Fetal Chromosome Research Articles

Результати комплексних пренатальних обстежень за наявності дисбалансу хромосоми 21 у плода

Purpose - to characterize the cases of chromosome 21 imbalance in fetuses of high-risk pregnant women, to describe prenatal cytogenetic diagnosis and associated ultrasound findings - structural anomalies and soft markers. Materials and methods. The results of complex prenatal examination of high-risk pregnant women in the Department of Fetal Medicine of the SI “Institute of Pediatrics, Obstetrics and Gynecology named after academician O.M. Lukyanova of the NAMS of Ukraine” during 5 years period were analyzed: results of ultrasound and cytogenetic exams of 200 cases of chromosome 21 imbalance in the fetus. Results. Among 4,748 prenatal cytogenetic testing of fetuses of high-risk women abnormal karyotypes with an imbalance of chromosome 21 were found in 200 (4.21%) cases. In the majority of cases Down's syndrome (DS) was diagnosed (n=199; 99.5%), in 1 (0.2%) case - deletion of chromosome 21. In DS, regular trisomy of chromosome 21 was found in 191 (95.97%) cases, translocant forms - in 5 (2.51%) cases, in 1 (0.5%) case there was there was an additional sex chromosome, and in 1 (0.5%) - a variant with two cell lines. In 1 (0.5%) case limited placental mosaicism was present, with a false negative result that required verification by the analysis of fetal lymphocytes obtained during cordocentesis. Advanced maternal age (≥35 years) was registered in less than half of fetal DS cases (n=92/199, 46.2%). The main indications for invasive procedures and their types are described. It was demonstrated that ultrasound findings (structural anomalies and/or “soft” markers for chromosomal pathology) were present in 78% of fetal chromosome 21 imbalance; nevertheless in 22% ultrasound findings were absent, and the indication for invasive procedures were advanced maternal age or isolated changes of biochemical markers. Conclusions. Chromosome 21 imbalance in fetuses is mainly represented by trisomy, cases of chromosome 21 deletion are extremely rare. Targeted ultrasound examination is important for screening and diagnosis of fetal chromosomal abnormalities. High-risk pregnant women shouldn’t be reassured in case of “normal” ultrasound exam results. Under certain conditions, it is advisable to perform placental biopsy in the II trimester of pregnancy, but only in specialized tertiary centers or departments. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Principles and Applications of Fetal Chromosome Number and Structure Analysis

A crucial diagnostic technique employed in prenatal diagnosis is examining the quantity and arrangement of fetal chromosomes. The fundamental premise of this study is to determine the chromosomal count in the fetal cells and detect any genetic or chromosomal abnormalities that may be present. A total of 46 chromosomes are typically present in the human body, organized into 23 pairs. These pairs include one pair of sex chromosomes and 22 pairs of autosomal chromosomes. This study enables the identification of chromosomal abnormalities, such as trisomy (the presence of an additional chromosome) and monosomy (the absence of a chromosome), which can have an impact on the health of the fetus. In addition to determining the number of chromosomes, this examination can also detect structural chromosome abnormalities like translocations, deletions, and duplications, which might potentially affect the health of the fetus. This investigation's findings provide significant insights to both patients and clinicians, enabling them to make more informed choices about continuing the pregnancy and receiving appropriate medical attention if genetic abnormalities are detected. This study can also be utilized for the identification of particular genetic illnesses associated with specific gene mutations, thereby aiding in treatment strategizing and postnatal readiness.

Chromosome analysis of foetal tissue from 1903 spontaneous abortion patients in 5 regions of China: a retrospective multicentre study

