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AbstractObjectivesMethodsResultsConclusionsTo examine the knowledge, confidence and practice of motor neuron disease (MND) clinicians toward discussing reproductive options with people who carry a causal variant in an MND gene (both clinically affected and asymptomatic).An online cross-sectional survey was distributed nationwide to UK MND clinicians and clinical geneticists and genetic counselors. The survey assessed respondents’ understanding on reproductive medicine techniques; their confidence in discussing reproductive medicine options and their access to information resources.Seventy six clinicians responded to the online survey (45 neurology clinicians and 31 clinical geneticists). MND clinicians had limited knowledge and low confidence in discussing reproductive medicine options. Geneticists were more likely to carry out reproductive genetic counseling with very few MND clinicians reporting undertaking these discussions. Further, 57% of the 45 MND clinicians surveyed reported to have never made a referral for reproductive genetic counseling. Multiple barriers to offering reproductive counseling or referral were identified including a lack of knowledge, lack of awareness of the different options, lack of clinic time and uncertainty around issues such as funding for PGT and whose responsibility it comes under.There is a need for training and education on reproductive options and referral for these options needs to be integrated within the health system. Developing more resources for both clinicians and patients is required as MND clinicians reported a lack of resources. [ABSTRACT FROM AUTHOR]

Little is known regarding the future reproductive decision‐making of parents of children with rare genetic conditions. Our research draws on data from an online survey and qualitative photo‐elicitation interviews with families living with Noonan Syndrome. We demonstrate how genetic knowledge and prenatal genetic testing become embedded in reproductive practices. Yet the idea of using selective genetic technologies to influence reproductive outcomes remains highly emotive. Our analysis reveals that for these parents, the rationalities of reproduction, although technologised and biomedicalised, remain centred on caring for their disabled child. Genetic subjectivities become entangled with responsibilities of care‐giving and emotion tied to the realities of living with disability. We argue that for these parents, reproductive decisions are relational and affective, situated within families and communities and shaped by access to emotional, financial, physical and temporal resources. Our findings provide new insights into the ontologies of selective genetic technologies and reproductive governance in families living with disability. [ABSTRACT FROM AUTHOR]

Objectives: To determine the clinical course of fetal isolated non‐immune‐mediated second‐degree atrioventricular block (AVB) and the factors associated with spontaneous recovery in these cases. Methods: Fetuses with isolated non‐immune‐mediated second‐degree AVB were recruited prospectively between 2014 and 2022. These fetuses were divided into two groups: those which recovered spontaneously and those which did not. Maternal and fetal characteristics and intrauterine and postnatal outcomes were compared between the two groups. Results: The study cohort included 20 fetuses with isolated non‐immune‐mediated second‐degree AVB, diagnosed at a median gestational age of 22.0 (range, 17.0–35.0) weeks. In 12 fetuses, 1:1 atrioventricular conduction was restored spontaneously in utero and there was no recurrence during the postnatal follow‐up period. In the remaining eight fetuses, second‐degree AVB was maintained and, in six of these, the pregnancy was terminated on parental request. Of the two liveborn children who had persistent second‐degree AVB prenatally, one had progressed to complete AVB at the latest follow‐up, at the age of 34 months, but was asymptomatic, without heart enlargement or dysfunction. The other child progressed to complete AVB after delivery and was diagnosed with type‐2 long QT syndrome. This infant died aged 2 months. Fetuses in the group that recovered spontaneously had earlier gestational age at diagnosis (median, 20.0 (range, 17.0–26.0) vs 24.5 (range, 18.0–35.0) weeks; P = 0.004) and higher atrial rate at diagnosis (median, 147 (range, 130–160) vs 138 (range, 125–149) bpm; P = 0.006) in comparison with the group that did not recover spontaneously. The best cut‐off values for prediction of failure to recover spontaneously were 22.5 weeks' gestational age at diagnosis and 144 bpm atrial rate at diagnosis, with sensitivities of 87.5% and 75.0%, respectively, and specificities of 92.0% and 87.5%, respectively. Conclusions: The outcome of 60% of fetuses with isolated non‐immune‐mediated second‐degree AVB was favorable. Earlier gestational age and higher atrial rate at diagnosis were associated with spontaneous reversion to normal sinus rhythm. Prenatal genetic testing should be performed in cases with persistent AVB, to exclude heritable disorders including long QT syndrome. These findings provide important information for clinical management and prenatal counseling in these cases. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: Noninvasive prenatal testing (NIPT) has increased the number of conditions that can be screened. However, the prevalence of conditions assessed by NIPT has remained stable. The "prevalence threshold," a novel epidemiological concept, uses a test's sensitivity and specificity to determine the prevalence below which a test's positive predictive value declines most sharply relative to disease prevalence. In this article, we calculated the prevalence threshold for common conditions assessed through NIPT and compared the value with the actual prevalence of each condition to best ascertain the reliability of NIPT results. Methods: Six databases and PubMed were searched from January 2010 to March 2023 for sensitivity and specificity parameters of common conditions tested through NIPT. Using an equation previously derived by the authors of the current paper, the prevalence threshold for each condition was calculated. The theoretical number of test iterations required to reach the prevalence threshold was also reported. Results: None of the conditions tested through the NIPT had a prevalence rate that met or exceeded the calculated prevalence threshold. Trisomy 21 had the greatest concordance between the prevalence rate and the prevalence threshold. In contrast, Angelman, Cri‐du‐chat, and Prader‐Willi syndromes had the most significant discordance. Apart from trisomy 21 and XXY, all remaining conditions required more than one test iteration to reach their respective prevalence threshold. Conclusion: We conclude that at the current prevalence levels, the positive predictive value of NIPT remains low, with the prevalence of disease levels significantly lower than the prevalence threshold for each condition tested. Synopsis: The positive predictive value of noninvasive prenatal testing remains low, with the prevalence of disease levels significantly lower than the prevalence threshold for each condition tested. [ABSTRACT FROM AUTHOR]

Purpose: In some cases of prenatal genetic testing, an ample amount of fetal DNA is needed, to allow for parallel testing (conducting several genetic tests simultaneously). This study investigated the association between amniotic fluid DNA concentration and various factors. We aimed to define the required amount of amniotic fluid to be extracted in amniocentesis, to allow parallel testing throughout gestational weeks. Methods: DNA concentration was analyzed from amniocentesis samples taken during the years 2016–2022. Sex association was also analyzed in postnatal whole blood samples from a separate cohort. Theoretical minimum volume of amniotic fluid needed to ensure enough DNA for chromosomal microarray analysis and exome sequencing was calculated. Results: We focused our analysis on 2573 samples, which were taken during weeks 17–23 and 30–35. DNA concentrations increased from weeks 17 to 21, with relatively stable concentrations thereafter. Significantly higher DNA concentrations were seen in pregnancies of female fetuses. DNA concentrations in postnatal whole blood samples did not show this association. Across most weeks, the volume needed to extract 2 µg of DNA from 95% of the samples was about 34 ml. Conclusion: DNA concentrations in amniotic fluid vary according to gestational age and are higher in pregnancies of female fetuses. This should be considered when determining the volume of fluid extracted and the timing of amniocentesis, with greater volumes needed in earlier stages of pregnancy. [ABSTRACT FROM AUTHOR]

