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Diagnostics (Basel, Switzerland) Aug 2023Non-invasive prenatal testing was first discovered in 1988; it was primarily thought to be able to detect common aneuploidies, such as Patau syndrome (T13), Edward... (Review)
Review
Non-invasive prenatal testing was first discovered in 1988; it was primarily thought to be able to detect common aneuploidies, such as Patau syndrome (T13), Edward Syndrome (T18), and Down syndrome (T21). It comprises a simple technique involving the analysis of cell-free foetal DNA (cffDNA) obtained through maternal serum, using advances in next-generation sequencing. NIPT has shown promise as a simple and low-risk screening test, leading various governments and private organizations worldwide to dedicate significant resources towards its integration into national healthcare initiatives as well as the formation of consortia and research studies aimed at standardizing its implementation. This article aims to review the reliability of NIPT while discussing the current challenges prevalent among different communities worldwide.
PubMed: 37568933
DOI: 10.3390/diagnostics13152570 -
American Journal of Obstetrics and... Dec 2020
Review
Topics: Abortion, Induced; Craniofacial Abnormalities; Female; Hedgehog Proteins; Holoprosencephaly; Humans; Microarray Analysis; Pregnancy; Prognosis; Triploidy; Trisomy 13 Syndrome; Trisomy 18 Syndrome; Ultrasonography, Prenatal
PubMed: 33168217
DOI: 10.1016/j.ajog.2020.08.178 -
Pediatrics in Review Jan 2023
Topics: Humans; Trisomy 13 Syndrome; Trisomy
PubMed: 36587017
DOI: 10.1542/pir.2022-005517 -
American Journal of Medical Genetics.... Mar 2021Children with trisomy 13 and 18 (previously deemed "incompatible with life") are living longer, warranting a comprehensive overview of their unique comorbidities and... (Review)
Review
Children with trisomy 13 and 18 (previously deemed "incompatible with life") are living longer, warranting a comprehensive overview of their unique comorbidities and complex care needs. This Review Article provides a summation of the recent literature, informed by the study team's Interdisciplinary Trisomy Translational Program consisting of representatives from: cardiology, cardiothoracic surgery, neonatology, otolaryngology, intensive care, neurology, social work, chaplaincy, nursing, and palliative care. Medical interventions are discussed in the context of decisional-paradigms and whole-family considerations. The communication format, educational endeavors, and lessons learned from the study team's interdisciplinary care processes are shared with recognition of the potential for replication and implementation in other care settings.
Topics: Child Advocacy; Chromosomes, Human, Pair 18; Clinical Decision-Making; Developmental Disabilities; Enteral Nutrition; Female; Fetal Monitoring; Heart Defects, Congenital; Humans; Infant Food; Infant Nutrition Disorders; Infant, Newborn; Intensive Care, Neonatal; Interdisciplinary Communication; Life Expectancy; Male; Muscle Hypotonia; Neoplasms; Palliative Care; Patient Care Team; Prenatal Diagnosis; Professional-Family Relations; Trisomy; Trisomy 13 Syndrome
PubMed: 33381915
DOI: 10.1002/ajmg.a.62051 -
American Journal of Medical Genetics.... Dec 2019The aim of the study is to determine the prevalence, outcomes, and survival (among live births [LB]), in pregnancies diagnosed with trisomy 13 (T13) and 18 (T18), by...
The aim of the study is to determine the prevalence, outcomes, and survival (among live births [LB]), in pregnancies diagnosed with trisomy 13 (T13) and 18 (T18), by congenital anomaly register and region. Twenty-four population- and hospital-based birth defects surveillance registers from 18 countries, contributed data on T13 and T18 between 1974 and 2014 using a common data-reporting protocol. The mean total birth prevalence (i.e., LB, stillbirths, and elective termination of pregnancy for fetal anomalies [ETOPFA]) in the registers with ETOPFA (n = 15) for T13 was 1.68 (95% CI 1.3-2.06), and for T18 was 4.08 (95% CI 3.01-5.15), per 10,000 births. The prevalence varied among the various registers. The mean prevalence among LB in all registers for T13 was 0.55 (95%CI 0.38-0.72), and for T18 was 1.07 (95% CI 0.77-1.38), per 10,000 births. The median mortality in the first week of life was 48% for T13 and 42% for T18, across all registers, half of which occurred on the first day of life. Across 16 registers with complete 1-year follow-up, mortality in first year of life was 87% for T13 and 88% for T18. This study provides an international perspective on prevalence and mortality of T13 and T18. Overall outcomes and survival among LB were poor with about half of live born infants not surviving first week of life; nevertheless about 10% survived the first year of life. Prevalence and outcomes varied by country and termination policies. The study highlights the variation in screening, data collection, and reporting practices for these conditions.
Topics: Female; Humans; Live Birth; Mortality; Population Surveillance; Pregnancy; Pregnancy Outcome; Prenatal Diagnosis; Prevalence; Registries; Trisomy 13 Syndrome; Trisomy 18 Syndrome
PubMed: 31566869
DOI: 10.1002/ajmg.a.61365 -
American Journal of Human Genetics Dec 2019The Netherlands launched a nationwide implementation study on non-invasive prenatal testing (NIPT) as a first-tier test offered to all pregnant women. This started on...
