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Objective: Uterine fibroids are monoclonal tumors, which are often genetically abnormal and associated with false‐positive genome‐wide cell‐free DNA (cfDNA) screening results, particularly when large. It is plausible that fibroids may also increase the risk of cfDNA failure by affecting fetal fraction or due to their genetic anomalies confounding cfDNA algorithms. We aimed to investigate a possible association between fibroids and cfDNA non‐informative results. Methods: This was a retrospective cohort study of women undergoing cfDNA screening for fetal chromosomal abnormalities between 2013 and 2020, comparing pregnancies with vs without uterine fibroids recorded on any obstetric ultrasound before 24 weeks' gestation. Univariable and multivariable logistic regression models were used to investigate the association between fibroids and cfDNA failure, adjusting for gestational age, maternal age, weight and height at blood sampling, mode of conception, multiple gestation and test platform (chromosome‐selective or genome‐wide). Analyses were stratified according to the number of fibroids and total fibroid volume. The impact of fibroids on fetal fraction was assessed using linear regression, adjusting for the same covariates. Results: Among 19 818 pregnancies undergoing cfDNA screening, fibroids were reported in 2038 (10.28%) and cfDNA failure at the first screening attempt occurred in 228 (1.15%) pregnancies. Non‐informative results occurred in 1.96% of pregnancies with fibroids and 1.06% of pregnancies without fibroids (adjusted odds ratio (aOR), 2.40 (95% CI, 1.65–3.48)). The risk of failure in the first screening attempt increased progressively with the number of fibroids (aOR, 5.05 (95% CI, 2.29–11.13) in women with four or more fibroids) and total fibroid volume, with greater than a 5‐fold and 14‐fold increase in risk among women with fibroid volumes of 100.1–400 mL (aOR, 5.52 (95% CI, 2.30–13.25)) and > 400 mL (aOR, 14.80 (95% CI, 4.50–48.69)), respectively. Although test failure was more common with chromosome‐selective than genome‐wide screening, fibroids similarly increased the risk of failure of both screening platforms. Compared to pregnancies without fibroids, those with fibroids had a fetal fraction on average 0.61% lower (adjusted mean difference, −0.61% (95% CI, −0.77% to −0.45%)). Conclusion: Uterine fibroids are associated with lower fetal fraction and an increased risk of cfDNA screening failure. The strength of this association increases with increasing fibroid number and volume. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. Linked article: There is a comment on this article by Li. Click here to view the Correspondence. [ABSTRACT FROM AUTHOR]

Objectives: Our aim was to examine the prenatal profiles of pregnancies affected by an atypical chromosomal aberration, focusing on pathogenic copy‐number variants (pCNVs). We also wanted to quantify the performance of combined first‐trimester screening (cFTS) and a second‐trimester anomaly scan in detecting these aberrations. Finally, we aimed to estimate the consequences of a policy of using non‐invasive prenatal testing (NIPT) rather than invasive testing with chromosomal microarray analysis (CMA) to manage pregnancies identified as high risk by cFTS. Methods: This was a retrospective review of the Danish Fetal Medicine Database of all pregnant women who underwent cFTS and a risk assessment for trisomy 21 between 1 January 2008 and 31 December 2018. Chromosomal aberrations diagnosed prenatally, postnatally or from fetal tissue following pregnancy loss or termination of pregnancy were identified. Chromosomal aberrations were grouped into one of six categories: triploidy; common trisomy (13, 18 or 21); monosomy X; other sex‐chromosome aberration (SCA); pCNV; and rare autosomal trisomy (RAT) or mosaicism. The prevalence of each aberration category was stratified by the individual cFTS markers and trisomy 21 risk estimate, and the size of each pCNV diagnosed by CMA was calculated. Results: We retrieved data on 565 708 pregnancies, of which 3982 (0.70%) were diagnosed with a fetal chromosomal aberration. cFTS identified 87% of the common trisomies, but it also performed well in identifying triploidies (86%), monosomy X (92%), atypical SCAs (58%) and RATs or mosaicisms (70%). pCNVs comprised 27% (n = 1091) of the chromosomal aberrations diagnosed overall, and the prevalence increased during the study period, as prenatal CMA was increasingly being performed. In pregnancies with a maternal age < 30 years, nuchal translucency (NT) thickness ≤ 95th centile, pregnancy‐associated plasma protein‐A (PAPP‐A) ≥ 1 multiple of the median, or trisomy 21 risk of ≤ 1 in 1000, the prevalence of pCNVs exceeded significantly the prevalence of trisomies 21, 18 and 13. Pregnancies affected by a pCNV had significantly increased NT and decreased levels of the maternal biomarkers PAPP‐A and β‐human chorionic gonadotropin compared with unaffected pregnancies. However, only 23% of these pregnancies screened positive on cFTS and 51% of pCNVs were not detected until after birth. Among high‐risk pregnancies, pCNVs comprised 14% of diagnosed aberrations, and when other atypical aberrations were considered, conventional NIPT (screening for trisomies 21, 18 and 13 and monosomy X) would miss 27% of all pathogenic aberrations diagnosed from invasive testing following a high‐risk cFTS result. Thus, 1 in 26 pregnancies at high risk following cFTS would be affected by a chromosomal aberration despite a normal result from conventional NIPT. In a contingent screening model using NIPT for the 'intermediate'‐risk group (trisomy 21 risk of 1 in 100–299), 50% of the aberrations would be missed. In our cohort, 79% of the pCNVs diagnosed were < 5Mb and therefore not detectable using current forms of 'genome‐wide' NIPT. Conclusions: As a by‐product of screening for trisomies 21, 18 and 13, most triploidies and the majority of atypical SCAs, RATs and mosaicisms are detected before birth. However, only 23% of pCNVs are associated with a high‐risk result according to cFTS and only half are diagnosed before birth. Replacing invasive testing with NIPT for high‐risk pregnancies would substantially decrease the first‐trimester detection of pathogenic chromosomal anomalies. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Non-invasive prenatal testing (NIPT) investigates placental DNA and may detect confined placental mosaicism (CPM). The aim of this study was to confirm CPM in the term placenta in cases with abnormal NIPT but normal follow-up cytogenetic studies of fetus and mother. Additionally we examined the distribution of abnormal cells over the placenta. Four chorionic villus (CV) biopsies from four placental quadrants were requested in cases where CPM was assumed. Both cell lineages of the CV, cytotrophoblast (CTB) and mesenchymal core (MC), were analyzed separately with SNP array. The chromosome aberration was confirmed in 67 % of the placentas. Three quarters of the CTB and MC biopsies from these mosaic placentas were uniformly normal (57 %) or abnormal (20 %), and a minority showed mosaicism. Among 16 cases of CPM where first trimester CV were examined as well, 11 had chromosomally normal results during pregnancy. Cytogenetic investigations of term placental biopsies suspected to be affected with CPM did not reveal the chromosome aberration in one third of the placentas. This is caused by the patchy pattern in which chromosomally abnormal cells are distributed over the placenta with the majority of the biopsies being uniformly normal. Further CPM research, including its clinical impact, requires the analysis of more than four biopsies to get insight into the extent of the affected part. Moreover, a subset of CPM type 1 and 3 seems to be only detectable with NIPT and not with first trimester CVS. • Confirming confined placental mosaicism (CPM) in term placentas is challenging. • CPM exhibits a patchy pattern over the placenta with most biopsies uniformly normal. • A subset of CPM type 1 and 3 seems to be only detectable with NIPT and not with CVS. [ABSTRACT FROM AUTHOR]

