scholarly journals Follow-up in Patients With Non-invasive Prenatal Screening Failures: A Reflection on the Choice of Further Prenatal Diagnosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Sha Liu ◽  
Hongqian Liu ◽  
Jianlong Liu ◽  
Ting Bai ◽  
Xiaosha Jing ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Prenatal Diagnosis ◽  
Pregnant Women ◽  
Prenatal Screening ◽  
Chromosomal Abnormalities ◽  
Detection Methods ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Non Invasive

BackgroundOur aim was to provide a theoretical basis for clinicians to conduct genetic counseling and choose further prenatal diagnosis methods for pregnant women who failed non-invasive prenatal screening (NIPS).MethodsA retrospective analysis was performed on pregnant women who had failed NIPS tests.ResultsAmong the 123,291 samples, 394 pregnant women did not obtain valid results due to test failures. A total of 378 pregnant women were available for follow-up, while 16 patients were lost to follow-up. Of these 378, 135 pregnant women chose further prenatal diagnosis through amniocentesis, and one case of dysplasia was recalled for postpartum chromosome testing. The incidence rate of congenital chromosomal abnormalities in those who failed the NIPS was 3.97% (15/378), which was higher than that of the chromosomal abnormalities in the common population (1.8%). Among the pregnant women who received prenatal diagnosis, the positive rates of chromosomal abnormalities in the chromosomal microarray analysis/copy number variation sequencing (CMA/CNV-seq) group and in the karyotyping group were 15.28 and 4.76%, respectively.ConclusionPrenatal diagnosis should be strongly recommended in posttest genetic counseling for pregnant women with NIPS failures. Further, high-resolution detection methods should be recommended for additional prenatal diagnoses.

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 Analysis of Prenatal Diagnosis Results and Pregnancy Outcome of Non-invasive Prenatal Screening High-risk Fetuses

2020 ◽  
Author(s):  
Yan Luo ◽  
Yanmei Sun ◽  
Haishen Tian ◽  
Hezhen Lu ◽  
Lishuang Ma ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
High Risk ◽  
Pregnant Women ◽  
Clinical Significance ◽  
Prenatal Screening ◽  
Trisomy 13 ◽  
Chromosomal Microarray Analysis ◽  
Non Invasive ◽  
Chromosomal Karyotype

Abstract BackgroundWith the development of whole-genome sequencing, small chromosomal deletions and duplications could be found by NIPT. This study is to evaluate the clinical significance of fetal chromosomal karyotype analysis and chromosomal microarray analysis (CMA) to clarify the clinical significance of 528 cases of high-throughput sequencing noninvasive prenatal screening suggesting high-risk cases. MethodsNon-invasive prenatal screening showed that the fetus 21, 18, 13, sex chromosomes, and other chromosomes are at high risk of aneuploidy and fetal chromosome copy number variations (CNVs) are at high risk, requiring prenatal diagnosis Pregnant women are the research objects. After obtaining informed consent, fetal cells were obtained by amniocentesis or umbilical vein puncture for chromosomal karyotype and CMA analysis. All cases of childbirth were followed up by telephone over a period of 1 year.Results Among 528 fetuses, 447 were at high risk of aneuploidy. The positive predictive value (PPV) for trisomy 21(T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosome aneuploidies (SCAs), and other chromosome aneuploidy was 85.24%, 51.52%, 12.5%, 50.82%, and 5.88% respectively. Another 81 cases of non-invasive prenatal screening suggest CNVs High risk. The PPV for CNVs was 34.57% .Among them, CNVs has a clear pathogenic significance can reach 24.69% . Follow-up of childbirth cases: Of the 62 pregnant women diagnosed with fetal SCA, 13 chose to continue their pregnancy, and the overall continued pregnancy rate was 20.97% (13/62); CNVs has no clear significance/no disease reported in 8 cases, 1 case After being lost to follow-up, all 7 cases chose to continue their pregnancy. One of the children was not informed about the specific situation; one girl had six fingers on both hands, and the rest had no abnormal growth; the remaining five children developed normally. ConclusionThis study has obtained relatively reliable PPV data for NIPT screening for chromosomal aneuploidy, which provides a reliable basis for clinical genetic counseling and treatment; it is recommended to perform prenatal diagnosis and perform chromosomal nucleus when non-invasive and high-risk prompts suspicious chromosomal abnormalities (over/under/microdeletion/microduplication). Type and CMA inspection, so that the inspection is more comprehensive and not easy to miss the diagnosis.

