Fetal Screening for Chromosomal Abnormalities

NeoReviews ◽  
2021 ◽  
Vol 22 (12) ◽  
pp. e805-e818
Author(s):  
Desiree G. Fiorentino ◽  
Francine Hughes
Keyword(s):  
Health Care Professionals ◽  
Genetic Screening ◽  
Chromosomal Abnormalities ◽  
Copy Number Variants ◽  
Accurate Method ◽  
Maternal Serum ◽  
Preimplantation Genetic Testing ◽  
Specific Test ◽  
Predictive Values ◽  
Reproductive Aged Women

With more and more reproductive-aged women opting to pursue genetic screening during pregnancy, health care professionals must understand the variety of testing options available as well as the advantages and limitations of each testing option. Presently, no single screening test is universally believed to be superior because the combination of the specific test and the population being tested determines the range of potential identifiable conditions as well as the positive predictive values. As a result, pre- and posttest counseling are not always straightforward and may require discussions with multiple specialists including genetic counselors, obstetricians, and pediatricians/neonatologists. The purpose of this review is to summarize the screening options currently available to pregnant women to determine their risk of having a child affected by a chromosomal disorder. Screening for chromosomal abnormalities using ultrasonography, maternal serum analytes, cell-free DNA, and preimplantation genetic testing will be discussed here. Advances in the field, including the possible future use of cell-based noninvasive prenatal screening (NIPS) as a more accurate method for genetic screening and the incorporation of screening for copy number variants (microdeletions and duplications) into traditional cell-free NIPS will also be reviewed.

scholarly journals Genome-wide cell-free DNA screening: a focus on copy-number variants

2021 ◽  
Author(s):  
Jill Rafalko ◽  
Erica Soster ◽  
Samantha Caldwell ◽  
Eyad Almasri ◽  
Thomas Westover ◽  
...  
Keyword(s):  
Copy Number ◽  
Chromosomal Abnormalities ◽  
Diagnostic Testing ◽  
Copy Number Variants ◽  
Cell Free Dna ◽  
Predictive Values ◽  
Free Dna ◽  
Genome Wide ◽  
Cfdna Screening ◽  
Diagnostic Outcomes

Abstract Purpose Of 86,902 prenatal genome-wide cell-free DNA (cfDNA) screening tests, 4,121 were positive for a chromosome abnormality. This study examines 490 cases screen-positive for one or more subchromosomal copy-number variants (CNV) from genome-wide cfDNA screening. Methods Cases positive for one or more subchromosomal CNV from genome-wide cfDNA screening and diagnostic outcomes were compiled. Diagnostic testing trends were analyzed, positive predictive values (PPVs) were calculated, and the type of chromosomal abnormalities ultimately confirmed by diagnostic testing were described. Results CNVs were identified in 0.56% of screened specimens. Of the 490 cases screen-positive for one or more CNV, diagnostic outcomes were available for 244 cases (50%). The overall PPV among the cases with diagnostic outcomes was 74.2% (95% CI: 68.1–79.5%) and 71.8% (95% CI: 65.5–77.4%) for “fetal-only” events. Overall, isolated CNVs showed a lower PPV of 61.0% (95% CI: 52.5–68.8%) compared to complex CNVs at 93.9% (95% CI: 86.6–97.5%). Isolated deletions/duplications and unbalanced structural rearrangements were the most common diagnostic outcomes when isolated and complex CNVs were identified by cfDNA screening, respectively. Conclusion Genome-wide cfDNA screening identifies chromosomal abnormalities beyond the scope of traditional cfDNA screening, and the overall PPV associated with subchromosomal CNVs in cases with diagnostic outcomes was >70%.

Improving diagnosis of acute appendicitis with atypical findings by Tc-99m HMPAO leukocyte scan

2002 ◽  
Vol 41 (01) ◽  
pp. 37-41 ◽  
Author(s):  
S. Shung-Shung ◽  
S. Yu-Chien ◽  
Y. Mei-Due ◽  
W. Hwei-Chung ◽  
A. Kao
Keyword(s):  
Acute Appendicitis ◽  
False Positive ◽  
False Positive Rate ◽  
Accurate Method ◽  
Clinical Findings ◽  
Pathological Findings ◽  
Lower Quadrant ◽  
Predictive Values ◽  
Positive Rate

