scholarly journals Expanded noninvasive prenatal testing for fetal aneuploidy and copy number variations and parental willingness for invasive diagnosis in a cohort of 18,516 cases

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yunsheng Ge ◽  
Jia Li ◽  
Jianlong Zhuang ◽  
Jian Zhang ◽  
Yanru Huang ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
High Risk ◽  
Pregnant Women ◽  
Copy Number ◽  
Prenatal Testing ◽  
Copy Number Variations ◽  
Trisomy 13 ◽  
Noninvasive Prenatal Testing ◽  
Predictive Values ◽  
Parental Willingness

Abstract Background Noninvasive prenatal testing (NIPT) has been wildly used to screen for common aneuplodies. In recent years, the test has been expanded to detect rare autosomal aneuploidies (RATs) and copy number variations (CNVs). This study was performed to investigate the performance of expanded noninvasive prenatal testing (expanded NIPT) in screening for common trisomies, sex chromosomal aneuploidies (SCAs), rare autosomal aneuploidies (RATs), and copy number variations (CNVs) and parental willingness for invasive prenatal diagnosis in a Chinese prenatal diagnosis center. Methods A total of 24,702 pregnant women were retrospectively analyzed at the Women and Children’s Hospital from January 2013 to April 2019, among which expanded NIPT had been successfully conducted in 24,702 pregnant women. The high-risk expanded NIPT results were validated by karyotype analysis and chromosomal microarray analysis. All the tested pregnant women were followed up for pregnancy outcomes. Results Of the 24,702 cases, successful follow-up was conducted in 98.77% (401/446) of cases with common trisomies and SCAs, 91.95% (80/87) of RAT and CNV cases, and 76.25% (18,429/24,169) of cases with low-risk screening results. The sensitivity of expanded NIPT was 100% (95% confidence interval[CI], 97.38–100%), 96.67%(95%CI, 82.78–99.92%), and 100%(95%CI, 66.37–100.00%), and the specificity was 99.92%(95%CI, 99.87–99.96%), 99.96%(95%CI, 99.91–99.98%), and 99.88% (95%CI, 99.82–99.93%) for the detection of trisomies 21, 18, and 13, respectively. Expanded NIPT detected 45,X, 47,XXX, 47,XXY, XYY syndrome, RATs, and CNVs with positive predictive values of 25.49%, 75%, 94.12%, 76.19%, 6.45%, and 50%, respectively. The women carrying fetuses with Trisomy 21/Trisomy 18/Trisomy 13 underwent invasive prenatal diagnosis and terminated their pregnancies at higher rates than those at high risk for SCAs, RATs, and CNVs. Conclusions Our study demonstrates that the expanded NIPT detects fetal trisomies 21, 18, and 13 with high sensitivity and specificity. The accuracy of detecting SCAs, RATs, and CNVs is still relatively poor and needs to be improved. With a high-risk expanded NIPT result, the women at high risk for common trisomies are more likely to undergo invasive prenatal diagnosis procedures and terminate their pregnancies than those with unusual chromosome abnormalities.

scholarly journals Parental willing to take invasive diagnosis after Expanded Noninvasive Prenatal Testing (expanded NIPT) in a cohort of 24768 cases

2020 ◽  
Author(s):  
Yunsheng Ge ◽  
Jia Li ◽  
Jianlong Zhuang ◽  
Jian Zhang ◽  
Yanru Huang ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Prenatal Testing ◽  
High Sensitivity ◽  
Copy Number Variations ◽  
Noninvasive Prenatal Testing ◽  
Predictive Values ◽  
Prenatal Test ◽  
Xyy Syndrome ◽  
Chromosomal Aneuploidies