Objective: We sought to analyze the genetic outcomes of fetuses with nuchal translucency (NT) > 95th centile, and determine whether prenatal genetic counseling, chromosomal microarray analysis (CMA) or non-invasive prenatal testing (NIPT) are truly beneficial for the outcomes of fetuses with increased NT > 95th centile and below 99th centile. Materials and methods: A total of 535 pregnant women were included in this study, with a fetal NT > 95th centile at 11–13+6 weeks of gestation from January 2017 to December 2020. 324 pregnant women with fetal NT > 95th centile and below 99th centile combined with other risk factors and NT > 99th centile received prenatal diagnostic karyotype analysis and CMA, and 211 pregnant women with fetal isolated increased NT > 95th centile and below 99th centile were selected to carry out NIPT. Results: A total of 211 pregnant women who underwent NIPT were included in the study, NIPT results showed that 8 high-risk cases were confirmed by prenatal diagnosis. Overall, the detection rate of NIPT was 3.79%. A total of 324 pregnant women with fetal NT > 95th centile and below 99th centile, along with other risk factors, and those with fetal NT > 99th centile, received karyotype analysis and CMA for prenatal diagnosis. Among them, a total of 73 genetic abnormalities were detected, including 45 cases of chromosomal aneuploidy, 7 cases of structural abnormalities, and 21 cases of copy number variations (CNVs) with a size of less than 10 Mb. In addition, the 73 women with genetic abnormalities are divided into three groups based on the NT measurement (Group 1: Fetuses with NT > 95th centile and below 99th centile, Group 2: Fetuses with NT > 99th centile, and Group 3: Fetuses with NT > 99th centile). 13.11% (8/61) of pathogenic genetic abnormalities (6 chromosomal aneuploidy, 1 structural abnormality, and 1 likely pathogenic CNV) will be missed if genetic counseling and prenatal genetic testing were not conducted in fetuses with increased NT > 95th centile and below 99th centile combined with other risks. Pathogenic CNVs were the most common abnormalities in group 3, and one likely pathogenic CNV was detected in group 1 and group 3, respectively, and a total of 14 CNVs of unknown clinical significance (VOUS) were detected. Conclusions: Through this study, we demonstrated that the critical value of NT > 95th centile for invasive detection or NIPT. Invasive testing combined with CMA may be recommended for fetuses with NT > 95th centile and below 99th centile and with other risks. But when isolated NT > 95th centile and below 99th centile, NIPT would be appropriate. [ABSTRACT FROM AUTHOR]

Background: Kagami–Ogata syndrome (KOS) and Temple syndrome (TS) are two imprinting disorders characterized by the absence or reduced expression of maternal or paternal genes in the chromosome 14q32 region, respectively. We present a rare prenatally diagnosed case of recurrent KOS inherited from a mother affected by TS. Case presentation: The woman's two affected pregnancies exhibited recurrent manifestations of prenatal overgrowth, polyhydramnios, and omphalocele, as well as a small bell-shaped thorax with coat-hanger ribs postnatally. Prenatal genetic testing using a single-nucleotide polymorphism array detected a 268.2-kb deletion in the chromosome 14q32 imprinted region inherited from the mother, leading to the diagnosis of KOS. Additionally, the woman carried a de novo deletion in the paternal chromosome 14q32 imprinted region and presented with short stature and small hands and feet, indicating a diagnosis of TS. Conclusions: Given the rarity of KOS as an imprinting disorder, accurate prenatal diagnosis of this rare imprinting disorder depends on two factors: (1) increasing clinician recognition of the clinical phenotype and related genetic mechanism, and (2) emphasizing the importance of imprinted regions in the CMA workflow for laboratory analysis. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study is to assess the carrier frequency and pathogenic variation of monogenetic diseases in a population of 114 subjects in Han Chinese from Hebei province who are undergoing assisted reproductive technology through the utilization of Expanded Carrier Screening (ECS). Methods: The study utilized a panel consisting of 155 severe monogenic recessive genetic diseases for ECS. Next-generation sequencing technology was employed to identify specific variants associated with ECS in a cohort of 114 subjects from 97 couples, comprising 97 females and 17 male spouses. Results: A total of 114 individuals received ECS. The carrier rate of pathogenic genes in the enrolled population was 44.74% (51/114). Among the 97 females, the carrier rate of pathogenic genes was higher in those without assisted reproduction indicators than in those with assisted reproduction indicators (59.09% vs. 41.33%). However, the carrier rate of pathogenic genes in males without assisted reproductive technology was slightly lower than that with assisted reproductive technology (40% vs. 41.67%). Among both female and male participants, the carrier rate of pathogenic genes between individuals without indicators of assisted reproduction and those with such indicators was 55.55% vs. 41.38%. In 51 carriers, 72.55% (37/51) carried one genetic variant, 25.49% (13/51) carried two genetic variants, and 1.96% (1/51) carried three genetic variants. A total of 38 pathogenic genes were detected in this study, and GJB2 and MMACHC were most common. The carrier rates of the two genes were both 5.26% (6/114). A total of 55 variations were detected, and c.235delC was most frequently found. The carrier rate was 3.51% (4/114). The incidence of couples carrying the same pathogenic genes was 1.03% (1/97). Conclusions: The findings elucidate the carrier rate of pathogenic genes among 155 severe monogenic recessive genetic diseases and underscore the significance of ECS as a preventive measure against congenital anomalies. When both partners carry the same genetic mutation for a monogenic disease, preventive strategies can be taken in offspring through preimplantation genetic testing (PGT), prenatal genetic testing, or the utilization of donor gametes. ECS is instrumental in assessing reproductive risk, guiding fertility-related decisions, and reducing the prevalence of monogenic recessive genetic disorders in subsequent generations. [ABSTRACT FROM AUTHOR]

Cleft lip and/or palate are prevalent congenital anomalies. Early and accurate diagnosis allows proper case management. The Objective: This retrospective cohort study aimed to investigate the association between cleft lip and palate and other congenital anomalies. Methods: This study analyzed 17 pregnancies prenatally diagnosed with cleft lip and palate. The investigations consisted of ultrasound examination, fetal karyotyping through amniocentesis, and family tree analysis. In the presence of an abnormal fetal karyotype, the parental karyotype was also indicated. Results: Of the 17 cases identified, 9 (52.94%) were syndromic and 8 (47.06%) were non-syndromic. The genetic syndromes identified in association with cleft lip and palate in this study included translocation syndrome (one case), Patau syndrome, trisomy 13 (seven cases), and Edwards syndrome, mosaic trisomy 18 (one case). Conclusions: A comprehensive approach ensures a thorough assessment and accurate diagnosis. Early detection and a multidisciplinary approach allow appropriate case management. [ABSTRACT FROM AUTHOR]

Background: Products of conception samples are often collected and analyzed to try to determine the cause of an early pregnancy loss. However, sample collection may not always be possible, and maternal cell contamination and culture failure can affect the analysis. Cell-free DNA-based analysis of a blood sample could be used as an alternative method in early pregnancy loss cases to detect if aneuploidies were present in the fetus. Methods: In this prospective study, blood samples from early pregnancy loss patients were analyzed for the presence of fetal aneuploidies using a modified version of a noninvasive prenatal testing assay for cell-free DNA analysis. Results from cell-free DNA analysis were compared against the gold standard, microarray analysis of products of conception samples. This study was registered with ClinicalTrials.gov, identifier: NCT04935138. Results: Of the 76 patient samples included in the final study cohort, 11 were excluded from performance calculations. The 65 patient samples included in the final analysis included 49 with an abnormal microarray result and 16 with a normal microarray result. Based on results from these 65 samples, the study found that genome-wide cell-free DNA analysis had a sensitivity of 73.5% with a specificity of 100% for the detection of fetal aneuploidies in early pregnancy loss cases. Conclusions: This prospective study provides further support for the utility of cell-free DNA analysis in detecting fetal aneuploidies in early pregnancy loss cases. This approach could allow for a noninvasive method of investigating the etiology of miscarriages to be made available clinically. [ABSTRACT FROM AUTHOR]

