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There are limited data on how neighborhood-level risk factors affect the likelihood of having prenatal diagnosis. Neighborhood social vulnerability can be quantified and ranked using the social vulnerability index (SVI), a tool that measures the cumulative effect of external stressors in the local environment that may affect health outcomes. The objective of the study was to determine the relationship between SVI and prenatal diagnosis among pregnant patients who received genetic counseling. Retrospective cohort study of all pregnant patients who had genetic counseling at two hospitals in New York between January 2019 and December 2022. For each patient, the address of residence was linked to an SVI score (primary exposure) based on census tract. SVI scores were subdivided into fifths and analyzed categorically. The primary outcome was prenatal diagnosis (yes/no). Multivariable logistic regression was performed. A total of 5,935 patients were included for analysis and 231 (3.9 %) had prenatal diagnosis. On regression analysis, no association between SVI and prenatal diagnosis was observed. Patients who had a diagnostic procedure were more likely to be English speaking (aOR 1.80; 95 % CI 1.13–2.87), carriers of a genetic disorder (aOR 1.94; 95 % CI 1.32–2.86), had increased NT (aOR 6.89; 95 % CI 3.65–13.00), abnormal NIPS (aOR 9.58; 95 % CI 5.81–15.80), or had fetal structural anomalies (aOR 10.60; 95 % CI 6.62–16.96). No differences were seen based on race and ethnicity group, insurance type, or marital status. SVI score does not affect rate of prenatal diagnosis. Findings may differ in other geographic regions and populations. [ABSTRACT FROM AUTHOR]

Background & Objective: Prenatal invasive procedures are used for diagnostic and therapeutic purposes. The present study aimed to assess the indications and early complications of invasive diagnostic tests. Materials & Methods: This retrospective descriptive study was conducted on 708 pregnant women who were referred for prenatal invasive tests in Tehran, Iran from May 2018 to April 2022. All medical records of the participants were reviewed and entered into the study. According to the implemented procedures, medical records were categorized into two chorionic villus sampling (CVS) and amniocentesis groups. The primary outcome was determining the frequent indications of invasive diagnostic tests and post-procedure complications. Results: Six hundred and sixty-eight medical records were included. Amniocentesis procedure was performed for 624 (93.7%) and 44 cases (6.3%) underwent CVS. The most frequent indication for invasive prenatal procedures was a history of abnormal findings related to the first trimester biomarkers followed by the abnormal findings of the second trimester biochemical markers, a history of high nuchal translucency>99th percentile, and abnormal biomarkers of sequential test. Comparing post-procedure complications, the results showed no significant difference between the CVS and amniocentesis groups (P=0.845). In the amniocentesis group, 2 cases had shown spontaneous abortion and 3 leakage of amniotic fluid, as well as two cases in the CVS group, had reported vaginal bleeding. Conclusion: Our results delineated that positive fetal aneuploidy screening tests together with increased nuchal translucency were the main indications of the invasive prenatal tests. Amniotic fluid leakage, vaginal bleeding, and spontaneous abortion should be considered as procedure-related complications. [ABSTRACT FROM AUTHOR]

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

Objective Approximately, 2% of women who undergo chorionic villi sampling (CVS) will subsequently undergo amniocentesis due to placental mosaicism or sampling/laboratory issues. Our objective was to compare obstetric outcomes in women who underwent both procedures with those who had CVS alone. Study Design Retrospective case-control study of patients with singleton pregnancies undergoing invasive testing from 2010 to 2020 was performed. All women who underwent CVS followed by amniocentesis were compared with a control group who underwent CVS alone matched (2:1) for age and year of pregnancy. Women with pregnancy loss at <16 weeks were excluded from the control group. Pregnancies terminated for genetic abnormalities were excluded. Obstetric outcomes were compared between cases and controls. Student t -test and Fisher's exact test were used for statistical comparison. Results During the study period 2,539 women underwent CVS, and 66 (2.6%) subsequently underwent amniocentesis. The 66 cases were compared with 132 age-matched controls who underwent CVS alone. Mean maternal age was 36.8 ± 3.4 years, and 43% of women were nulliparous. Amniocentesis was performed due to sampling or laboratory issues in 33% of cases, placental mosaicism in 44%, and further diagnostic testing in 23%. There were no pregnancy losses or stillbirths in either group. Those who had two invasive procedures delivered at similar gestational ages and birthweights and did not have higher rates of adverse outcomes compared with those who underwent CVS alone. Conclusion Patients considering CVS who are concerned about the possibility that a second invasive procedure could be required should be reassured that this does not appear to be associated with higher rates of adverse outcomes. Due to study size, we cannot exclude the possibility of small differences in uncommon outcomes, such as pregnancy loss or stillbirth. Key Points Amniocentesis may be recommended after CVS due to mosaicism, sampling issues, or further testing. Amniocentesis after CVS is not associated with pregnancy loss or other adverse outcomes compared. Patients who have both CVS and amniocentesis deliver at similar gestational ages and birthweights. [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]

