) gene have been extensively described in adults and children. Herein, the prenatal ultrasound phenotype and pregnancy outcomes of fetuses with Xp22.33/Yp11.32 microdeletions were analyzed to improve our understanding, diagnosis, and monitoring of this genetic condition in the fetal stage. A total of 9,100 pregnant women referred to tertiary units for prenatal diagnosis were evaluated by chromosomal microarray analysis(CMA). Seven (0.08 %) fetuses had Xp22.33/Yp11.32 microdeletions, ranging from 243 kb to 1.1 Mb, that comprised SHOX. The ultrasonic phenotypes differed among these fetuses, with three fetuses presenting abnormal bone development, one had labial-palatal deformity and strawberry head, two had an abnormal ultrasonic soft marker, and one had no abnormalities. After genetic counseling, only one couple underwent pedigree assessment, which confirmed the paternal origin of the microdeletion. This infant presented delayed speech development, whereas other three infants showed a typical postnatal development. In three cases, the parents chose to terminate the pregnancy. The ultrasonic phenotype of fetuses with Xp22.33/Yp11.32 microdeletions resulting in SHOX heterozygosity loss is variable. Prenatal CMA can quickly and effectively diagnose Xp22.33/Yp11.32 microdeletions and SHOX loss, which may help prenatal counseling. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to evaluate the pregnancy outcomes of patients who applied to our clinic between the 11th and 14th weeks of pregnancy and whose nuchal translucency (NT) measurement was ≥1.5 multiples of the median (MoM). Material and Methods: The study included 85 patients whose NT measurement was determined ≥1.5 MoM and pregnancy results were available. Demographic characteristics of the patients, prenatal invasive diagnostic test results, fetal anomaly screening, fetal echocardiography (ECHO) results, and neonatal and obstetric results were evaluated. Results: Abnormal karyotype was detected in 10.6% (n=9) of the patients. Trisomy 21 was the most common chromosomal anomaly. Fetal structural anomaly was detected in 29.4% (n=25) of the patients. A structural fetal anomaly was detected in 21% (n=13) of fetuses with normal karyotypes and 66.7% (n=6) of fetuses with abnormal karyotypes. Cardiac anomalies were found to be the most common anomalies with 9.7% (n=6) in patients with normal karyotype. NT and NT MoM values in patients with fetal structural (both p=0.001) or chromosomal anomalies (p=0.011, and p=0.019, respectively) were found significantly higher than those without. NT and NT MoM values in patients whose pregnancies resulted in fetal loss were found significantly higher than in patients who had a live birth (both p=0.001). Conclusion: Increasing NT or NT MoM values indicate an increase in the risk of chromosomal anomalies, structural anomalies, and poor pregnancy outcomes in the fetus. Fetal anomaly screening and fetal ECHO should be recommended in patients with increased NT, even if a normal karyotype is detected. [ABSTRACT FROM AUTHOR]

Objective: In the study, we investigated the genetic etiology of the ventricular septal defect (VSD) and comprehensively evaluated the diagnosis rate of prenatal chromosomal microarray analysis (CMA) and exome sequencing (ES) for VSD to provide evidence for genetic counseling. Methods: We carried out chromosomal microarray analysis (CMA) on 468 fetuses with VSD and exome sequencing (ES) on 51 fetuses. Results: In our cohort, 68 (14.5%) VSD fetuses received a genetic diagnosis, including 61 (13.03%, 61/468) cases with chromosomal abnormalities and seven (13.7%, 7/51) cases with gene sequence variants. The detection rate of total pathogenic and likely pathogenic gene variations in the non-isolated VSD group (61/335, 18.2%, 55 by QF-PCR/karyotype/CMA + 6 by ES) was significantly higher than that in the isolated VSD group (7/133, 5.3%, 6 by QF-PCR/karyotype/ CMA + 1 by ES, p = 0.000). The most common copy number variation (CNV) was 22q11.2 microdeletion syndrome. Additionally, we found six previously unreported variants, which expanded the variation spectrum of VSD-related genes. Conclusion: In this study, CNVs and sequence variants were found in 13.03% and 13.7% of cases, respectively. ES can be recommended for fetuses with VSD without chromosome abnormalities and pathogenic CNVs, especially those that are combined with other ultrasound abnormalities. [ABSTRACT FROM AUTHOR]

Background: Few co-occurrence cases of mosaic aneuploidy and uniparental disomy (UPD) chromosomes have been reported in prenatal periods. It is a big challenge for us to predict fetal clinical outcomes with these chromosome abnormalities because of their highly heterogeneous clinical manifestations and limited phenotype attainable by ultrasound. Methods: Amniotic fluid samples were collected from four cases. Karyotype, chromosome microarray analysis, short tandem repeats, and whole exome sequencing were adopted to analyze fetal chromosomal aneuploidy, UPD, and gene variation. Meanwhile, CNVseq analysis proceeded for cultured and uncultured amniocytes in case 2 and case 4 and MS-MLPA for chr11 and chr15 in case 3. Results: All four fetuses showed mosaic chromosomal aneuploidy and UPD simultaneously. The results were: Case 1: T2(7%) and UPD(2)mat(12%). Case 2: T15(60%) and UPD(15)mat(40%). Case 3: 45,X(13%) and genome-wide paternal UPD(20%). Case 4: <10% of T20 and > 90% UPD(20)mat in uncultured amniocyte. By analyzing their formation mechanism of mosaic chromosomal aneuploidy and UPD, at least two adverse genetic events happened during their meiosis and mitosis. The fetus of case 1 presented a benign with a normal intrauterine phenotype, consistent with a low proportion of trisomy cells. However, the other three fetuses had adverse pregnancy outcomes, resulting from the UPD chromosomes with imprinted regions involved or a higher level of mosaic aneuploidy. Conclusion: UPD is often present with mosaic aneuploidy. It is necessary to analyze them simultaneously using a whole battery of analyses for these cases when their chromosomes with imprinted regions are involved or known carriers of a recessive allele. Fetal clinical outcomes were related to the affected chromosomes aneuploidy and UPD, mosaic levels and tissues, methylation status, and homozygous variation of recessive genes on the UPD chromosome. Genetic counseling for pregnant women with such fetuses is crucial to make informed choices. [ABSTRACT FROM AUTHOR]