Purpose: While cell-free DNA (cfDNA) screening has emerged as a screening modality for common aneuploidies, further research and several publications over the past decade suggested some correlation between the low concentrations of cfDNA and a number of pregnancy-related complications. The primary goal of this systematic review and meta-analysis was to assess the potential value of low-ff levels in the prediction of subsequent PE/PIH, GDM, SGA/FGR, and PTB. The meta-analysis results aim at summarizing the currently available literature data and determining the clinical relevance of this biochemical marker and the potential necessity for additional investigation of its utility in complications other than the detection of common aneuploidies. Methods: This systematic review and meta-analysis was designed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. It included all observational studies that reported low -ff levels after the performance of non-invasive prenatal testing (NIPT) as part of the screening for chromosomal abnormalities and their association with adverse pregnancy outcomes, namely the subsequent development of hypertensive disorders of pregnancy, gestational diabetes, preterm birth, and the detection of small for gestational age fetuses or growth-restricted fetuses. The Medline (1966–2041), Scopus (2004–2024), Clinicaltrials.gov (2008–2024), EMBASE (1980–2024), Cochrane Central Register of Controlled Trials CENTRAL (1999–2024) and Google Scholar (2004–2024) databases were used in our primary search along with the reference lists of electronically retrieved full-text papers. The date of our last search was set at February 29, 2024. Results: Our search identified 128 potentially relevant studies and,overall, 8 studies were included in the present systematic review that enrolled a total of 72,507 patients. Low ff of cfDNA cfDNA was positively associated with HDP (OR 1.66, 95% CI 1.34, 2.06, I-square test: 56%). Low ff of cfDNA was positively associated with GDM (OR 1.27, 95% CI 1.03, 1.56, I-square test: 76%). Furthermore, low ff levels were positively associated with SGA/FGR (OR 1.63, 95% CI 1.32, 2.03, I-square test: 0%). Low ff levels were positively correlated with the risk for PTB but the association did not manage to reach a statistical significant level (OR 1.22, 95% CI 0.89, 1.67, I-square test: 66%). Conclusion: Our study suggests that low ff is associated with increased risk of adverse perinatal outcomes, including PE/PIH, GDM, and SGA/FGR. However, the relationship between ff and PTB remains unclear due to conflicting evidence. It should be emphasized that further research is needed to reveal the underlying mechanisms behind the association of low ff with adverse pregnancy outcomes and explore its potential role in an overall prenatal screening, which could potentially not be limited to detecting aneuploidies. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions In Japan, noninvasive prenatal testing (NIPT) has been performed by facilities accredited by the Japanese Society of Obstetrics and Gynecology since 2013. However, since 2016, with the implementation of NIPT, which can only be performed by blood sampling, non‐obstetricians have been involved in prenatal testing. Therefore, in July 2022, a new government‐involved NIPT certification system based on Health Sciences Council guidelines was introduced to ensure access to prenatal testing information for pregnant women.This survey was conducted in February 2023 and was the first survey after the certification system implementation. We conducted a web‐based survey of 1227 pregnant women and nursing mothers who underwent NIPT after July 2022 to evaluate their experiences.Respondents were categorized by certification status as certified (C: 56%), non‐certified (non‐C: 23%), or uncertain (Q: 20%). The C group with a higher mean age at examination (35.0 ± 4.5 years) paid lower examination fees, received longer pre‐ and post‐examination explanations, and underwent more weekday examinations (80%) than the other groups. Most respondents, 67%, 48%, and 53% in the C, non‐C, and Q groups, respectively (p < 0.0001), stated that “NIPT needs to be regulated by the government or academic societies.” The non‐C group was more likely to say, “Insufficient post‐test explanations at the laboratory made me more anxious,” than the other groups when the testing results were non‐negative (p = 0.015).Despite government regulation, some pregnant women choose convenience over certified facilities, risking inadequate care. The government should ensure that NIPT is a safe option for all pregnant women. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of the presence or absence of fetal anomalies and soft markers diagnosed by ultrasound on positive predictive value (PPV) 21, 18 and 13 in pregnancies with a high-risk cfDNA result. Methods: Retrospective study including singleton pregnancies with high-risk NIPT results for common trisomies followed by invasive testing. The cases were grouped by gestational age at the time of invasive testing and by the presence or absence of fetal abnormalities or soft markers. The ultrasound was considered abnormal if at least one major defect or a soft marker was detected. Results: A total of 173 women were included. Median maternal and gestational age was 37.7 years and 14.0 weeks, respectively. CfDNA test result showed high-risk for trisomy 21 and trisomy 18 or 13 in 119 and 54 cases, respectively. The "pre-ultrasound" PPV for trisomy 21 and for trisomy 18 or 13 were 98.3% and 68.4%, respectively. In case of a high-risk result for trisomy 21 and no fetal anomalies, the PPV was 86.7% while it was 100% if there were anomalies or markers present. In the case of a high-risk result for trisomy 18 or 13, the PPV was 9.5% if the ultrasound examination was normal and 100% if the ultrasound examination was abnormal. Conclusion: This study suggests that a detailed ultrasound examination performed after a cfDNA result that is high-risk for one of the common autosomal trisomies adds significantly to establishing an individualized risk assessment. This is particularly true in cases with a high-risk result for trisomies 18 or 13. [ABSTRACT FROM AUTHOR]

