Taiwanese Clinical Experience with Noninvasive Prenatal Testing for DiGeorge Syndrome

2021 ◽  
pp. 1-6
Author(s):  
Tzu-Yi Lin ◽  
T’sang-T’ang Hsieh ◽  
Po-Jen Cheng ◽  
Tai-Ho Hung ◽  
Kok-Seong Chan ◽  
...  
Keyword(s):  
High Risk ◽  
Digeorge Syndrome ◽  
Prenatal Testing ◽  
Cardiac Anomaly ◽  
Comparative Genomic ◽  
Noninvasive Prenatal Testing ◽  
Maternal Fetal Medicine ◽  
Chromosome 22Q11 ◽  
Predictive Rate

<b><i>Objective:</i></b> DiGeorge syndrome (DGS) is associated with microdeletions of chromosome 22q11. It is the second most common cause of congenital heart disease and is an important consideration whenever a conotruncal cardiac anomaly is identified. The availability of noninvasive prenatal testing (NIPT) is altering the practice of prenatal genetics and maternal-fetal medicine, resulting in a decline in invasive testing. Antenatal ultrasound and other biomarkers have their own limitation. NIPT was proposed to screen DGS with cell-free DNA in Taiwan. Here, we present our experience of prenatal diagnosis of DGS in our center. <b><i>Methods:</i></b> This was a retrospective study between November 1, 2019, and August 31, 2020, in Taiwan. Data were collected from 7,826 pregnant women self-referred for DGS screening with massive parallel shotgun sequencing-based NIPT. High-risk cases subsequently received amniocentesis for array comparative genomic hybridization (aCGH) to confirm the diagnosis. Characteristics of pregnancies were documented when participants received the test. Report of NIPT was completed 2 weeks after the test. Follow-up on high-risk cases was completed by telephone interview on January 30, 2021. <b><i>Results:</i></b> Thirteen cases showed high risk by NIPT, and 7 cases were confirmed by aCGH. The sensitivity and specificity were 100% (95% confidence interval [CI] 64.57–100.00%) and 99.92% (95% CI 99.83–99.96%). The prevalence of DGS was 1 in 1,118 pregnancies. The positive predictive rate was 53.85% (95% CI 29.14–76.79%). One true positive (TP) showed US anomaly, and 5 TPs selected termination. <b><i>Discussion/Conclusion:</i></b> NIPT demonstrated good performance in DGS screening. Detection of 22q11.2 deletion could be combined with routine screening to facilitate proper intervention.

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.

Attitudes and Knowledge of Maternal-Fetal Medicine Fellows Regarding Noninvasive Prenatal Testing

2015 ◽  
Vol 25 (1) ◽  
pp. 73-78 ◽  
Author(s):  
Paul Swaney ◽  
Emily Hardisty ◽  
Lauren Sayres ◽  
Samantha Wiegand ◽  
Neeta Vora
Keyword(s):  
Prenatal Testing ◽  
Noninvasive Prenatal Testing ◽  
Maternal Fetal Medicine ◽  
Fetal Medicine ◽  
Attitudes And Knowledge

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 Incidental Detection of Maternal Neoplasia in Noninvasive Prenatal Testing

2018 ◽  
Vol 64 (2) ◽  
pp. 329-335 ◽  
Author(s):  
Nilesh G Dharajiya ◽  
Daniel S Grosu ◽  
Daniel H Farkas ◽  
Ron M McCullough ◽  
Eyad Almasri ◽  
...  
Keyword(s):  
Clinical Laboratory ◽  
Controlled Trial ◽  
Uterine Fibroids ◽  
Prenatal Testing ◽  
Circulating Tumor Dna ◽  
Malignant Neoplasms ◽  
Noninvasive Prenatal Testing ◽  
Fetal Aneuploidy ◽  
Depth Analysis