Background and Purpose: The application of classical cytogenetic and DNA‐based molecular techniques to detect cell lineages of mosaicism derived from cultured or noncultured fetal cells may result in discordant results. This retrospective study aimed to assess the inconsistent diagnostic outcomes, technical availability, and limitations of chromosomal microarray analysis (CMA) and karyotyping for mosaicism. Methodology: A total of 75 fetuses diagnosed with mosaicism by karyotype analysis or CMA were selected, and the results from both the methods were compared and further analyzed. Results: A total of 42 (56%, 42/75) CMA results were consistent with karyotypes, consisting of 22 cases of mosaic sex chromosomal abnormalities, 8 routine autosomal aneuploidy cases, 8 other autosome aneuploidy cases, 3 large cryptic genomic rearrangements, and 1 small supernumerary marker chromosome. Discrepancy between karyotype analysis and CMA was observed in 33 (44%, 33/75) mosaicisms involving 15 sex chromosomal abnormalities, 1 routine autosomal aneuploidies, 5 other autosome aneuploidy cases, 8 large cryptic genomic rearrangements, and 4 small supernumerary marker chromosomes. Conclusion: Considering the disparities between methods as well as the cell populations analyzed, both CMA and karyotype analysis have their own advantages and disadvantages. Therefore, CMA should ideally be used in combination with karyotyping to detect more cases of mosaicism than using either test alone. [ABSTRACT FROM AUTHOR]

Aim: To investigate the detectability of noninvasive prenatal screening (NIPS) with conventional sequencing depth to detect fetal copy number variants. Methods: We performed a retrospective study in a total of 19 144 pregnant women. Their cell‐free plasma DNA were assessed for trisomy 21, trisomy 18, trisomy 13, sex chromosome aneuploidies, and genome‐wide copy number variants by NIPS at conventional sequencing depth. Results: Three hundred seventy‐four cases (2.0%, 374/19 144) with abnormal results were detected, which including 84 cases (0.4%, 84/19 144) with high risk of trisomy 21, 18, and 13, 90 cases (0.5%, 90/19 144) with high risk of sex chromosome abnormalities (SCA), and 44 cases (0.2%, 44/19 144) with high risk of other chromosome aneuploidies. One hundred fifty‐six cases (0.8%, 156/19 144) with high risk of copy number variations (CNVs) were also detected. In following prenatal diagnosis, composite positive predictive value (PPV) of trisomy 21, 18, and 13 was 69.6% (48/69). The PPV of SCAs was 37.3% (19/51). And the PPVs for CNVs was detected as 51.0% (<5 Mb), 71.4% (5 Mb ≤ CNV ≤10 Mb), 56.5% (>10 Mb). Finally, a follow‐up about the pregnancy outcomes were conducted for all available cases. Conclusions: NIPS yielded high PPVs for trisomy 21, 18, and 13 aneuploidies and moderate PPVs for SCAs and CNVs. The screening effectiveness was closely related to the size of CNV fragments. Larger CNVs, especially larger than 5 Mb, could be detected more accurately by NIPS in our analytic technique. Meanwhile, diagnostic confirmation by microarray analysis was highly recommended. [ABSTRACT FROM AUTHOR]

Objective: A rolling circle amplification (RCA) based commercial methodology using cell-free (cf)DNA to screen for common trisomies became available in 2018. Relevant publications documented high detection but with a higher than expected 1% false positive rate. Preliminary evidence suggested assay variability was an issue. A multi-center collaboration was created to explore this further and examine whether subsequent manufacturer changes were effective. Methods: Three academic (four devices) and two commercial (two devices) laboratories provided run date, chromosome 21, 18, and 13 run-specific standard deviations, number of samples run, and reagent lot identifications. Temporal trends and between-site/device consistency were explored. Proportions of run standard deviations exceeding pre-specified caps of 0.4%, 0.4% and 0.6% were computed. Results: Overall, 661 RCA runs between April 2019 and July 30, 2022 tested 39,756 samples. In the first 24, subsequent 9, and final 7 months, proportions of capped chromosome 21 runs dropped from 39% to 22% to 6.0%; for chromosome 18, rates were 76%, 36%, and 4.0%. Few chromosome 13 runs were capped using the original 0.60%, but capping at 0.50%, rates were 28%, 16%, and 7.6%. Final rates occurred after reformulated reagents and imaging software modifications were fully implemented across all devices. Revised detection and false positive rates are estimated at 98.4% and 0.3%, respectively. After repeat testing, failure rates may be as low as 0.3%. Conclusion: Current RCA-based screening performance estimates are equivalent to those reported for other methods, but with a lower test failure rate after repeat testing. [ABSTRACT FROM AUTHOR]

