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180 hot topic(s) found with the query "Prenatal testing"

Prenatal Genome-Wide Sequencing analysis (Exome or Genome) in detecting pathogenic Single Nucleotide Variants in fetal Central Nervous System Anomalies: systematic review and meta-analysis.
Enrica Marchionni et al. Eur J Hum Genet 2024 3 (Posted: Mar 18, 2024 9AM)

From the abstract: "Prenatal Exome (pES) or Genome (pGS) Sequencing analysis showed a significant incremental diagnostic yield over karyotype and chromosomal microarray analysis (CMA) in fetal structural anomalies. Optimized indications and detection rates in different fetal anomalies are still under investigation. The aim of this study was to assess the incremental diagnostic yield in prenatally diagnosed Central Nervous System (CNS) anomalies. Meta-analysis showed a substantial diagnostic improvement in performing Prenatal Genome-Wide Sequencing analysis (Exome or Genome) over karyotype and CMA in CNS anomalies. "

Detection of chromosomal abnormalities and monogenic variants in fetal cfDNA for prenatal diagnosis.
et al. Nat Med 2024 2 (Posted: Feb 16, 2024 4PM)

From the abstract: " In a prospective study involving 1,090 high-risk pregnancies, a comprehensive screening test of fetal cell-free DNA successfully detected pathogenic aneuploidies, microdeletions and monogenic variants linked to fetal anomalies. The inclusion of monogenic conditions alongside chromosomal abnormalities in this test resulted in a 60.7% increase in the detection rate for suspected fetal structural abnormalities."

Prospective prenatal cell-free DNA screening for genetic conditions of heterogenous etiologies.
Jinglan Zhang et al. Nat Med 2024 1 (Posted: Jan 23, 2024 7AM)

From the abstract: "In this multicenter and observational study, pregnant women at elevated risk for fetal genetic conditions were enrolled for a cfDNA screening test based on coordinative allele-aware target enrichment sequencing. This test encompasses the following three of the most frequent pathogenic genetic variations: aneuploidies, microdeletions and monogenic variants. The cfDNA screening results were compared to invasive prenatal or postnatal diagnostic test results for 1,090 qualified participants. The comprehensive cfDNA screening detected a genetic alteration in 135 pregnancies with 98.5% sensitivity and 99.3% specificity relative to standard diagnostics. "

Prenatal Genetic Testing Is Rapidly Evolving. Here’s Why That Matters.
M Holmes, Huffington Post, January 12, 2024 (Posted: Jan 14, 2024 10AM)

From the article: " In the context of pregnancy, the role of DNA testing is to uncover genetic disease in a fetus. (An additional bonus for parents is learning the baby’s sex, which many are eager to know.) Unfortunately, genetic testing in pregnancy often isn’t as conclusive or uncomplicated as the DNA testing police use to determine whether someone was at the scene of a crime."

Psychological impact of additional findings detected by genome-wide Non-Invasive Prenatal Testing (NIPT): TRIDENT-2 study
IM Bakkeren et al, EJHG, December 7, 2023 (Posted: Dec 07, 2023 8AM)

From the abstract: "A total of 227 (56.5%) women completed the questionnaire. Most (60.2%) chose to know additional findings because they wanted as much information as possible about the health of their fetus. Almost all (92%) stated that receiving the additional finding was unexpected, a shock, and/or they were in disbelief, for 85% it caused a lot of worry. Post-test, high anxiety (STAI) levels were reported in 15.5% of women, and 7.5% reported severe distress (IES). Women who gave birth to an affected child (n?=?10) experienced most psychological impact (STAI and IES). Eighty-six percent of women with a fetal aberration would opt for additional findings again, compared to 49.2% of women whose result was confined to the placenta. "

Ready or not, genomic screening of fetuses is already here
NB Gold et al, Genetics in Medicine, October 17, 2023 (Posted: Oct 17, 2023 9AM)