scholarly journals Prenatal diagnosis of 2193 pregnant women with invasive indications for chromosomal abnormalities in southern China: a retrospective study

2020 ◽  
Author(s):  
Xiaodong Gu ◽  
Sudong Liu ◽  
Huaxian Wang ◽  
Ruiqiang Weng ◽  
Xuemin Guo ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
High Risk ◽  
Pregnant Women ◽  
Genetic Screening ◽  
Prenatal Screening ◽  
Chromosomal Abnormalities ◽  
Prenatal Testing ◽  
Chromosome Abnormalities ◽  
Screening Methods ◽  
Non Invasive

Abstract Background: Although a variety of non-invasive techniques are used for prenatal genetic screening and diagnosis, our knowledge remains limited regarding the relationship between high-risk prenatal indications and fetal chromosomal abnormalities.Methods: We retrospectively investigated the prenatal genetic screening and karyotype analysis results of pregnant women who had undergone invasive prenatal testing in Prenatal Diagnosis Department of Meizhou People’s Hospital during Jan. 1, 2015 to Dec. 31, 2019. We analyzed the frequencies of chromosome abnormalities in women with high-risk indications.Results: A total of 2,193 pregnant women who had underwent invasive prenatal testing were included in our analysis. Chromosomal abnormalities occurred in 10.3% of these women, and rate increased with maternal age (P < 0.001). The frequencies of chromosome abnormalities varied for women with different high-risk indications, which was 10.3% (226/2193) for abnormal ultrasound results, 3.3% (31/938) for positive serum screening test results, 61.4% (78/127) for positive NIPT results, 9.3% (13/140) for AMA and 11.1% (10/90) for obstetric/family history. Follow up data showed that 380 pregnant women opted for termination the pregnancy, including 211 (55.5%) due to karyotype abnormalities and 169 (45.5%) due to abnormal ultrasonic outcomes.Conclusion: Our data suggested that the prenatal screening methods have high false positive rates. NIPT is the most accurate non-invasive prenatal screening. Apart from karyotype abnormality, abnormal ultrasound results alone accounted for a big part of pregnancy termination.

scholarly journals Diagnostic accuracy and value of chromosomal microarray analysis for chromosomal abnormalities in prenatal detection: a prospective clinical study

2020 ◽  
Author(s):  
Hailong Huang ◽  
Yan Wang ◽  
Min Zhang ◽  
Na Lin ◽  
Gang An ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Microarray Analysis ◽  
Operating Characteristic ◽  
Chromosomal Abnormalities ◽  
Area Under The Curve ◽  
Diagnostic Value ◽  
Chromosomal Microarray ◽  
Prospective Clinical Study ◽  
Chromosomal Microarray Analysis ◽  
Success Rates

Abstract Background Chromosomal microarray analysis (CMA) has emerged as a primary diagnostic tool for the evaluation of developmental delay and structural malformations in children. The aim of this study was to compare the accuracy and diagnostic value of CMA and karyotyping on chromosomal abnormalities in Fujian province of South China. Methods In the study, 410 samples were obtained from pregnant women between March 2015 and December 2016, including 3 villus (0.73%, 3/410), 296 amniotic fluid (72.20%, 296/410), and 111 umbilical cord blood (27.07%, 111/410). Each sample was screening for chromosomal abnormalities by both using CMA and karyotyping. Results The success rates of CMA and karyotyping were 100% (410/410) and 99.27% (407/410), respectively. 61 (14.88%, 61/410) samples were presented with chromosomal abnormalities using CMA, whereas 47 (11.46%, 47/410) samples were shown with chromosomal abnormalities using karyotyping. 31 (7.56%, 31/410) samples with normal karyotypes were found to have chromosomal abnormalities using CMA. Receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) of CMA on the diagnosis of chromosomal abnormalities was 0.93, with 90.68% sensitivity and 94.40% specificity. The AUC of karyotyping on the diagnosis of chromosomal abnormalities was 0.90, with 87.56% sensitivity and 91.22% specificity. Conclusions Our data demonstrated that CMA has a better diagnostic value for screening chromosomal abnormalities, especially for pregnant women with normal karyotypes.