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(1) Background: To examine the incidence of the prenatal diagnosis of the renal double-collecting system (rDCS) and describe its clinical outcome and associated genetic abnormalities. (2) Methods: This retrospective study included women who attended the obstetric clinic for early fetal anatomic sonography with findings of a renal DCS. Diagnosis was conducted by an expert sonographer using defined criteria. (3) Results: In total, 29,268 women underwent early ultrasound anatomical screening at 14–16 weeks, and 383 cases of rDCS were diagnosed (prevalence: 1:76). Associated abnormalities were diagnosed in eleven pregnancies; four had chromosomal aberrations. No chromosomal abnormalities were reported in isolated cases. Ectopic uretrocele and dysplastic kidney were diagnosed in 6 (1.5%) and 5 (1.3%) fetuses, respectively. One girl was diagnosed with vesicoureteral reflux and recurrent UTIs, and two boys were diagnosed with undescended testis. The recurrence rate of rDCS was 8% in subsequent pregnancies. (4) Conclusions: In light of its benign nature, we speculate that isolated rDCS may be considered a benign anatomic variant, but a repeat examination in the third trimester is recommended to assess hydronephrosis. [ABSTRACT FROM AUTHOR]

Purpose: The application value of ultrasound soft indicators in prenatal diagnosis was evaluated by copy number variation sequencing (CNV-seq).Methods: The authors conducted a retrospective analysis of 422 pregnant women who underwent CNV-seq testing at Luoyang Maternal and Child Health Hospital between January 2020 and November 2021. The women had presented with abnormal ultrasound soft markers; those identified as high-risk through non-invasive prenatal screening were excluded.Results: A total of 43 abnormal cases were detected in 422 pregnant women, including 24 aneuploidy (including chimerism) and 19 pathogenic or likely pathogenic copy number variations (CNVs). Based on the characteristics of ultrasound soft indicators, pregnant women were divided into five groups: isolated nuchal translucency (NT) group, combined NT group, isolated soft indicators group, combined soft indicators group and combined non-NT group. The abnormality detection rates in the five groups were 12.38% (13/105), 36.11% (13/36), 3.74% (4/103), 3.08% (2/63) and 10.09% (11/109), respectively. Statistical tests showed that the detection rate in the NT thickening combined with other abnormalities group was significantly higher than the other four groups, while there was no statistical difference in the detection rate among the other four groups.Conclusion: When NT thickening is combined with other abnormalities, it is more likely to indicate chromosome abnormalities or CNVs, so it should be regarded seriously upon finding, and pregnant women should be referred for prenatal diagnosis according to the examination results. In addition, NT thickening is an important indicator for prenatal diagnosis and should be considered regardless of whether it occurs independently. The authors recommend CNV-seq for prenatal diagnosis to prevent missing small fragments of CNVs during traditional karyotyping. [ABSTRACT FROM AUTHOR]

Objective: To investigate the efficiency of non-invasive prenatal testing (NIPT) in cases with different cutoffs of nuchal translucency (NT). Methods: The study retrospectively analyses pregnancies with NT ≥ 2.5 mm who underwent NIPT. Results of NT, NIPT, chromosomal diagnostic and pregnancy outcomes were collected. Results: Study group was composed of 1470 single pregnancies, including 864 with NT 2.5–2.9 mm, 350 with NT 3.0–3.4 mm and 256 with NT ≥ 3.5 mm. Non-significant differences were found in the positive predictive value (PPV) of NIPT between different cutoffs of NT. There was one false positive case with NT 4.3 mm, screening for 47,XYY in NIPT showed normal in diagnostic testing. For cases with normal NIPT results, the residual risk is 1:20 (5%, 95%CI: 0.1–10.1%) in fetuses with NT 3.0–3.4 mm and 1:15 (6.5%, 95%CI: 1.4%-11.5%) in fetuses with NT ≥ 3.5 mm. These false negative cases included one trisomy 21, seven pathogenic CNVs, one uniparental disomy and one single gene disorders. Conclusion: Our findings demonstrated that the PPV of NIPT for screening chromosomal aberrations were similarly in different NT cutoffs, while false positive case does exist. After normal in NIPT, risk for chromosomal aberrations remained, especially pathogenic CNV and even common trisomy. Therefore, prenatal diagnosis was recommended and CMA was suggested to apply in pregnancies with NT ≥ 3.0 mm. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the value of fetal nasal bone hypoplasia and other prenatal risk factors in predicting chromosomal abnormalities. Methods: In this retrospective cohort study, we collected data on singleton pregnancies diagnosed with fetal nasal bone hypoplasia during second-trimester ultrasound. Fetal karyotyping and chromosomal microarray analysis (CMA) were performed, and pregnancy outcomes were assessed. The association between fetal nasal bone hypoplasia and chromosomal abnormalities was evaluated according to whether other prenatal risk factors were observed. Results: Our final analysis included 351 pregnancies, of which 62 (17.7%) fetuses had chromosomal abnormalities, including 36 cases of trisomy-21, six cases of trisomy-18, one case each of trisomy-13, and 47, XYY syndrome, and 18 cases of copy number variations (CNVs). Among the 243 cases of isolated nasal bone hypoplasia, 28 (11.5%) cases of chromosomal aberrations were identified. The incidence was significantly higher if other soft markers or structural abnormalities were simultaneously detected. Pregnancy was terminated in 43 aneuploid fetuses and nine fetuses detected with CNVs. The parents of the fetuses diagnosed with 47, XYY syndrome and the other nine CNVs chose to continue the pregnancy, and no abnormalities were detected in the newborns. Furthermore, we found that other prenatal risk factors should be considered in evaluating the likelihood of chromosomal abnormalities in fetuses with nasal bone hypoplasia. Conclusions: Nasal bone hypoplasia is a highly specific soft marker that is associated with multiple chromosomal abnormalities. The risk of chromosomal abnormalities increases when combined with structural abnormalities or increased nuchal translucency (NT). Chromosomal microarray analysis is a powerful prenatal test for chromosomal abnormalities, which may be warranted in fetuses with nasal bone hypoplasia. [ABSTRACT FROM AUTHOR]