Purpose: Prenatal genetic screens and diagnostic tests are vital components of prenatal care. The first prenatal visit is a critical time in the decision-making process when patients decide whether to use these tests in addition to address a series of other essential prenatal care aspects. We conducted this study to examine the role of a shared decision-making (SDM) instrument to support these discussions. Methods: We conducted a cluster randomized controlled trial of patients allocated to an SDM tool or usual care at their first prenatal visit. Participants completed a baseline survey to measure decision-making needs and preferences. Direct observation was conducted and analyzed using the OPTION scale to measure SDM during prenatal genetic testing discussions. Results: Levels of SDM were similar across groups (P = 0.081). The highest levels of SDM were observed during screening test discussions (NEST 2.4 ± 0.9 v. control 2.6 ± 1.0). Lowest levels were observed in discussions about patients' preference for risk versus diagnostic information (NEST 1.0 ± 1.1 v. control 1.2 ± 1.3). Conclusion: Study findings demonstrate the need for targeted patient-focused and provider-focused efforts to improve SDM to enhance patients' informed decision making about these options. Importantly, patients' baseline knowledge and attitudes need to be considered given that patients with less knowledge may need more carefully crafted communication. Highlights: Choices about whether, when, and how to use prenatal genetic tests are highly preference-based decisions, with patients' baseline attitudes about these options as a major driver in health care discussions. The decision-making process is also shaped by patient preferences regarding a shared or informed decision-making process for medical decisions that are highly personal and have significant ramifications for obstetric outcomes. There is a need to develop targeted efforts to improve decision making and enhance patients' ability to make informed decisions about prenatal genetic tests in early pregnancy. [ABSTRACT FROM AUTHOR]

Background/Objectives: Non-Invasive prenatal test (NIPT) is used as a universal or contingent test after prior risk assessment. Screening is mainly performed for common trisomies (T21, T13, T18), although other chromosomal anomalies may be detected. Our objective was to study the performance of GWNIPT in the detection of chromosomal abnormalities in pregnancies in which an invasive prenatal study was performed and in early pregnancy losses, in comparison with the reference test. Method: VeriSeqTM NIPT Solution v2, a genome-wide NIPT (GWNIPT), was performed prior to invasive testing in fetal diagnostic study cases (FDS, n = 155) and in early pregnancy losses (EPL, n = 68). Results: In the FDS group, the diagnostic test (QFPCR, array and karyotype) detected anomalies in 32 pregnancies (21%), in twenty of them (61%) also detected by GWNIPT. Eleven of the twelve cases undetected by GWNIPT were balanced translocations (n = 4) or deletions/duplications <7 Mb (n = 7). In the EPL group, GWNIPT detected anomalies in 46% of cases (31/68) but comparison with reference test (QFPCR and karyotype) in products of conception (POC) was only possible in 18 cases. Concordant results between POC and GWNIPT test were obtained in 16 of the 18 cases. In EPL, with GWNIPT testing, common trisomies accounted for 25.8% of cases (8/31), rare trisomies 54.8% (17/31) and microdeletions/duplications 16.1% (5/31). Conclusions: The GWNIPT test may be useful in clinical practice in prenatal and in EPL's genetic diagnosis when the appropriate sample is not available. [ABSTRACT FROM AUTHOR]

Introduction: 4q35 deletion is a rare chromosomal syndrome with a wide range of phenotypes, which can be challenging to detect through prenatal ultrasound. This study aimed to summarize the fetal phenotypes of patients with 4q35 deletion. Case Presentation: The study included four fetuses with 4q35 deletion, with detailed records of prenatal ultrasound and genetic testing results. These cases included following phenotypes, fetal growth restriction (FGR) (2/4), cystic hygroma (2/4), single umbilical artery (1/4), and fused kidney (1/4). One case was terminated, while the other three were born and showed no obvious abnormalities at the 1-year follow-up. Previous reports have described the fetal phenotype of 4q35 deletion in 6 patients from five families, with prenatal phenotypes including FGR (2/6), cardiac structural abnormalities (1/6), brain ventriculomegaly (1/6), oligohydramnios (1/6), and multicystic dysplastic kidneys (1/6). Conclusion: Overall, the phenotypes of fetuses with 4q35 deletion are diverse, with FGR potentially being a significant phenotype in these cases. [ABSTRACT FROM AUTHOR]

Introduction: CHARGE syndrome is an autosomal dominant genetic disorder with known pattern of features. The aim of the study was to present the fetal features of CHARGE syndrome to gain awareness that the antenatal characteristics can be very nonspecific. Case Presentation: This was a retrospective study of 13 cases with CHARGE syndrome diagnosed by prenatal or postnatal genetic testing and physical examination. Two (15.4%; 2/13) had normal ultrasound scans during pregnancy. One (7.7%; 1/13) with first-trimester cystic hygroma presented intrauterine fetal demise at 16 weeks gestation. The remaining 10 (76.9%; 10/13) cases had abnormal ultrasound features in utero; among these, 1 had an increased nuchal translucency in the first trimester, 5 had second-trimester abnormal ultrasounds including micrognathia, cardiac defects, and facial defects, and 4 third-trimester abnormal ultrasounds including micrognathia, isolated fetal growth restriction, and polyhydramnios. Among the 11 cases with abnormal prenatal ultrasound scans, no fetus could reach the diagnostic criteria of CHARGE syndrome if only based on the results of ultrasound. However, the diagnosis was made in all cases when CHD7 defects were detected. Discussion/Conclusion: The CHARGE syndrome presents non-specific abnormal ultrasound markers in utero. Exome sequencing in the genetic workup will aid in prenatal diagnosis of this syndrome. [ABSTRACT FROM AUTHOR]

Non-invasive prenatal testing (NIPT) is usually performed beyond 10 weeks of gestation, because earlier in pregnancy, the fetal fraction is low, resulting in failure to obtain reliable results. This study aimed to evaluate the clinical performance of NIPT earlier in pregnancy using a method for cell-free DNA (cfDNA) analysis that eliminates the need for polymerase chain reaction (PCR), DNA sequencing, or microarrays (Vanadis® system, PerkinElmer, Waltham, MA, USA). Cell-free DNA was extracted from the maternal plasma of 30 singleton pregnancies at 6–9 weeks of gestation (group 1) and at 11–14 weeks of gestation of the same patients (group 2). The mean crown-rump length (CRL) and gestational age in group A was 16.12 mm and that in group B was 61.45 mm. In group A, results were obtained in all, but one, cases (97%). From the remaining pregnancies, one miscarried at 8 weeks and, therefore, the follow-up NIPT at 12 weeks could not be performed. The fetal sex was diagnosed correctly in the 28 cases that had a successful early test, and the results were in accordance with the examination at 12 weeks. There were no cases of aneuploidies and disomy was diagnosed correctly in all. The "Vanadis" prenatal NIPT assay can successfully be used early during the first trimester at 6–9 weeks of gestation (early NIPT) to identify the fetal sex. Further studies are needed to explore the diagnostic potential for aneuploidies. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the prenatal diagnosis, parental verification, and pregnancy outcomes of three fetuses with 17ql2 microdeletion syndrome. Methods: We retrospectively reviewed 46 singleton pregnancies with anomalies in the urinary system who underwent amniocentesis from Feb 2022 to October 2023 in the Prenatal Diagnosis Center of Lianyungang Maternal and Child Health Hospital. These fetuses were subjected to chromosomal microarray analysis (CMA) and/or trio whole-exome sequencing (Trio-WES). We specifically evaluated these cases' prenatal renal ultrasound findings and clinical characteristics of the affected parents. Results: Three fetuses were diagnosed as 17q12 microdeletions, and the detection rate was 6.5% in fetuses with anomalies in the urinary system (3/46). The heterogeneous deletions range from 1.494 to 1.66 Mb encompassing the complete hepatocyte nuclear factor 1 homeobox B (HNF1B) gene. Fetuses with 17q12 deletion exhibited varied renal phenotypes. Moreover, the clinical phenotypes of the affected parents differed greatly in the two cases (case 2 and case 3) in which the deletion was inherited. For case 3, the mother manifested classic symptoms of 17q12 deletion syndrome as well as unreported characteristics, such as very high myopia. Conclusion: Our findings demonstrate the necessity and significance of offering prenatal genetic testing when various renal anomalies are detected. In addition, our study broadens the phenotypic spectrum of 17q12 deletions. Most importantly, our findings may allow timely supportive genetic counseling and guidance for pregnancy in affected families, e.g., with the help of preimplantation genetic testing (PGT). [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: This study aims to evaluate maternal reassurance, satisfaction, and anxiety after two different strategies for the first-trimester screening for aneuploidies. Methods: Patients between 11 + 3 and 13 + 6 weeks of gestation attending the first-trimester screening at Department of Mother and Child, University Hospital Federico II, Naples, Italy have been recruited and randomly allocated to contingent screening or universal cell-free fetal DNA testing (cffDNA). Questionnaires to measure reassurance, satisfaction, and anxiety have been filled twice: (Q1) after randomization and (Q2) after receiving results. Anxiety was measured by an Italian-version short form of the state scale of the Spielberger State–Trait Anxiety Inventory (STAI); child-related anxiety was measured by the 11-item Pregnancy-Related Anxiety Questionnaire—Revised Regardless of Parity (PRAQ-R2 scale); fear of bearing a physically or mentally handicapped child was measured considering only four items (item 4, 9, 10, and 11) of the PRAQ-R2 scale. Results: 431 patients were recruited: 205 (49%) were randomized in the contingent screening arm, 226 (51%) in the cfDNA arm. Maternal reassurance, satisfaction, and anxiety were not different in the two groups. Conclusion: A contingent screening for aneuploidies in the first trimester seems able to ensure the same maternal reassurance and satisfaction as a cfDNA analysis in the low-risk population and to not affect maternal anxiety. [ABSTRACT FROM AUTHOR]