Summary Aim: Even with careful observation, the overall false-positive rate of laparotomy remains 10-15% when acute appendicitis was suspected. Therefore, the clinical efficacy of Tc-99m HMPAO labeled leukocyte (TC-WBC) scan for the diagnosis of acute appendicitis in patients presenting with atypical clinical findings is assessed. Patients and Methods: Eighty patients presenting with acute abdominal pain and possible acute appendicitis but atypical findings were included in this study. After intravenous injection of TC-WBC, serial anterior abdominal/pelvic images at 30, 60, 120 and 240 min with 800k counts were obtained with a gamma camera. Any abnormal localization of radioactivity in the right lower quadrant of the abdomen, equal to or greater than bone marrow activity, was considered as a positive scan. Results: 36 out of 49 patients showing positive TC-WBC scans received appendectomy. They all proved to have positive pathological findings. Five positive TC-WBC were not related to acute appendicitis, because of other pathological lesions. Eight patients were not operated and clinical follow-up after one month revealed no acute abdominal condition. Three of 31 patients with negative TC-WBC scans received appendectomy. They also presented positive pathological findings. The remaining 28 patients did not receive operations and revealed no evidence of appendicitis after at least one month of follow-up. The overall sensitivity, specificity, accuracy, positive and negative predictive values for TC-WBC scan to diagnose acute appendicitis were 92, 78, 86, 82, and 90%, respectively. Conclusion: TC-WBC scan provides a rapid and highly accurate method for the diagnosis of acute appendicitis in patients with equivocal clinical examination. It proved useful in reducing the false-positive rate of laparotomy and shortens the time necessary for clinical observation.

scholarly journals Performance of Cell-Free DNA Screening for Fetal Common Aneuploidies and Sex Chromosomal Abnormalities: A Prospective Study from a Less Developed Autonomous Region in Mainland China

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 478
Author(s):  
Yunli Lai ◽  
Xiaofan Zhu ◽  
Sheng He ◽  
Zirui Dong ◽  
Yanqing Tang ◽  
...  
Keyword(s):  
Sex Chromosome ◽  
Chromosomal Abnormalities ◽  
False Negative ◽  
Prenatal Testing ◽  
Read Depth ◽  
Trisomy 13 ◽  
Prognostic Information ◽  
Aneuploidy Screening ◽  
Predictive Values ◽  
Risk Result

To evaluate the performance of noninvasive prenatal screening (NIPS) in the detection of common aneuploidies in a population-based study, a total of 86,262 single pregnancies referred for NIPS were prospectively recruited. Among 86,193 pregnancies with reportable results, follow-up was successfully conducted in 1160 fetuses reported with a high-risk result by NIPS and 82,511 cases (95.7%) with a low-risk result. The screen-positive rate (SPR) of common aneuploidies and sex chromosome abnormalities (SCAs) provided by NIPS were 0.7% (586/83,671) and 0.6% (505/83,671), respectively. The positive predictive values (PPVs) for Trisomy 21, Trisomy 18, Trisomy 13 and SCAs were calculated as 89.7%, 84.0%, 52.6% and 38.0%, respectively. In addition, less rare chromosomal abnormalities, including copy number variants (CNVs), were detected, compared with those reported by NIPS with higher read-depth. Among these rare abnormalities, only 23.2% (13/56) were confirmed by prenatal diagnosis. In total, four common trisomy cases were found to be false negative, resulting in a rate of 0.48/10,000 (4/83,671). In summary, this study conducted in an underdeveloped region with limited support for the new technology development and lack of cost-effective prenatal testing demonstrates the importance of implementing routine aneuploidy screening in the public sector for providing early detection and precise prognostic information.

Genetic Screening in Infertile Mexican Men: Chromosomal Abnormalities, Y Chromosome Deletions, and Androgen Receptor CAG Repeat Length

2008 ◽  
Vol 29 (6) ◽  
pp. 654-660 ◽  
Author(s):  
S. G. Martinez-Garza ◽  
M. C. Gallegos-Rivas ◽  
M. Vargas-Maciel ◽  
J. M. Rubio-Rubio ◽  
M. E. de los Monteros-Rodriguez ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Y Chromosome ◽  
Genetic Screening ◽  
Chromosomal Abnormalities ◽  
Repeat Length ◽  
Cag Repeat ◽  
Chromosome Deletions ◽  
Mexican Men

scholarly journals False Positive Values of Biomarkers of Prenatal Screening on Chromosomopathy as Indicators of a Risky Pregnancy