Hemophilia A (HA) is an X-linked recessive disorder caused by mutations in the factor VIII ( FVIII) gene leading to deficient blood coagulation. The current standard of care is frequent infusions of plasma-derived FVIII or recombinant B-domain-deleted FVIII (BDD-FVIII). While this treatment is effective, many patients eventually develop FVIII inhibitors that limit the effectiveness of the infused FVIII. As a monogenic disorder, HA is an ideal target for gene or cell-based therapy. Several studies have investigated allogeneic stem cell therapy targeting in utero or postnatal treatment of HA but have not been successful in completely correcting HA. Autologous in utero transplantation of mesenchymal stem cells is promising for treatment of HA due to the naive immune status of the fetal environment as well as its potential to prevent transplant rejection and long-term FVIII inhibitor formation. HA can be diagnosed by chorionic villus sampling performed during the first trimester (10 to 13 wk) of gestation. In this study, we used an established protocol and isolated placenta-derived mesenchymal stromal cells (PMSCs) from first trimester chorionic villus tissue and transduced them with lentiviral vector encoding the BDD-FVIII gene. We show that gene-modified PMSCs maintain their immunophenotype and multipotency, express, and secrete high levels of active FVIII. PMSCs were then transplanted at embryonic day 14.5 (E14.5) into wild-type fetuses from time-mated pregnant mice. Four days after birth, pups were checked for engraftment, and varying levels of expression of human green fluorescent protein were found in the organs tested. This study shows feasibility of the approach to obtain PMSCs from first trimester chorionic villus tissue, genetically modify them with the FVIII gene, and transplant them in utero for cell-mediated gene therapy of HA. Future studies will involve evaluation of long-term engraftment, phenotypic correction in HA mice, and prevention of FVIII inhibitor development by this approach.

After in vitro fertilization with a single embryo, the parents learned about being pregnant with twins in the 10th week with various indications that an embryonic mix-up could have taken place. The affected couple thus expressed the urgent desire for a clarification of parenthood considering an abortion. However, the prenatal test results would not have been available until the 14/15th week of pregnancy. Legally, then, severe physical or mental distress of the pregnant woman must be claimed by physicians to justify an abortion after the twelfth week. However, a lack of genetic relatedness could lead to serious psychological distress for the parents, making a pregnancy termination possible even after the twelfth week, which is discussed in this case study alongside the interdisciplinary team's ethical, legal, and medical considerations.For the invasive relationship testing, cultivated chorionic villi samples (CVS) from both unborn and saliva samples from the putative parents were genetically analyzed using classical short tandem repeats (STR) analysis. The perfect match of both CVS profiles suggested the occurrence of an unusual late twin shaft, for which, fortunately, parenthood could be confirmed. To our knowledge, this is the first report on a prenatal investigation of a suspected embryo mix-up after assisted reproductive technology (ART), in which parenthood should be fixed. We want to draw attention to this unthinkable scenario, which may increase in the future with ART-induced rising multiple pregnancies., (© 2024. The Author(s).)

Abstract Background Fetoplacental discrepancies occur in approximately 1–2% of analyzed prenatal cases. They are typically due to confined placental mosaicism, where an aberration is observed in the placental cells but not found in the fetal cells. Confined placental mosaicism usually involves aneuploidies and more sparsely structural chromosomal aberrations. To the best of our knowledge, this is the first reported case of a discrepancy in the analyses of chorionic villus sampling and amniocentesis involving two different structural chromosomal aberrations of chromosome 21. Case presentation We report a 33-year-old woman who was referred for a non-invasive prenatal testing due to an increased risk of trisomy 21 gleaned from a combined ultrasound and blood test. The non-invasive prenatal testing showed an increased risk of trisomy 21 with a normalized coverage signal that did not match the fetal cell-free DNA fraction. Rapid aneuploidy detection performed on uncultured chorionic villi indicated mosaicism for trisomy 21. The follow-up analyses revealed discordant chromosomal aberrations: 46,XY,der(21)t(10;21)(p11.21;q10) in the analysis of the chorionic villus sampling and 46,XY, + 21,der(21;21)(q10;q10) in the analysis of the amniocentesis. Thus, the analyses indicated mosaicism for a cell line containing trisomy 21 and a cell line containing a partially duplicated short arm of chromosome 10 in the chorionic villi and complete trisomy 21 resulting from an isochromosome 21 in the amniotic fluid. The analyses of the lymphocytes and the fibroblasts of the woman were normal. Conclusions We propose a multiple-step mechanism as a possible theoretical explanation for the formation of these discordant structural chromosomal aberrations in the chorionic villi and amniotic fluid. With this case report, we want to highlight the importance of understanding the possible underlying embryological mechanisms when interpreting results from different prenatal analyses.