Objectives: The performance of non‐invasive prenatal screening using cell‐free DNA testing of maternal blood in twin pregnancy is underevaluated, while serum marker‐based strategies yield poor results. This study aimed to assess the performance of non‐invasive prenatal screening for trisomy 21 in twin pregnancy as a first‐tier test. Secondary objectives were to assess its failure rate and factors associated with failure. Methods: This retrospective cohort study included twin pregnancies in which non‐invasive prenatal screening using cell‐free DNA was performed as the primary screening strategy between May 2017 and October 2019. We used the NIPT VeriSeq® test for in‐vitro diagnosis and set a fetal fraction cut‐off of 4% for monochorionic pregnancies and 8% for dichorionic ones. Clinical data and pregnancy outcome were collected from physicians or midwives via a questionnaire or were retrieved directly on‐site. We calculated the performance of non‐invasive cell‐free DNA screening for trisomy 21, analyzed its failure rate and assessed potentially associated factors. Results: Among 1885 twin pregnancies with follow‐up, there were six (0.32%) confirmed cases of trisomy 21. The sensitivity of non‐invasive prenatal screening for trisomy 21 was 100% (95% CI, 54.1–100%) and the false‐positive rate was 0.23% (95% CI, 0.06–0.59%). The primary failure rate was 4.6%, with 4.0% being due to insufficient fetal fraction. A successful result was obtained for 65.4% of women who underwent a new blood draw, reducing the overall failure rate to 2.8%. Maternal body mass index, gestational age at screening as well as chorionicity were significantly associated with the risk of failure. Conclusion: This study provides further evidence of the high performance, at an extremely low false‐positive rate, of non‐invasive prenatal screening in twins as part of a primary screening strategy for trisomy 21. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Obtaining a genetic diagnosis of a primary mitochondrial disease (PMD) is often framed as a diagnostic odyssey. Yet, even after receiving a diagnosis, parents of affected children experience ongoing therapeutic and prognostic uncertainty and considerable psychosocial challenges. Semi-structured interviews (N = 24) were conducted with parents of 13 children (aged 2–19 years) with a genetically confirmed PMD. Paternal (N = 11) and maternal (N = 13) perspectives were obtained, and thematic analysis was performed on all interviews. A genetic diagnosis was valuable and empowering for parents, despite eliciting varied emotional responses. While the diagnosis helped focus management decisions, families often felt overwhelmed and unsupported in navigating the healthcare system. Most parents reported a serious impact on their romantic relationship. The sources of social support varied, with a preference for established friendship and family support networks over disease-specific community support groups. Most parents favored prenatal genetic testing in the event of a future pregnancy. This study provides insight into the lived experiences of parents after a genetic diagnosis of PMD in their children. The findings draw awareness to supportive care needs and highlight important gaps that should be addressed to ensure that parents feel supported within a holistic framework of management for PMDs. [ABSTRACT FROM AUTHOR]

Increasingly, pregnant people in the United States are choosing to give at birth at home, and certified professional midwives (CPMs) often attend these births. Care by midwives, including home birth midwives, has the potential to decrease unnecessary medical interventions and their associated health care costs, as well as to improve maternal satisfaction with care. However, lack of integration into the health care system affects the ability of CPMs to access standard medications and testing for their clients, including prenatal screening. Genetics and genomics are now a routine part of prenatal screening, and genetic testing can contribute to identifying candidates for planned home birth. However, research on genetics and midwifery care has not, to date, included the subset of midwives who attend the majority of planned home births, CPMs. The purpose of this study was to examine CPMs' access to, and perspectives on, one aspect of prenatal care, genetic counselors and genetic counseling services. Using semi-structured interviews and a modified grounded theory approach to narrative analysis, we identified three key themes: (1) systems-level issues with accessing information about genetic counseling and genetic testing; (2) practice-level patterns in information delivery and self-awareness about knowledge limitations; and (3) client-level concerns about the value of genetic testing relative to difficulties with access and stress caused by the information. The results of this study can be used to develop decision aids that include information about genetic testing and genetic counseling access for pregnant people intending home births in the United States. [ABSTRACT FROM AUTHOR]

This document summarizes a study on prenatal screening for copy number variants (CNVs) in the Duchenne muscular dystrophy (DMD) gene using non-invasive prenatal testing (NIPT) data. The study analyzed data from a large population of reproductive-age women in China and identified 33 different pathogenic/likely pathogenic maternal CNVs in the DMD gene. The study found that approximately 40% of offspring inherited true-positive maternal CNVs, and 1.63% of male offspring could potentially be prenatally diagnosed and managed using this method. The study provides important information for genetic counseling and DMD/BMD screening worldwide. [Extracted from the article]

Background: Prenatal genetic testing is done throughout pregnancy to identify or diagnose birth defects. These tests aim to help families make educated decisions regarding pregnancy and reproduction, as well as aid healthcare providers in providing optimal care for pregnant women. Prenatal blood screening is performed twice during pregnancy. Aim: The present study aims to assess the Effectiveness of video assisted teaching programme on level of knowledge and attitude regarding prenatal genetic testing among antenatal mother. Materials and Methods: A Quasi experimental, one group pre and post experimental research design was used for this study. The study conducted in SMCH. A total of 60 study participants were recruited by using a non probability convenient sample technique, based on inclusion criteria. Results: The analysis revealed that most of the antenatal mothers, 24 (40%) were aged between 21 and 25 years, 33 (55%) had higher secondary education, 34 (56.6%) were private employees, 43 (71.6%) were Hindus, 46 (76.7%) were residing in urban area, 40 (66.6%) had an income of between INR 10,000 and 20,000, and 48 (80%) and 3 (30%) had friends/relatives and health care professionals as source of information. Conclusion: The study found that video education on genetic testing improved patients’ and increased quality of life.