From the paper: "Over the past decade, genomic sequencing has transformed our ability to provide diagnoses for fetuses who have abnormal imaging findings. The diagnostic yield of exome sequencing is 31% in fetuses with sonographic abnormalities who previously had a non-diagnostic karyotype and chromosomal microarray; this yield is even higher in fetuses with specific anomalies. Among apparently healthy fetuses and those with minor sonographic differences, one study found that 2.9%, or approximately 1 in 35, harbored pathogenic or likely pathogenic genetic variants. "

The completion of indicated paternal prenatal genetic and carrier testing at a public hospital in Los Angeles, California
MT Nguyen et al, Genet in Med Open, September 2023 (Posted: Sep 05, 2023 9AM)

From the abstract: "In this primarily low-income, publicly insured, Spanish-speaking population, we identified 98 pregnancies for which partner genetic screening or testing was indicated. Only 26.5% (n=26) completed testing, which did not vary by indication, parental age, parental race, parity, or primary language. Completion of partner genetic screening or testing was significantly linked to earlier gestational age at referral for genetic counseling (19.1 versus 21.5 weeks, p=0.006). Less than one-third of pregnancies received indicated partner genetic screening or testing. Early referral to genetic counseling may improve partner testing completion rates, which could avoid invasive and unnecessary diagnostic testing in the pregnant patient."

Screening during IVF for inherited diseases can greatly reduce costs of care
L Flynn, MedicalXpress, July 2023 (Posted: Jul 10, 2023 7AM)

For prospective parents who are carriers of many inherited diseases, using in vitro fertilization along with genetic testing would significantly lower health care expenditures, according to a new study. Preimplantation genetic diagnostic testing during IVF, or PGD-IVF, is now being used to screen for single-gene defect conditions such as cystic fibrosis, sickle cell disease and Tay-Sachs disease, along with nearly 400 others.

Limitations, concerns and potential: attitudes of healthcare professionals toward preimplantation genetic testing using polygenic risk scores
M Siermann et al, EJHG, March 20, 2023 (Posted: Mar 21, 2023 9AM)

We found that most healthcare professionals were concerned about the prematurity of introducing PGT-P into clinical practice. They had various ethical considerations, such as concerns related to validity and utility of PGT-P, limited embryos and options, and difficulties for prospective parents regarding comprehension and informed decision-making. Positive aspects were also identified, e.g., regarding reproductive autonomy and potential health benefits. Overall, most healthcare professionals considered that clinical implementation of PGT-P is premature.

Cell-Free Fetal DNA and Non-Invasive Prenatal Diagnosis of Chromosomopathies and Pediatric Monogenic Diseases: A Critical Appraisal and Medicolegal Remarks
S Gullo et al. J Per Med, December 17, 2022 (Posted: Dec 20, 2022 8AM)

Noninvasive prenatal screening (NIPS) for fetal chromosome abnormalities in a general-risk population: An evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG)
JS Dungan et al, Genetics in Medicine, December 16, 2022 (Posted: Dec 16, 2022 9AM)

Evidence consistently demonstrated improved accuracy of NIPS compared with traditional screening methods for trisomies 21, 18, and 13 in singleton and twin gestations. Identification of rare autosomal trisomies and other microdeletion syndromes with NIPS is an emerging area of interest. ACMG strongly recommends NIPS over traditional screening methods for all pregnant patients with singleton and twin gestations for fetal trisomies 21, 18, and 13 and strongly recommends NIPS be offered to patients to screen for fetal sex chromosome aneuploidy.

Experiences of pregnant women with genome-wide non-invasive prenatal testing in a national screening program
KRM van der Meij et al, EJHG, December 9, 2022 (Posted: Dec 09, 2022 6AM)

Pregnant women’s perspectives should be included in the dialogue surrounding the expanding offers of non-invasive prenatal testing (NIPT), especially now that technological possibilities are rapidly increasing. This study evaluated women’s experiences with the offer of genome-wide (GW) first-tier NIPT in a national screening program. A nationwide pre-and post-test questionnaire was completed by 473 pregnant women choosing between targeted NIPT (trisomies 21, 18 and 13 only) and GW-NIPT (also other findings) within the Dutch TRIDENT-2 study.