BackgroundAbnormal foetal tissue chromosome karyotypes are one of the important pathogenic factors for spontaneous abortion (SA). To investigate the age and abnormal foetal karyotypes of 1903 couples who experienced SA.MethodsA retrospective multicentre study collected age and foetal tissue karyotypes CNV-seq data of 1903 SA couples from 6 hospitals in 5 regions from January 2017 to March 2022. The distribution and correlation of abnormal foetal tissue karyotypes were evaluated by using regions and age.ResultsIn our study, 1140 couples (60.5% of the total) had abnormal foetal tissue chromosome karyotypes in all regions. We found that there were differences in the number of abnormal foetal tissue chromosome karyotypes, of which the incidence of trisomy was higher. At the same time, the populations situated in the eastern region had a more triploid (15.5%) distribution, trisomy (58.1%) in the southern region, mosaicism (14.8%) and microduplication (31.7%) in the southwestern region, microdeletion (16.7%) in the northern region. There are variances across areas, and it is more common in the north. The incidence risk of prenatal chromosomal abnormalities varied according to age group.ConclusionThe findings of this study suggest that the karyotypes of patients with abnormal foetal tissue chromosome abortion in different regions were different. Meanwhile, patients ≥ 35 years old had a higher risk of abnormal foetal tissue chromosome abortion.

Prenatal cfDNA Screening for Emanuel Syndrome and Other Unbalanced Products of Conception in Carriers of the Recurrent Balanced Translocation t(11;22): One Laboratory's Retrospective Experience.

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

The effectiveness of non-invasive prenatal test technology and the prenatal screening algorithm based on various methods for determining foetal aneuploidy.

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

Guideline for the application of chromosomal microarray analysis in prenatal diagnosis (2023)

After the promulgation of the first edition of expert consensus on the application of chromosomal microarray analysis (CMA) technology in prenatal diagnosis in 2014, after 8 years of clinical and technical development, CMA technology has become a first-line diagnosis technology for fetal chromosome copy number deletion or duplication abnormalities, and is widely used in the field of prenatal diagnosis in China. However, with the development of the industry and the accumulation of experience in case diagnosis, the application of CMA technology in many important aspects of prenatal diagnosis, such as clinical diagnosis testimony, data analysis and genetic counseling before and after testing, needs to be further standardized and improved, so as to make the application of CMA technology more in line with clinical needs. The revision of the guideline was led by the National Prenatal Diagnostic Technical Expert Group, and several prenatal diagnostic institutions such as Peking Union Medical College Hospital were commissioned to write, discuss and revise the first draft, which was discussed and reviewed by all the experts of the National Prenatal Diagnostic Technical Expert Group, and was finally formed after extensive review and revision. This guideline is aimed at the important aspects of the application of CMA technology in prenatal diagnosis and clinical diagnosis, from the clinical application of evidence, test quality control, data analysis and interpretation, diagnosis report writing, genetic counseling before and after testing and other work specifications are elaborated and introduced in detail. It fully reflects the integrated experience, professional thinking and guidance of the current Chinese expert team on the prenatal diagnosis application of CMA technology. The compilation of the guideline for the application of CMA technology in prenatal diagnosis will strive to promote the standardization and advancement of prenatal diagnosis of fetal chromosome diseases in China.

Defining the scope of extended NIPS in Western China: evidence from a large cohort of fetuses with normal ultrasound scans

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

A Systematic Review and Meta-analysis of Cell-Free DNA Testing for Detection of Fetal Sex Chromosome Aneuploidy