Establishing the diagnosis of a fetal genetic disease in utero expands decision-making opportunities for individuals during pregnancy and enables providers to tailor prenatal care and surveillance to disease-specific risks. The selection of prenatal genetic tests is guided by key details from fetal imaging, family and obstetrical history, suspected diagnoses and mechanisms of disease, an accurate understanding of what abnormalities each test is designed to detect, and, at times, the gestational age at which testing is initiated. Pre- and posttest counseling, by or in conjunction with providers trained in genetics, ensure an accurate understanding of genetic tests, their potential results and limitations, estimated turnaround time for results, and the clinical implications of their findings. As prenatal diagnosis and testing options continue to expand rapidly, it is increasingly important for obstetrical providers to understand how to choose appropriate genetic testing and contextualize the clinical implications of their results.

The text discusses the structural constraints that affect decisions about participation in genomic and precision medicine. It highlights disparities and delays in access to genetic services for patients with low incomes and underserved racial and ethnic groups. These disparities can be attributed to inadequate preparation for genomic medicine at the health system and provider levels. The text also mentions barriers at the patient level, such as high out-of-pocket costs and lack of coverage for clinical genetic testing. The importance of empirical research in understanding and resolving these barriers is emphasized, particularly in underrepresented populations. The text includes four primary research papers that explore the influence of context and diverse lived experiences on decisions about participation in genomic and precision medicine. These papers highlight the need for further study and collaboration within the ELSI research community. [Extracted from the article]

Hereditary breast and ovarian cancer (HBOC) syndrome is responsible for approximately 10% of breast cancers (BCs). The HBOC gene panel includes both high-risk genes, i.e., a four times higher risk of BC (BRCA1, BRCA2, PALB2, CDH1, PTEN, STK11 and TP53), and moderate-risk genes, i.e., a two to four times higher risk of BC (BARD1, CHEK2, RAD51C, RAD51D and ATM). Pathogenic germline variants (PGVs) in HBOC genes confer an absolute risk of BC that changes according to the gene considered. We illustrate and compare different BC risk estimation models, also describing their limitations. These models allow us to identify women eligible for genetic testing and possibly to offer surgical strategies for primary prevention, i.e., risk-reducing mastectomies and salpingo-oophorectomies. [ABSTRACT FROM AUTHOR]

Purpose: The trend of delaying childbirth has resulted in a growing number of advanced-aged women who are opting for preimplantation genetic testing (PGT) to screen for monogenic diseases or structural chromosomal rearrangements (PGT-M and PGT-SR). This increase in demand necessitates the development of a clinical predictive model for live birth outcomes in these women. Therefore, the objective of this study is to construct a comprehensive predictive model that assesses the likelihood of achieving a successful live birth in advanced-aged women undergoing PGT-M and PGT-SR treatments. Methods: A retrospective cohort study of 37–45-year-old women undergoing preimplantation genetic testing for monogenic disease or structural chromosomal rearrangement cycles from 2010 to 2021 was conducted at a university hospital reproductive centre. The purpose was to develop a clinical predictive model for live birth in these women. The main outcome studied was the cumulative live birth rate in the first or subsequent cycles. Developing a decision tree enabled a comprehensive study of clinical parameters and expected outcomes. Results: The analysis included 158 women undergoing 753 preimplantation genetic testing cycles. The cumulative live birth rate was 37.342% (59/158). Decision tree analysis revealed that women aged ≤ 40.1 or women > 40.1 with one or more top-quality transferable embryos in their first cycle had the best chance for a live baby (56% and 41%, respectively). Those older than 40.1 without top-quality embryos and seven or fewer dominant follicles had no live births. A Kaplan–Meier curve showed that for autosomal dominant diseases, there was a negligible increase in live birth rate after three cycles, compared to six cycles in autosomal recessive inheritance. Conclusion: In older women, the chance of delivering after repeated cycles is higher in those with at least one top-quality unaffected embryo in their first preimplantation genetic testing cycle. Additional preimplantation genetic testing cycles after three in carriers of an autosomal dominant disorder and six in those with an autosomal recessive disorder should be considered prudently. [ABSTRACT FROM AUTHOR]

Distinct miRNA expression patterns may reflect anomalies related to fetal congenital malformations such as spinal bifida (SB). The aim of this preliminary study was to determine the maternal miRNA expression profile of women carrying fetuses with SB. Therefore, six women carrying fetuses with SB and twenty women with euploid healthy fetuses were enrolled in this study. Using NanoString technology, we evaluated the expression level of 798 miRNAs in both plasma and amniotic fluid samples. A downregulation of miR-1253, miR-1290, miR-194-5p, miR-302d-3p, miR-3144-3p, miR-4536-5p, miR-548aa + miR-548t-3p, miR-548ar-5p, miR-548n, miR-590-5p, miR-612, miR-627-5p, miR-644a, and miR-122-5p, and an upregulation of miR-320e, let-7b-5p, miR-23a-3p, miR-873-3p, and miR-30d-5p were identified in maternal amniotic fluid samples in SB when compared to the control group. The target genes of these miRNAs play a predominant role in regulating the synthesis of several biological compounds related to signaling pathways such as those regulating the pluripotency of stem cells. Moreover, the maternal plasma expression of miR-320e was increased in pregnancies with SB, and this marker could serve as a valuable non-invasive screening tool. Our results highlight the SB-specific miRNA signature and the differentially expressed miRNAs that may be involved in SB pathogenesis. Our findings emphasize the role of miRNA as a predictive factor that could potentially be useful in prenatal genetic screening for SB. [ABSTRACT FROM AUTHOR]

Key Clinical Message: CHARGE syndrome is a rare genetic disorder characterized by several distinct features. The presence of fetal ear abnormalities could be the early indicator of CHARGE syndrome. Subsequent prenatal diagnosis is essential to confirm the disorder. This is significant because the patient may receive genetic counseling and appropriate disposal based on the accurate diagnosis. CHARGE syndrome is a rare genetic disorder with multiple specific clinical features. The prenatal diagnosis is crucial but rarely achieved. We report a fetus with fetal external ear abnormality detected by ultrasound at 22nd week of gestation. Postnatal examination revealed an external ear abnormality, a mild atrial septal defect, and other clinical signs of CHARGE syndrome. A de novo pathogenic nonsense mutation in the CHD7 gene (c.406C > T, p.Q136X in exon 2) was identified to cause the disorder. Our study demonstrated that prenatal diagnosis and genetic testing were recommended to obtain a solid diagnosis of CHARGE syndrome when fetal external ear abnormality was detected by ultrasound examination. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is the most common malignancy in women of reproductive age. This study sought to explore the postcancer conception and pregnancy experience of young BC survivors to inform counseling. Methods: In the Young Women's Breast Cancer Study (NCT01468246), a multicenter, prospective cohort, participants diagnosed at age ≤40 years with stage 0‐III BC who reported ≥1 postdiagnosis live birth were sent an investigator‐developed survey. Results: Of 119 eligible women, 94 (79%) completed the survey. Median age at diagnosis was 32 years (range, 17–40) and at first postdiagnosis delivery was 38 years (range, 29–47). Most had stage I or II (77%) and HR+ (78%) BC; 51% were nulligravida at diagnosis. After BC treatment, most (62%) conceived naturally, though 38% used assisted reproductive technology, 74% of whom first attempted natural conception for a median of 9 months (range, 2–48). Among women with a known inherited pathogenic variant (n = 20), two underwent preimplantation genetic testing. Of 59 women on endocrine therapy before pregnancy, 26% did not resume treatment. Hypertensive disorders of pregnancy (20%) was the most common obstetrical condition. Nine percent of newborns required neonatal intensive care unit admission and 9% had low birth weight. Conclusion: Among women with live births after BC treatment, most conceived naturally and having a history of BC did not appear to negatively impact pregnancy complications, though the high rate of hypertensive disorders of pregnancy warrants further investigation. The prolonged period of attempting natural conception for some survivors suggests the potential need for improved understanding and counseling surrounding family planning goals after BC. In a cohort of 94 women surveyed with one or more live birth(s) after breast cancer treatment, although most conceived naturally, observations suggest potential gaps in counseling related to use of artificial reproductive technology and future childbearing when planning endocrine therapy. History of breast cancer did not appear to negatively impact pregnancy complications, though a higher rate of hypertensive disorders of pregnancy was observed compared with prior studies of breast cancer survivors, requiring further investigation. [ABSTRACT FROM AUTHOR]