scholarly journals The Genetic Etiology Diagnosis of Fetal Growth Restriction Using Single-Nucleotide Polymorphism-Based Chromosomal Microarray Analysis

2021 ◽  
Vol 9 ◽  
Author(s):  
Yu'e Chen ◽  
Yingjun Xie ◽  
Yuying Jiang ◽  
Qi Luo ◽  
Lijing Shi ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Microarray Analysis ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Detection Rate ◽  
Chromosomal Abnormalities ◽  
Karyotype Analysis ◽  
Growth Restriction ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis

Background: An increase in pathogenic copy number variants (pCNVs) has been recognized to associate with fetal growth restriction (FGR). Here, we aim to explore the application value of chromosomal microarray analysis (CMA) in prenatal diagnosis of FGR.Methods: Prenatal ultrasound was applied to identify FGR. A total of 149 pregnant women with FGR were enrolled in our study. All subjects underwent karyotype analysis and CMA to reveal the chromosomal abnormalities.Results: In this study, all subjects were successfully detected by karyotype and CMA analyses. Of these subjects, the chromosomal abnormalities detection rate was 5.37% (8/149) for karyotyping and 13.42% (20/149) for CMA, respectively. Among them, an 8.05% (12/149) incremental yield of CMA over karyotype analysis was observed (p = 0.004). In addition, a significant difference of pCNV detection rate was observed between the groups with different high-risk factors (p = 0.005). The FGR with structural anomalies group showed the highest pCNV detection rate (33.33%), followed by the FGR with non-structural anomalies group (8.77%) and the isolated FGR group (8.06%).Conclusion: In conclusion, CMA technology showed an effective application value in etiology diagnosis of FGR. We believe that CMA should be recommended as first-line detection technology for prenatal diagnosis in FGR.

Non-invasive prenatal screening of fetal sex chromosomal abnormalities: perspective of pregnant women

2012 ◽  
Vol 25 (12) ◽  
pp. 2616-2619 ◽  
Author(s):  
Tze Kin Lau ◽  
Mei Ki Chan ◽  
Pui Shan Salome Lo ◽  
Hon Yee Connie Chan ◽  
WaiSze Kim Chan ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Prenatal Screening ◽  
Chromosomal Abnormalities ◽  
Fetal Sex ◽  
Non Invasive

scholarly journals Prenatal diagnosis of 4953 pregnant women with indications for genetic amniocentesis in Northeast China

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Rulin Dai ◽  
Yang Yu ◽  
Qi Xi ◽  
Xiaonan Hu ◽  
Haibo Zhu ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Pregnant Women ◽  
Northeast China ◽  
Prenatal Screening ◽  
Chromosomal Abnormalities ◽  
False Negative ◽  
Screening Methods ◽  
Serological Screening ◽  
Diagnostic Center ◽  
Positive Results

Abstract Background Several different technologies are used for prenatal screening procedures and genetic diagnostic technologies. We aimed to investigate the rates of chromosomal abnormalities in cases with different abnormal prenatal indications and to determine the relationships between fetal chromosomal abnormalities and indicators of prenatal abnormalities in Northeast China. Methods We evaluated 4953 16- to 23-week singleton gestation cases using amniocentesis and a total of 3583 participants received serological screening. Fetal chromosomal analyses were performed for all samples using fluorescence in situ hybridization and karyotyping. Results Among these samples, 204 (4.12%) had fetal chromosomal abnormalities. A total of 3583 participants received serological screening, among whom 102 (2.85%) exhibited positive results. A total of 309 participants had ultrasonography; 42 (13.6%) of these had abnormalities. Among 97 participants who had non-invasive prenatal testing (NIPT), 59 (61%) had positive results. Among 1265 participants with advanced maternal age, 78 (6.2%) had abnormal results. Conclusion The serological screening and NIPT that were included in the prenatal screening methods all had false positive and false negative rates. Although they are both prenatal screening techniques, maternal serum screening cannot be replaced by NIPT. The pregnancy women should accept NIPT in a qualified prenatal diagnostic center. We recommend that pregnant women at high or critical risk undergoing prenatal screening should confirm the fetal karyotype through amniocentesis. Moreover, if women receive a positive result via NIPT, they should not have a pregnancy termination without undergoing further prenatal diagnosis.

scholarly journals Chromosomal Abnormality in Fetuses with Isolated Antenatal Hydronephrosis: Update for Prenatal Diagnosis and Genetic Counseling