Maternal carrier screening with single-gene NIPS provides accurate fetal risk assessments for recessive conditions.
Hoskovec Jennifer et al. Genetics in medicine : official journal of the American College of Medical Genetics 2022 12 (Posted: Dec 02, 2022 6AM)

The purpose of this study was to evaluate the clinical performance of carrier screening for cystic fibrosis, hemoglobinopathies, and spinal muscular atrophy with reflex single-gene noninvasive prenatal screening (sgNIPS), which does not require paternal carrier screening. An unselected sample of 9151 pregnant individuals from the general US pregnant population was screened for carrier status. Overall, 98.7% of pregnant individuals received an informative result (no-call rate = 1.3%), either a negative carrier report or, if identified as heterozygous for a pathogenic variant, a reflex sgNIPS report.

Application of exome sequencing for prenatal diagnosis of fetal structural anomalies: clinical experience and lessons learned from a cohort of 1618 fetuses
F Fu et al, Genome Medicine, October 28, 2022 (Posted: Oct 28, 2022 1PM)

We performed pES in 1618 fetal cases with positive ultrasound findings but negative for karyotyping and chromosome microarray analysis between January 2014 and October 2021, including both retrospective (n=565) and prospective (n=1053) cohorts. Altogether, 229 fetal cases (14.2%) received a molecular diagnosis, with a higher positive rate in the retrospective than the prospective cohort (17.3% vs. 12.4%, p<0.01). The diagnostic rates were highest in fetuses with skeletal anomalies (30.4%) and multiple organ involvements (25.9%), and lowest in fetuses with chest anomalies (0%).

Lasker Award Honors Development of Noninvasive Prenatal DNA Test
B Mueller, NY Times, September 28, 2022 (Posted: Sep 29, 2022 8AM)

Discovery of Cell-Free Fetal DNA in Maternal Blood and Development of Noninvasive Prenatal Testing 2022 Lasker-DeBakey Clinical Medical Research Award
YMD Lo et al, JAMA, September 28, 2022 (Posted: Sep 28, 2022 0PM)

The global adoption of non invasive prenatal testing has accelerated research into other diagnostic applications of plasma DNA, now generally referred to as liquid biopsies. The ability of plasma DNA sequencing to interrogate the fetal genome has prompted us and others to develop similar methods for investigating the circulating tumor genome. Cell-free DNA in bodily fluids is a treasure trove for molecular diagnostics and has opened up a noninvasive window into human health.

Stressful start causes chromosome errors in human embryos
T Cavazza et al, Nature, September 16, 2022 (Posted: Sep 20, 2022 5AM)

Analysis of early human embryos reveals that DNA duplication after fertilization is highly inefficient. This causes DNA damage, chromosome breaks and abnormal numbers of chromosomes, impairing embryo development.

Exome sequencing for structurally normal fetuses—yields and ethical issues
H Daum et al, EJHG, September 7, 2022 (Posted: Sep 07, 2022 7AM)

Rare autosomal trisomies detected by non-invasive prenatal testing
P Benn, EJHG, August 31, 2022 (Posted: Aug 31, 2022 7AM)

Current methods for NIPT are based on the analysis of cell-free DNA in maternal plasma, which is a mixture of DNA derived from trophoblasts (commonly, but erroneously, called “fetal DNA”) and DNA from maternal cells. The proportion of DNA that is fetal is variable and the ability to detect a minor mosaic abnormal cell line will be dependent on both the fetal fraction and the laboratory methods used (for example, the depth of sequencing).

Rapid Nanopore Sequencing–Based Screen for Aneuploidy in Reproductive Care
S Wei et al, NEJM, August 18, 2022 (Posted: Aug 17, 2022 5PM)

Aneuploid pregnancies are a major cause of pregnancy loss, fetal structural anomalies, and developmental delays. Consequently, the identification of genetic abnormalities is an important component of prenatal and fertility care. We developed and validated a new short-read–based approach for library preparation, sequencing, and data analysis that enables accurate, inexpensive, and same-day genomewide aneuploidy detection with the use of a palm-sized, nanopore-based DNA sequencer.

