scholarly journals Adoption of a non-invasive prenatal test (NIPT) in prenatal screening in Moscow: first results

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Anton S. Olenev ◽  
Elena E. Baranova ◽  
Olesya V. Sagaydak ◽  
Alexandra M. Galaktionova ◽  
Ekaterina S. Kuznetsova ◽  
...  
Keyword(s):  
High Risk ◽  
Trisomy 21 ◽  
Sex Chromosome ◽  
Screening Method ◽  
Invasive Procedure ◽  
Trisomy 13 ◽  
Molecular Karyotyping ◽  
Chromosomal Anomalies ◽  
Maternal Weight ◽  
First Results

The objective — To assess the effectiveness of including NIPT in the structure of prenatal diagnostics in Moscow. Material and Methods — Totally 5,181 pregnancies undergoing screening for fetal trisomy using NIPT during the period from 01.04.2020 to 30.09.2020 in Russia. According to the results of biochemical blood test, the patients were divided into two groups: group of high risk (cut-off ≥1:100) (n=208) and group of intermediate risk (cut-off 1:101 – 1:2500) (n=4,973). Patients at high-risk cell-free DNA (cfDNA) were offered an invasive procedure, followed by genetic analysis (cytogenetic or molecular karyotyping). Results — Among the analysed samples, 117 (2.3%) had a high risk of the following common fetal chromosome abnormalities by NIPT: trisomy 21 in 50 cases, trisomy 18 in 17 cases, trisomy 13 in 5 cases, and sex chromosome aneuploidy (SCA) in 22 cases. Additionally, rare autosomal trisomies and/or subchromosomal arrangements were revealed in 23 cases. We found associations between cfDNA concentration and high risk of aneuploidies (particularly trisomy 21) and fetal sex and between low fetal fraction (FF) and body mass index (BMI) as well as maternal weight. Additionally, a high risk of trisomy 21 was associated with the term gestation. Conclusion — The effectiveness of technological resources that are based on cfDNA testing for detecting abnormal fetal chromosome numbers and other chromosomal anomalies is high and reduce rates of false positive results. Therefore, NIPT should be more widely used as a first-line screening method.

scholarly journals The Clinical Application of Non-invasive Prenatal Genetic Testing in the Screening of Fetal Chromosomal Diseases

2021 ◽  
Author(s):  
Yu Pang ◽  
chaohong wang ◽  
Junxiang Tang ◽  
Jiansheng Zhu
Keyword(s):  
High Risk ◽  
Clinical Application ◽  
Trisomy 21 ◽  
Sex Chromosome ◽  
Chromosomal Abnormalities ◽  
Reference Value ◽  
Prenatal Testing ◽  
Trisomy 13 ◽  
Non Invasive ◽  
Chromosome Aneuploidy

Abstract Objective：To explore the efficacy and clinical application value of non-invasive prenatal testing (non-invasive prenatal testing, NIPT) for screening fetal chromosomal abnormalities. Methods: NIPT was performed on 25,517 pregnant women. The high-risk samples were compared with amniotic fluid and cord blood chromosome karyotype analysis. Some samples were further verified by microarray (CMA), and pregnancy outcomes were followed up. Results: Of all the cases examined, 25502 cases were detected successfully, and a total of 294 high-risk samples (1.15%) were detected, of which further diagnosis was made in 208 cases, true positive samples were detected in 96 cases, and further tests were refused in 86 cases.71 cases (0.28%) of autosomal aneuploid high-risk samples were detected and 51 cases were diagnosed, including 44 cases of trisomy 21 (T21), 5 cases of trisomy 18 (T18), and 2 cases of trisomy 13 (T13). The PPV was 90.90%, 45.45% and 33.33%, respectively. Thirteen high-risk samples of trisomy 21, 18, and 13 were detected, and 1 case was confirmed as T21 mosaic PPV was 8.33% NPV was 100%. High-risk samples of sex chromosome aneuploidy (SCA) were detected in 72 cases (0.28%), 23 cases were diagnosed, and the PPV was 40.07%. The PPV was 12.00%, 50.00%, 72.73% and 75.00%, respectively, and the PPV was 12.00%, 50.00%, 72.73% and 75.00%, respectively. High-risk samples of copy number variation (CNV) were detected in 104 cases (0.41%), and 18 cases were diagnosed, with a PPV of 32.14%. Other high-risk samples of chromosome aneuploidy were detected in 34 cases (0.13%), and 3 cases were diagnosed as T2, T9, and T16, respectively. PPV is 8.70%.Conclusion: NIPT is suitable for trisomy 21, 18, and 13 screening, especially for T21. It also has a certain reference value for SCA and microdeletion and microduplication syndromes（MMS）, and it is not recommended for screening for other chromosomal aneuploidies.