The Netherlands launched a nationwide implementation study on non-invasive prenatal testing (NIPT) as a first-tier test offered to all pregnant women. This started on April 1, 2017 as the TRIDENT-2 study, licensed by the Dutch Ministry of Health. In the first year, NIPT was performed in 73,239 pregnancies (42% of all pregnancies), 7,239 (4%) chose first-trimester combined testing, and 54% did not participate. The number of trisomies 21 (239, 0.33%), 18 (49, 0.07%), and 13 (55, 0.08%) found in this study is comparable to earlier studies, but the Positive Predictive Values (PPV)-96% for trisomy 21, 98% for trisomy 18, and 53% for trisomy 13-were higher than expected. Findings other than trisomy 21, 18, or 13 were reported on request of the pregnant women; 78% of women chose to have these reported. The number of additional findings was 207 (0.36%); these included other trisomies (101, 0.18%, PPV 6%, many of the remaining 94% of cases are likely confined placental mosaics and possibly clinically significant), structural chromosomal aberrations (95, 0.16%, PPV 32%,) and complex abnormal profiles indicative of maternal malignancies (11, 0.02%, PPV 64%). The implementation of genome-wide NIPT is under debate because the benefits of detecting other fetal chromosomal aberrations must be balanced against the risks of discordant positives, parental anxiety, and a potential increase in (invasive) diagnostic procedures. Our first-year data, including clinical data and laboratory follow-up data, will fuel this debate. Furthermore, we describe how NIPT can successfully be embedded into a national screening program with a single chain for prenatal care including counseling, testing, and follow-up.
Topics: Adolescent; Adult; Chromosome Aberrations; Down Syndrome; Female; Follow-Up Studies; Genetic Testing; Genome, Human; Health Plan Implementation; Humans; Middle Aged; Netherlands; Pregnancy; Pregnancy Trimester, First; Prenatal Diagnosis; Prognosis; Trisomy 13 Syndrome; Trisomy 18 Syndrome; Young Adult
PubMed: 31708118
DOI: 10.1016/j.ajhg.2019.10.005 -
Science (New York, N.Y.) Sep 2019We report a robust, versatile approach called CRISPR live-cell fluorescent in situ hybridization (LiveFISH) using fluorescent oligonucleotides for genome tracking in a...
We report a robust, versatile approach called CRISPR live-cell fluorescent in situ hybridization (LiveFISH) using fluorescent oligonucleotides for genome tracking in a broad range of cell types, including primary cells. An intrinsic stability switch of CRISPR guide RNAs enables LiveFISH to accurately detect chromosomal disorders such as Patau syndrome in prenatal amniotic fluid cells and track multiple loci in human T lymphocytes. In addition, LiveFISH tracks the real-time movement of DNA double-strand breaks induced by CRISPR-Cas9-mediated editing and consequent chromosome translocations. Finally, by combining Cas9 and Cas13 systems, LiveFISH allows for simultaneous visualization of genomic DNA and RNA transcripts in living cells. The LiveFISH approach enables real-time live imaging of DNA and RNA during genome editing, transcription, and rearrangements in single cells.
Topics: CRISPR-Cas Systems; Cell Line, Tumor; DNA; DNA Breaks, Double-Stranded; Gene Editing; Genetic Vectors; HEK293 Cells; Humans; In Situ Hybridization, Fluorescence; Microscopy, Fluorescence; Molecular Imaging; RNA; RNA, Guide, CRISPR-Cas Systems; T-Lymphocytes
PubMed: 31488703
DOI: 10.1126/science.aax7852 -
Genetics in Medicine : Official Journal... Jul 2022Noninvasive prenatal screening (NIPS) using cell-free DNA has been assimilated into prenatal care. Prior studies examined clinical validity and technical performance in... (Review)
Review
PURPOSE
Noninvasive prenatal screening (NIPS) using cell-free DNA has been assimilated into prenatal care. Prior studies examined clinical validity and technical performance in high-risk populations. This systematic evidence review evaluates NIPS performance in a general-risk population.
METHODS
Medline (PubMed) and Embase were used to identify studies examining detection of Down syndrome (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosome aneuploidies, rare autosomal trisomies, copy number variants, and maternal conditions, as well as studies assessing the psychological impact of NIPS and the rate of subsequent diagnostic testing. Random-effects meta-analyses were used to calculate pooled estimates of NIPS performance (P < .05). Heterogeneity was investigated through subgroup analyses. Risk of bias was assessed.
RESULTS
A total of 87 studies met inclusion criteria. Diagnostic odds ratios were significant (P < .0001) for T21, T18, and T13 for singleton and twin pregnancies. NIPS was accurate (≥99.78%) in detecting sex chromosome aneuploidies. Performance for rare autosomal trisomies and copy number variants was variable. Use of NIPS reduced diagnostic tests by 31% to 79%. Conclusions regarding psychosocial outcomes could not be drawn owing to lack of data. Identification of maternal conditions was rare.
CONCLUSION
NIPS is a highly accurate screening method for T21, T18, and T13 in both singleton and twin pregnancies.
Topics: Cell-Free Nucleic Acids; Down Syndrome; Female; Humans; Noninvasive Prenatal Testing; Pregnancy; Prenatal Diagnosis; Sex Chromosome Aberrations; Trisomy; Trisomy 13 Syndrome; Trisomy 18 Syndrome
PubMed: 35608568
DOI: 10.1016/j.gim.2022.03.019 -
American Journal of Obstetrics and... Dec 2019
Topics: Acrocephalosyndactylia; Amniocentesis; Chorionic Villi Sampling; Ciliary Motility Disorders; Diagnosis, Differential; Encephalocele; Female; Genetic Testing; Humans; Imaging, Three-Dimensional; Microarray Analysis; Pallister-Hall Syndrome; Polycystic Kidney Diseases; Polydactyly; Pregnancy; Prognosis; Retinitis Pigmentosa; Sex Distribution; Smith-Lemli-Opitz Syndrome; Trisomy 13 Syndrome; Ultrasonography, Prenatal
PubMed: 31787158
DOI: 10.1016/j.ajog.2019.09.023