BackgroundMultiple testing to understand global changes in gene expression based on genetic and epigenetic modifications is evolving. Chorionic villi, obtained for prenatal testing, is limited, but can be used to understand ongoing human pregnancies. However, optimal storage, processing and utilization of CVS for multiple platform testing have not been established.ResultsLeftover CVS samples were flash-frozen or preserved in RNAlater. Modifications to standard isolation kits were performed to isolate quality DNA and RNA from samples as small as 2-5 mg. RNAlater samples had significantly higher RNA yields and quality and were successfully used in microarray and RNA-sequencing (RNA-seq). RNA-seq libraries generated using 200 versus 800-ng RNA showed similar biological coefficients of variation. RNAlater samples had lower DNA yields and quality, which improved by heating the elution buffer to 70 °C. Purification of DNA was not necessary for bisulfite-conversion and genome-wide methylation profiling. CVS cells were propagated and continue to express genes found in freshly isolated chorionic villi.ConclusionsCVS samples preserved in RNAlater are superior. Our optimized techniques provide specimens for genetic, epigenetic and gene expression studies from a single small sample which can be used to develop diagnostics and treatments using a systems biology approach in the prenatal period. © 2016 John Wiley & Sons, Ltd.

Background: Chromosomal mosaicism can be detected in different stages of early life: in cleavage stage embryos, in blastocysts and biopsied cells from blastocysts during preimplantation genetic testing for aneuploidies (PGT-A) and later during prenatal testing, as well as after birth in cord blood. Mosaicism at all different stages can be associated with adverse pregnancy outcomes. There is an onward discussion about whether blastocysts diagnosed as chromosomally mosaic by PGT-A should be considered safe for transfer. An accurate diagnosis of mosaicism remains technically challenging and the fate of abnormal cells within an embryo remains largely unknown. However, if aneuploid cells persist in the extraembryonic tissues, they can give rise to confined placental mosaicism (CPM). Non-invasive prenatal testing (NIPT) uses cell-free (cf) DNA released from the placenta in maternal blood, facilitating the detection of CPM. In literature, conflicting evidence is found about whether CPM is associated with fetal growth restriction (FGR) and/or other pregnancy outcomes. This makes counselling for patients by clinicians challenging and more knowledge is needed for clinical decision and policy making.Objective and Rationale: The objective of this review is to evaluate the association between CPM and prenatal growth and adverse pregnancy outcomes. All relevant literature has been reviewed in order to achieve an overview on merged results exploring the relation between CPM and FGR and other adverse pregnancy outcomes.Search Methods: The following Medical Subject Headings (MESH) terms and all their synonyms were used: placental, trophoblast, cytotrophoblast, mosaicism, trisomy, fetal growth, birth weight, small for gestational age and fetal development. A search in Embase, PubMed, Medline Ovid, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar databases was conducted. Relevant articles published until 16 July 2020 were critically analyzed and discussed.Outcomes: There were 823 articles found and screened based on their title/abstract. From these, 213 articles were selected and full text versions were obtained for a second selection, after which 70 publications were included and 328 cases (fetuses) were analyzed. For CPM in eight different chromosomes (of the total 14 analyzed), there was sufficient evidence that birth weight was often below the 5th percentile of fetal growth standards. FGR was reported in 71.7% of CPM cases and preterm birth (<37 weeks of delivery) was reported in 31.0% of cases. A high rate of structural fetal anomalies, 24.2%, in cases with CPM was also identified. High levels of mosaicism in CVS and presence of uniparental disomy (UPD) were significantly associated with adverse pregnancy outcomes.Wider Implications: Based on the literature, the advice to clinicians is to monitor fetal growth intensively from first trimester onwards in case of CPM, especially when chromosome 2, 3, 7, 13, 15, 16 and 22 are involved. In addition to this, it is advised to examine the fetuses thoroughly for structural fetal anomalies and raise awareness of a higher chance of (possibly extreme) premature birth. Despite prematurity in nearly a fifth of cases, the long-term follow-up of CPM life borns seems to be positive. More understanding of the biological mechanisms behind CPM will help in prioritizing embryos for transfer after the detection of mosaicism in embryos through PGT-A. [ABSTRACT FROM AUTHOR]