scholarly journals Chances and Challenges of New Genetic Screening Technologies (NIPT) in Prenatal Medicine from a Clinical Perspective: A Narrative Review

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 501
Author(s):  
Ivonne Bedei ◽  
Aline Wolter ◽  
Axel Weber ◽  
Fabrizio Signore ◽  
Roland Axt-Fliedner
Keyword(s):  
Down Syndrome ◽  
Trisomy 21 ◽  
Maternal Age ◽  
Sex Chromosome ◽  
Screening Program ◽  
Diagnostic Yield ◽  
Screening Method ◽  
First Trimester ◽  
Diagnostic Methods ◽  
Trisomy 13

In 1959, 63 years after the death of John Langdon Down, Jérôme Lejeune discovered trisomy 21 as the genetic reason for Down syndrome. Screening for Down syndrome has been applied since the 1960s by using maternal age as the risk parameter. Since then, several advances have been made. First trimester screening, combining maternal age, maternal serum parameters and ultrasound findings, emerged in the 1990s with a detection rate (DR) of around 90–95% and a false positive rate (FPR) of around 5%, also looking for trisomy 13 and 18. With the development of high-resolution ultrasound, around 50% of fetal anomalies are now detected in the first trimester. Non-invasive prenatal testing (NIPT) for trisomy 21, 13 and 18 is a highly efficient screening method and has been applied as a first-line or a contingent screening approach all over the world since 2012, in some countries without a systematic screening program. Concomitant with the rise in technology, the possibility of screening for other genetic conditions by analysis of cfDNA, such as sex chromosome anomalies (SCAs), rare autosomal anomalies (RATs) and microdeletions and duplications, is offered by different providers to an often not preselected population of pregnant women. Most of the research in the field is done by commercial providers, and some of the tests are on the market without validated data on test performance. This raises difficulties in the counseling process and makes it nearly impossible to obtain informed consent. In parallel with the advent of new screening technologies, an expansion of diagnostic methods has begun to be applied after invasive procedures. The karyotype has been the gold standard for decades. Chromosomal microarrays (CMAs) able to detect deletions and duplications on a submicroscopic level have replaced the conventional karyotyping in many countries. Sequencing methods such as whole exome sequencing (WES) and whole genome sequencing (WGS) tremendously amplify the diagnostic yield in fetuses with ultrasound anomalies.

scholarly journals Evaluation of a novel screening method for fetal aneuploidy using cell-free DNA in maternal plasma

2019 ◽  
Vol 27 (1) ◽  
pp. 1-8
Author(s):  
Richard P Porreco ◽  
Matthew Sekedat ◽  
Allan Bombard ◽  
Thomas J Garite ◽  
Kimberly Maurel ◽  
...  
Keyword(s):  
Test Performance ◽  
Trisomy 21 ◽  
Sex Chromosome ◽  
Screening Method ◽  
Sequencing Technology ◽  
Cell Free Dna ◽  
Predictive Values ◽  
Fetal Aneuploidy ◽  
Free Dna ◽  
Equivalent Test

Objective To evaluate the test performance of a novel sequencing technology using molecular inversion probes applied to cell-free DNA screening for fetal aneuploidy. Methods Two cohorts were included in the evaluation; a risk-based cohort of women receiving diagnostic testing in the first and second trimesters was combined with stored samples from pregnancies with fetuses known to be aneuploid or euploid. All samples were blinded to testing personnel before being analyzed, and validation occurred after the study closed and results were merged. Results Using the new sequencing technology, 1414 samples were analyzed. The findings showed sensitivities and specificities for the common trisomies and the sex chromosome aneuploidies at >99% (Trisomy 21 sensitivity 99.2 CI 95.6–99.2; specificity 99.9 CI 99.6–99.9). Positive predictive values among the trisomies varied from 85.2% (Trisomy 18) to 99.0% (Trisomy 21), reflecting their prevalence rates in the study. Comparisons with a meta-analysis of recent cell-free DNA screening publications demonstrated equivalent test performance. Conclusion This new technology demonstrates equivalent test performance compared with alternative sequencing approaches, and demonstrates that each chromosome can be successfully interrogated using a single probe.

scholarly journals Efficiency of Non-invasive Prenatal Screening in Pregnant Women at Advanced Maternal Age