Abstract BACKGROUND Noninvasive prenatal testing (NIPT) uses cell-free DNA (cfDNA) as an analyte to detect copy-number alterations in the fetal genome. Because maternal and fetal cfDNA contributions are comingled, changes in the maternal genome can manifest as abnormal NIPT results. Circulating tumor DNA (ctDNA) present in cases of maternal neoplasia has the potential to distort the NIPT readout to a degree that prevents interpretation, resulting in a nonreportable test result for fetal aneuploidy. METHODS NIPT cases that showed a distortion from normal euploid genomic representation were communicated to the caregiving physician as nonreportable for fetal aneuploidy. Follow-up information was subsequently collected for these cases. More than 450000 pregnant patients who submitted samples for clinical laboratory testing &gt;3 years are summarized. Additionally, in-depth analysis was performed for &gt;79000 research-consented samples. RESULTS In total, 55 nonreportable NIPT cases with altered genomic profiles were cataloged. Of these, 43 had additional information available to enable follow-up. A maternal neoplasm was confirmed in 40 of these cases: 18 malignant, 20 benign uterine fibroids, and 2 with radiological confirmation but without pathological classification. CONCLUSIONS In a population of pregnant women who submitted a blood sample for cfDNA testing, an abnormal genomic profile not consistent with fetal abnormalities was detected in about 10 out of 100000 cases. A subset of these observations (18 of 43; 41.9%) was attributed to maternal malignant neoplasms. These observational results suggest the need for a controlled trial to evaluate the potential of using cfDNA as an early biomarker of cancer.

scholarly journals Audit of the first > 7500 noninvasive prenatal aneuploidy tests in a Swiss genetics center

2021 ◽  
Author(s):  
Anahita Bajka ◽  
Michael Bajka ◽  
Fabian Chablais ◽  
Tilo Burkhardt
Keyword(s):  
Pregnancy Outcome ◽  
False Positive Rate ◽  
Prenatal Testing ◽  
Accurate Method ◽  
Test Results ◽  
Data Set ◽  
Single Nucleotide ◽  
Noninvasive Prenatal Testing ◽  
Positive Rate

Abstract Objectives Noninvasive prenatal testing (NIPT) is actually the most accurate method of screening for fetal chromosomal aberration (FCA). We used pregnancy outcome record to evaluate a complete data set of single nucleotide polymorphism-based test results performed by a Swiss genetics center. Materials and methods The Panorama® test assesses the risk of fetal trisomies (21, 18 and 13), gonosomal aneuploidy (GAN), triploidy or vanishing twins (VTT) and five different microdeletions (MD). We evaluated all 7549 test results meeting legal and quality requirements taken in women with nondonor singleton pregnancies between April 2013 and September 2016 classifying them as high or low risk. Follow-up ended after 9 months, data collection 7 months later. Results The Panorama® test provided conclusive results in 96.1% of cases, detecting 153 FCA: T21 n = 76, T18 n = 19, T13 n = 15, GAN n = 19, VTT n = 13 and MD n = 11 (overall prevalence 2.0%). Pregnancy outcome record was available for 68.6% of conclusive laboratory results, including 2.0% high-risk cases. In this cohort the Panorama® test exhibited 99.90% sensitivity for each trisomy; specificity was 99.90% for T21, 99.98% for T18 and 99.94% for T13. False positive rate was 0.10% for T21, 0.02% for T18 and 0.06% for T13. Conclusion SNP-based testing by a Swiss genetics center confirms the expected accuracy of NIPT in FCA detection.

scholarly journals Is heparin a placental anticoagulant in high-risk pregnancies?