NIH-funded researchers develop same-day test to detect abnormal fetal chromosomes STORK helps identify cause of miscarriage and potentially improves in vitro fertilization process
NIH, August 17, 2022 Brand (Posted: Aug 17, 2022 5PM)

Scientists funded by the National Institutes of Health have developed a same-day test to identify abnormal fetal chromosomes. The Short-read Transpore Rapid Karyotyping (STORK) test can detect extra or missing chromosomes (i.e., aneuploidy) using samples collected from prenatal tests, such as amniocentesis and chorionic villus sampling, as well as tissue obtained from miscarriage and biopsies from pre-implantation embryos produced using in vitro fertilization (IVF).

Assessing clinical utility of preconception expanded carrier screening regarding residual risk for neurodevelopmental disorders.
Boonsawat Paranchai et al. NPJ genomic medicine 2022 7 (1) 45 (Posted: Jul 31, 2022 7AM)

Rare autosomal trisomies detected by non-invasive prenatal testing: an overview of current knowledge
L Lanoo et al, EJHG, July 27, 2022 (Posted: Jul 27, 2022 10AM)

Non-invasive prenatal testing has been introduced for the detection of Trisomy 13, 18, and 21. Using genome-wide screening also other “rare” autosomal trisomies (RATs) can be detected with a frequency about half the frequency of the common trisomies in the large population-based studies. Large prospective studies and clear clinical guidelines are lacking to provide adequate counseling and management to those who are confronted with a RAT as a healthcare professional or patient.

Cost-effectiveness frameworks for comparing genome and exome sequencing versus conventional diagnostic pathways: A scoping review and recommended methods.
Ferket Bart S et al. Genetics in medicine : official journal of the American College of Medical Genetics 2022 7 (Posted: Jul 15, 2022 5AM)

We recommend the following considerations for each clinical scenario. For prenatal testing, performing comparative analyses of costs of ES strategies and postpartum care, as well as genetic diagnoses and pregnancy outcomes. For early diagnosis in pediatrics, modeling quality-adjusted life years (QALYs) and costs over =20 years for rapid turnaround GS/ES. For hereditary cancer syndrome testing, modeling cumulative costs and QALYs for the individual tested and first/second/third-degree relatives. For tumor profiling, not restricting to treatment uptake or response and including QALYs and costs of downstream outcomes. For screening, modeling lifetime costs and QALYs and considering consequences of low penetrance and GS/ES reanalysis.

Systematic evidence-based review: The application of noninvasive prenatal screening using cell-free DNA in general-risk pregnancies
NC Rose et al, Genetics in Medicine, May 23, 2022 (Posted: May 24, 2022 8AM)

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. NIPS is a highly accurate screening method for T21, T18, and T13 in both singleton and twin pregnancies.

Ethically robust reproductive genetic carrier screening needs to measure outcomes that matter to patients
L Dive et al, EJHG, May 18, 2022 (Posted: May 18, 2022 7AM)

Same performance of exome sequencing before and after fetal autopsy for congenital abnormalities: toward a paradigm shift in prenatal diagnosis?
N Bourgon et al, EJHG, May 16, 2022 (Posted: May 16, 2022 8AM)

The alarming rise of complex genetic testing in human embryo selection- Companies are marketing polygenic risk scores as part of IVF well ahead of a full understanding of the potential benefits — or dangers.
Nature editorial, March 21, 2022 (Posted: Mar 23, 2022 11AM)

Polygenic embryo testing: understated ethics, unclear utility
J Johnston, Nature Medicine, March 21, 2022 (Posted: Mar 22, 2022 11AM)

New technologies are expanding the reach and accessibility of preimplantation genetic testing of human embryos. But what these advances can deliver is still unclear, and a frank assessment of their profound ethical implications is urgently needed.

NIPT and the concerns regarding ‘routinisation’
R Horn, EJHG, February 7, 2022 (Posted: Feb 07, 2022 0PM)

Despite NIPT’s advantages, offering the test as a public health service raises important ethical questions. One major concern is that NIPT could become routinised, as ‘just another pregnancy test’ and that this risks further undermining reproductive autonomy, a risk that has been associated with genetic prenatal testing for many decades. The concern is that routinisation of NIPT could affect the level of informed choice.