ABSTRACT Noninvasive prenatal screening has become a valuable tool in detecting a variety of disorders and abnormalities, including sex chromosome aneuploidies (SCAs). The test uses cell-free DNA (cfDNA) analysis to identify risk for chromosomal abnormalities, which can then be more fully investigated using other tests. Much of previous research focused on cfDNA has assessed autosomal aneuploidies, but few studies have specifically focused on SCAs. The aim of this systematic review and meta-analysis was to assess the accuracy of cfDNA testing in identifying SCAs in singleton pregnancies. Studies were identified by keywords associated with cfDNA, SCA, and noninvasive prenatal testing, and studies were included based on relevance. Inclusion criteria were limited to singleton pregnancies that underwent cfDNA testing with confirmation by diagnostic genetic testing between January 1, 2010 and December 1, 2021. A total of 21 articles were selected for the final meta-analysis. All included studies reported results for monosomy X (45,X), representing nearly 13,000 tests with 254 confirmed positive results, 133 false-positives, and 18 false-negatives. Estimated sensitivity based on this sample was 98.8%, with specificity of 99.4%. Positive and negative predictive values were 14.5% and 100%, respectively. Of the 21 included studies, 16 also reported results for Klinefelter syndrome (47,XXY), representing just over 11,000 tests with 62 confirmed positive results, 10 false-positives, and 11 false-negatives. Estimated sensitivity was 100% and specificity was 100%, with positive predictive value of 97.7% and negative predictive value of 100%. Thirteen of 21 studies included reported results for triple X syndrome (47,XXX), representing roughly 10,000 tests with 38 confirmed positive results, 18 false-positives, and 1 false-negative. This showed an estimated sensitivity of 100% and specificity of 99.9%, with positive predictive value of 61.6% and negative predictive value of 100%. Finally, 9 of the studies included in this meta-analysis reported results for Jacobs syndrome (47,XYY), representing approximately 8500 tests with 22 confirmed positive results, 2 false-positives, and no false-negatives. This led to an estimated sensitivity and specificity of 100%, with positive and negative predictive values also 100%. These results provide evidence that cfDNA testing is effective in identification of SCAs in pregnancies at high risk. This particular population limits the generalizability of the findings but adds to the literature surrounding the effectiveness and accuracy of this method. The analysis used strict criteria to define the studies that were included, yet still included a large sample of tests (12,000), which adds to the statistical and practical significance of the analysis. Generalizing the findings of this study is difficult based on both the fact that the sample did not include low-risk individuals and that positive predictive values varied greatly with prevalence, impacting clinical significance. Overall, cfDNA testing for SCAs has both high sensitivity and specificity, along with a high negative predictive value of 99.99% or above for each SCA examined. Further research is needed to confirm these findings and extend knowledge to a more diverse population.

The relationship of maternal polymorphisms of genes related to meiosis and DNA damage repair with fetal chromosomal stability.

To evaluate the association between maternal polymorphisms of NANOS3 rs2016163, HELQ rs4693089, PRIM1 rs2277339, TLK1 rs10183486, ERCC6 rs2228526, EXO1 rs1635501, DMC1 rs5757133, and MSH5 rs2075789 and fetal chromosomal abnormality. This retrospective case-control study included 571 women with fetal chromosome abnormalities (330 pregnant women diagnosed with fetal aneuploidy, 241 with fetal de novo structural chromosome pregnancy) and 811 healthy pregnant women between January 2018 and April 2022. All the above polymorphisms were tested using SNaPshot. All the eight polymorphisms were analyzed for genotypes, alleles, under dominant and recessive genetic models. Significant distribution differences of TLK1 rs10183486 in fetal chromosome structural abnormality were found between the case group and control subjects who were<35 years of age [Genotype: p=0.029; Dominant: OR (95 %CI)=0.46 (0.25-0.82), p=0.01 and allele: OR (95 %CI)=0.47 (0.27-0.82), p=0.01 respectively], while no difference was found in the recessive model [OR (95 %CI)=2.49 (0.31-20.40), p=0.39]. In advanced age subgroups for fetal aneuploidy, significant differences were found in genotypes analysis of PRIM1 rs2277339 (p=0.008), allele analysis of TLK1 rs10183486 [OR (95 %CI)=0.62 (0.42-0.91), p=0.02]. For thefetal chromosome structural abnormality population, HELQ rs4693089 revealed a significant distribution difference (p=0.01) but not in the allele, dominant and recessive genetic models analysis (p>0.05 individually). For older women, maternal PRIM1 rs2277339 and TLK1 rs10183486 polymorphisms may be associated with fetal aneuploidy, while HELQ rs4693089 may be associated with fetal chromosome structural abnormality. Also, carriers of T allele of TLK1 rs10183486 have a lower risk of fetal chromosome structural abnormality in younger women.

Overview of Noninvasive Prenatal Testing (NIPT) for the Detection of Fetal Chromosome Abnormalities; Differences in Laboratory Methods and Scope of Testing.

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

Ethical concerns surrounding sex prediction using noninvasive prenatal screening from pediatric endocrinologists' perspective.