Abstract BackgroundThe main aims of the study were to investigate the performance of expanded noninvasive prenatal test (expanded NIPT) in screening for common trisomies, sex chromosomal aneuploidies (SCAs), rare autosomal aneuploidies (RATs) and copy number variations (CNVs) and parental willing to taking invasive prenatal diagnosis after expanded NIPT in China.ResultsOf the 24,736 cases, successful follow-up was conducted in 92.2% (411/446) cases. The sensitivity of expanded NIPT test was 98.61%,90.91% and 100% and specificity was 99.91%,99.95% and 99.87% for the detection of trisomies 21, 18 and 13 respectively. Expanded NIPT detected 45, XO, 47, XXX, 47, XXY, XYY syndrome, RATs and CNVs with positive predictive values of 57.39%, 19.61%, 75%, 79.41%, 77.78%, 10% and 56.25% respectively. The women carrying fetuses with T21/T18/T13 underwent invasive prenatal diagnosis and terminated their pregnancies at higher rates than those positive for SCAs, RATs and CNVs.ConclusionsOur study demonstrates that the expanded NIPT detects fetal trisomies 21,18 and 13 with high sensitivity and specificity. The accuracy of detecting SCAs, RATs and CNVs is still relatively poor and needed to be improved. With a positive expanded NIPT result, the women at high risk for common trisomies are more willing to take invasive prenatal diagnosis and terminate their pregnancies.* the first two authors contribute equally to this study.

scholarly journals A retrospective study of noninvasive prenatal testing for chromosome aneuploidies and subchromosomal copy number variations in 24359 single pregnancies

2020 ◽  
Author(s):  
yuefang Liu ◽  
Longfei Cheng ◽  
Yuan Peng ◽  
Zhe Liang ◽  
Xin Jin ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Copy Number ◽  
False Negative ◽  
Prenatal Testing ◽  
Clinical Information ◽  
Copy Number Variations ◽  
Trisomy 13 ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis

Abstract Background: With the development of whole-genome sequencing, small subchromosomal deletions and duplications could be found by non-invasive prenatal testing(NIPT). Our study is aimed to review the efficacy of NIPT as a screening test for aneuploidies and subchromosomal copy number variations (CNVs) in 24359 single pregnancies.Methods: A total of 24359 single pregnancies with different clinical features were retrospectively analyzed. Pathogenicity of abnormal NIPT results were assessed according to American College of Medical Genetics and Genomics(ACMG). Chromosome aneuploidies and subchromosomal CNVs were confirmed by karyotyping and chromosomal microarray analysis(CMA). Results: A total of 442 pregnancies (442/24359,1.9%) were with abnormal NIPT results. The positive predictive value (PPV) for trisomy 21(T21), trisomy 18 (T18), trisomy 13 (T13), and sex chromosome aneuploidies (SCAs) was 84.8%, 54.2%, 11.1% an 40.5% respectively. The PPV for subchromosomal CNVs was 59.0% (46/78). The clinical information, prenatal diagnosis results and follow-up results of 46 true positive cases, 6 cases with subchromosomal CNVs inconsistent with NIPT and 1 case of false negative were also demonstrated in detail.Conclusion: Our data have potential significance in demonstrating the significance of NIPT not only for common whole chromosome aneuploidies but also for subchromosomal CNV. Besides, the clinical information, prenatal diagnosis results and follow-up results of 52 cases with subchromosomal CNV and 1 case of false negative would provide important guidance for genetic counseling.

scholarly journals The Value of Non-Invasive Prenatal Testing in the Diagnosis of Birth Defects: Insights from a Large Multicentre Study in Southern China

2021 ◽  
Author(s):  
Meiying Cai ◽  
Na Lin ◽  
Xuemei Chen ◽  
Ying Li ◽  
Min Lin ◽  
...  
Keyword(s):  
Multicentre Study ◽  
Pregnant Women ◽  
Chromosomal Abnormalities ◽  
Southern China ◽  
Prenatal Testing ◽  
Copy Number Variations ◽  
Trisomy 13 ◽  
Detection Rates ◽  
Non Invasive ◽  
Large Multicentre Study

Abstract Non-invasive prenatal testing (NIPT) is a fast, safe, and non-disruptive diagnostic method. At present, few studies have evaluated the screening efficiency of NIPT positive predictive value (PPV) in study subjects. Here, the results of NIPT in pregnant women were retrospectively analysed, and the detection rate, PPV and follow-up data were evaluated to determine its clinical value. A large multicentre study was conducted involving 52,855 pregnant women who received NIPT. Based on gestational age, amniotic fluid or umbilical cord blood were extracted for simultaneous karyotype and chromosome microarray analysis (CMA) in NIPT-positive patients. Among the 52,855 cases, 754 were NIPT-positive, with a positivity rate of 1.4%. Karyotype analysis and/or CMA confirmed 323 cases of chromosomal abnormalities, with a PPV of 45.1%. PPV of Trisomy 21 (T21), Trisomy 18 (T18), Trisomy 13 (T13), sex chromosomal aneuploidies (SCA) and copy number variations (CNV) were 78.9%, 35.3%, 22.2%, 36.9% and 32.9%, respectively. The PPV of T21, T18, and T13 increased with age whereas, the PPV of SCA and CNVs had little correlation with age. The PPV was significantly high in patients with advanced age along with an abnormal ultrasound.NIPT had a high PPV for T21, and a low PPV for T13 and T18, while screening for SCA and CNVs showed clinical significance. However, in case of NIPT screening for SCA and CNVs, simultaneous karyotype and CMA should be performed to increase the detection rates. Interventional prenatal diagnosis is still required in NIPT-positive cases to avoid false positives or unnecessary termination of pregnancy.