2020 ◽  
Author(s):  
Xiaoyan Zhou ◽  
Yan Wang ◽  
Lulu Meng ◽  
Jianxin Tan ◽  
Fengchang Qiao ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Chromosomal Abnormalities ◽  
Genetic Diagnosis ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Detection Rates ◽  
Antenatal Hydronephrosis ◽  
Prenatal Genetic Diagnosis ◽  
Group A ◽  
Group B

Abstract Background: The prenatal finding of fetuses with antenatal hydronephrosis (ANH) gives a significant dilemma for the clinicians. Which patients require invasive prenatal diagnosis? Though previous literatures have recommended the use of chromosomal microarray analysis (CMA)for fetuses with CAKUT, the cutoff value for CMA have no current consensus on fetuses with ANH. In this article, we aimed to detect chromosomal abnormalities in fetuses with isolated severe ANH (anterior-posterior renal pelvic diameter (APRPD) ≥ 10mm) by CMA, summarized the literatures and proposed recommendations for the prenatal genetic diagnosis according to APRPD.Methods: Fetuses (n=84) with isolated severe ANH (APRPD ≥ 10mm) were evaluated by CMA. According to APRPD measurements at second trimester, we classified the cases into two groups: (1) Group A: cases with APRPD of 10–15 mm(N=57); (2) Group B: cases with APRPD ≥ 15 mm(N=27).The prenatal and postnatal outcomes were assessed by ultrasonic examination and telephone follow-up.Results: Overall, one case with 18 trisomy was identified. Clinically significant copy number variants (pathogenic or likely pathogenic CNVs) were identified in 11.9% (10/84) cases, including 3.5% (3/84) of pathogenic CNVs. The detection rates were 5.2% (3/57), 25.9% (7/27) for group A and group B, respectively. There was statistically significant differences in the frequency of clinic significant CNVs in the two groups (p＜0.05). Conclusion: CMA is valuable in prenatal genetic diagnosis of fetuses with severe ANH（APRPD ≥ 10mm）, regardless of whether other ultrasonic abnormalities were observed. This cohort should be followed up during the pregnancy.

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 Application of Chromosome Microarray Analysis and Karyotype Analysis in Diagnostic Assessment of Abnormal Down's Syndrome Screening Results

2021 ◽  
Author(s):  
Han Kang ◽  
Lingxi Wang ◽  
Xingyu Li ◽  
Chonglan Gao ◽  
Yamei Xie ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Pregnant Women ◽  
Microarray Analysis ◽  
Sex Chromosome ◽  
Karyotype Analysis ◽  
Down's Syndrome ◽  
Down’S Syndrome ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Balanced Translocation

Abstract Background: Although screening for fetal aneuploidy with the use of cell-free DNA obtained from maternal plasma is highly effective, biomarkers screening is in extensive use in economically underdeveloped areas and poor population. This study aims to explore the application value of chromosomal microarray analysis (CMA) and karyotype analysis in prenatal diagnosis for pregnant women with abnormal Down’s syndrome (DS) screening results.Methods: The study recruited 813 pregnant women with abnormal DS screening results from Chengdu Women’s and Children’s Central Hospital. They underwent amniocentesis to obtain fetal amniotic fluid for CMA and G-band karyotype analysis. An Affymetrix CytoScan 750 K Array chip was used for CMA analysis according to the manufacturer’s instructions.Results: In total, CMA identified 21/813 abnormal results, which was more efficient than karyotype analysis(10/813, P<0.001.) CMA is equivalent to traditional karyotype analysis for the prenatal diagnosis of aneuploidies. However, CMA identified 1.60% more copy number variants(CNVs) than karyotype analysis. These pathogenic/likely pathogenic(P/LP) CNVs ranged from 159Kb deletion to 3616Kb deletion. 53.8% of them were recurrent pathogenic CNVs associated with risk of neurodevelopmental disorders. CMA identified 7 variants of uncertain significance (VUS) results, including 6 microduplication and 1 microdeletion, with the size ranged from 840kb-1484kb. Karyotype analysis identified 2 mosaic sex chromosome aneuploidy, 2 balanced translocation and 1 mosaic balanced translocation, which could not be identified by CMA. Conclusions: Performing both CMA and karyotype analysis simultaneously is more beneficial to pregnant women with abnormal DS screening results.

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