2020 ◽  
Author(s):  
Hui Zhu ◽  
Xiaoxiao Jin ◽  
Yuqing Xu ◽  
Weihua Zhang ◽  
Xiaodan Liu ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Predictive Value ◽  
Trisomy 21 ◽  
Maternal Age ◽  
Prenatal Screening ◽  
Screening Method ◽  
Advanced Maternal Age ◽  
Trisomy 13 ◽  
Sensitivity Specificity ◽  
Fetal Aneuploidies

Abstract Background To evaluate the efficiency of noninvasive prenatal screening (NIPS) in the prenatal screening for fetal aneuploidies in pregnant women at advanced maternal age (AMA). Methods From February 1, 2015, to December 31, 2018, 29,343 pregnant women at AMA underwent NIPS and followed-up were recruited. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for detecting fetal chromosomal aneuploidies were analyzed. The relationship between maternal age and common fetal chromosomal aneuploidy was observed. Results The sensitivity, specificity, PPV, NPV of NIPS for detecting fetal trisomy 21 were 99.11%, 99.96%, 90.98%, and 100%, respectively. These same parameters for detecting fetal trisomy 18 were 100%, 99.94%, 67.92%, and 100%, respectively. Finally, these parameters for detecting trisomy 13 were 100%, 99.96%, 27.78%, and 100%, respectively. The prevalence of fetal trisomy 21 increased with maternal age. There were significant differences in the prevalence of fetal trisomy 21 among the groups I (35-37-year-old), II (38-40-year-old) and III (41-year-old and older) (P < 0.05). Conclusion It is indicated that NIPS is an effective prenatal screening method in pregnant women at AMA.

scholarly journals Efficiency of Non-invasive Prenatal Screening in Pregnant Women at Advanced Maternal Age

2020 ◽  
Author(s):  
Hui Zhu ◽  
Xiaoxiao Jin ◽  
Yuqing Xu ◽  
Weihua Zhang ◽  
Xiaodan Liu ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Predictive Value ◽  
Trisomy 21 ◽  
Maternal Age ◽  
Prenatal Screening ◽  
Screening Method ◽  
Advanced Maternal Age ◽  
Trisomy 13 ◽  
Noninvasive Prenatal Screening ◽  
Fetal Aneuploidies

Abstract Background: To evaluate the efficiency of noninvasive prenatal screening (NIPS) in the prenatal screening for fetal aneuploidies in pregnant women at advanced maternal age (AMA). Results: From February 1, 2015, to December 31, 2018, 29,443 pregnant women at AMA underwent NIPS and followed-up were recruited. Their detailed clinical data and follow-up outcomes were collected and analyzed. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of NIPS for detecting fetal trisomy 21 were 99.11%, 99.96%, 90.98%, and 100%, respectively. These same parameters for detecting fetal trisomy 18 were 100%, 99.94%, 67.92%, and 100%, respectively. Finally, these parameters for detecting trisomy 13 were 100%, 99.96%, 27.78%, and 100%, respectively. The prevalence of fetal trisomy 21 increased with maternal age. There were significant differences in the prevalence of fetal trisomy 21 among the groups I (35-37-year-old), II (38-40-year-old) and III (41-year-old and older) ( P <0.05). Conclusion: It is indicated that NIPS is an effective prenatal screening method in pregnant women at AMA. Keywords: Advanced maternal age, Trisomy, Noninvasive prenatal screening, Fetal aneuploidies , Prenatal screening method

scholarly journals Isolated Echogenic Cardiac Focus: Assessing Association with Trisomy 21 by Combining Results from a Prenatal Center with a Bayesian Meta-Analysis

2019 ◽  
Vol 05 (03) ◽  
pp. E98-E106
Author(s):  
Elisabeth Wrede ◽  
Alexander Johannes Knippel ◽  
Pablo Emilio Verde ◽  
Ruediger Hammer ◽  
Peter Kozlowski
Keyword(s):  
Trisomy 21 ◽  
Meta Analysis ◽  
False Positive Rate ◽  
A Priori ◽  
Low Risk ◽  
Trisomy 13 ◽  
Chromosomal Anomalies ◽  
Second Trimester ◽  
Likelihood Ratios ◽  
Positive Rate