Background: Fetoplacental discrepancies occur in approximately 1–2% of analyzed prenatal cases. They are typically due to confined placental mosaicism, where an aberration is observed in the placental cells but not found in the fetal cells. Confined placental mosaicism usually involves aneuploidies and more sparsely structural chromosomal aberrations. To the best of our knowledge, this is the first reported case of a discrepancy in the analyses of chorionic villus sampling and amniocentesis involving two different structural chromosomal aberrations of chromosome 21. Case presentation: We report a 33-year-old woman who was referred for a non-invasive prenatal testing due to an increased risk of trisomy 21 gleaned from a combined ultrasound and blood test. The non-invasive prenatal testing showed an increased risk of trisomy 21 with a normalized coverage signal that did not match the fetal cell-free DNA fraction. Rapid aneuploidy detection performed on uncultured chorionic villi indicated mosaicism for trisomy 21. The follow-up analyses revealed discordant chromosomal aberrations: 46,XY,der(21)t(10;21)(p11.21;q10) in the analysis of the chorionic villus sampling and 46,XY, + 21,der(21;21)(q10;q10) in the analysis of the amniocentesis. Thus, the analyses indicated mosaicism for a cell line containing trisomy 21 and a cell line containing a partially duplicated short arm of chromosome 10 in the chorionic villi and complete trisomy 21 resulting from an isochromosome 21 in the amniotic fluid. The analyses of the lymphocytes and the fibroblasts of the woman were normal. Conclusions: We propose a multiple-step mechanism as a possible theoretical explanation for the formation of these discordant structural chromosomal aberrations in the chorionic villi and amniotic fluid. With this case report, we want to highlight the importance of understanding the possible underlying embryological mechanisms when interpreting results from different prenatal analyses. [ABSTRACT FROM AUTHOR]

Objective: To explore the use of a new molecular work-up based on the stepwise use of Quantitative Fluorescence PCR (QF-PCR) extended to eight chromosomes and single nucleotide polymorphism array (SNP-array) in chorionic villi obtained by chorionic villi sampling (CVS) offered to women experiencing an early pregnancy loss. Methods: During a 3-year period (January 2016–December 2018), CVS was offered to women experiencing an early pregnancy loss before the evacuation of the products of conception (POC) to retrieve chorionic villi, irrespective of the number of previous losses. A new molecular work-up was prospectively assayed encompassing a first QF-PCR round (with the 21, 18, 13, 7, X, and Y chromosomes), a second QF-PCR round (with the 15, 16, and 22 chromosomes), and a high resolution SNP-array in those cases with normal QF-PCR results. A control group in which POC were collected after surgical uterine evacuation was used to be compared with the intervention group. Results: Around 459 women were enrolled in the intervention group (CVS) and 185 in the control group (POC after uterine evacuation). The QF-PCR testing success rates were significantly higher in the intervention group (98.5%: 452/459) as compared to the control group (74%: 109/147; p < 0.001), while the chromosomal anomaly rate at the two QF-PCR rounds was similar between the two groups: 52% (234/452) in the intervention and 42% (46/109) in the control group (p = 0.073). The SNP-array was performed in 202 QF-PCR normal samples of the intervention group and revealed 67 (33%) atypical chromosomal anomalies (>10 Mb), 5 (2.5%) submicroscopic pathogenic copy number variants, and 2 (1%) variant of uncertain significance (VOUS). Conclusion: Eighty-two percent of women experiencing an early pregnancy loss opted for a CVS. The testing success rates were higher in the intervention group (CVS; 98%) as compared to the control group (POC; 74%). The overall yields were 52% by QF-PCR (including three complete hydatiform moles), and 16% by SNP-array, including 15% atypical chromosomal anomalies and 1.1% submicroscopic pathogenic copy number variants. [ABSTRACT FROM AUTHOR]

Introduction: Congenital ichthyosis represents a wide spectrum of diseases. This article reviews prenatal testing for ichthyosis., Methods: We used pubmed.ncbi.nlm.nih.gov to search for 38 types of congenital ichthyosis combined with 17 words related to prenatal testing., Results: Search resulted in 408 publications covering 13 types of ichthyoses and four types of tests., Discussion: Biochemical testing is diagnostic in trichothiodystrophy, but nonspecific in X-linked ichthyosis and Refsum syndrome. Except in X-linked ichthyosis, biochemical testing requires invasive procedures to obtain fetal skin biopsy, amniocytes, or chorionic villus samples. It is superior to histological and cytological examination of fetal skin biopsy or amniocytes because keratinization occurs later in pregnancy and microscopy cannot differentiate between ichthyosis types. Imaging is more acceptable due to noninvasiveness and routine use, although ultrasonography is operator-dependent, nonspecific, and captures abnormalities at late stage. Molecular tests are described in at-risk pregnancies but testing of free fetal DNA was not described.