Genetic counseling of mosaic and non-mosaic tetrasomy 9p remains difficult because of the possible associated congenital abnormalities, cytogenetic discrepancy in various tissues, true-positive and false-positive diagnosis in non-invasive prenatal testing (NIPT), uniparental disomy (UPD) 9, tissue-limited mosaicism, perinatal progressive decrease of the aneuploid cell line, phenotypic normal carriers and possible favorable fetal outcome in the cases with mosaic tetrasomy 9p at amniocentesis. This article presents a comprehensive review of various counseling issues concerning mosaic and non-mosaic tetrasomy 9p at prenatal diagnosis, and the information provided is very useful for genetic counseling under such circumstances.

Trisomy 7 is the most common observed type of rare autosomal trisomies (RATs) detected at expanded genome-wide non-invasive prenatal testing (NIPT). Genetic counseling of NIPT trisomy 7-positive pregnancies remains to be not easy because the parents may worry about the likelihood of adverse pregnancy outcomes, fetal abnormality and the necessity of invasive procedures for confirmation of fetal mosaic trisomy 7 and uniparental disomy (UPD) 7. This review provides a comprehensive information on the update issues concerning genetic counseling of NIPT trisomy 7-positive pregnancies.

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]

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

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]

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

Background: Deletion mutations have been confirmed to be closely related to the occurrence and progression of different hereditary diseases and tumors. Specifically, the deletion of a small number of bases is more challenging to be captured and differentiated. In non-invasive prenatal testing (NIPT) and liquid biopsy targeting circulating tumor DNA, obtaining accurate mutation abundance in targeted DNA is a crucial step in the detection process. However, the quantification of mutation abundance with existing methods is not accurate enough. Results: Herein, we developed the '' Auto-Reading'' probe detection system based on our previous work. Through theoretical modeling and experimental calculations, we verified the successful application of our system in NIPT and early cancer diagnosis, enabling effective discrimination of different mutant abundances. Significance: Our method overcomes the interference of reaction concentrations on signal detection, allowing direct quantification of mutation abundance without the need for purification of PCR products. The detection system is cost-effective and feasible for laboratory use. We believe the system will facilitate broad applications in mutation detection.

Objective: We present low-level mosaic trisomy 21 at amniocentesis and cordocentesis in a pregnancy associated with a favorable fetal outcome. Case Report: A 26-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of positive non-invasive prenatal testing (NIPT) for trisomy 21 at 16 weeks of gestation. Amniocentesis revealed a karyotype of 47,XX,+21[3]/46,XX[17], and multiplex ligation-dependent probe amplification (MLPA) on uncultured amniocytes revealed rsa X(P095) × 2, (13, 18, 21) × 2. She underwent cordocentesis (cord blood sampling) at 21 weeks of gestation which revealed a karyotype of 47,XX,+21[2]/46,XX[48]. At 27 weeks of gestation, she was referred to our hospital for genetic counseling, and repeat amniocentesis revealed a karyotype of 46,XX in 20/20 colonies. Quantitative fluorescent polymerase chain reaction (QF-PCR) analysis on the DNA extracted from uncultured amniocytes and parental bloods excluded uniparental disomy (UPD) 21. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed arr (1–22,X) × 2, Y × 0 with no genomic imbalance. Interphase fluorescence in situ hybridization (FISH) analysis on 104 uncultured amniocytes detected one cell (1/104 = 0.9%) with trisomy 21, while the rest cells were disomy 21, compared with 0% (0/100) in the normal control. The woman was encouraged to continue the pregnancy. The pregnancy was carried to 38 weeks of gestation, and a 2771-g female baby was delivered no phenotypic abnormality. aCGH analysis on the cord blood showed arr (1–22,X) × 2, Y × 0 with no genomic imbalance. The umbilical cord had a karyotype of 47,XX,+21[3]/46,XX[37]. The placenta had a karyotype of 46,XX. When follow-up at age 3½ months, the neonate was phenotypically normal and had normal development. The peripheral blood had a karyotype of 46,XX in 40/40 cells. Interphase FISH analysis on buccal mucosal cells detected normal disomy 21 cells in 100/100 cells. Conclusion: Low-level mosaic trisomy 21 at amniocentesis and cordocentesis in the second trimester can be associated with perinatal progressive decrease of the trisomy 21 cell line and a favorable fetal outcome.