When They Warn of Rare Disorders, These Prenatal Tests Are Usually Wrong
S Kliff et al, NY Times, January 2, 2022 (Posted: Jan 02, 2022 4PM)

Noninvasive prenatal testing, or NIPT — performs much worse when it looks for less common conditions. Most are caused by small missing pieces of chromosomes called microdeletions. Others stem from missing or extra copies of entire chromosomes. They can have a wide range of symptoms, including intellectual disability, heart defects, a shortened life span or a high infant mortality rate.

The Imperative of Responsible Innovation in Reproductive Medicine.
Mastenbroek Sebastiaan et al. The New England journal of medicine 2021 11 (22) 2096-2100 (Posted: Nov 25, 2021 9AM)

Responsible innovation requires that novel, potentially risky reproductive technologies be the subject of careful research that proceeds in a stepwise fashion from preclinical investigation to clinical trials and, ultimately, to long-term follow-up studies. Given the lack of high-level evidence of the effectiveness for PGT-A and the potential for adverse consequences, the use of PGT-A is best limited at present to the research setting.

Noninvasive prenatal diagnosis of monogenic disorders based on direct haplotype phasing through targeted linked-read sequencing
C Chen et al, BMC Medical Genomics, October 9, 2021 (Posted: Oct 10, 2021 7AM)

Though massively parallel sequencing has been widely applied to noninvasive prenatal screen for common trisomy, the clinical use of massively parallel sequencing to noninvasive prenatal diagnose monogenic disorders is limited. This study was to develop a method for directly determining paternal haplotypes for noninvasive prenatal diagnosis of monogenic disorders without requiring proband’s samples.

The ethical landscape(s) of non-invasive prenatal testing in England, France and Germany: findings from a comparative literature review
A Perrot et al, EJHG, October 4, 2021 (Posted: Oct 04, 2021 6AM)

Since 2019, England, France and Germany have started offering NIPT as a publicly funded second-tier test for common chromosomal aneuploidies (trisomy 21, 18 and/or 13). Despite these benefits, the introduction of NIPT into routine prenatal care also raises a number of ethical concerns. In this paper, we analyze how these issues are discussed differently across countries, echoing the different socio-political particularities and value-systems that shape the use and regulation of NIPT in a specific country.

Decision-making and experiences of preimplantation genetic diagnosis in inherited heart diseases: a qualitative study
L Yeates et al, EJHG, September 21, 2021 (Posted: Sep 21, 2021 7AM)

Non-invasive prenatal testing (NIPT) and pregnant women’s views on good motherhood: a qualitative study
E Garcia et al, EJHG, August 17, 2021 (Posted: Aug 17, 2021 7AM)

Routinization of prenatal screening with the non-invasive prenatal test: pregnant women’s perspectives
KRM van der Meij et al, EJHG, August 13, 2021 (Posted: Aug 13, 2021 8AM)

A questionnaire was completed by 751 pregnant women after receiving counseling for prenatal screening. Of the respondents, the majority (75.5%) made an informed choice for prenatal screening as measured by the multidimensional measure of informed choice (MMIC). Education level and religious affiliation were significant predictors of informed choice.

A New Kind of Embryo Genetics Screening Makes Big Promises on Little Evidence And yet you can buy the tests.
KW Davis, Slate, July 2021 (Posted: Jul 25, 2021 6AM)

These tests aren’t necessarily bad or inaccurate. Rather, the science is incomplete—a puzzle with many missing pieces. Beyond a company’s pictures of parents smiling at chubby babies, what’s important to understand is that current PRS tests are of limited use, and most babies are born healthy despite risks for many conditions. Before using a PRS test for embryo screening, prospective parents need to ask themselves: “What are my goals, and what problem am I trying to solve by learning this information?