Background: Congenital diseases are still an important medical, social, and economic problem all over the world. In North Cyprus, in addition to other reasons, early prenatal diagnostic measures are undertaken to prevent births with thalassemia major, a locally widespread genetic disease., Aim: This study aims to evaluate the results of prenatal invasive diagnostic tests performed in a private obstetrics clinic in Northern Cyprus and show the diagnosis process of thalassemia and chromosomal anomalies., Materials and Methods: This study is a retrospective, descriptive study. Chorionic villus sampling (CVS) results and the amniocentesis tests performed between 1990 and 2022 are evaluated. Thalassemia and chromosome analysis of samples obtained by CVS and amniocentesis tests were performed. To diagnose alpha or beta thalassemia and sickle cell, 239 CVS was performed. And to diagnose chromosomal anomalies, 396 CVS and amniocentesis were performed., Results: The mean age of the 480 pregnant women included in the study was 31.12 years (18-46) and 30% of them were older than 34 years. The most common indications for invasive prenatal diagnostic test (IPDT) were; mother/father thalassemia minor/major, advanced maternal age, high risk of ultrasonography erase findings, and the noninvasive screening test. The result of IPDT detected 7.3% chromosomal anomaly and 69.5% thalassemia and sickle cell anemia. Of the 239 CVS performed to diagnose alpha or beta thalasemia and sickle cell, 23.4% beta major, 42.3% beta minor, and 2.1% alpha minor were diagnosed. Of the 396 CVS and amniocentesis performed to diagnose chromosomal anormalies; 2.8% of Down syndrome and 4.54% of other chromosomal anomalies were diagnosed., Conclusion: IPDT is important in correctly diagnosing fetal anomalies at the prenatal stage to help families decide at the right time., (Copyright © 2024 Copyright: © 2024 Nigerian Journal of Clinical Practice.)

Background Advances in genetic screening can identify patients at high risk for common genetic conditions early in pregnancy and can facilitate early diagnosis and early abortion. Less common abnormalities might only be diagnosed with invasive testing is performed after structural abnormalities are identified. Objective Our objective was to compare gestational age (GA) at diagnosis and abortion for genetic abnormalities identified based on screening with abnormalities that were not discovered after screening. Study Design All prenatal diagnostic procedures from 2012 to 2017 were reviewed, and singleton pregnancies terminated following diagnosis of genetic abnormalities were identified. Cases diagnosed as the result of screening tests were compared with remaining cases. Conditions were considered “screened for” if they can be suspected by cell-free DNA testing, biochemistry, carrier screening, or if the patient was a known carrier of a single-gene disorder. When abnormal karyotype, microarray, or Noonan's syndrome was associated with abnormal NT, these cases were considered “screened for.” GA at abortion was the primary outcome. Fisher's exact test and Mann–Whitney's U test were used for statistical comparison. Results In this study, 268 cases were included. A total of 227 (85%) of abortions were performed for “screened for” disorders, with 210 (93%) of these for karyotype abnormalities, 5 (2%) for microarray abnormalities, and 12 (5%) for single-gene disorders. Forty-one (15%) of abortions were performed for conditions not included in screening, with 8 (19%) of those for karyotype abnormalities, 25 (61%) for microarray abnormalities, and 8 (19%) for single-gene disorders. Invasive testing and abortion occurred at earlier median GA for those with conditions that were screened for: 122/7 versus 155/7 weeks, p ≤0.001 and 135/7 versus 200/7 weeks; p ≤0.001. Conclusion Most abortions were for abnormalities that can be suspected early in pregnancy. As many structural abnormalities associated with rare conditions are not identifiable until the mid-trimester, prenatal diagnosis and abortion occurred significantly later. Physicians and patients should be aware of the limitations of genetic screening.

Objectives: Phacomatoses are a group of neuro-oculo-cutaneous syndromes/ neurocutaneous disorders, involving structures arising from the embryonic ectoderm. Most of phacomatoses including the most common ones:, neurofibromatosis type I and type II (NF1, NF2) and tuberosclerosis complex (TSC), are autosomal dominant genetic disorders with full penetrance and variable expression. As no effective treatment exists, the only way to prevent the disease, is by prenatal genetic diagnosis (either chorionic villus sampling-CVS or amniocentesis-AC) and termination of pregnancy or performing preimplantation genetic testing (PGT). As the risk for an affected offspring is 50% in every pregnancy of an affected parent, prenatal, and preimplantation testing are of great importance. However, those procedures are associated with technical and ethical concerns. This chapter shortly reviews the common phacomatoses emphasizes their genetics and inheritance. We will review the common methods for prenatal and preimplantation diagnoses and discuss its use in common phacomatoses. Conclusion: Phacomatoses are common autosomal dominant genetic conditions with variable expression. Ante-natal genetic diagnosis is an appropriate approach for family planning in individuals affected by phacomatosis or parents of an affected child. [ABSTRACT FROM AUTHOR]