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

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

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

Summary: Non‐invasive prenatal tests (NIPT) to predict fetal red cell or platelet antigen status for alloimmunised women are provided for select antigens. This study reports on massively parallel sequencing (MPS) using a red cell and platelet probe panel targeting multiple nucleotide variants, plus individual identification single nucleotide polymorphisms (IISNPs). Maternal blood samples were provided from 33 alloimmunised cases, including seven with two red cell antibodies. Cell‐free and genomic DNA was sequenced using targeted MPS and bioinformatically analysed using low‐frequency variant detection. The resulting maternal genomic DNA allele frequency was subtracted from the cell‐free DNA counterpart. Outcomes were matched against validated phenotyping/genotyping methods, where available. A 2.5% subtractive allele frequency threshold was set after comparing MPS predictions for K, RhC/c, RhE/e and Fya/Fyb against expected outcomes. This threshold was used for subsequent predictions, including HPA‐15a, Jka/Jkb, Kpa/Kpb and Lua. MPS outcomes were 97.2% concordant with validated methods; one RhC case was discordantly negative and lacked IISNPs. IISNPs were informative for 30/33 cases as controls. NIPT MPS is feasible for fetal blood group genotyping and covers multiple blood groups and control targets in a single test. Noting caution for the Rh system, this has the potential to provide a personalised service for alloimmunised women. [ABSTRACT FROM AUTHOR]

Since its debut in 2011, Non-Invasive Prenatal Testing (NIPT) has continually demonstrated its effectiveness in detecting an expanding number of diseases. NIPT offers a less invasive approach to prenatal chromosomal disease screening, providing prospective parents with vital information to better prepare for their potential pregnancy outcomes. NIPT was primarily designed for screening trisomy 13, 18, and 21. However, its scope has since broadened to encompass microdeletions and autosomal dominant monogenic diseases. Conversely, the normalization of NIPT can have unintended consequences. Some patients opt for NIPT without any medical indications, driven by a desire to remain cautious. This over-screening for chromosomal abnormalities can exacerbate pregnancy-related anxiety, as individuals might feel pressured into taking the test unnecessarily. While NIPT can be highly successful when conducted correctly, it is not infallible, and obstetricians play a crucial role in managing patient expectations. This includes providing genetic counseling to individuals with relevant genetic information regarding their personal and family histories. In the context of NIPT, a bioinformatics analysis is performed on a cell-free DNA (cfDNA) sample extracted from the mother’s placenta to determine the fetal fraction (FF). This FF measurement is vital for quality control and ensuring statistical confidence in the test results. Raising awareness among clinicians about the significance of FF enhances patient care and alleviate concerns about the possibility of failed NIPT. This paper aims to explore the ongoing debates and more specifically the significance and pitfalls of NIPT on a psychosocial and ethical scale, all while highlighting the importance of genetic counseling.

Hypospadias is one of the most common congenital malformations of the male external genitalia and urethra, the main manifestation of which is meatus dystopia. There is a steady increase in the frequency of its occurrence in many countries of the world. Hypospadias have various forms of severity, which significantly affects the patient's management tactics, the volume of surgical treatment and the further prognosis for the boy's life. The article describes a case of early prenatal diagnosis of the coronary form of hypospadias in the fetus at 15 weeks of gestation, followed by postnatal verification of the diagnosis. The possibilities of echography in the early detection of distal forms of hypospadias using an integrated approach in the assessment of external genitalia in a male fetus are shown. This complex of hypospadias markers includes an assessment of the size of the penis, the presence of a curvature of its body, the shape of the head of the penis and the presence of signs of cleavage of the foreskin, which are manifested by its rounding. The ineffectiveness of the long-used «tulip» sign for the early diagnosis of distal forms of hypospadias has been demonstrated. The comparison of the echographic picture of the structure of the genitals in normal and hypospadias at 12 and 15 weeks of pregnancy was carried out.

Abstract Background In developing countries, pregnant women have insufficient knowledge about cell-free DNA screening. Reports from developed countries have found that various tools in prenatal genetic counseling can improve the knowledge of pregnant women who undergo cell-free DNA screening. Data are limited from developing countries where women have different baseline socio-educational backgrounds. The objective of this study was to compare the effects of an animated educational video combined with traditional counseling versus traditional counseling alone in changing pregnant women’s knowledge of cell-free DNA screening. Methods This study was a randomized control trial at an antenatal clinic. Eligible subjects who were Thai pregnant women, were randomized to either view or not view the 4-minute animated educational video explaining cell-free DNA screening. Both groups received traditional counseling. The women were asked to complete a Thai questionnaire assessing knowledge of the screening before and after intervention. The questionnaire consisted of three sections: demographic data of the research participants and their existing awareness about cell-free DNA testing; performance and limitations of cell-free DNA screening; and participants’ attitudes toward the positive screening. Primary outcome was the change in knowledge scores. Secondary outcomes were attitudes toward positive screening test, levels of satisfaction with counseling, and screening acceptance rates. Results Data from 83 women in the video group and 82 in the non-video group were analyzed. The knowledge score (range 0–18) change after counseling was significantly higher in the video group than the non-video group (+ 7.1 ± 3.3 vs + 4.2 ± 2.5; p = 0.03). There were no significant differences in attitudes toward positive screening test (p = 0.83), levels of satisfaction (p = 0.24), or screening acceptance rates (p = 0.15) between the groups. Conclusions Adding the video to traditional counseling was better than traditional counseling alone in improving pregnant women’s knowledge about cell-free DNA screening. Trial registration The study was retrospectively registered with the Thai Clinical Trials Registry (TCTR20210917001, 17/09/2021).