Screening for autosomal recessive and X-linked conditions during pregnancy and preconception: a practice resource of the American College of Medical Genetics and Genomics (ACMG).
Gregg Anthony R et al. Genetics in medicine : official journal of the American College of Medical Genetics 2021 7 (Posted: Jul 22, 2021 7AM)

Carrier screening began 50 years ago with screening for conditions that have a high prevalence in defined racial/ethnic groups (e.g., Tay-Sachs disease in the Ashkenazi Jewish population; sickle cell disease in Black individuals). Cystic fibrosis was the first medical condition for which panethnic screening was recommended, followed by spinal muscular atrophy. Next-generation sequencing allows low cost and high throughput identification of sequence variants across many genes simultaneously.

Direct-to-consumer prenatal testing for multigenic or polygenic disorders: a position statement of the American College of Medical Genetics and Genomics (ACMG)
ACMG Board of Directors, Genetics in Medicine, June 28, 2021 (Posted: Jun 28, 2021 7AM)

While the issues surrounding direct-to-consumer testing for monogenic disease or disease caused by copy-number variants are complicated, they are even more complex for disorders that exhibit polygenic inheritance. As a result of increasing data points, the need for interpretation of and counseling about any type of genetic testing regarding these disorders has become exponentially more complex, and in most instances, is not a part of general clinical genetics practice. In this context, the emergence of direct-to-consumer testing for multi/polygenic diseases is particularly troubling.

Genome-wide cell-free DNA screening: a focus on copy-number variants
J Rafalko et al, Genetics in Medicine, June 21, 2021 (Posted: Jun 21, 2021 8AM)

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. 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.

Utility of noninvasive genome-wide screening: a prospective cohort of obstetric patients undergoing diagnostic testing.
Guseh Stephanie et al. Genetics in medicine : official journal of the American College of Medical Genetics 2021 3 (Posted: Mar 31, 2021 8AM)

While NIPS is an excellent screening test for common aneuploidies, genome-wide NIPS misses clinically significant findings detected on routine diagnostic testing. False positive and false negative cases highlight the importance of pretest counseling regarding NIPS limitations, especially in the setting of fetal anomalies.

Three years of clinical experience with a genome-wide cfDNA screening test for aneuploidies and copy-number variants
E Soster et al, Genetics in Medicine, March 17, 2021 (Posted: Mar 17, 2021 1PM)

Pregnant women have unprecedented choices for prenatal screening and testing. Cell-free DNA (cfDNA) offers the option to screen for aneuploidy of all chromosomes and genome-wide copy-number variants (CNVs), expanding screening beyond the common trisomies (“traditional” cfDNA). We sought to review the utilization trends and clinical performance characteristics of a commercially available genome-wide cfDNA test, with a subset having available diagnostic testing outcomes.

Cell-free DNA analysis of maternal blood in prenatal screening for chromosomal microdeletions and microduplications: a systematic review.
Familiari Alessandra et al. Prenatal diagnosis 2021 (Posted: Mar 16, 2021 10AM)

The pooled PPV of cfDNA testing in screening for microdeletion and microduplication syndromes was about 40%, ranging from 29% to 91%, for an overall FPR <0.1%. No confirmatory analysis was available in cases that did not undergo invasive testing, which were most cases with a negative test, and therefore, the negative predictive value cannot be determined.

Prenatal Exome Sequencing: Background, Current Practice and Future Perspectives-A Systematic Review.
Guadagnolo Daniele et al. Diagnostics (Basel, Switzerland) 2021 Feb 11(2) (Posted: Feb 09, 2021 10AM)

Introduction of Next Generation Sequencing technologies has a significant impact on prenatal diagnosis. Prenatal Exome Sequencing is performed with increasing frequency in fetuses with anomalies and negative chromosomal analysis. Diagnostic value varies, and the role of incidental or inconclusive findings and negative results has not been fully ascertained.

Beyond diagnostic yield: prenatal exome sequencing results in maternal, neonatal, and familial clinical management changes
LK Tolusso et al, Genetics in Medicine, January 13, 2021 (Posted: Jan 13, 2021 10AM)

Previous studies have reported that prenatal exome sequencing (pES) can detect monogenic diseases in fetuses with congenital anomalies with diagnostic yields ranging from 6% to 81%, but there are few reports of its clinical utility. We conducted a study of patients who had pES to determine whether results led to clinical management changes.