Introduction: Circulating fetal extravillous trophoblasts may offer a superior alternative to cell-free fetal DNA for noninvasive prenatal testing. Cells of fetal origin are a pure source of fetal genome; hence, unlike the cell-free noninvasive prenatal test, the fetal cell-based noninvasive prenatal test is not expected to be affected by maternal DNA. However, circulating fetal cells from previous pregnancies may lead to confounding results.Material and Methods: To study whether fetal trophoblast cells persist in maternal circulation postpartum, blood samples were collected from 11 women who had given birth to a boy, with blood sampling at 1-3 days (W0), 4-5 weeks (W4-5), around 8 weeks (W8) and around 12 weeks (W12) postpartum. The existence of fetal extravillous trophoblasts was verified either by X and Y chromosome fluorescence in situ hybridization analysis or by short tandem repeat analysis. To exclude technological bias in isolating fetal cells, blood samples were also collected from 10 pregnant women between a gestational age of 10 and 14 weeks, the optimal time frame for cell-based noninvasive prenatal test sampling. All the samples were processed according to protocols established by ARCEDI Biotech for fetal extravillous trophoblast enrichment and isolation.Results: Fetal extravillous trophoblasts were found in all the 10 samples from pregnant women between a gestational age of 10 and 14 weeks. However, only 4 of 11 blood samples taken from women at 1-3 days postpartum rendered fetal extravillous trophoblasts, and only 2 of 11 samples rendered fetal extravillous trophoblasts at 4 weeks postpartum.Conclusions: In this preliminary dataset on few pregnancies, none of the samples rendered any fetal cells at or after 8 weeks postpartum, showing that cell-based noninvasive prenatal testing based on fetal extravillous trophoblasts is unlikely to be influenced by circulating cells from previous pregnancies. [ABSTRACT FROM AUTHOR]

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Introduction: Chorionic villus sampling (CVS) remains essential for first-trimester genetic diagnosis, yet clinical volume may be insufficient to train new clinicians in the technique. Available simulation models are expensive, require animal parts or specialized resins, and cannot be stored for repeated use., Methods: We present a model for trans-abdominal CVS (TA-CVS) which is constructed from readily available materials costing less than $10 and can be refrigerated and re-used to train maternal-fetal medicine fellows in CVS., Results: All three attending physicians performing TA-CVS at our institution described the model as an accurate visual and tactile simulation, prompting its integration into our fellowship curriculum. To date, two senior fellows have achieved competency on the simulator and begun to perform clinical CVS under supervision, one of whom is an author on this paper. Both fellows and attendings indicated that the simulator provided a valuable tool for repeated practice prior to clinical CVS. Simulators are now maintained on the unit and have been re-used for 3 months and dozens of simulated procedures each without any apparent qualitative degradation in performance., Discussion/conclusion: We describe a low-cost easily constructed, durable, high-fidelity simulator for TA-CVS., (© 2023 S. Karger AG, Basel.)