Introduction: Noninvasive prenatal testing (NIPT) can be used to detect fetal chromosomal abnormalities early in pregnancy. As eligibility criteria broaden and screening targets expand, gauging public acceptability of NIPT becomes increasingly important. Leveraging social media as a rich source of public discourse, the purpose of this study was to understand public opinions and attitudes toward NIPT on the social media platform Reddit. Methods: We applied content and natural language processing techniques (i.e., sentiment analysis) to textual data collected from 4 Reddit communities focusing on the NIPT content posted from September 2012 to September 2022 (367 posts and 7,822 comments in total). Results: Content analysis findings indicated that social media users consider NIPT to be worthwhile. Reasons NIPT was perceived to be not worthwhile related to unwanted anxiety, and the fact that NIPT results would not change anything about their approach to pregnancy were also expressed. The sentiment analysis identified more positive than negative emotions; the mean sentiment scores ranged from 0.48 to 1.22, depending on the specific Lexicon used. Specific emotions (i.e., trust, fear) were also identified. Conclusion: Our novel approach to understanding public perception and attitudes toward NIPT yielded results that are consistent with conventional patient-oriented research methods. These findings may not only contribute to ongoing improvements in prenatal patient care, research, and policy but also indicate that sentiment analysis applied to social media data can serve as a suitable means to assess public acceptability of NIPT, particularly as public dialogue on this topic increases over time. [ABSTRACT FROM AUTHOR]

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: In developing countries, pregnant women have insufficient knowledge about cell-free DNA screening. Reports from developed countries have found that various tools in prenatal genetic counseling can improve the knowledge of pregnant women who undergo cell-free DNA screening. Data are limited from developing countries where women have different baseline socio-educational backgrounds. The objective of this study was to compare the effects of an animated educational video combined with traditional counseling versus traditional counseling alone in changing pregnant women's knowledge of cell-free DNA screening. Methods: This study was a randomized control trial at an antenatal clinic. Eligible subjects who were Thai pregnant women, were randomized to either view or not view the 4-minute animated educational video explaining cell-free DNA screening. Both groups received traditional counseling. The women were asked to complete a Thai questionnaire assessing knowledge of the screening before and after intervention. The questionnaire consisted of three sections: demographic data of the research participants and their existing awareness about cell-free DNA testing; performance and limitations of cell-free DNA screening; and participants' attitudes toward the positive screening. Primary outcome was the change in knowledge scores. Secondary outcomes were attitudes toward positive screening test, levels of satisfaction with counseling, and screening acceptance rates. Results: Data from 83 women in the video group and 82 in the non-video group were analyzed. The knowledge score (range 0–18) change after counseling was significantly higher in the video group than the non-video group (+ 7.1 ± 3.3 vs + 4.2 ± 2.5; p = 0.03). There were no significant differences in attitudes toward positive screening test (p = 0.83), levels of satisfaction (p = 0.24), or screening acceptance rates (p = 0.15) between the groups. Conclusions: Adding the video to traditional counseling was better than traditional counseling alone in improving pregnant women's knowledge about cell-free DNA screening. Trial registration: The study was retrospectively registered with the Thai Clinical Trials Registry (TCTR20210917001, 17/09/2021). [ABSTRACT FROM AUTHOR]

To determine maternal factors associated with low fetal fraction (FF). To determine the proportion of women who receive a result from repeat non-invasive prenatal testing (NIPT) testing. To identify any significant associations between pregnancy interventions or outcomes and low FF. Retrospective observational study of 4465 women undergoing antenatal screening by targeted cell free DNA (cfDNA) testing at an Irish tertiary maternity hospital between January 2017 and December 2022. Patients who failed to obtain a result after the first NIPT were analyzed in two cohorts; those who received a result on a repeat sample and those who failed to ever achieve a result despite a second, third or fourth cfDNA test. Risk of insufficient FF significantly increased with elevated maternal BMI (OR 1.07; 95% CI 1.01–1.13, p = 0.03) and in-vitro fertilization (IVF) (OR 3.4; 95% CI 1.19–9.4, p = 0.02). Women with no result were more likely to have diagnostic invasive testing (p < 0.01), but had no increased risk of aneuploidy. Repeated failed NIPT attempts due to low FF were significantly associated with the subsequent development of hypertensive diseases of pregnancy (p = 0.03). Greater than 70% of patients who were unsuccessful in a first or second attempt at NIPT due to low FF yielded a result following a second or third sample. High BMI and IVF conceptions are greater contributors to low FF than fetal aneuploidy. Repeating NIPT yields a result in greater than 70% of cases. Fetal fraction (FF) in prenatal cfDNA testing is influenced by maternal and pregnancy factors including body mass index (BMI) and IVF. Low FF has been associated with adverse pregnancy outcomes including fetal aneuploidy and hypertensive diseases of pregnancy. In a large Irish population, increasing maternal BMI and in-vitro fertilization are the most significant contributors to repeated test failures due to low FF. Greater than 70% of patients with test failure due to low FF will receive a result on 2nd and 3rd NIPT attempts. Patients with no result from NIPT were more likely to undergo diagnostic invasive testing but the risk of aneuploidy was not significantly increased. [ABSTRACT FROM AUTHOR]

Noninvasive prenatal testing (NIPT) analyzes placental cell-free DNA in maternal blood for genetic abnormalities, especially in pregnant women of advanced maternal age. It is a high-sensitivity and specificity test used for screening fetal chromosome trisomy 13, 18, 21, sex chromosome aneuploidy, and rare fetal chromosome aneuploidy. Rarely there were cases in which it was used to diagnose maternal cancer. We will discuss a case of metastatic breast cancer diagnosed by NIPT and current knowledge on the use of this technology in diagnosing cancer during pregnancy.