Background: Combined first‐trimester screening (cFTS) for fetal anomalies involves maternal serum screening for biochemical markers and measurement of the nuchal translucency (NT) by ultrasound. Noninvasive prenatal screening (NIPS) analyses cell‐free DNA present in a maternal blood sample for presence of fetal chromosomal aneuploidies. Aims: To compare NIPS with cFTS as frontline screening in a public hospital in Australia. Materials and methods: Women were offered NIPS in addition to the usual cFTS routinely offered to all women at a public hospital in NSW, Australia. The cFTS sample was collected at ten weeks' gestation and the NIPS sample at 12 weeks' gestation at the ultrasound appointment. Results: In a low‐risk population of 997 women, frontline NIPS had a screen‐positive rate of 0.5% (5/997) vs 4.2% (42/997) with cFTS. cFTS correctly identified one trisomy 21 case and one trisomy 18 case; however, there were two trisomy 18 false negatives. Of five positive NIPS calls, four were correctly identified as trisomy 21 (one) and trisomy 18 (three); there were no NIPS false negatives. Overall, the false‐positive rate with NIPS was 0.1% vs 4.0% by cFTS. Conclusions: The lower screen‐positive rate with NIPS for common trisomies was a result of the significantly lower false‐positive rate with NIPS. Consequently, NIPS as first‐line screening, even if funded by the hospital, may provide cost savings. We believe NIPS should be used from ten weeks' gestation in conjunction with morphology ultrasound for routine first‐trimester prenatal management. [ABSTRACT FROM AUTHOR]

Background: Pathogenic mutations in EVC or EVC2 gene can lead to Ellis‐van Creveld (EvC) syndrome, which is a rare autosomal recessive skeletal dysplasia disorder. This study aimed to determine pathogenic gene variations associated with EvC syndrome in fetuses showing ultrasound anomalies. Methods: A 32‐year‐old pregnant woman from Quanzhou, China was investigated. In her pregnancy examination, the fetus exhibited multiple fetal malformations, including a narrow thorax, short limbs, postaxial polydactyly, cardiac malformations, and separation of double renal pelvis. Karyotype, chromosomal microarray analysis and whole exome sequencing were performed for prenatal genetic etiology analysis. Results: Chromosome abnormalities and copy number variants were not observed in the fetus using karyotype and chromosomal microarray analysis. Using whole exome sequencing, two compound heterozygous variants NM_147127.5:c.[2484G>A(p.Trp828Ter)];[871‐2_894del] in EVC2 gene were identified in the fetus as pathogenic variants inherited from parents. Conclusions: The study is the first to identify two rare compound variants in EVC2 gene in a Chinese family using whole exome sequencing. The application of whole‐exome sequencing would be helpful in fetal etiological diagnosis with ultrasound anomalies. [ABSTRACT FROM AUTHOR]

Prenatal cell-free DNA screening (cfDNA) can identify fetal chromosome abnormalities beyond common trisomies. Emanuel syndrome (ES), caused by an unbalanced translocation between chromosomes 11 and 22, has lacked a reliable prenatal screening option for families with a carrier parent. A cohort of cases (n = 46) sent for cfDNA screening with indications and/or results related to ES was queried; diagnostic testing and pregnancy outcomes were requested and analyzed. No discordant results were reported or suspected; there were ten true positives with diagnostic confirmation, six likely concordant positives based on known translocations and consistent cfDNA data, and twenty-six true negatives, by diagnostic testing or birth outcomes. For cases with parental testing, all affected ES cases had maternal translocation carriers. Expanded cfDNA may provide reassurance for t(11;22) carriers with screen negative results, and screen positive results appear to reflect a likely affected fetus, especially with a known maternal translocation. Current society guidelines support the use of expanded cfDNA screening in specific circumstances, such as for translocation carriers, with appropriate counseling. Diagnostic testing is recommended for prenatal diagnosis of ES and other chromosome abnormalities in pregnancy. To our knowledge, this cohort is the largest published group of cases with prenatal screening for carriers of t(11;22). [ABSTRACT FROM AUTHOR]