Noninvasive prenatal screening (NIPS) with predicted fetal sex chromosomes included in the results has become increasingly available for pregnant individuals. Predicted fetal sex chromosome results from NIPS are interpreted so as to equate sex chromosomes with sex and gender. As pediatric endocrinologists, we worry about how this use of NIPS harmfully reinforces sex and gender binaries and sets potentially inaccurate assumptions about what the identified chromosomes mean. We use a hypothetical case based on our clinical experience in which the NIPS report of fetal sex does not conform to expectations at birth to highlight ethical concerns surrounding this practice. The use of NIPS for fetal sex chromosome prediction has the potential to perpetuate stigma and bring psychological harm to parents and their future children, particularly those who are intersex, transgender, and gender diverse. The medical community should adopt an approach to the use of NIPS for fetal sex chromosome prediction that recognizes the spectrums of sex and gender to avoid reproducing stigma towards sex- and gender-diverse individuals and associated harms.

Analysis of Fetal Chromosome Abnormalities by Karyotpye

Prenatal screening is a crucial method employed during the fetal stage to detect and intervene early, thereby ensuring the health of newborn babies. This approach serves to enhance the overall quality of the population and mitigate the severe consequences associated with birth defects. Prenatal screening encompasses various techniques, including epidemiological investigations, fetal imaging ultrasound, maternal blood screening, and amniotic fluid screening by karotype technique. The process involves extracting fetal chromosomes from cells present in the amniotic fluid, followed by cell culture and hypotonic treatment. Subsequently, these chromosomes are stained with G-band and examined under a microscope. The results obtained from prenatal screening in a sample of 121 patients, with an average age of 32 ± 6.69, indicated that 21% of pregnant women had experienced a miscarriage, 23.1% had previously given birth to a malformed baby, 8.3% of families had a genetic disease, and 5% of parents exhibited chromosomal abnormalities. Among the 51 patients screened using the Double test, 26.45% of fetuses exhibited a high risk of birth defects, whereas the Tripple test identified a high risk in 9.09% of the 19 cases. Chromosome analysis of the 121 cases revealed that 15.7% of the fetuses exhibited chromosomal abnormalities, with Edwards syndrome accounting for 5.78%, Down syndrome accounting for 4.96%, chromosomal abnormalities accounting for 3.30%, Patau syndrome accounting for 0.83%, and Turner syndrome accounting for 0.83%. Age over 35 years (r = 0.08 and OR = 0.63), history of miscarriage (r = 0.05 and OR = 1.38), family history of hereditary disease (r = 0.04 and OR = 1.38), and parental chromosomal mutations (r = 0.01 and OR = 1.08) were all found to have a strong positive correlation with fetal abnormalities. Additionally, positive correlations were observed between the results of ultrasound screening (r = 0.22 and OR = 5.48) and blood screening (r = 0.14 and OR = 1.22).&#x0D; Prenatal screening, Amniocentesis, Karyotype, Chromosome, fetal chromosome.&#x0D; &#x0D; &#x0D;

P-520 Risk factors for early pregnancy loss in women undergoing in vitro fertilization-embryo transfer