Purpose: Deficiency of 21-hydroxylase (21-OHD) is an autosomal recessively inherited disorder that is characterized by adrenal insufficiency and androgen excess. This study was performed to investigate the clinical utility of prenatal diagnosis of 21-OHD using molecular genetic testing in families at risk. Methods: This study included 27 pregnant women who had previously borne a child with 21-OHD. Fetal tissues were obtained using chorionic villus sampling (CVS) or amniocentesis. After the genomic DNA was isolated, Sanger sequencing of CYP21A2 and multiplex ligation-dependent probe amplification were performed. The clinical and endocrinological findings were reviewed retrospectively. Results: A total of 39 prenatal genetic tests was performed on 27 pregnant women and their fetal tissues. The mean gestational age at the time of testing was 11.7 weeks for CVS and 17.5 weeks for amniocentesis. Eleven fetuses (28.2%) were diagnosed with 21-OHD. Among them, 10 fetuses (90.9%) harbored the same mutation as siblings who were previously diagnosed with 21-OHD. Among these, 4 fetuses (3 males and 1 female) identified as affected were born alive. All 4 patients have been treated with hydrocortisone, 9a-fludrocortisone, and sodium chloride since a mean of 3.7 days of life. The male patients did not show hyponatremia and dehydration, although they harbored pathogenic variants associated with the saltwasting type of 21-OHD. Conclusion: This study demonstrated the diagnostic efficacy and clinical consequences of diagnosis by prenatal genetic testing in families at risk for 21-OHD. All patients identified as affected were treated with hydrocortisone and 9a-fludrocortisone early after birth, which can prevent a life-threatening adrenal crisis. [ABSTRACT FROM AUTHOR]

The article explores the limitations of systematic reviews and meta-analyses in evaluating the clinical usefulness of genomic investigations in prenatal diagnosis. It discusses issues such as publication bias, limited phenotyping, and variations in statistical analyses. The article also addresses challenges specific to cell-free DNA screening, including bias in combining rare anomalies and follow-up bias. While acknowledging the importance of these studies, the authors stress the need to consider their limitations when interpreting results. The article suggests alternative approaches to determine the diagnostic yield of genomic tests and emphasizes the significance of optimal study design and reporting. [Extracted from the article]

Background: To explore reasons for the failure of noninvasive prenatal test (NIPT) for cell‐free fetal DNA (cffDNA) in maternal peripheral blood, and discuss appropriate treatment schemes after the failure of the test. Methods: Altogether 41,136 pregnant women participated in NIPT. Blood samples were taken again from pregnant women who failed the first blood collection upon their informed consent. Prenatal genetic counseling or prenatal diagnosis was recommended for pregnant women with final NIPT failure. Results: The first failure rate of NIPT was 0.737% (303/41136), and the reason for the failure was the low ratio of cffDNA in 135 (44.6%) of the 303 pregnant women. After the second or third blood sampling, the final failure rate was 0.182% (75/41136). The low ratio of cffDNA was the main reason for test failure in 42 (56.0%) of the 75 pregnant women who finally failed NIPT, among whom 44 (58.7%) had underlying diseases, including 21 (47.7%) with more than two coexisting underlying diseases. Only 27 (36.0%) of the 75 pregnant women with NIPT failure underwent interventional prenatal diagnosis. Conclusions: The main reason for NIPT failure was the low ratio of cffDNA. Postponing the gestational weeks of blood collection may improve the success rate. Resampling and retesting upon informed consent in pregnant women who failed the first test could improve the success rate. For pregnant women who finally failed NIPT, it is suggested strengthening the genetic counseling, prenatal examination, and ultrasound evaluation, and carry out interventional prenatal diagnosis if necessary. [ABSTRACT FROM AUTHOR]

Background: Beta thalassemia, related to HBB mutation and associated with elevated hemoglobin A2 (HbA2), is an important genetic hemoglobinopathy with high incidences of disease and carrier rates in Singapore. Carrier screening is essential to facilitate prenatal counseling and testing. However, when individuals with elevated HbA2 do not have an identifiable HBB disease‐associated variant, there is ambiguity on risk to their offspring. Methods: We describe a case report of a proband with elevated HbA2, no identifiable HBB disease‐associated variant, whose partner was a beta thalassemia carrier. Through clinical HBB gene sequencing, multiplex ligation‐dependent probe amplification (MLPA) analysis, as well as targeted Nanopore long read sequencing of selected genes, we performed a complete analysis of HBB including the promoter region, 5′UTR and coding gene sequence, as well as evaluation for potential modifier variants and other rare structural variants. Results: This process identified that the proband was heterozygous for KLF1:c.544T>C (p.Phe182Leu), a potential functional polymorphism previously known to be associated with benign elevated HbA2 levels. The presence of disease variants in the HBB locus was excluded. Conclusion: This finding provided clarity and enabled family planning for the proband and her family. [ABSTRACT FROM AUTHOR]

The aim: to study of the prognostic value of endometrial receptivity and preimplantation genetic diagnosis of embryos, and their influence on the effectiveness of in vitro fertilization (IVF) programs. We also evaluate the importance of this factor in comparison with other potential causes of infertility. Materials and methods: This prospective cohort study included 123 infertile women who underwent in vitro fertilization (IVF) treatment. 93 patients had repeated unsuccessful implantation attempts and were divided into three groups: group 1 - patients who were treated using genetically untested embryos according to a standard fixed stimulation protocol, group 2 - patients who were treated using euploid embryos after preimplantation genetic screening according to standard fixed protocol; group 3 - patients who underwent treatment using euploid embryos after pre-implantation genetic screening and determination of the implantation window with subsequent modification of the stimulation protocol, according to the endometrial examination result. 30 patients had a first attempt at IVF, which was carried out using genetically untested embryos, according to a standard fixed protocol, and made up the control group (CG). Determination of the window of implantation was carried out by triple aspiration biopsy of the endometrium during the luteal phase of the menstrual cycle since the endometrium is most susceptible to implantation during this period. Samples were analyzed using scanning electron microscopy. Based on the results obtained, the endometrial preparation protocol was individualized for the next attempt. preimplantation genetic testing (PGT) of embryos was carried out by the next generation (NGS) method. Statistical analysis was performed using IBM SPSS V25.0 for Windows software. Results: According to the obtained results, patient characteristics, screening rates, IVF cycle characteristics, and the number, quality, and stage of transferred embryos were compared between groups. The rate of clinical pregnancy was 46.7 % among patients of group 1.70 % among patients of group 2, 82.8 % among patients of group 3 and 50.0 % of the control group and statistically significantly different between groups (χ2=10.955, p=0.012). The rate of live birth was 43.3 % among patients of group 1, 53.3 % among patients of group 2, 72.4 % among patients of group 3 and 43.3 % - of the control group, however, it did not differ statistically significantly between groups (χ2=6.639, р=0.084). Conclusions: The unique window of implantation and the embryonic factor are among the main reasons for multiple failed implantation attempts. Personalization of the endometrial preparation protocol and preimplantation embryo diagnosis are effective methods to improve IVF outcomes. [ABSTRACT FROM AUTHOR]