Background: Balanced chromosome aberrations are reported in about 1:30 couples with recurrent pregnancy loss (RPL). Karyotyping of both parents is necessary to identify these aberrations. Genome-wide non-invasive prenatal testing (NIPT) in case of recurrent pregnancy loss could be a more efficient way to identify couples at increased risk for carrying a balanced chromosome rearrangement. The aim of this study was to evaluate whether the potential fetal imbalances caused by parental balanced aberrations detected in our center are large enough to be detectable by genome-wide non-invasive prenatal testing (NIPT). Material and methods: From January 1970 until May 2020 our laboratory received 30,863 unique requests for karyotyping due to RPL. We have identified 16,045 couples and evaluated all abnormal cytogenetic results to assess the minimal size of the involved chromosomal segments in potential unbalanced products of the rearrangements. Results: In the presented cohort we detected 277 aberrant balanced translocations/inversions in females and 185 in males amongst 16,045 couples with RPL, which can be translated to a risk of 1:35 (2.9%, 95% CI 2.6–3.2%). Our study showed that the vast majority (98.7%, 95% CI 97.1–99.5%) of these balanced aberrations will potentially cause a fetal imbalance > 10 Mb, which is detectable with genome-wide NIPT if it was performed during one of the miscarriages. Conclusions: Our study suggests that genome-wide NIPT is able to reveal most unbalanced products of balanced chromosomal rearrangements carried by couples with RPL and therefore can potentially identify balanced chromosomal aberration carriers. Moreover, our data suggest that these couples can be offered NIPT in case they decline invasive testing in future pregnancies. [ABSTRACT FROM AUTHOR]

Background: Ventricular septal defect (VSD) is the most common subtype of congenital heart disease. In the present study, we aimed to determine whether chromosome aberration was associated with the occurrence of VSD and evaluate the association of VSD size, location and chromosome aberration with adverse outcomes in the Chinese fetuses. Methods: Fetuses with VSD and comprehensive follow-up data were included and evaluated retrospectively. Medical records were used to collect epidemiological data and foetal outcomes. For VSD fetuses, conventional karyotype and microarray analysis were conducted. After adjusting confounding factors by using multivariable logistic regression analyses, the association between chromosome variations and VSD occurrence was explored. The association between defect size, location and chromosome aberrations and adverse foetal outcomes was also investigated. Results: Chromosome aberration was the risk factor for VSD occurrence, raising 6.5-fold chance of developing VSD. Chromosome aberration, peri-membranous site and large defect size of VSD were significant risk factors of adverse fetal outcome. Chromosome aberrations, including pathogenic copy number variations (CNVs) and variations of uncertain significance (VUS), were both risk factors, increasing the risk of the adverse fetal outcome by 55.9 times and 6.7 times, respectively. The peri-membranous site would increase 5.3-fold risk and defects larger than 5 mm would increase the 7.1-fold risk for poor fetal outcome. Conclusions: The current investigation revealed that chromosomal abnormalities, large defects, and the peri-membranous site were all risk factors for poor fetal outcomes. Our study also indicated that chromosome aberration was one of risk factors for the VSD occurrence. [ABSTRACT FROM AUTHOR]

Object: To investigate the chromosome abnormalities associated with absent or hypoplastic fetal nasal bone. Methods: Patients with fetal nasal bone anomalies (NBA) referred to our center for prenatal diagnosis between 2017 and 2021 were retrospectively evaluated. All these patients underwent chromosomal microarray and/or karyotyping and received genetic counseling before and after testing. Results: Among 320 fetuses with NBA, chromosomal abnormalities were diagnosed in 89 (27.8%) cases, including 53 cases of trisomy 21, which was the most common type of chromosomal aneuploidy, accounting for 59.6% of all detected abnormalities. In addition to aneuploidies, 29 cases of copy number variants (CNVs) were detected. In cases of isolated NBA with low-risk screening results and without other risk factors, the incidence of fetal chromosomal aneuploidies and pathogenic CNVs is 5.3% (7 in 132 cases). Conclusion: This study suggests that parents of fetuses should be informed about the possibility of fetal aneuploidy and pathogenic CNVs and that discussion with the parents is also recommended, providing data support and reference for clinical counseling. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to evaluate the performance of noninvasive prenatal testing (NIPT) for the detection of chromosomal aneuploidies and copy number variations (CNVs) in twin pregnancies. Method: A cohort of 2010 women with twin pregnancies was recruited. 1331 patients opted for NIPT, and 679 patients opted for expanded NIPT (NIPT-plus). All high-risk patients were advised to undergo invasive prenatal diagnosis. All participants were followed up until 6 months after birth. Results: Twenty-two cases were predicted to have a high risk of chromosome abnormalities by NIPT, of which 14 pregnant women underwent invasive prenatal diagnosis. The 14 cases included 3 cases of trisomy 21, 1 case of trisomy 18, 1 case of trisomy 7, 2 cases of sex chromosome aneuploidies (SCAs), and 7 cases of CNVs, of which the confirmed cases numbered 2, 1, 0, 1, and 0, respectively. Twenty cases were predicted to have a high risk of chromosome abnormalities by NIPT-plus, of which 16 pregnant women underwent invasive prenatal diagnosis. The 16 cases included 1 case of trisomy 21, 1 case of trisomy 7, 7 cases of SCAs, and 7 cases of CNVs, of which were confirmed in 1, 0, 3, and 2, respectively. No false-negative result was reported during the follow-up period. Conclusion: The NIPT/NIPT-plus has excellent performance in the detection of chromosome aneuploidies in twin pregnancies. But for CNVs, the effectiveness of NIPT is poor, and the NIPT-plus have a certain detection efficiency. It is worth noting that pre- and post-genetic counseling is especially important, and the chorionicity, mode of conception, clinical indications, and fetal fraction should be considered as influencing factors. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to characterize the pathological types, diagnosis, chromosomal abnormalities, and postnatal clinical manifestations of right and double aortic arch malformations in fetuses. Methods: In this retrospective study, all fetuses diagnosed with right or double aortic arch anomalies for whom conventional two‐dimensional echocardiography combined with spatio‐temporal image correlation was performed at our tertiary referral center between December 2012 and December 2021 were included. Results: In total, 234 fetuses with aortic arch abnormalities were identified. Forty‐one cases lost to follow‐up. One hundred ninety‐three cases were included in this study. One hundred eighty‐seven cases with right aortic arch. Six cases with double aortic arch. Most cases of right aortic arch with aberrant left subclavian artery (77/101, 76.2%) were isolated lesions, whereas most of those with mirror‐image branching (45/75, 60%) were associated with intracardiac or extracardiac anomalies. Chromosomal abnormalities were screened prenatally in 113 fetuses with right aortic arch, among whom three with aberrant left subclavian artery (3/63, 4.8%) and eight with mirror‐image branching (8/50, 16%) had chromosome anomalies (p < 0.05). Furthermore, three cases had microdeletion 22q11.2 and these were significantly associated with intracardiac malformations. Conclusions: Most cases of isolated right aortic arch do not present with clinical symptoms except isolated left subclavian artery and isolated left brachiocephalic trunk. In addition, the risk of chromosomal abnormalities in patients with isolated right aortic arch is very low. We recommend that pregnant women should be informed of the risks and benefits of undergoing invasive prenatal chromosomal detection. [ABSTRACT FROM AUTHOR]