Abstract Study question What are the risk factors for early pregnancy loss (EPL) in infertility patients undergoing in vitro fertilization-embryo transfer (IVF-ET) cycles? Summary answer The risk factors for EPL were maternal age, 14-day β-human chorionic gonadotrophin(β-hcg) levels and cycle type. What is known already Pregnancy obtained through assisted reproductive technology still has a high risk of spontaneous early pregnancy abortion, and the cause of which is unclear. It not only affects the rate of ongoing pregnancy and live birth, but also increases the psychological and economic burden of patients. At present, there have been many studies on the risk factors of early pregnancy loss in IVF/ICSI-ET at domestic and overseas, but the results are different, which may be related to the selection of different research objects, sample size and statistical methods. Study design, size, duration A retrospective study of 6107 embryo transfer cycles collected from January 2018 to December 2018 was performed. The cycles were divided into the EPL group (n = 987) and the live birth group (n = 5120) according to the cycle outcomes. Participants/materials, setting, methods Baseline data and clinically relevant indicators were compared between the two groups, including maternal age, infertility years, infertility type, body mass index (BMI), tubal factor, ovulatory dysfunction, endometriosis, male factor, antral follicle count (AFC), single gene related genetic disease, follicle-stimulating hormone (FSH), estradiol (E2), luteinizing hormone (LH), 14-day β-hcg levels, prolactin (PRL), progesterone (P), testosterone (T), anti-Müllerian hormone (AMH), cycle type and the number of transplanted embryos. Main results and the role of chance The EPL rate of the infertility patients undergoing fresh/frozen-thaw embryo transfer cycle was 16.16%. Univariate analysis showed that there were statistically significant differences between the two groups in maternal age, AFC, 14-day β-hcg levels, T, AMH, infertility years, cycle type, infertility types, chromosome disease and male factors (P &amp;lt; 0.05). The results of binary logistics regression analysis showed that maternal age, 14-day β-hcg levels and cycle type were related factors to EPL (P &amp;lt; 0.05). Limitations, reasons for caution This study lacked some baseline data, such as adverse pregnancy history, abortion history, and previous transplant failure history, and male factors such as BMI, age, semen results, smoking history. The information about fetal chromosomes was also missing. Wider implications of the findings Clinical prevention and treatment of risk factors can be targeted to improve pregnancy outcomes after transplantation. Trial registration number none

The Ongoing Challenge of Achieving Precise Diagnosis of Fetal Chromosome Disorders by FISH in Autopsies

The Ongoing Challenge of Achieving Precise Diagnosis of Fetal Chromosome Disorders by FISH in Autopsies

Prenatal diagnosis of non-mosaic sex chromosome abnormalities: a 10-year experience from a tertiary referral center.

The aim of this study was to explore the frequency and profile of non-mosaic sex chromosome abnormalities detected in prenatal diagnosis over the past 10 years. We retrospectively reviewed pregnancies diagnosed with non-mosaic sex chromosome abnormalities between January 2012 and December 2021, using karyotyping and/or single nucleotide polymorphism (SNP) array. Maternal age, indications for testing, and outcomes were recorded. Traditional karyotyping identified 269 (0.90 %) cases of non-mosaic sex chromosome abnormalities among 29,832 fetuses, including 249 cases of numerical abnormalities, 15 unbalanced structural abnormalities, and 5 balanced structural abnormalities. The overall detection rate of common sex chromosome aneuploidies (SCAs) was 0.81 %, with 47,XXY, 47,XXX, 47,XYY, and 45,X accounting for 0.32 , 0.19, 0.17, and 0.13 % respectively. All showed a fluctuating upward trend over the study period, except for 45,X. During the first five years (2012-2016), the major indication for testing was advanced maternal age (AMA), followed by abnormal ultrasound, abnormal noninvasive prenatal testing (NIPT), and abnormal maternal serum screening (MSS). In the second five years (2017-2021), the most frequent indication was abnormal NIPT, followed by AMA, abnormal ultrasound, and abnormal MSS. Among the 7,780 cases that underwent SNP array in parallel, an additional 29 clinically significant aberrations were detected. The most frequent aberration was a microdeletion in the Xp22.31 region, which was associated with X-linked ichthyosis. Fetal sex chromosome abnormalities are important findings in prenatal diagnosis. The application of NIPT and SNP array technology has greatly improved the detection of SCAs and submicroscopic aberrations associated with sex chromosomes.

Genetic counseling for fetal sex prediction by NIPT: Challenges and opportunities.