scholarly journals Lower detectability of non-invasive prenatal testing compared to prenatal diagnosis in high-risk pregnant women

2019 ◽  
Vol 7 (14) ◽  
pp. 319-319 ◽  
Author(s):  
Jing Wang ◽  
Zhi-Wei Wang ◽  
Qin Zhou ◽  
Bin Zhang ◽  
Ting Yin ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
High Risk ◽  
Pregnant Women ◽  
Prenatal Testing ◽  
Non Invasive

scholarly journals Comprehensive Evaluation of Non-invasive Prenatal Screening to Detect Fetal Copy Number Variations

2021 ◽  
Vol 12 ◽  
Author(s):  
Jing Wang ◽  
Bin Zhang ◽  
Lingna Zhou ◽  
Qin Zhou ◽  
Yingping Chen ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Pregnant Women ◽  
Copy Number ◽  
Prenatal Screening ◽  
Comprehensive Evaluation ◽  
Copy Number Variations ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Non Invasive ◽  
Pathogenic Cnvs

ObjectiveTo evaluate the effectiveness of non-invasive prenatal screening (NIPS) in prenatal screening of fetal pathogenic copy number variants (CNVs).Materials and MethodsWe evaluated the prenatal screening capacity using traditional and retrospective approaches. For the traditional method, we evaluated 24,613 pregnant women who underwent NIPS; cases which fetal CNVs were suggested underwent prenatal diagnosis with chromosomal microarray analysis (CMA). For the retrospective method, we retrospectively evaluated 47 cases with fetal pathogenic CNVs by NIPS. A systematic literature search was performed to compare the evaluation efficiency.ResultsAmong the 24,613 pregnant women who received NIPS, 124 (0.50%) were suspected to have fetal CNVs. Of these, 66 women underwent prenatal diagnosis with CMA and 13 had true-positive results. The positive predictive value (PPV) of NIPS for fetal CNVs was 19.7%. Among 1,161 women who did not receive NIPS and underwent prenatal diagnosis by CMA, 47 were confirmed to have fetal pathogenic CNVs. Retesting with NIPS indicated that 24 of these 47 cases could also be detected by NIPS, representing a detection rate (DR) of 51.1%. In total, 10 publications, namely, six retrospective studies and four prospective studies, met our criteria and were selected for a detailed full-text review. The reported DRs were 61.10–97.70% and the PPVs were 36.11–80.56%. The sizes of CNVs were closely related to the accuracy of NIPS detection. The DR was 41.9% (13/31) in fetuses with CNVs ≤ 3 Mb, but was 55.0% (11/20) in fetuses with CNVs > 3 Mb. Finally, to intuitively show the CNVs accurately detected by NIPS, we mapped all CNVs to chromosomes according to their location, size, and characteristics. NIPS detected fetal CNVs in 2q13 and 4q35.ConclusionThe DR and PPV of NIPS for fetal CNVs were approximately 51.1% and 19.7%, respectively. Follow-up molecular prenatal diagnosis is recommended in cases where NIPS suggests fetal CNVs.

scholarly journals A Novel Graphic-Aided Algorithm (gNIPT) Improves the Accuracy of Noninvasive Prenatal Testing

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Qingwen Zhu ◽  
Jing Wang ◽  
Xiaoning Xu ◽  
Shiying Zhou ◽  
Zhengli Liao ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Copy Number ◽  
False Negative ◽  
Prenatal Testing ◽  
Maternal Blood ◽  
Negative Control ◽  
Trisomy 13 ◽  
Singleton Pregnancy ◽  
Noninvasive Prenatal Testing ◽  
Number Variation