Objective: The purpose was to evaluate the effectiveness of a non-invasive prenatal test (NIPT) using mass parallel sequencing (MPS) to detect trisomy 13, 18, 21 and fetal sex chromosome abnormalities in maternal blood samples by isolating freely circulating foetal extracellular DNA (eDNA), and to develop an algorithm for prenatal screening. Material and Methods: The research methods used included blood sampling from patients, isolation of eDNA, determination of DNA concentration and quality, library preparation for sequencing, MPS using an Illumina HiSeq2000, positive and negative control samples, monitoring, and analysis of results using the distributed algorithms platform based on calculations of z-value and the average absolute deviation. Pregnant women were divided into two groups based on gestational age at sampling, group 1; 9-14 weeks and group 2; 15-27 weeks. Results: A total of 377 pregnant women were included with a mean (range) age of 33 (23-44) years. The mean gestational age at the time of blood sampling in group 1 was 11 (9-14) weeks, and in group 2 was 21 (15-27) weeks. In the first group, three cases of trisomy 18 chromosomes were detected in patients aged 43 years old, and female children were subsequently born with Edwards syndrome. In the second group, one case of trisomy 21 was detected in a patient aged 36 years and the pregnancy was terminated at 25 weeks. Conclusion: The analysis of freely circulating foetal eDNA was a sensitive method for detecting chromosomal abnormalities. The study has a practical significance, since the NIPT for frequent aneuploidy considerably exceeds the effectiveness of traditional screening methods and allows identifying chromosomal disorders starting from the 9th week of the gestation period. [ABSTRACT FROM AUTHOR]

Although nearly all noninvasive prenatal testing is currently based on analyzing circulating maternal cell-free DNA, the technical methods usedvary considerably. We review the different methods. Based on validation trials and clinical experience, there are mostly relatively small differences in screening performance for trisomies 21, 18, and 13 in singleton pregnancies. Recent reports show low no-call rates for all methods, diminishing its importance when choosing a laboratory. However, method can be an important consideration for twin pregnancies, screening for sex chromosome abnormalities, microdeletion syndromes, triploidy, molar pregnancies, rare autosomal trisomies, and segmental imbalances, and detecting maternal chromosome abnormalities. [ABSTRACT FROM AUTHOR]

Noninvasive prenatal screening with cell-free DNA is now considered a first-line screening for common aneuploidies. Advancements in existing laboratory techniques now allow to interrogate the entirety of the fetal genome, and many commercial laboratories have expanded their screening panels to include screening for rare autosomal aneuploidies and copy number variants. Here, we review the currently available data on the performance of fetal cell-free DNA to detect rare autosomal aneuploidies and copy number variants that are associated with clinically significant microdeletion and microduplication syndromes and the current position of medical societies on routine screening for these syndromes. [ABSTRACT FROM AUTHOR]

Cell-free DNA (cfDNA) screening has high detection for the common fetal autosomal aneuploidies, but is not diagnostic. The positive predictive value should be utilized in counseling after a positive cell-free DNA screen, and diagnostic testing should be offered for confirmation. cfDNA screening does not report a result in ~3% of cases; nonreportable results indicate an increased risk for aneuploidy and some adverse perinatal outcomes. False-positive cfDNA screening occurs due to confined placental mosaicism, maternal copy number variants, mosaicism, and cancer. Pretest education and counseling should be provided with emphasis on the potential benefits, risks, and limitations before cfDNA screening. [ABSTRACT FROM AUTHOR]