Blood ◽  
2011 ◽  
Vol 118 (18) ◽  
pp. 4780-4788 ◽  
Author(s):  
John C. P. Kingdom ◽  
Sascha Drewlo
Keyword(s):  
High Risk ◽  
Intrauterine Growth Restriction ◽  
Prenatal Testing ◽  
Maternal Blood ◽  
Cellular Functions ◽  
Noninvasive Prenatal Testing ◽  
Beneficial Effects ◽  
Villous Trophoblast ◽  
Randomized Control ◽  
Pathology Data

Abstract Randomized control trials show beneficial effects of heparin in high-risk pregnancies to prevent preeclampsia and intrauterine growth restriction. However, the lack of placental pathology data in these trials challenges the assumption that heparin is a placental anticoagulant. Recent data show that placental infarction is probably associated with abnormalities in development of the placenta, characterized by poor maternal perfusion and an abnormal villous trophoblast compartment in contact with maternal blood, than with maternal thrombophilia. At-risk pregnancies may therefore be predicted by noninvasive prenatal testing of placental function in mid-pregnancy. Heparin has diverse cellular functions that include direct actions on the trophoblast. Dissecting the non–anticoagulant actions of heparin may indicate novel and safer therapeutic targets to prevent the major placental complications of pregnancy.

scholarly journals Noninvasive prenatal testing in routine clinical practice for a high-risk population

Medicine ◽  
2016 ◽  
Vol 95 (41) ◽  
pp. e5126 ◽  
Author(s):  
Guijie Qi ◽  
Jianping Yi ◽  
Baosheng Han ◽  
Heng Liu ◽  
Wanru Guo ◽  
...  
Keyword(s):  
Clinical Practice ◽  
High Risk ◽  
Prenatal Testing ◽  
Routine Clinical Practice ◽  
High Risk Population ◽  
Noninvasive Prenatal Testing ◽  
Risk Population

scholarly journals Next-generation sequencing: a follow-up of 36,913 singleton pregnancies with noninvasive prenatal testing in central China

2020 ◽  
Vol 37 (12) ◽  
pp. 3143-3150
Author(s):  
Wan Lu ◽  
Ting Huang ◽  
Xin-Rong Wang ◽  
Ji-Hui Zhou ◽  
Hui-Zhen Yuan ◽  
...  
Keyword(s):  
High Risk ◽  
Sex Chromosome ◽  
Chromosomal Abnormalities ◽  
False Positive Rate ◽  
Prenatal Testing ◽  
Central China ◽  
Jiangxi Province ◽  
Noninvasive Prenatal Testing ◽  
Predictive Values ◽  
Risk Pregnancy

Abstract Purpose To evaluate the noninvasive prenatal testing (NIPT) results of 36,913 cases in Jiangxi province of central China and explore its application value in prenatal screening and diagnosis. Methods This retrospective analysis included 36,913 singleton pregnant women who underwent NIPT because of moderate-/high-risk pregnancy or voluntary requirements between January 2017 and December 2019 in our hospital. Chromosomal abnormalities such as trisomies 21, 18, and 13 (T21, T18, T13) and sex chromosome aneuploidies (SCAs) were judged by standard Z-score analysis. Positive NIPT results were confirmed by amniocentesis and karyotyping. Pregnancy outcomes were followed up via telephone interview. Results A total of 1.01% (371/36,913) positive cases were detected by NIPT, comprising 137, 46, 31, and 157 cases of T21, T18, T13, and SCAs, respectively. A total of 116 of T21, 27 of T18, 13 of T13, and 51 of SCAs were confirmed to be true positive; all normal cases that had been followed up were verified to be true negative. The NIPT sensitivity in T21, T18, T13, and SCAs was 100.00% individually, whereas the specificity was 99.94% (36,488/36,509), 99.95% (36,579/36,598), 99.95% (36,594/36,612), and 99.72% (36,472/36,574), respectively. Furthermore, the negative predictive values of T21, T18, T13, and SCAs were all 100%, while the positive predictive values were 84.67%, 58.70%, 41.94%, and 33.33%, respectively. Conclusion NIPT is highly sensitive and has a low false positive rate in testing clinically significant fetal aneuploidies of general reproductive women. However, this technique cannot substitute for amniocentesis and karyotyping, and detailed genetic counseling is also essential for the high-risk group of NIPT.

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