Abstract Objective To investigate the clinical relevance of an isolated echogenic cardiac focus (iECF) as a marker for trisomy 21 using a large second-trimester collective including a low-risk subgroup. Materials and Methods We retrospectively evaluated 1 25 211 pregnancies from 2000–2016 and analyzed all iECF cases with regard to chromosomal anomalies. It consisted of an early second-trimester collective from 14+0−17+6 weeks (n=34 791) and a second-trimester anomaly scan collective from 18+0–21+6 weeks. Two a priori risk subgroups (high and low risk) of the latter were built based on maternal age and previous screening test results using a cut-off of 1:300. Likelihood ratios (LR) of iECF for the detection of trisomy 21, trisomy 13, trisomy 18 and structural chromosomal anomalies were estimated. Results In total, 1 04 001 patients were included. An iECF was found in 4416 of 1 02 847 euploid fetuses (4.29%) and in 64 of 557 cases with trisomy 21 (11.49%) giving a positive LR of 2.68 (CI: 2.12–3.2). The sensitivity was 11.5% at a false-positive rate of 4.29% (CI:4.17–4.42) with p≤0.01%. In the high-and low-risk subgroups, the prevalence of iECF was comparable: 5.08% vs. 5.05%. The frequency of trisomy 21 was 0.39%, 98/24 979 vs 0.16%, 69/44 103. LR+was 3.86 (2.43–5.14) and 2.59 (1.05–4). For both subgroups the association of iECF with trisomy 21 was statistically significant. The prevalence of structural chromosomal anomalies in the second-trimester anomaly scan collective was 0.08% (52/68 967), of which 2 showed an iECF. Conclusion The detection of an iECF at the time of 14+0–21+6 weeks significantly increases the risk for trisomy 21 in the high-risk and in the low-risk subgroups and does not statistically change the risks for trisomy 13/18 or structural abnormalitie.

Non-invasive Prenatal Testing (NIPT)

2019 ◽  
Author(s):  
Courtney Manning ◽  
Mary-Alice Abbott
Keyword(s):  
High Risk ◽  
Screening Test ◽  
Sex Chromosome ◽  
Diagnostic Testing ◽  
Prenatal Testing ◽  
Trisomy 18 ◽  
Trisomy 13 ◽  
Non Invasive ◽  
Risk Result ◽  
Cell Free Fetal Dna

Non-invasive prenatal testing (NIPT) is a screening test that can determine if a pregnancy is at high risk for the common aneuploidies by analyzing cell-free fetal DNA in the maternal bloodstream. The screening includes trisomy 21, trisomy 18, and trisomy 13, with the option of screening for sex chromosome aneuploidy and fetal sex. Traditionally this testing is offered to women that are at high risk for these aneuploidies, most commonly women of advanced maternal age. Individuals that receive a high risk result on NIPT should be offered diagnostic testing to confirm the result. New forms of NIPT have recently emerged, however the use of this technology as a screening test for other genetic conditions is not currently recommended by national professional society guidelines. Patients should be counseled and consented for NIPT, as this is an optional screening test. This review contains 2 tables, and 39 references. Keywords: NIPT, non-invasive prenatal testing, aneuploidy, Down syndrome, trisomy 18, trisomy 13, Turner syndrome, microdeletions, diagnostic testing

PRENATAL DIAGNOSIS FOR TRISOMY 21, 18 AND 13 BY QUANTITATIVE FLUORESCENT POLYMERASE CHAIN REACTION AMONG PREGNANT WOMEN WITH HIGH RISK

2018 ◽  
Vol 8 (4) ◽  
pp. 88-95
Author(s):  
Thi Ha Thi Minh ◽  
Nghia Le Trung ◽  
Nhan Nguyen Viet ◽  
Duc Vo Van ◽  
Uyen Le Thanh Nha ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
High Risk ◽  
Pregnant Women ◽  
Trisomy 21 ◽  
Maternal Age ◽  
First Trimester ◽  
Nuchal Translucency ◽  
Trisomy 18 ◽  
Trisomy 13 ◽  
Β Hcg

Introduction: Prenatal diagnosis of trisomy 21, 18 and 13 plays a very important role in the improving population quality. This study was aimed at (1) Identifying the prevalence of trisomy 21, 18 and 13 by QFPCR from amniotic cells of high-risk pregnancies; and (2) Evaluating the association between diagnosed trisomies and some characteristics of mother and fetus. Objectives and methods: 170 pregnant women with high risk of having trisomy 21, 18 or 13 fetuses during first trimester screening (gestation age from 11 weeks to 13 weeks 6 days). DNA was extracted from amniocytes for prenatal diagnosis using QF-PCR. Results: The prevalence of trisomies was 9.4%, among which trisomy 21 and trisomy 18 accounted for 68.8% and 31.2%, respectively; none of them was trisomy 13. There was the significant association between diagnosed trisomies and maternal age (cut-off 30.5 years old) and nuchal translucency thickness (cut-off 1.95 mm). MoM median of free β-hCG increased in trisomy 21 group (4.35, p = 0.021) and decreased in trisomy 18 group (0.13, p < 0.001) as compared to the non-trisomy group (2.28). MoM median of serum PAPP-A decreased in trisomy 18 group (0.14, p = 0.004) as compared to the non-trisomy group (0.54). Conclusion: Prenatal diagnosis by QF-PCR detected remarkable prevalence of fetuses with trisomy 21 và 18. There was the significant association between diagnosed trisomies and maternal age, nuchal translucency thickness, free β-hCG and serum PAPP-A. Key words: prenatal diagnosis, trisomy, QF-PCR