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

Objective: We present high-level mosaicism for 45,X in 45,X/46,X,+mar at amniocentesis in a pregnancy associated with positive non-invasive prenatal testing (NIPT) for Turner syndrome, normal male external genitalia and positive SRY in the fetus, a favorable fetal outcome, postnatal decrease of the 45,X cell line and cytogenetic discrepancy in various tissues. Case report: A 35-year-old, gravida 2, para 1, woman underwent amniocentesis at 16 weeks of gestation because of positive NIPT for Turner syndrome (Z score = −11.72 for X chromosome) at 10 weeks of gestation. Amniocentesis revealed a karyotype of 45,X[13]/46,X,+mar[8]. Simultaneous molecular analysis on the DNA extracted from uncultured amniocytes revealed the results of arr (X) × 1, (Yp) × 0–1 (0.63), (Yq) × 0, (1–22) × 2 in array comparative genomic hybridization (aCGH) and rsa(X) × 1, Yp11.31 × 0–1, Yq11.21 × 0, (13, 18, 21) × 2 in multiplex ligation-dependent probe amplification (MLPA). The parental karyotypes were normal. Prenatal ultrasound revealed normal male external genitalia. She was referred for genetic counseling, and continuing pregnancy was advised. A 2875-g male baby was delivered at 38 weeks of gestation with normal male external genitalia. The karyotypes of cord blood, umbilical cord and placenta were 46,X,+mar[27]/45,X[13], 46,X,+mar[24]/45,X[16] and 45,X[22]/46,X,+mar[18], respectively. SRY testing on cord blood revealed a positive result. When follow-up at age two months, the neonate was normal in development. The karyotype of peripheral blood was 46,X,+mar[25]/45,X[13]/46,X,idic r(Y) [2]. Interphase fluorescence in situ hybridization (FISH) analysis on 103 buccal mucosal cells using Yp11.2-specific probe RP11-119E4 and Xp22.31-specific probe RP11-143E20 showed that 90 cells (90/103 = 87%) had double Yp signals, 3 cells (3/103 = 3%) had single Yp signal and 10 cells (10/103 = 10%) had no Yp signal. Conclusion: High-level mosaicism for 45,X in 45,X/46,X,+mar at amniocentesis with positive Yp and SRY can be associated with a favorable fetal outcome, postnatal decrease of the 45,X cell line and cytogenetic discrepancy in various tissues.

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.

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 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.

Objective: We present low-level mosaic trisomy 2 at amniocentesis in a pregnancy associated with positive non-invasive prenatal testing (NIPT) and chorionic villus sampling (CVS) results for trisomy 2, maternal uniparental disomy (UPD) 2, perinatal progressive decrease of the aneuploid cell line, cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, intrauterine growth restriction (IUGR) and a favorable fetal outcome. Case Report: A 35-year-old, primigravid woman underwent amniocentesis at 16 weeks of gestation because both NIPT at 9 weeks of gestation and CVS at 11 weeks of gestation revealed trisomy 2. This pregnancy was conceived by in vitro fertilization (IVF) and embryo transfer (ET). Amniocentesis revealed a karyotype of 47,XY,+2[11]/46,XY[19]. Prenatal ultrasound findings were normal. She was referred to the hospital for genetic counseling at 20 weeks of gestation, and repeat amniocentesis performed at 24 weeks of gestation revealed a karyotype of 46,XY (22/22 colonies). The parental karyotypes were normal. Quantitative fluorescent polymerase chain reaction (QF-PCR) analysis on the DNA extracted from uncultured amniocytes and parental bloods revealed maternal uniparental heterodisomy of chromosome 2. Simultaneous molecular cytogenetic analysis on uncultured amniocytes showed the results of arr 2p25.3q37.3 × 2.4 with a log2 ratio = 0.26, consistent with 40% mosaicism for trisomy 2 by array comparative genomic hybridization (aCGH), and 28% (28/100 cells) mosaicism for trisomy 2 by interphase fluorescence in situ hybridization (FISH). Despite IUGR on fetal ultrasound, the woman was advised to continue the pregnancy, and a 2252-g phenotypically normal male baby was delivered at 38 weeks of gestation. The karyotypes of cord blood, umbilical cord and placenta were 46,XY (40/40 colonies), 46,XY (40/40 colonies) and 47,XY,+2[9]/46,XY[31], respectively. QF-PCR analysis on cord blood, umbilical cord and placenta confirmed uniparental heterodisomy of chromosome 2 in the cord blood and umbilical cord, and maternal origin of trisomy 2 in the placenta. FISH analysis on buccal mucosal cells at age 1.5 months revealed 8.7% (9/104 cells) mosaicism for trisomy 2. When follow-up at age four months, the neonate manifested a normal phenotype except intermittent hypoventilation. Molecular analysis of the PHOX2B gene revealed a normal result. When follow-up at age one year, he manifested normal development. Conclusion: Mosaic trisomy 2 at prenatal diagnosis should alert the possibility of UPD 2 and include a UPD 2 testing. Low-level mosaic trisomy 2 at amniocentesis can be associated with perinatal progressive decrease of the aneuploid cell line and a favorable fetal outcome.

Objective: We present low-level mosaic trisomy 13 at amniocentesis in a pregnancy associated with a positive non-invasive prenatal testing (NIPT) result suspicious of trisomy 13, a chorionic villus sampling (CVS) result of mosaic trisomy 13, cytogenetic discrepancy in various tissues and a favorable fetal outcome. Case report: A 29-year-old, gravida 2, para 1, woman underwent amniocentesis at 20 weeks of gestation because of a positive NIPT result (Z-score = 20.9, positive ≥3) suspicious of trisomy 13 at 11 weeks of gestation and a CVS result of mosaic trisomy 13 at 14 weeks of gestation. At 14 weeks of gestation, CVS revealed the multiplex ligation-dependent probe amplification (MLPA) result of rea X,Y (P095) × 1, 13 (P095) × 3, 18,21 (P095) × 2/X,Y (P095) × 1, 13,18,21 (P095) × 2 and a karyotype of 48,XY,+13,+mar [9]/47,XY,+mar[16]. She was referred to the hospital for genetic counseling at 15 weeks of gestation, and cytogenetic analysis of parental blood revealed 47,XY,+mar in the father and 46, XX in the mother. Fluorescence in situ hybridization (FISH) analysis on the paternal blood showed that the extra dicentric marker was derived from chromosome 15 without the locus SNRPN (15q11.2), and the result was 47,XY,+mar.ish dic(15) (D15Z1++, SNRPN-, PML-)[20]. Amniocentesis at 20 weeks of gestation revealed a karyotype of 47,XY,+mar pat (20/20). Simultaneous interphase FISH analysis on uncultured amniocytes revealed 32% (32/100 cells) mosaicism for trisomy 13. Quantitative fluorescence polymerase chain reaction (QF-PCR) analysis using the DNA extracted from the parental bloods and uncultured amniocytes excluded uniparental disomy (UPD) 13. Prenatal ultrasound findings were normal. The woman was advised to continue the pregnancy, and a phenotypically normal 2708-g male baby was delivered at 38 weeks of gestation, The cord blood, umbilical cord and placenta had the karyotypes of 47,XY,+mar pat and did not have UPD 13. When follow-up at age two months, the neonate was phenotypically normal. FISH analysis on buccal mucosal cells detected 5.3% (5/95 cells) mosaicism for trisomy 13, compared with 0% in the normal control. Conclusion: Low-level mosaic trisomy 13 at amniocentesis can be associated with a positive NIPT result suspicious of trisomy 13, a CVS result of mosaic trisomy 13, cytogenetic discrepancy in various tissues and a favorable fetal outcome.