Non-invasive prenatal testing (NIPT) has grown in ubiquity in the last decade and is now endorsed by Society for Maternal Fetal Medicine and American College of Obstetricians and Gynecologists as a screening tool for aneuploidy in all patients. Past studies have demonstrated a tendency among obstetrics patients to focus on the ability of NIPT to predict fetal sex chromosomes; however, data on the experiences of genetic counselors (GCs) counseling on NIPT and fetal sex prediction are limited. This mixed-methods study aimed to explore how GCs counsel about NIPT and fetal sex prediction, as well as the use of gender-inclusive language in this setting. A 36-item survey with multiple choice, Likert scale, and open-ended questions was distributed to GCs who currently offer NIPT to patients. Quantitative data were analyzed using R and qualitative data were manually analyzed and coded via inductive content analysis. A total of 147 individuals completed at least some portion of the survey. A majority of participants (68.5%) reported frequent interchangeable use of the terms 'sex' and 'gender' by patients. A majority (72.9%) of participants reported that they rarely or never discuss the difference between these terms in sessions (Spearman's rho = 0.17, p = 0.052). Seventy-five respondents (59.5%) indicated that they had taken continuing education courses on inclusive clinical practices for trans and gender-diverse (TGD) patients. Several themes arose from free responses; the most frequently identified themes were the need for thorough pretest counseling that properly describes the scope of NIPT and the challenge of discrepant pretest counseling by other healthcare providers. Results from our research identified challenges and misconceptions GCs face when offering NIPT and various tactics implemented to mitigate these. Our study highlighted the need for the standardization of pretest counseling regarding NIPT, additional guidance from professional organizations, and continuing education focused on gender-inclusive language and clinical practices.

Clinical application of noninvasive prenatal testing in twin pregnancies: a single-centre experience

Objectives To evaluate the clinical efficiency of non-invasive prenatal testing (NIPT) for fetal chromosomal aneuploidy screening in twin pregnancies. Methods A total of 1650 women with twin pregnancies were enrolled in the study, which underwent NIPT at the Southwest Hospital, Army Medical University, Chongqing, China from January 2013 to June 2022. Fetal karyotyping analysis was conducted in high-risk patients, with subsequent follow-up on pregnancy outcomes. Results In 1650 pregnancies, NIPT results showed ten cases of the fetal chromosome aneuploidy, of which six cases were true positive and four cases were false positive. The sensitivity, specificity, positive predictive value (PPV), and false-positive rate (FPR) of trisomy 21 were 100%, 99.79%, 57.14%, and 0.18%, respectively. Sensitivity, specificity, PPV, and FPR of trisomy 18 were 100%, 99.94%, 50%, and 0.06%, respectively. The sensitivity, specificity, PPV, and FPR of trisomy 13 were 100%, 100%, 100%, and 0%, respectively. No false negatives were detected and the negative predictive value (NPV) was 100% of the total. Eleven pregnancies failed the NIPT test with no-call due to the low fetal fraction (< 4%). Conclusions NIPT is a high-performing routine primary prenatal screening test in twin pregnancies, with high sensitivity and specificity in screening for fetal aneuploidy.

The Impact of Isolated Increased Nuchal Translucency ≥95th Centile on Perinatal Outcome: A Prospective Cohort Study from a North Indian Genetic Center

Abstract Objectives The aim of this study was to determine the chromosomal abnormalities and other adverse outcomes like miscarriages, intrauterine deaths, structural defects, and genetic syndromes in fetuses with increased nuchal translucency (NT) more than or equal to 95th centile. This study also compared the outcomes in fetuses with NT between 95th and 99th centile and more than 99th centile. Study Design A prospective cohort of 182 patients with isolated increased NT was evaluated by invasive testing. Fetal chromosomes were examined by fluorescent in situ hybridization and karyotype or chromosomal microarray. Euploid pregnancies were followed-up with level II ultrasound and fetal echocardiography. For pregnancies progressing to delivery, the neonates were followed-up till the age of 3 months. Final outcome was reported as normal or abnormal. Collated data for perinatal outcomes was analyzed and compared between fetuses with NT 95th and 99th centile (group I) and NT more than 99th centile (group II). Results Of the 202 patients recruited, 182 patients consented for invasive testing and chromosomal analysis. Of the 182 patients, group I (NT 95–99th centile) included 92 patients and group II 90 patients. Chromosomal abnormalities were present in 50 (27.4%), 14 (7.6%) in group I, and 36 (19.4%) in group II. Of the 132 euploid pregnancies, adverse outcomes were present in 22 (16%) fetuses, 7 (5.3%) in group I, and 15(11.7%) in group II. A normal outcome was present in 110 (60.4%) pregnancies of the 182 fetuses with NT more than or equal to 95th centile. Normal outcome observed in group I was 77.1% and in group II, it was 43.4%. Conclusion An increased NT is associated with poor perinatal outcomes in 39.6% patients. Chromosomal analysis and follow-up for adverse outcome in fetuses with NT more than or equal to 95th centile is important to enable a take home neonatal rate of 60.4%. No pregnancy with increased NT should be discontinued without detailed fetal evaluation for genetic disorders, structural malformation, and fetal growth.