Impact of prenatal exome sequencing for fetal genetic diagnosis on maternal psychological outcomes and decisional conflict in a prospective cohort
AN Talati et al, Genetics in Medicine, November 20, 2020 (Posted: Nov 20, 2020 8AM)

The Last Children of Down Syndrome- Prenatal testing is changing who gets born and who doesn’t. This is just the beginning.
S Zhang, The Atlantic, December 2020 (Posted: Nov 18, 2020 9AM)

High-throughput fetal fraction amplification increases analytical performance of noninvasive prenatal screening
NC Welker et al, Genetics in Medicine, November 15, 2020 (Posted: Nov 16, 2020 7AM)

The percentage of a maternal cell-free DNA (cfDNA) sample that is fetal-derived (the fetal fraction; FF) is a key driver of the sensitivity and specificity of noninvasive prenatal screening (NIPS). On certain NIPS platforms, >20% of women with high body mass index (and >5% overall) receive a test failure due to low FF (<4%).

Screening embryos for polygenic conditions and traits: ethical considerations for an emerging technology.
Lázaro-Muñoz Gabriel et al. Genetics in medicine : official journal of the American College of Medical Genetics 2020 Oct (Posted: Oct 28, 2020 8AM)

Polygenic embryo screening (PES)—the use of polygenic risk scores for complex phenotypes as a component of preimplantation genetic testing (PGT)—has emerged as a commercially available service, despite almost no public deliberation about its ethical, clinical, and societal implications.

Expanding Use of Clinical Genome Sequencing and the Need for More Data on Implementation
KT Philips et al, JAMA October 26, 2020 (Posted: Oct 27, 2020 8AM)

This Viewpoint discusses the importance of understanding how next-generation genomic sequencing is being implemented—for whom noninvasive prenatal testing, whole-exome and -genome sequencing for suspected genetic disorders, and tumor sequencing is being used and who is paying for it—as precondition for knowing how the technologies can best serve patients.

Exome Sequencing for Prenatal Diagnosis in Nonimmune Hydrops Fetalis.
Sparks Teresa N et al. The New England journal of medicine 2020 Oct (Posted: Oct 08, 2020 8AM)

The cause of most fetal anomalies is not determined prenatally. Exome sequencing has transformed genetic diagnosis after birth, but its usefulness for prenatal diagnosis is still emerging. In this large case series of 127 fetuses with unexplained non immune hydrops fetalis, we identified a diagnostic genetic variant in approximately one third of the cases.

What is the meaning of a 'genomic result' in the context of pregnancy?
Shkedi-Rafid Shiri et al. European journal of human genetics : EJHG 2020 Sep (Posted: Sep 16, 2020 10AM)

As professional organizations develop guidelines on the use of genomic testing during pregnancy, we highlight the difficulties of discovering variants with uncertain clinical significance, and susceptibility to adult-onset diseases. We aim to foster international discussions about how decisions on disclosure are made and how uncertainty is communicated.

Genome-wide noninvasive prenatal screening for carriers of balanced reciprocal translocations
NJ Flowers et al, Genetics in Medicine, August 18, 2020 (Posted: Aug 18, 2020 8AM)

Balanced reciprocal translocation carriers are at increased risk of producing gametes with unbalanced forms leading to miscarriage, fetal anomalies, and birth defects. This study assesses whether genome-wide cell-free DNA based noninvasive prenatal screening could provide an alternative to prenatal diagnosis for carriers of these chromosomal rearrangements.

How will new genetic technologies, such as gene editing, change reproductive decision-making? Views of high-risk couples
I van Dijke et al, EJHG, August 9, 2020 (Posted: Aug 10, 2020 9AM)

Couples at increased risk of having offspring with a specific genetic disorder who want to avoid having an affected child have several reproductive options including prenatal diagnosis, and preimplantation genetic testing. In the future, non-invasive prenatal diagnosis, germline gene editing and somatic gene editing might become available.