scholarly journals Analysis of cell-free DNA in a consecutive series of 13,607 routine cases for the detection of fetal chromosomal aneuploidies in a single center in Germany

2020 ◽  
Author(s):  
Heike Borth ◽  
Anna Teubert ◽  
Ralf Glaubitz ◽  
Sarah Knippenberg ◽  
Nargül Kutur ◽  
...  
Keyword(s):  
High Risk ◽  
Failure Rate ◽  
Trisomy 21 ◽  
Trisomy 13 ◽  
Specific Method ◽  
Consecutive Series ◽  
Single Center ◽  
Monosomy X ◽  
Chromosomal Aneuploidies

Abstract Purpose Noninvasive prenatal testing (NIPT) is a highly sensitive and specific method for detection of fetal chromosomal aneuploidies from maternal plasma. The objective of this study was to determine the performance of a new paired-end sequencing-based NIPT assay in 13,607 pregnancies from a single center in Germany. Methods Samples from 13,607 pregnant women who previously underwent NIPT were analyzed using VeriSeq NIPT Solution v2 assay for presence of common fetal trisomies and monosomy X. Follow-up to determine clinical truth was carried out. Results Of the 13,607 cases, 13,509 received a NIPT call resulting in a low study failure rate of 0.72%. There were 188 (1.4%) high-risk calls: 117 trisomy 21, 34 trisomy 18, 23 trisomy 13, one trisomy 21 + 13, and 13 monosomy X. High sensitivities and specificities of ≥ 98.89% were reported for all four aneuploidy conditions. Of the high-risk cases, clinical follow-up data were available for 77.1% (145/188). Clinical follow-up of high-risk calls revealed an overall positive predictive value of 84.8% (potential range 65.4–88.3%). NIPT results were provided for samples across a range of fetal fractions, down to 2% fetal fraction. Conclusion The VeriSeq NIPT Solution v2 assay detected fetal chromosomal aneuploidies across a range of fetal fractions with high sensitivities and specificities observed based on known clinical outcomes, a high overall PPV, and a low failure rate.

scholarly journals Combined First-trimester Screening of Trisomy 21 in Women of Different Ages in Southwest Iran

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Mehran Dorostghoal ◽  
Mojgan Barati ◽  
Mojgan Harfsheno
Keyword(s):  
High Risk ◽  
Trisomy 21 ◽  
Maternal Age ◽  
Screening Method ◽  
First Trimester ◽  
First Trimester Screening ◽  
Cross Sectional ◽  
Different Ages ◽  
Trimester Screening ◽  
Southwest Iran

Background: There is evidence that the incidence of trisomy 21 has a direct linear relationship with maternal age, and older women are at a higher risk for giving birth to neonates with Down syndrome (DS). Objectives: The present study aimed to evaluate the performance and effectiveness of combined first-trimester screening (FTS) for DS in women of different ages in Southwest Iran. Methods: In this cross-sectional study, FTS was conducted on 7192 pregnant women in the 11th to 13th week of gestational age, referred to the Narges Medical Genetics and Prenatal Diagnosis Laboratory, Ahvaz, Iran. Amniocentesis and cytogenetic analysis were performed in all women with an estimated risk of 1 in 100 and above. Results: The FTS detection rate of DS was 83.3%, with the false positive rates of 2.1% and 13.5% in young women and those over 35 years, respectively. A significant correlation (r = 0.137, P < 0.001) was observed between the high risk of DS (1:100) and maternal age. The high risk of DS was found to be higher in women over 35 years of age than those under 35 years old (6.67% vs. 1.95%). Total DS prevalence was 2.64 per 1000 cases. The prevalence of DS in women under and over 35 years of age was 1.95 and 6.67 per 1000 pregnancies, respectively. Conclusions: First-trimester screening is an effective method for estimating the risk of DS in women under or over 35 years of age. Although an advanced maternal age is associated with a higher prevalence of DS, clinicians should recommend FTS as the first-line screening method regardless of maternal age.

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