Maternal genetic polymorphisms in the major mitotic checkpoint genes MAD1L1 and MAD2L1 associated with the risk of survival in abnormal chromosomal fetuses.

Background: The genetic etiology of fetal chromosome abnormalities remains unknown, which brings about an enormous burden for patients, families, and society. The spindle assembly checkpoint (SAC) controls the normal procedure of chromosome disjunction and may take part in the process. Objective: The aim of this study was to explore the association between polymorphisms of MAD1L1 rs1801368 and MAD2L1 rs1283639804, involved in SAC and fetal chromosome abnormalities. Methods: The case-control study collected 563 cases and 813 health controls to test the genotypes of MAD1L1 rs1801368 and MAD2L1 rs1283639804 polymorphisms by polymerase chain reaction-restrictive fragment length polymorphism methods (PCR-RFLP). Results: MAD1L1 rs1801368 polymorphism was associated with fetal chromosome abnormalities alone or combined to lower homocysteine (HCY) levels (alone: dominant: OR: 1.75, 95%CI: 1.19-2.57, and p = 0.005; CT vs. CC: OR = 0.73, 95%CI: 0.57-0.94, and p = 0.016; lower HCY: C vs. T: OR = 0.74, 95%CI: 0.57-0.95, and p = 0.02; dominant: OR = 1.75, 95%CI: 0.79-1.92, and p = 0.005). No significant differences were found in other genetic models or subgroups (p > 0.05, respectively). MAD2L1 rs1283639804 polymorphism revealed a sole genotype in the studied population. HCY is significantly associated with fetal chromosome abnormalities in younger groups (OR: 1.78, 95%CI: 1.28-2.47, and p = 0.001). Conclusion: The results implied that the polymorphism of MAD1L1 rs1801368 may become the susceptibility factor to fetal chromosome abnormalities alone or combined to lower HCY levels but not to MAD2L1 rs1283639804 polymorphism. In addition, HCY significantly affects fetal chromosomal abnormalities in younger women.

Positive cfDNA screening results for 22q11.2 deletion syndrome-Clinical and laboratory considerations.

Introduction: Non-invasive prenatal screening (NIPS) via cell-free DNA (cfDNA) screens for fetal chromosome disorders using maternal plasma, including 22q11.2 deletion syndrome (22q11.2DS). While it is the commonest microdeletion syndrome and has potential implications for perinatal management, prenatal screening for 22q11.2DS carries some inherent technical, biological, and counseling challenges, including varying deletion sizes/locations, maternal 22q11.2 deletions, confirmatory test choice, and variable phenotype. Materials and methods: This study addresses these considerations utilizing a retrospective cohort of 307 samples with screen-positive 22q11.2 NIPS results on a massively parallel sequencing (MPS) platform. Results: Approximately half of the cases reported ultrasound findings at some point during pregnancy. In 63.2% of cases with diagnostic testing, observed positive predictive values were 90.7%-99.4%. cfDNA identified deletions ranging from <1Mb to 3.55Mb, with significant differences in confirmed fetal versus maternal deletion sizes; estimated cfDNA deletion size was highly concordant with microarray findings. Mosaicism ratio proved useful in predicting the origin of a deletion (fetal versus maternal). Prediction of deletion size, location, and origin may help guide confirmatory testing. Discussion: The data shows that MPS-based NIPS can screen for 22q11.2DS with a high PPV, and that collaboration between the laboratory and clinicians allows consideration of additional metrics that may guide diagnostic testing and subsequent management.