Objective: We present low-level mosaic trisomy 21 at amniocentesis associated with a favorable fetal outcome. Case report: A 31-year-old primigravid woman underwent non-invasive prenatal testing (NIPT) at 12 weeks of gestation, and the result was normal. She underwent amniocentesis at 16 weeks of gestation because of fetal choroid plexus cyst, and the result was 47,XX,+21[5]/46,XX[32]. Repeat amniocentesis was performed at 19 weeks of gestation, and the result was 47,XX,+21[5]/46,XX[15]. Simultaneous array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed the result of arr (21) × 3 [0.10], consistent with 10% mosaicism for trisomy 21. Prenatal ultrasound findings were unremarkable. She was referred for genetic counseling at 22 weeks of gestation, and the third amniocentesis was performed at 25 weeks of gestation, and the result was 46,XX (20/20 colonies). The parental karyotypes were normal. Simultaneous quantitative fluorescence polymerase chain reaction (QF-PCR) analysis on the DNA extracted from uncultured amniocytes and parental bloods excluded uniparental disomy (UPD) 21. aCGH analysis on uncultured amniocytes revealed arr 21q11.2q22.3 × 2.1 (log2 ratio = 0.1), consistent with 10–15% mosaicism for trisomy 21. Fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes revealed 30% (30/100 cells) mosaicism for trisomy 21. The woman was advised to continue the pregnancy, and a phenotypically normal 2800-g female baby was delivered at 38 weeks of gestation. The karyotype of cord blood, umbilical cord and placenta were 47,XX,+21[1]/46,XX[39]. 47,XX,+21[4]/46,XX[36] and 46,XX (40/40 cells), respectively. When follow-up at age two months, the neonate was phenotypically normal. The peripheral blood had a karyotype of 47,XX,+21[1]/46,XX[39], and FISH analysis on buccal mucosal cells revealed 8.4% (7/83 cells) mosaicism for trisomy 21, compared with 0% in the normal control. Conclusion: Low-level mosaic trisomy 21 at amniocentesis can be associated with a negative NIPT result, cytogenetic discrepancy in various tissues, perinatal progressive decrease of the aneuploid cell line and a favorable fetal outcome.

The use of non-invasive prenatal testing (NIPT) technology has revolutionized the practice of prenatal screening. The assay’s validity and reliability have been demonstrated in both low- and high-risk pregnancies. Despite its excellent screening parameters, its reliability is often overestimated due to confusing and incorrect terminology that appears in private NIPT reports. Herein, we provide a brief explanation of the potential implications at two different levels: patient and provider. We conclude with a call to redesign the way information is presented on NIPT reports to avoid stressing patients, enhance transparency in clinical counselling, and perhaps most critically, to prevent medical decisions that may not be warranted solely based on the NIPT results.

Objective: To analyze the efficacy of noninvasive prenatal genetic testing (NIPT) in detecting fetal sex chromosome abnormalities and copy number variation (CNV), compare the efficacy between NIPT and serological screening alone, and further analyze the fetal sex chromosome abnormalities and CNV differentiation in pregnant women of different ages, so as to provide a reference for the prevention and control of fetal birth defects. Methods: Clinical data from 22,692 pregnant women admitted to our hospital from January 2013 to December 2022 were retrospectively analyzed. All participants underwent serological screening and NIPT screening to compare fetal chromosomal abnormalities between the two screening modalities. 145 women whose fetus were diagnosed as sex chromosome abnormalities and 36 women whose fetus were diagnosed as CNV abnormalities based on NIPT screening were selected for prenatal diagnosis by amniocentesis or karyotyping. Taking prenatal diagnosis as the standard, the four-grid table method was used to detect the positive predictive value of NIPT screening for fetal sex chromosomal abnormalities and CNV. According to the age, pregnant women were divided into 18–30 years old (n = 9844), 31–35 years old (n = 7612), >35 years old (n = 5236), and then the detection rates of sexual fetal chromosomal abnormalities, CNV and total chromosomal abnormalities were compared in pregnant women. Results: Among the 22,692 pregnant women in this study, the high-risk proportion of serologic screening with 4.38% was higher than that of NIPT screening with 1.93% (P 10 Mb were 33.33% and 66.67%, respectively. There were 12 cases of prenatal diagnosis of fetal CNV, among which the NIPT-screened positive predictive values of fetal copy number deletion, duplicate, deletion and duplicate were 50.00%, 57.14% and 100.00%, respectively, with an overall predictive value of 58.33%. The positive predictive value of CNV in NIPT screening was higher than that of serological screening without statistically significant difference (P > 0.05). The results of NIPT screening showed that the detection rate of fetal sex chromosome abnormalities and total abnormalities of pregnant women over 35 years of age was significantly higher than that of pregnant women aged 18–30 and 31–35 years (P

This article investigates how non-invasive prenatal testing and the incorporation of genomic sequencing into newborn screening postnatally are transforming perinatal care. They improve the accuracy of prenatal and neonatal screening, allowing for early interventions and personalized therapies. Non-invasive prenatal testing before birth and saliva-sample-based newborn genomic sequencing after birth can be collectively referred to as non-invasive perinatal testing. Non-invasive prenatal testing is particularly useful for aneuploidy, whereas performance markers worsen as DNA abnormalities shrink in size. Screening for clinically actionable diseases in childhood would be crucial to personalized medical therapy, as the postnatal period remains appropriate for screening for the great majority of monogenic disorders. While genomic data can help diagnose uncommon diseases, challenges like ethics and equity necessitate joint approaches for appropriate integration in this revolutionary journey toward personalized care.