LEGAL ASPECTS RELATING TO PRENATAL DIAGNOSIS The guidance also clarifies legal aspects in relation to termination of pregnancy for a germline cancer susceptibility gene variant. Prenatal and pre-implantation genetic testing for monogenic disorders for germline cancer susceptibility gene variants: UK joint consensus guidance Although it is anticipated that there would be fewer requests for prenatal diagnosis or PGT-M for moderate penetrance genes and sex-specific variable penetrance genes, sensitive reproductive counselling by an appropriately trained genetic/genomic healthcare professional and case discussion in multidisciplinary forums is recommended. Testing for germline pathogenic variants in cancer susceptibility genes is now commonplace and routine practice, in order to guide management of individuals with cancer and to determine surveillance and risk-reduction options for those at increased genetic risk. [Extracted from the article]

Concurrent microduplication and microdeletion of the chromosome 22q11.2 region are a rarely reported phenomenon. We describe a case of germline 22q11.21 microduplication syndrome with concurrent mosaic 22q11.2 deletion in a pregnant patient, identified by chromosomal microarray and FISH after noninvasive prenatal genetic screening (cfDNA) results discordant with family history. The patient was referred to maternal-fetal medicine (MFM) at 14 weeks' gestation secondary to an SNP-based cfDNA result of a suspected maternal 22q11.2 deletion and a fetal risk of 1 in 2 for 22q11.2 deletion syndrome. The patient reported a similar cfDNA result in a previous pregnancy; however postnatal chromosomal microarray on that child identified an atypical 22q11.21 microduplication. We report the maternal chromosomal microarray findings of a germline 726 kb 22q11.21 duplication and a mosaic 1.33 Mb 22q11.2 deletion and highlight the copy number variant data generated by cfDNA in this unique case. This family adds to the limited literature of concurrent 22q11.2 microduplication and microdeletion carriers. [ABSTRACT FROM AUTHOR]

Objective: To describe indications, test types, and results of prenatal diagnostic genetic amniocentesis among Ethiopian pregnant women. Methods: This study was a descriptive study on prenatal diagnostic genetic testing among Ethiopian pregnant women with certain indications and it was conducted at St. Paul's Hospital Millennium Medical College (Addis Ababa, Ethiopia) from January 2017 to April 2023. Data on sociodemographic characteristics, genetic testing indications, types, and results were collected electronically. Data were analysed using SPSS version 23. Results: A total of 159 cases were analysed. The commonest indication for genetic testing among the study subjects was major fetal structural anomalies identified on specialized prenatal anatomic scanning of the index pregnancy detected in 71(44.7%) cases. Down syndrome and Edward syndrome were the commonest genetic aberrations detected accounting for 6.3% (10/159) and 4.4% (7/159), respectively. Among the rare genetic aberration detected were Di-George syndrome (0.6%) and Duchenne muscular dystrophy (0.6%). Conclusion: Findings of our study underscore the importance of diagnostic prenatal testing in a Sub-Saharan Africa setting, as common (trisomy 21&18) and rare genetic defects were identified using this important prenatal diagnostic testing. Considering the implications of detecting chromosomal abnormalities for future counselling and care, carrier state in parents for some chromosomal anomalies, and planning post-natal management of some abnormalities that are associated with aneuploidies (notably cardiac anomalies), initiation of diagnostic prenatal genetic testing service at tertiary public health facilities should be acted up on. [ABSTRACT FROM AUTHOR]

Advancements in ultrasound technology and the integration of cell-free DNA testing into standard prenatal screening services have made it more feasible to identify fetal sex at an early stage. Fetal sex determination through sonography relies on different factors, depending on the gestational stage. In the late second trimester, it is determined by directly visualizing the external genitalia. However, in the late first and early second trimesters, it primarily relies on the direction of the genital tubercle, known as the sagittal sign. Other sonographic landmarks, like the fetal scrotum, midline raphe of the penis, labial lines, uterus, descended testis, and the direction or origin of the fetal micturition jet in males, can aid in the fetal sex determination accuracy. However, malformed external genitalia can lead to inaccurate results. This article focuses on the sonographic determination of fetal sex during the late first trimester, early second trimester and late second trimester, utilizing both transvaginal and transabdominal ultrasound techniques. Additionally, we explore various elements that have contributed to the precision of fetal sex determination. While ultrasound examination of the external genitalia is typically sufficient, there are certain situations where it becomes crucial to identify the internal genitalia for precise prenatal diagnosis and thorough counseling. This paper aims at reviewing these situations in which the evaluation of the external genital organs is necessary, as well as the ways in which ultrasound can be used in the diagnosis of genital malformations. [ABSTRACT FROM AUTHOR]

Background: Limb-girdle muscular dystrophy (LGMD) is a group of inherited neuromuscular disorders characterized by atrophy and weakness in the shoulders and hips. Over 30 subtypes have been described in five dominant (LGMD type 1 or LGMDD) and 27 recessive (LGMD type 2 or LGMDR). Each subtype involves a mutation in a single gene and has high heterogeneity in age of onset, expression, progression, and prognosis. In addition, the lack of understanding of the disease and the vague, nonspecific symptoms of LGMD subtypes make diagnosis difficult. Even as next-generation sequencing (NGS) genetic testing has become commonplace, some patients remain undiagnosed for many years. Methods: To identify LGMD-associated mutations, Targeted sequencing was performed in the patients and Sanger sequencing was performed in patients and family members. The in silico analysis tools such as Fathmm, M-CAP, Mutation Taster, PolyPhen 2, PROVEAN, REVEL, SIFT, MaxEntScan, Spliceailookup, Human Splicing Finder, NetGene2, and Fruitfly were used to predict the influence of the novel mutations. The pathogenicity of the mutation was interpreted according to the ACMG guidelines. Results: In this study, six patients from four different Vietnamese families were collected for genetic analysis at The Center for Gene and Protein Research and The Department of Molecular Pathology Faculty of Medical Technology, Hanoi Medical University, Hanoi, Vietnam. Based on clinical symptoms and serum creatine kinase (CK) levels, the patients were diagnosed with limb-girdle muscular dystrophies. Five mutations, including four (c.229C>T, p.Arg77Cys; exon one to three deletion; c.983 + 5G>C; and c.257_258insTGGCT, p.Phe88Leufs*125) in the SGCA gene and one (c.946-4_946-1delACAG) in the CAPN3 gene, were detected in six LGMD patients from four unrelated Vietnamese families. Two homozygous mutations (c.983 + 5G>C and c.257_258insTGGCT) in the SGCA gene were novel. These mutations were identified as the cause of the disease in the patients. Conclusion: Our results contribute to the general understanding of the etiology of the disease and provide the basis for definitive diagnosis and support genetic counseling and prenatal screening. [ABSTRACT FROM AUTHOR]

Background: Prenatal genetic testing, in particular non-invasive prenatal testing (NIPT), as well as screening for risks associated with pregnancy, and counseling, play pivotal roles in reproductive healthcare, offering valuable information about the health of the fetus to expectant parents. This study aims to delve into the perspectives and experiences of women considering genetic testing and screening during pregnancy, focusing on their decision-making processes and the implications for informed consent. Methods: A nationwide qualitative study was conducted in Switzerland, involving in-depth interviews with women who were 1 to 2 years post-partum, covered by basic compulsory Swiss insurance, including women with a migration background. Thematic analysis was employed to identify key themes and patterns in the data. Results: The findings underscore the significance of effective communication during prenatal counseling, suggesting that healthcare providers could not only convey technical information but also support women in their decision-making processes. Women need comprehensive information about genetic testing and its implications, as well as the reasons for screening during pregnancy, as there might be a need to bridge knowledge gaps and clarify misconceptions. Furthermore, the study highlights the multifaceted nature of decision-making, with women considering factors such as uncertainty, values, emotional responses, and societal support systems. The concept of acceptance emerged as a crucial theme, with some women expressing their readiness to love and accept their child, regardless of genetic anomalies or disabilities. Conclusion: This study offers valuable insights into the perspectives and needs of women regarding prenatal genetic testing, screening, and counseling in Switzerland. It underscores the importance of enhancing the clinical interaction and informed consent process by providing comprehensive information, addressing misconceptions, and supporting women in decision-making about pregnancy management and the management of the child's health, following prenatal genetic testing, including NIPT. These findings can inform healthcare providers and policymakers in improving the quality of prenatal counseling, ensuring informed consent, and supporting women in making well-informed and meaningful decisions about genetic testing, and on the use of screening during pregnancy. [ABSTRACT FROM AUTHOR]