Noninvasive Prenatal Testing (NIPT) has advanced the detection of fetal chromosomal aneuploidy by analyzing cell-free DNA in peripheral maternal blood. The statistic Z-test that it utilizes, which measures the deviation of each chromosome dosage from its negative control, is now widely accepted in clinical practice. However, when a chromosome has loss and gain regions which offset each other in the z-score calculation, merely using the Z-test for the result tends to be erroneous. To improve the performance of NIPT in this aspect, a novel graphic-aided algorithm (gNIPT) that requires no extra experiment procedures is reported in this study. In addition to the Z-test, this method provides a detailed analysis of each chromosome by dividing each chromosome into multiple 2 Mb size windows, calculating the z-score and copy number variation of each window, and visualizing the z-scores for each chromosome in a line chart. Data from 13537 singleton pregnancy women were analyzed and compared using both the normal NIPT (nNIPT) analysis and the gNIPT method. The gNIPT method had significantly improved the overall positive predictive value (PPV) of nNIPT (88.14% vs. 68.00%, p=0.0041) and the PPV for trisomy 21 (T21) detection (93.02% vs. 71.43%, p=0.0037). There were no significant differences between gNIPT and nNIPT in PPV for trisomy 18 (T18) detection (88.89% vs. 63.64%, p=0.1974) and in PPV for trisomy 13 (T13) detection (57.14% vs. 50.00%, p=0.8004). One false-negative T18 case in nNIPT was detected by gNIPT, which demonstrates the potency of gNIPT in discerning chromosomes that have variation in multiple regions with an offsetting effect in z-score calculation. The gNIPT was also able to detect copy number variation (CNV) in chromosomes, and one case with pathogenic CNV was detected during the study. With no additional test requirement, gNIPT presents a reasonable solution in improving the accuracy of normal NIPT.

scholarly journals Prenatal diagnosis of fetal chromosomal abnormalities among 2318 pregnant women with indications in southern China: a retrospective study

2020 ◽  
Author(s):  
Xiaodong Gu ◽  
Sudong Liu ◽  
Huaxian Wang ◽  
Ruiqiang Weng ◽  
Xuemin Guo ◽  
...  
Keyword(s):  
Cord Blood ◽  
Pregnant Women ◽  
Copy Number ◽  
Chromosomal Abnormalities ◽  
Southern China ◽  
Chorionic Villus ◽  
Prenatal Testing ◽  
Copy Number Variations ◽  
Chromosomal Anomalies ◽  
Chromosomal Polymorphisms

Abstract Background To investigate the frequency of fetal chromosomal abnormalities among women with abnormal ultrasound, abnormal biochemical marker screening or noninvasive prenatal testing results, advanced maternal age, or history of miscarriage in southern China. Methods We retrospectively analyzed prenatal samples from pregnant women between 2015 and 2019. Conventional karyotyping was performed using GTG banding. Copy number variation sequencing was used when indicated to identify chromosomal abnormalities. Results A total of 2,318 prenatal samples (188 chorionic villus samples, 2,003 amniotic fluids, and 127 cord blood) were analyzed. The frequency of chromosomal abnormalities was 12.4% (288/2,318) in prenatal samples, and frequency in chorionic villus samples (23.9%) was higher than in amniotic fluids (13.5%) and in cord blood (5.0%; P < 0.001). Numerical anomalies were detected in 195 (8.4%) cases and the most common abnormality were trisomy 21 (103/2,318; 4.4%), trisomy 18 (31/2,318; 1.3%) and monosomy X (18/2,318; 0.8%). Sructural anomalies were found in 29 (1.3%) cases, rare anomalies such as deletions (4 cases), duplications (2 cases), and complex rearrangement (1 case), were detected. Two cases with common chromosomal polymorphisms, inv(9)(p11q12) and inv(9)(p11q13), associated with recurrent spontaneous abortion, were detected. Five fetuses had normal karyotypes and definite pathogenic copy number variations, with microdeletions at 16p13.11, 16p12.1 (2 cases), and 17p12 and a microduplication at 7q11.23; all had normal phenotypes after birth. Conclusion Our study indicated that fetal chromosomal anomalies can be detected in early gestation and provided valuable information for interpretation of chromosomal polymorphisms and copy number variations.

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