Complete trisomy 5 is a rare and lethal abnormality. Mosaic trisomy 5 presents in various phenotypes, ranging from a clinically normal fetus to fetuses presenting uterine growth restriction, congenital heart anomalies, multiple dysmorphic features and psychomotor development abnormalities. Although rare, there are cases of a normal psychomotor development regardless of the associated low fetal growth frequently associated with mosaic trisomy 5. This is the first case report to date of a live fetus with complete trisomy 5 reported in chorionic villus sampling and mosaic trisomy 5 in amniotic fluid with a concomitant Ebstein anomaly. Diagnosis of mosaic trisomy 5 represents a challenge for the clinical team and patients, as the information regarding this syndrome is scarce and based mostly on case reports of liveborns, which may introduce a selection bias when counselling the parents., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: In 2011, it was decided to implement chromosomal microarray in prenatal testing in the Central Denmark Region, mainly due to the expected higher diagnostic yield. Chromosomal microarray was introduced gradually for an increasing number of pregnancies and without a transition period where both karyotyping and chromosomal microarray were performed: first malformations (2011), then large nuchal translucency (2013), then high risk at combined first trimester risk screening (2016) and finally for all indications (2018). This retrospective study summarizes 11 years of using chromosomal microarray in invasive prenatal testing and presents the effect on diagnostic yield and turnaround time. Furthermore, the concerns when introducing chromosomal microarray are presented and discussed., Material and Methods: Registry data from the Danish Fetal Medicine Database, the regional fetal medicine database, the Danish Cytogenetic Central Register and the local laboratory database at Department of Clinical Genetics were all combined, and a cohort of 147 158 singleton pregnancies with at least one ultrasound examination was established RESULTS: Of the 147 158 pregnancies, invasive sampling was performed (chorionic villi or amniocytes) in 8456, corresponding to an overall invasive rate of 5.8%. Between 2016 and 2018, 3.4% (95% confidence interval [CI] 2.8-4.2%; n = 86) of the invasive samples (n = 2533) had a disease causing copy number variant and 5.3% (95% CI 4.4-6.2%; n = 133) had trisomies and other aneuploidies. The turnaround time more than halved from 14 days to an average of 5.5 days for chorionic villus sampling., Conclusions: Chromosomal microarray identified 5.3% trisomies and 3.4% copy number variants, thereby increased the diagnostic yield by more than 64% compared with karyotype only and it also more than halved the turnaround time. Some preliminary concerns proved real, eg prenatal counseling complexity, but these have been resolved over time in a clinical path with expert consultations., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objective: To assess the value of using flat-sided culture tubes for preparing chromosomes through chorionic villi (CV) and amniotic fluid (AF) cell cultures during prenatal diagnosis., Methods: From February to March 2020, 157 CV samples and 147 AF samples subjected to prenatal diagnosis at the Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region were selected as the study subjects. For each sample, one flat-sided tube and one flask culture were set up by following the standard protocols. The methods were evaluated by comparing the cell growth, experimental process, quality of chromosome preparation and costs., Results: The success rates for the culturing of CV and AF samples by the flat-sided culture tube method were 97.45% (153/157) and 97.96% (144/147), respectively. By contrast, the success rates for the conventional flask method were 98.72% (155/157) for CV and 98.64% (145/147) for AF samples. No significant difference was found between the two methods (P > 0.05). The average harvest time required by the flat-sided culture tube method was 8.45 days for CV and 9.43 days for AF cultures, whilst the average harvest time for conventional flask method was 9.05 days and 9.54 days, respectively. The flat-sided culture tube method for CV had required significantly shorter average harvest time than the conventional method (P < 0.001). No statistical significant difference was found in the average harvest time for AF by the two methods (P > 0.05). The conventional culturing method had required three containers with two sample transfers. By contrast, the flat-sided culture tube method was carried out in one tube without any sample transfer. The average total amount of medium used was 3.91 mL for each flat-sided culture tube and 6.26 mL for each conventional flask., Conclusion: The flat-sided culture tube method can provide a simple, cost-effective and error-reducing procedure for the CV and AF samples culture during prenatal diagnosis.

In order to contribute to the knowledge of type and frequency of chromosome abnormalities in early pregnancy losses, we analyzed the cytogenetic results from a large series of first trimester miscarriages, using a diagnostic approach with a high success rate and no maternal contamination. A total of 1,119 consecutive chorionic villi samples were obtained before evacuation, and karyotypes were prepared after short-term culture (STC). In 603 samples, a long-term culture (LTC) was also performed. The overall and individual frequencies of the different types of chromosome abnormalities were established, including placental mosaicisms, and their relationship with maternal age and gestational weeks was assessed. An abnormal karyotype was detected in 70.3% of the samples. Single autosomal trisomy was the most frequent abnormality (64.6% of the abnormal cases), followed by triploidy (13.1%) and monosomy X (10.4%). Chromosome rearrangements were found in 5.2%, combined abnormalities in 8.9%, and placental mosaicism in 3.5% of the cases with STC and LTC performed. Individual trisomies behaved differently with respect to maternal age and intrauterine survival. Due to the combination of STC and LTC, our study offers reliable information on the incidence and type of chromosome abnormalities and placental mosaicism in miscarriages and contributes to define the cytogenetic implication in their etiology. [ABSTRACT FROM AUTHOR]

The article discusses the study that determined the total fetal loss rates of transabdominal chorionic villus sampling, transcervical chorionic villus sampling and amniocentesis. Topics discussed include no statistically noticeable differences found between the total fetal loss rates of three procedures, and transabdominal chorionic villus sampling, transcervical chorionic villus sampling and amniocentesis to be equal methods for invasive prenatal testing in relation to their abortion risk.

