Noninvasive Prenatal Testing for Whole Fetal Chromosomal Aneuploidies: A Multicenter Prospective Cohort Trial in Taiwan

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.

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Expanded Noninvasive Prenatal Testing for Chromosomal aneuploidies and Copy Number Variants in a Cohort of 16128 Single Pregnancies

10.21203/rs.3.rs-810119/v1 ◽

2021 ◽

Author(s):

Jing He ◽

Xuan Feng ◽

Xing Wang ◽

Qinghua Zhang ◽

Lei Zheng ◽

...

Keyword(s):

Copy Number ◽

Chromosomal Abnormalities ◽

Copy Number Variants ◽

Prenatal Testing ◽

True Positive ◽

Noninvasive Prenatal Testing ◽

Cell Free Fetal Dna ◽

Monogenic Diseases ◽

Positive Rate ◽

Chromosomal Aneuploidies

Abstract Background: Noninvasive prenatal testing (NIPT) is based on second-generation genomic sequencing technology to scan cell-free fetal DNA originating from the placenta in maternal plasma. As the depth of sequencing increases, it can be used to focus on chromosomal aneuploidies, copy number variants (CNVs), and monogenic diseases. It can significantly improve the accuracy of prenatal screening and reduces the number of invasive testing.Methods: In this study, we retrospectively analyzed 16128 naturally conceived singleton pregnancies who underwent expanded NIPT to calculate the true positive rate (TPR) of chromosomal aneuploidies and CNVs, and analyzed the potential influence of maternal sex chromosome abnormalities (SCAs) and maternal CNVs on expanded NIPT results.Results: After invasive prenatal diagnosis and follow-up, 103 pregnancies were found to be true-positive, including 73 cases of chromosomal abnormalities and 30 cases of CNVs. The TPR of T21 was 84.62%, T18 was 50.00%, T13 was 22.22%, SCA was 34.06%, and CNVs was 40.28%. In addition, we found that the positive rate of aneuploidies increased with maternal age and that maternal SCAs accounted for 13.33% of the 60 false positive cases of SCAs.Conclusion: Expanded NIPT showed high sensitivity and specificity in detecting diseases of chromosomal abnormalities. It also shows good performance in detecting CNVs, but maternal SCAs and CNVs confused some NIPT results, indicating it is still necessary to study the potential maternal influence on expanded NIPT results and to report related clinical validation studies.

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Maternal Mosaicism Is a Significant Contributor to Discordant Sex Chromosomal Aneuploidies Associated with Noninvasive Prenatal Testing

Clinical Chemistry ◽

10.1373/clinchem.2013.215145 ◽

2014 ◽

Vol 60 (1) ◽

pp. 251-259 ◽

Cited By ~ 156

Author(s):

Yanlin Wang ◽

Yan Chen ◽

Feng Tian ◽

Jianguang Zhang ◽

Zhuo Song ◽

...

Keyword(s):

Sex Chromosome ◽

Massively Parallel Sequencing ◽

Prenatal Testing ◽

Maternal Plasma ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Noninvasive Prenatal Testing ◽

The Common ◽

Chromosomal Aneuploidies ◽

Sex Chromosome Aneuploidies

Abstract BACKGROUND In the human fetus, sex chromosome aneuploidies (SCAs) are as prevalent as the common autosomal trisomies 21, 18, and 13. Currently, most noninvasive prenatal tests (NIPTs) offer screening only for chromosomes 21, 18, and 13, because the sensitivity and specificity are markedly higher than for the sex chromosomes. Limited studies suggest that the reduced accuracy associated with detecting SCAs is due to confined placental, placental, or true fetal mosaicism. We hypothesized that an altered maternal karyotype may also be an important contributor to discordant SCA NIPT results. METHODS We developed a rapid karyotyping method that uses massively parallel sequencing to measure the degree of chromosome mosaicism. The method was validated with DNA models mimicking XXX and XO mosaicism and then applied to maternal white blood cell (WBC) DNA from patients with discordant SCA NIPT results. RESULTS Sequencing karyotyping detected chromosome X (ChrX) mosaicism as low as 5%, allowing an accurate assignment of the maternal X karyotype. In a prospective NIPT study, we showed that 16 (8.6%) of 181 positive SCAs were due to an abnormal maternal ChrX karyotype that masked the true contribution of the fetal ChrX DNA fraction. CONCLUSIONS The accuracy of NIPT for ChrX and ChrY can be improved substantially by integrating the results of maternal-plasma sequencing with those for maternal-WBC sequencing. The relatively high frequency of maternal mosaicism warrants mandatory WBC testing in both shotgun sequencing– and single-nucleotide polymorphism–based clinical NIPT after the finding of a potential fetal SCA.