2011 ◽  
Vol 30 (2) ◽  
pp. 126-130 ◽  
Author(s):  
Jasmina Durković ◽  
Luka Anđelić ◽  
Bojana Mandić ◽  
Denis Lazar
Keyword(s):  
Genetic Screening ◽  
False Positive ◽  
Prenatal Screening ◽  
Protein A ◽  
First Trimester ◽  
Maternal Serum ◽  
Fetal Hypoxia ◽  
Beta Hcg ◽  
First Trimester Of Pregnancy ◽  
Fetal Karyotype

False Positive Values of Biomarkers of Prenatal Screening on Chromosomopathy as Indicators of a Risky PregnancyGenetic screening on chromosomopathy has been performed on 2000 pregnant women in their first trimester of pregnancy by determining Pregnancy associated plasma protein-A and free-beta HCG biomarkers in maternal serum. After obtaining a normal fetal karyotype, the pathological values of the biomarkers have been correlated with other pregnancy disorders, and the possible causes of the positive genetic screening have been tested. 340 false positive biomarkers (17%) have been detected. The increased free-beta HCG (48.24%) had a significant influence. A significant correlation (p > 0.01) between the increased free-beta HCG and bleeding during pregnancy has been established. Complications occurred in 78.52% pregnancies with pathological biomarkers, MISSed in 13.82%, miscarriages in 10.88%, induced pregnancy terminations caused by fetal anomalies in 8.82% and births with disturbed fetal vitality in 45%. The research results have shown a significant correlation (p > 0.01) between the increased value of the free-beta HCG biomarkers and fetal hypoxia. The false positive genetic screening, caused by the increased free-beta HCG, can indicate placental dysfunction and fetal vitality disruption.

scholarly journals Design and reporting considerations for genetic screening tests

2019 ◽  
Author(s):  
Jill Hagenkord ◽  
Birgit Funke ◽  
Emily Qian ◽  
Madhuri Hegde ◽  
Kevin B Jacobs ◽  
...  
Keyword(s):  
Genetic Screening ◽  
World Health ◽  
Screening Tests ◽  
Clinical Indication ◽  
Test Design ◽  
Design Strategies ◽  
Predictive Values ◽  
Inherited Diseases ◽  
Health Communities ◽  
Health Organization

Testing asymptomatic individuals for unsuspected conditions is not new to the medical and public health communities and protocols to develop screening tests are well-established. However, the application of screening principles to inherited diseases presents unique challenges. Unlike most screening tests, the natural history and disease prevalence of most rare inherited diseases in an unselected population are unknown. It is difficult or impossible to obtain a “truth set” cohort for clinical validation studies. As a result, it is not possible to accurately calculate clinical positive and negative predictive values for “likely pathogenic” genetic variants, which are commonly returned in genetic screening assays. In addition, many of the genetic conditions included in screening panels do not have clinical confirmatory tests. All of these elements are typically required to justify the development of a screening test, according to the World Health Organization screening principles. Nevertheless, as the cost of DNA sequencing continues to fall, more individuals are opting to undergo genomic testing in the absence of a clinical indication. Despite the challenges, reasonable estimates can be deduced and used to inform test design strategies. Here, we review test design principles and apply them to genetic screening.

scholarly journals Design and reporting considerations for genetic screening tests

2019 ◽  
Author(s):  
Jill Hagenkord ◽  
Birgit Funke ◽  
Emily Qian ◽  
Madhuri Hegde ◽  
Kevin B Jacobs ◽  
...  
Keyword(s):  
Genetic Screening ◽  
World Health ◽  
Screening Tests ◽  
Clinical Indication ◽  
Test Design ◽  
Design Strategies ◽  
Predictive Values ◽  
Inherited Diseases ◽  
Health Communities ◽  
Health Organization

Testing asymptomatic individuals for unsuspected conditions is not new to the medical and public health communities and protocols to develop screening tests are well-established. However, the application of screening principles to inherited diseases presents unique challenges. Unlike most screening tests, the natural history and disease prevalence of most rare inherited diseases in an unselected population are unknown. It is difficult or impossible to obtain a “truth set” cohort for clinical validation studies. As a result, it is not possible to accurately calculate clinical positive and negative predictive values for “likely pathogenic” genetic variants, which are commonly returned in genetic screening assays. In addition, many of the genetic conditions included in screening panels do not have clinical confirmatory tests. All of these elements are typically required to justify the development of a screening test, according to the World Health Organization screening principles. Nevertheless, as the cost of DNA sequencing continues to fall, more individuals are opting to undergo genomic testing in the absence of a clinical indication. Despite the challenges, reasonable estimates can be deduced and used to inform test design strategies. Here, we review test design principles and apply them to genetic screening.

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