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]

Objective: To evaluate the impact of detailed late first‐trimester ultrasound (LFTU) on the positive predictive value (PPV) of a high‐risk non‐invasive prenatal test (NIPT) result for various chromosomal abnormalities. Methods: This was a retrospective study of all cases undergoing invasive prenatal testing from three tertiary providers of obstetric ultrasound over 4 years, each using NIPT as a first‐line screening test. Data were collected from pre‐NIPT ultrasound, NIPT, LFTU, placental serology and later ultrasound examinations. Prenatal testing for chromosomal abnormalities was performed by microarray, initially using array comparative genomic hybridization and then single nucleotide polymorphism (SNP) array for the last 2 years. Uniparental disomy testing was performed by SNP array during all 4 years. The majority of NIPT tests were analyzed using the Illumina platform, initially confined to the assessment of the common autosomal trisomies, sex chromosome aneuploidies and rare autosomal trisomies (RAT), then extending to genome‐wide analysis for the last 2 years. Results: Amniocentesis or chorionic villus sampling (CVS) was performed on 2657 patients, 1352 (51%) of whom had undergone prior NIPT, with 612 (45%) of these returning a high‐risk result and meeting the inclusion criteria for the study. LFTU findings significantly affected the PPV of the NIPT result for trisomies 13 (T13), 18 (T18) and 21 (T21), monosomy X (MX) and RAT but not for the other sex chromosomal abnormalities or segmental imbalances (> 7 Mb). Abnormal LFTU increased the PPV close to 100% for T13, T18, T21, MX and RAT. The magnitude of the change in PPV was highest for the most severe chromosomal abnormalities. When LFTU was normal, the incidence of confined placental mosaicism (CPM) was highest in those with a high‐risk NIPT result for T13, followed by T18 and T21. After normal LFTU, the PPV for T21, T18, T13 and MX decreased to 68%, 57%, 5% and 25%, respectively. Conclusions: LFTU after a high‐risk NIPT result can alter the PPV for many chromosomal abnormalities, assisting counseling regarding invasive prenatal testing and pregnancy management. The high PPVs of NIPT for T21 and T18 are not sufficiently modified by normal LFTU findings to alter management. These at‐risk patients should be offered CVS for earlier diagnosis, particularly given the low rate of CPM associated with these aneuploidies. Patients with a high‐risk NIPT result for T13 and normal LFTU findings often wait for amniocentesis or avoid invasive testing altogether given the low PPV and higher rate of CPM in this context. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. Linked article: There is a comment on this article by Han and Li. Click here to view the Correspondence. [ABSTRACT FROM AUTHOR]

Prenatal screening has evolved rapidly following the introduction of non‐invasive prenatal testing (NIPT), with screening now available for an increasing number of conditions. We explored the attitudes and expectations of women within the context of using NIPT to detect multiple different single gene and chromosome conditions during pregnancy. An online survey was used to assess these issues with a sample of 219 women from Western Australia. In our study, the majority of women (96%) support of the concept of expanded NIPT for single gene and chromosome conditions provided the test involves no risk to the pregnancy and can provide the parents with relevant medical information about the fetus at any stage of pregnancy. 80% believed that expanded NIPT for single gene and chromosome conditions should be available at any stage during pregnancy and 68% of women indicated that test cost would be a factor in determining their participation in testing. Under half (43%) of the women favored an option to terminate a pregnancy at any stage if the fetus had a medical condition that would interfere with day to day functioning. The majority (78%) of women believed that testing for multiple genetic conditions would provide reassurance and lead to the delivery of a healthy child. [ABSTRACT FROM AUTHOR]

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

Purpose: To report a rare type of Pallister-Killian syndrome (PKS) diagnosed prenatally by the utility of non-invasive prenatal testing (NIPT). Methods: NIPT was performed in the first trimester. Conventional karyotyping and chromosomal microarray analysis (CMA) were performed on the amniotic samples in the second trimester. Copy number variation sequencing (CNV-seq) was used for the validation of fetal skin and the placental tissue after pregnancy termination. Results: NIPT results showed increased signal from chromosome 12p. Subsequent prenatal diagnostic testing by karyotype revealed 47, XY, +i (12p), and CMA displayed four copies of 12p: 12p13.33-12p11.1(173786_34835641) × 4. The CNV-seq results of the fetal skin and the fetal side of placenta showed four copies of 12p13.33-p11 and an estimated chimeric duplication of 34.08 Mb (chimerism ratio: 10%) in 12 p13.33-p11, respectively. However, no abnormality was detected by CNV-seq at the maternal side of placenta. Conclusions: Our findings suggest that a positive signal from chromosome 12p on NIPT should raise suspicion for PKS. With the wide application of NIPT, the true positive of incidental finding is expected to increase. [ABSTRACT FROM AUTHOR]

Twin pregnancy presents unique considerations for aneuploidy screening. Pre-test counseling regarding benefits, alternatives, and options for aneuploidy screening should be provided to all patients carrying twin pregnancy. This article aims to review the options for aneuploidy screening in twin pregnancy including the potential benefits and limitations. [ABSTRACT FROM AUTHOR]