Compared with single pregnancy, twin pregnancy meets more difficulties in terms of the prenatal screening and the prenatal diagnosis which is also a research hotspot at present. The modern technologies in the serum markers of fetal, ultrasonic application and non-invasive prenatal testing (NIPT) remarkably promoted the prenatal screening and prenatal diagnosis. The combined method of serum screening and ultrasound screening is significative for those twin pregnancies in the first trimester as a subsidiarity, while the ultrasound screening is helpful for the fetal deformity screening of those twin pregnancies in the second and last trimester. There have been more and more reports on the application of NIPT in the twin pregnancy. The application of invasive prenatal screening, including amniocentesis and chorionic villus sampling, will be less and less due to the risks of fetal loss and potential infection, although it is still used as a conclusive method. With the application and development of modern technologies of prenatal screening and prenatal diagnosis, the prenatal screening and prenatal diagnosis of twin pregnancy will be more dependable in the near future. [ABSTRACT FROM AUTHOR]

Screening procedures for chromosomal abnormalities in fetuses are a standard of care for pregnant women. Ultrasound and maternal serum analysis are traditional prenatal screening methods with detection rates between 75%-95%, and considerable false-negative and false-positive results. Also, both require follow up by invasive diagnostic tests in screen-positive cases, mostly amniocentesis and chorionic villi sampling, which are associated with notable risk of pregnancy loss. One of the innovative non-invasive prenatal testing (NIPT) options is the analysis of cell-free DNA (cfDNA) in plasma, which is detected in maternal circulation in a relatively high concentration. Commercial tests for cfDNA in maternal blood have recently become available. Cell-free DNA detection tests do not separate fetal from maternal DNA but use full cfDNA complement and analyze difference in total amount of sequenced DNA fragments, with the help of sophisticated data analysis software. It seems that cfDNA technology testing is highly accurate and has a very high sensitivity, so the difference compared to routine serum sample screening shows its significant superiority. However, cfDNA positive results still need confirmation by the invasive testing. The cell-free DNA analysis aims to become the first choice NIPT option due to its safety and high accuracy rate. The final goal is to develop the reliable method that could eventually replace invasive prenatal testing procedures. [ABSTRACT FROM AUTHOR]

Objectives: Explore health-care seeking behaviour among couples with pregnancies at-risk of monogenic disorders and compare time duration for obtaining Prenatal Genetic Test (PGT) results based on (i) amniocentesis and Chorionic Villus Sampling (CVS) (ii) in-house testing and out-sourced testing. Report the spectrum of monogenic disorders in our cohort., Methods: Medical records of women consulting prenatal genetic counselling clinic at Aga Khan University Hospital, Karachi from December-2015 to March-2021 with history of miscarriage or a monogenic disorder in previous children were reviewed., Results: Forty-three pregnancies in 40 couples were evaluated, 37(93%) were consanguineous. Twenty-five (63%) couples consulted before and 15(37%) after conception. Thirty-one (71%) pregnancies underwent CVS at the mean gestational age of 13-weeks and 6-days ± 1-week and 3-days and amniocentesis at 16-weeks and 2-days ± 1-week and 4-days. PGT for 30 (70%) pregnancies was outsourced. The mean number of days for in-house PGT was 16.92 ± 7.80 days whereas for outsourced was 25.45 ± 7.7 days. Mean duration from procedure to PGT result was 20.55 days after CVS compared to 28.75 days after amniocentesis. Eight (18%) fetuses were homozygous for disease-causing variant for whom couples opted for termination of pregnancy (TOP). Twenty-six monogenetic disorders were identified in 40 families., Conclusion: Proactive health-care seeking behaviour and TOP acceptance is present amongst couples who have experienced a genetic disorder., (© 2023. The Author(s).)

Objectives: We aimed to compare cell-based NIPT (cbNIPT) to chorionic villus sampling (CVS) and to examine the test characteristics of cbNIPT in the first clinical validation study of cbNIPT compared to cell-free NIPT (cfNIPT)., Material and Methods: Study 1: Women (N = 92) who accepted CVS were recruited for cbNIPT (53 normal and 39 abnormal). Samples were analyzed with chromosomal microarray (CMA). Study 2: Women (N = 282) who accepted cfNIPT were recruited for cbNIPT. cfNIPT was analyzed using sequencing and cbNIPT by CMA., Results: Study 1: cbNIPT detected all aberrations (32/32) found in CVS: trisomies 13, 18 and 21 (23/23), pathogenic copy number variations (CNVs) (6/6) and sex chromosome aberrations (3/3). cbNIPT detected 3/8 cases of mosaicism in the placenta. Study 2: cbNIPT detected all trisomies found with cfNIPT (6/6) and had no false positive (0/246). One of the three CNVs called by cbNIPT was confirmed by CVS but was undetected by cfNIPT, two were false positives. cbNIPT detected mosaicism in five samples, of which two were not detected by cfNIPT. cbNIPT failed in 7.8% compared to 2.8% in cfNIPT., Conclusion: Circulating trophoblasts in the maternal circulation provide the potential of screening for aneuploidies and pathogenic CNVs covering the entire fetal genome., (© 2023 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)