In the setting of a normal first-trimester ultrasound, an amniocentesis may be a better option than chorionic villous sampling for invasive diagnostic testing after a cell-free DNA high risk for trisomy 13, given the high rates of confined placental mosaicism. In unaffected fetuses, other evaluations should be considered depending on the cell-free DNA results, including maternal karyotyping for monosomy X, uniparental disomy testing for chromosomes with imprinted genes, serial growth scans for trisomy 16, and a workup for maternal malignancy for multiple aneuploidies or autosomal monosomy. [ABSTRACT FROM AUTHOR]

Background: Standard noninvasive prenatal screening(NIPS) is an accurate and reliable method to screen for common chromosome aneuploidies, such as trisomy 21, 18 and 13. Extended NIPS has been used in clinic for not only aneuploidies but also copy number variants(CNVs). Here we aim to define the range of chromosomal abnormalities that should be able to identify by NIPS in order to be an efficient extended screening test for chromosomal abnormalities. Methods: A prospective study was conducted, involving pregnant women without fetal sonographic structural abnormalities who underwent amniocentesis. Prenatal samples were analyzed using copy number variation sequencing(CNV-seq) to identify fetal chromosomal abnormalities. Results: Of 28,469 pregnancies included 1,022 (3.59%) were identified with clinically significant fetal chromosome abnormalities, including 587 aneuploidies (2.06%) and 435 (1.53%) pathogenic (P) / likely pathogenic (LP) CNVs. P/LP CNVs were found in all chromosomes, but the distribution was not uniform. Among them, P/LP CNVs in chromosomes 16, 22, and X exhibited the highest frequencies. In addition, P/LP CNVs were most common on distal ends of the chromosomes and in low copy repeat regions. Recurrent microdeletion/microduplication syndromes (MMS) accounted for 40.69% of total P/LP CNVs. The size of most P/LP CNVs (77.47%) was < 3 Mb. Conclusions: In addition to aneuploidies, the scope of extended NIPS should include the currently known P/LP CNVs, especially the regions with recurrent MMS loci, distal ends of the chromosomes, and low copy repeat regions. To be effective detection should include CNVs of < 3 Mb. Meanwhile, sufficient preclinical validation is still needed to ensure the clinical effect of extended NIPS. [ABSTRACT FROM AUTHOR]

Introduction: Chromosomal aberrations are the most important etiological factors for birth defects. Optical genome mapping is a novel cytogenetic tool for detecting a broad range of chromosomal aberrations in a single assay, but relevant clinical feasibility studies of optical genome mapping in prenatal diagnosis are limited. Material and methods: We retrospectively performed optical genome mapping analysis of amniotic fluid samples from 34 fetuses with various clinical indications and chromosomal aberrations detected through standard‐of‐care technologies, including karyotyping, fluorescence in situ hybridization, and/or chromosomal microarray analysis. Results: In total, we analyzed 46 chromosomal aberrations from 34 amniotic fluid samples, including 5 aneuploidies, 10 large copy number variations, 27 microdeletions/microduplications, 2 translocations, 1 isochromosome, and 1 region of homozygosity. Overall, 45 chromosomal aberrations could be confirmed by our customized analysis strategy. Optical genome mapping reached 97.8% concordant clinical diagnosis with standard‐of‐care methods for all chromosomal aberrations in a blinded fashion. Compared with the widely used chromosomal microarray analysis, optical genome mapping additionally determined the relative orientation and position of repetitive segments for seven cases with duplications or triplications. The additional information provided by optical genome mapping will be conducive to characterizing complex chromosomal rearrangements and allowing us to propose mechanisms to explain rearrangements and predict the genetic recurrence risk. Conclusions: Our study highlights that optical genome mapping can provide comprehensive and accurate information on chromosomal aberrations in a single test, suggesting that optical genome mapping has the potential to become a promising cytogenetic tool for prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Background: Intellectual disability (ID) consists of a broad range of disorders characterized by low general intellectual functioning (IQ below 70). ID etiologic causes are heterogeneous, ranging from environmental to chromosomal and monogenic conditions. Although many autosomal genes responsible for ID are expected, only a small number of these have been identified, and up to now most progress has been made in X-linked translocation ID area; but many autosomal genes play a crucial role in the development of a central nervous system. Any change which leads to lose or reduce the function or changes the expression of them; high or low, even have a damaging effect on the functional protein might lead to different phenotypes like developmental delay, growth retardation, or intellectual disabilities. Result & conclusion: In this paper, we discuss the importance of balanced chromosomal translocations in the cause of newborn intellectual disabilities. Balanced translocation is the result of breaking off two chromosomes and reattaching in a way that the sections of two chromosomes have switched places. These rearrangements are found as de novo events in 1/2000 live births and give rise to some congenital anomalies which are the product of submicroscopic deletions, duplications, inversion or disruption, activation, or inactivation of a gene or different genes located at or near the breakpoints in the basepair level. These apparently balanced translocations due to positional effect lead to abnormal phenotype. Conclusion: Cryptic genomic imbalances which cause mentality are very rare conditions but new technologies like NGS long-read genome sequencing could detect breakpoint effects on live birth health and discover a new way for prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Wolf-Hirschhorn syndrome (WHS) (OMIM 194190) is a contiguous gene syndrome with an estimated prevalence of around 1 in 50 000 births. The syndrome is caused by the deletion of a critical region (Wolf-Hirschhorn Syndrome Critical region-WHSCR) on chromosome 4p16.3. Its core features are typical facial gestalt, growth retardation, intellectual disability, developmental delay, and seizures. Prenatal diagnosis of WHS helps clinicians and parents make informed decisions about pregnancy management. In this research, a 31-year-old woman (gravida 1, para 0) underwent amniocentesis at 18 weeks gestation because of the short nasal bone of the fetus on prenatal ultrasound. Chromosomal microarray analysis (CMA) on uncultured amniocytes revealed a de novo 11.36-Mb deletion on chromosome 4p16.3p15.33, spanning from position 40 000 to 11 400 000 (hg19). After genetic counselling and being informed of the unfavorable prognosis, the parents decided to terminate the pregnancy. We provide a detailed description of a de novo 11.36-Mb deletion on chromosome 4p16.3p15.33 (Wolf-Hirschhorn syndrome). CMA has more advantages than karyotype analysis in detecting chromosomal microdeletions/ microduplications. A combination of karyotype analysis, CMA, prenatal ultrasound, and genetic counseling is helpful for the prenatal diagnosis of chromosomal deletions/duplications. [ABSTRACT FROM AUTHOR]