Non-invasive prenatal testing (NIPT) can be used to determine the chromosomal sex of the fetus at an early stage in a pregnancy. The use of NIPT for fetal sex determination raises concerns about potential selective termination of pregnancy by prospective parents who desire a child of a particular sex. Although sex selection for medical reasons is generally accepted, non-medical sex selection (NMSS) has been the subject of considerable controversy. In this article, we explore the current regulatory landscape around reproductive genetic testing techniques that may lead to NMSS, both internationally and within Australia. Specifically, we contrast the approach to regulating preimplantation genetic testing (PGT) with the minimal regulation of NIPT in Australia as a case study for reform. We examine ethical concerns raised in relation to NMSS, which form the basis of the current moratorium on the use of PGT for NMSS. We then highlight some key differences between using PGT for NMSS and NIPT for fetal sex determination to determine whether access to the latter should be regulated and, if so, how. We conclude that there is insufficient evidence to restrict access to NIPT for fetal sex determination and, based on our Australian case study, recommend a facilitative approach to regulating NIPT that would support individuals to make informed reproductive decisions. [ABSTRACT FROM AUTHOR]

Objective: The application value of mid-term ultrasound combined with non-invasive prenatal gene screening (NIPT) in the detection of chromosomal abnormalities in fetuses. Methods: 2000 mid-term pregnant women who underwent prenatal examination at Shijiazhuang Maternal and Child Health Hospital from August 2019 to December 2021 were selected, all of whom underwent ultrasound examination and NIPT screening. Using the results of amniocentesis or high-throughput sequencing after induction of labor as the gold standard, the four grid table method was used to analyze the application value of mid pregnancy ultrasound combined with NIPT in the detection of chromosomal abnormalities. Results: Among the 2000 pregnant women in the second trimester, ultrasound examination detected a total of 37 cases with abnormal soft indicators and 30 cases with abnormal structural indicators. NIPT screening 17 high-risk pregnant women, including 11 cases of trisomy 21 syndrome and 6 cases of trisomy 18 syndrome. The sensitivity, specificity, positive predictive value, negative predictive value, missed diagnosis rate, misdiagnosis rate, and accuracy of NIPT combined with ultrasound soft and structural indicators in diagnosing fetal chromosomal abnormalities were 95.00%, 99.95%, 95.00%, 99.95%, 5.00%, 0.05%, and 99.90%, respectively. Conclusion: The combination of mid pregnancy ultrasound and NIPT examination detected can improve the sensitivity of screening high-risk chromosomal abnormalities in fetuses, reduce the missed diagnosis rate, and have important value for early detection of chromosomal abnormalities in fetuses, thereby improving fertility quality. [ABSTRACT FROM AUTHOR]

Objective: To assess the performance of diverse prenatal diagnostic approaches for nuchal translucency (NT) thickening and to investigate the optimal prenatal screening or diagnostic action with a NT thickening of 95th percentile-3.50 mm. Methods: A retrospective analysis of 2,328 pregnancies with NT = 95th percentile through ultrasound-guided transabdominal chorionic villus sampling (CVS), amniocentesis, or cordocentesis obtained clinical samples (chorionic villi, amniotic fluid, and cord blood), and real-time quantitative fluorescent PCR (QF-PCR), chromosome karyotyping (CS), chromosome microarray analysis (CMA), or whole exome sequencing (WES) were provided to identify genetic etiologies. Results: In this study, the incidence of chromosomal defects increased with NT thickness. When NT = 6.5 mm, 71.43% were attributed to genetic abnormalities. The 994 gravidas with fetal NT thickening underwent short tandem repeat (STR), CS, and CMA. In 804 fetuses with normal karyotypes, CMA detected 16 (1.99%) extra pathogenic or likely pathogenic copy number variations (CNVs). The incremental yield of CMA was only 1.16% (3/229) and 3.37% (10/297) in the group with NT 95th percentile-2.99 mm and NT 3.0-3.49 mm, separately. Among the 525 gravidas with fetal NT thickening who underwent STR, CMA, and WES, the incremental yield of WES was 4.09% (21/513). In the group of NT 95th percentile-2.99 mm, there were no additional single-nucleotide variations (SNVs) detected in WES, while in 143 cases with NT of 3.0-3.49 mm, the incremental yield of WES was 5.59% (8/143). Conclusion: In the group of NT 95th percentile-3.0 mm, since chromosomal aneuploidy and chromosomal copy number variation were the primary causes and the additional contribution of CMA and WES was not significant, we recommend NIPT-Plus for pregnant women with a NT thickening of 95th percentile-3.0 mm first. In addition, comprehensive prenatal genetic testing involving CMA and WES can benefit pregnancies with NT thickening of 3.0-3.49 mm. [ABSTRACT FROM AUTHOR]

Background: Infantile myofibromatosis (IM) is a rare disorder characterized by the formation of nodules in the skin, muscle, bone, and, more rarely, visceral organs. Very few cases are detected prenatally, and the final diagnosis cannot be made until pathology is completed after birth. Here, we present a case of disseminated form IM (DFIM) with a diagnosis established on prenatal genetic grounds. Case presentation: A woman at 23 weeks of gestation was referred for ultrasound evaluation of fetal kidney abnormality. Generalized masses in the skin and muscle of the fetus developed at 28 weeks. Prenatal genetic testing identified the pathogenic heterozygous variant c.1681C > T (p.R561C) of the PDGFRB gene inherited from the asymptomatic father. Intrauterine demise occurred at 31 weeks. Autopsy confirmed DFIM with involvement of the heart and kidney. All cases of prenatally detected IM were reviewed, revealing an association of high mortality with DFIM. Conclusions: Prenatal IM diagnosis is difficult. Initial detection is always based on ultrasound. DFIM has high mortality. The germline p.R561C mutation in PDGFRB may cause fetal demise due to severe visceral involvement of IM. Prenatal genetic testing provides a diagnosis before pathological results are available, leading to better counseling and management of pregnancy with a fetus with IM. [ABSTRACT FROM AUTHOR]

As the prevalence of pregnancies with advanced maternal age increases, the risk of fetal chromosomal abnormalities is on the rise. Therefore, prenatal genetic screening and diagnosis have become essential elements in contemporary obstetrical care. Trophoblast retrieval and isolation from the cervix (TRIC) is a non-invasive procedure that can be utilized for prenatal genetic diagnosis. The method involves the isolation of fetal cells (extravillous trophoblasts) by transcervical sampling; along with its non-invasiveness, TRIC exhibits many other advantages such as its usefulness in early pregnancy at 5 weeks of gestation, and no interference by various fetal and maternal factors. Moreover, the trophoblast yields from TRIC can provide valuable information about obstetrical complications related to abnormal placentation even before clinical symptoms arise. The standardization of this clinical tool is still under investigation, and the upcoming advancements in TRIC are expected to meet the increasing need for a safe and accurate option for prenatal diagnosis. [ABSTRACT FROM AUTHOR]