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ENDOSONOGRAPHIC MEASUREMENTS OF TUMOR THICKNESS AND SURFACE AREA TO PREDICT TUMOR RESPONSE AFTER NEOADJUVANT CHEMORADIOTHERAPY IN PATIENTS WITH ESOPHAGEAL CANCER; A MULTICENTER PROSPECTIVE COHORT STUDY

10.1055/s-0038-1637200 ◽

2018 ◽

Author(s):

RD van der Bogt ◽

BJ Noordman ◽

KK Krishnadath ◽

CAM Roumans ◽

EJ Schoon ◽

...

Keyword(s):

Esophageal Cancer ◽

Cohort Study ◽

Surface Area ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Tumor Response ◽

Neoadjuvant Chemoradiotherapy ◽

Tumor Thickness ◽

Multicenter Prospective Cohort Study ◽

Multicenter Prospective Cohort

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Faculty Opinions recommendation of A multicenter prospective cohort study of quality of life and economic outcomes after cataract surgery in Vietnam: the VISIONARY study.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718488558.793497616 ◽

2014 ◽

Author(s):

Mark Packer

Keyword(s):

Quality Of Life ◽

Cohort Study ◽

Cataract Surgery ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Economic Outcomes ◽

Multicenter Prospective Cohort Study ◽

Multicenter Prospective Cohort

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Faculty Opinions recommendation of Long-term clinical outcomes of patients with invasive cutaneous squamous cell carcinoma treated with Mohs micrographic surgery: A 5-year, multicenter, prospective cohort study.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.736141837.793571075 ◽

2020 ◽

Author(s):

Desiree Ratner

Keyword(s):

Squamous Cell Carcinoma ◽

Cohort Study ◽

Cell Carcinoma ◽

Prospective Cohort ◽

Cutaneous Squamous Cell Carcinoma ◽

Mohs Micrographic Surgery ◽

Micrographic Surgery ◽

Multicenter Prospective Cohort Study ◽

Multicenter Prospective Cohort

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Parenting the Child With Down Syndrome: Understanding—but Going Beyond—the “Down Syndrome Advantage”

The Oxford Handbook of Down Syndrome and Development ◽

10.1093/oxfordhb/9780190645441.013.6 ◽

2020 ◽

Author(s):

Robert M. Hodapp ◽

Ellen G. Casale

Keyword(s):

Socioeconomic Status ◽

Down Syndrome ◽

Behavior Problems ◽

Prenatal Testing ◽

Children With Autism ◽

Facial Features ◽

Cultural Resources ◽

Noninvasive Prenatal Testing ◽

Birth Parents ◽

Children With Down Syndrome

Compared to parents of children with other types of intellectual disabilities, parents of children with Down syndrome experience less stress and more rewards, although this “Down syndrome advantage” mostly occurs compared to parents of children with autism and before groups are equated. Behaviorally, children with Down syndrome display more sociable interactional styles and baby-faced facial features, along with fewer instances of severe behavior problems. Demographically, parents of children with (versus without) Down syndrome average 5 years older when giving birth; parents are more often well educated, married, of higher socioeconomic status, and they likely provide these children greater financial and cultural resources. In most industrialized societies, rates of Down syndrome seem steady, with easily available, noninvasive prenatal testing counteracted by increasing numbers of women giving birth at older ages. Parenting children with Down syndrome relates to characteristics of children, their parents, and society, all of which intersect in important, underexplored ways.

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