Unbalanced chromosome abnormalities (UBCA) are large genomic region variations that often result in minimal clinical effects. Copy number variants (CNVs), such as microdeletions and microduplications in 15q11.2, have been linked to various health issues, making prenatal diagnosis and genetic counselling challenging. Microdeletions and microduplications in the genomic region 15q11.2 are associated with congenital heart defects, autism, schizophrenia, epilepsy, mental retardation and developmental delay. The literature on this microduplication is confusing and extensive, which is a great difficulty for prenatal diagnosis and genetic counselling. A 35-year-old female undergoing amniocentesis at Week 19 due to advanced maternal age revealed a normal 46,XX karyotype through G-banding analysis. However, Chromosomal microarray analysis (CMA) on the same amniocytes detected a 550-Kb maternally inherited chromosomal microduplication in 15q11.2. An integrated approach combining karyotype analysis, CMA, genetic counseling, and prenatal ultrasound is crucial for the accurate prenatal diagnosis of UBCAs and CNVs. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the incidence of chromosome anomalies in different types of congenital gastrointestinal obstruction and assess pregnancy outcomes of fetuses with congenital gastrointestinal obstruction. Methods: A total of 64 cases with gastrointestinal obstruction between January 2014 and December 2020 were enrolled in this study. They were divided into three groups according to sonographic images. Group A: isolated upper gastrointestinal obstruction; Group B: isolated lower gastrointestinal obstruction; Group C: non-isolated gastrointestinal obstruction. The rate of chromosome anomalies in different groups was calculated. Pregnant women with amniocentesis were followed up by medical records and telephone. The follow-up included pregnancy outcomes and development of the live born infants. Result: From January 2014 to December 2020, there were 64 fetus with congenital gastrointestinal obstruction underwent chromosome microarray analysis(CMA), the overall detection rate of CMA testing was 14.1%(9/64). The detection rate of Group A, B and C were 16.2%, 0 and 25.0% respectively. 9 fetuses with abnormal CMA results were all terminated. Among 55 fetuses with normal chromosomes, 10(18.2%) fetuses were not found to have any gastrointestinal obstruction after birth. 17(30.9%) fetuses were diagnosed with gastrointestinal obstruction and underwent surgical treatment after birth, one of which had lower gastrointestinal obstruction combined with biliary obstruction and died due to liver cirrhosis. 11(20.0%) pregnancy were terminated due to multiple abnormalities. 5(9.1%) fetuses were intrauterine death. 3(5.5%) fetuses were neonatal deaths. 9(16.4%) fetuses were lost to follow-up. Conclusion: It is crucial to understand whether the gastrointestinal tract abnormality is isolated or associated to other findings. The risk of chromosomal abnormalities in fetuses with isolated lower gastrointestinal obstruction is lower than upper gastrointestinal obstruction. While genetic abnormalities excluded, a promising prognosis is expected for fetuses with congenital gastrointestinal obstruction. [ABSTRACT FROM AUTHOR]

Objective: To identify the additional diagnostic value of CNV‐seq over conventional karyotyping on the part of chromosomal abnormalities in prenatal diagnosis. Method: This was a systematic review conducted in accordance with PRISMA criteria. In order to clarify related research, PubMed, Web of Science databases (including Core Collection, BIOSIS Previews, MEDLINE, and so on), The Cochrane Library and Wiley Online Library were searched with the terms: "prenatal diagnosis," "CNV‐seq," "karyotyping," published from January 2010 to May 2022. No language restrictions. RenMan 5.4 was used for the meta‐analysis. Results: Eight studies were included in this systemic review and meta‐analysis, including 11 091 pregnant women with high‐risk pregnancy factors or with structurally abnormal fetus under ultrasound. CNV‐seq detected a 2% (95% CI, −0% to 4%) additional chromosomal anomalies over conventional karyotyping in the six series. A 4% (95% CI, 3%–6%) pooled mean incremental yield of pathogenic CNVs by CNV‐seq over karyotyping was observed, with a 1%–16% range. Conclusion: CNV‐seq, applied in prenatal diagnosis, may detect more chromosomal abnormalities when compared with karyotyping. With the advantages of wide coverage, high throughput, high resolution, no culture, good compatibility, and adjustable sequencing depth, CNV‐seq has high application value in prenatal diagnosis. [ABSTRACT FROM AUTHOR]