Non-invasive prenatal testing (NIPT): societal pressure or freedom of choice? A vignette study of Dutch citizens' attitudes.
Kater-Kuipers Adriana et al. European journal of human genetics : EJHG 2020 Aug (Posted: Aug 07, 2020 7AM)

Application of exome sequencing for prenatal diagnosis: a rapid scoping review.
Pratt Misty et al. Genetics in medicine : official journal of the American College of Medical Genetics 2020 Aug (Posted: Aug 05, 2020 8AM)

Few studies reported clinical outcomes related to impact, decision-making, and clinical utility. Qualitative studies (n?=?6) provided useful insights into patient and health-care provider experiences with exome sequencing.

An approach to integrating exome sequencing for fetal structural anomalies into clinical practice.
Vora Neeta L et al. Genetics in medicine : official journal of the American College of Medical Genetics 2020 Jan (Posted: Jan 25, 2020 8AM)

We investigated the diagnostic and clinical performance of trio exome sequencing (ES) in parent-fetus trios where the fetus had sonographic abnormalities but normal karyotype, microarray and, in some cases, normal gene-specific sequencing. In 21/102 (20.6%) fetuses, ES provided a positive-definitive or positive-probable diagnosis.

The use of fetal exome sequencing in prenatal diagnosis: a points to consider document of the American College of Medical Genetics and Genomics (ACMG)
KG Monaghan et al. Genetics in Medicine, January 8, 2020 (Posted: Jan 08, 2020 9AM)

The following points to consider document was developed with the intent to assist referring physicians, laboratory geneticists, genetic counselors, and other medical professionals in understanding the complexity and implications of ES testing as its utilization is increasing in prenatal care.

Why using genetic risk scores on embryos is wrong
E Birney blog, November 11, 2019 (Posted: Nov 12, 2019 8AM)

Polygenic risk scores are statistical models of the genetic component of the variation in traits in individuals observed in the population; they are not models of which bits of the limited possibilities of a genomes will impact a trait given particular parents.

TRIDENT-2: National Implementation of Genome-Wide Non-Invasive Prenatal Testing as a First-Tier Screening Test in the Netherlands
AJHG, November 7, 2019 (Posted: Nov 08, 2019 9AM)

The Netherlands launched a nationwide implementation study on non-invasive prenatal testing (NIPT) as a first-tier test offered to all pregnant women. n the first year, NIPT was performed in 73,239 pregnancies (42% of all pregnancies), 7,239 (4%) chose first-trimester combined testing.

Screening embryos for complex genetic traits called premature
J Kaiser, Science, October 25, 2019 (Posted: Oct 26, 2019 10AM)

This is the first to empirically test the viability of screening embryos” for traits that are influenced by many genes. Such tests are based on a polygenic risk score, a tool for evaluating a person's likelihood of a disease or trait that has emerged over the past decade. The ethical debate over this brave new expansion of embryo screening is just beginning.

Preconception carrier screening yield: effect of variants of unknown significance in partners of carriers with clinically significant variants.
Fridman Hila et al. Genetics in medicine : official journal of the American College of Medical Genetics 2019 Oct (Posted: Oct 20, 2019 11AM)

Expanded preconception carrier screening (ECS) identifies at-risk couples (ARCs) for multiple diseases. ECS reports currently include only pathogenic/likely pathogenic variants (P/LPVs). Variants of unknown significance (VUS) are not reported. The study examined the impact of VUS on ECS yield in an Ashkenazi Jewish cohort.

The wild west of prenatal genetic testing
A Ramchandani, Mashable, August 2019 (Posted: Sep 06, 2019 7AM)

Low-pass genome sequencing versus chromosomal microarray analysis: implementation in prenatal diagnosis.
Wang Huilin et al. Genetics in medicine : official journal of the American College of Medical Genetics 2019 Aug (Posted: Aug 27, 2019 7AM)

Outcomes in pregnancies with a confined placental mosaicism and implications for prenatal screening using cell-free DNA.
Grati Francesca Romana et al. Genetics in medicine : official journal of the American College of Medical Genetics 2019 Aug (Posted: Aug 09, 2019 8AM)

Recent trends in prenatal genetic screening and testing.
Pös Ondrej et al. F1000Research 2019 8 (Posted: Jun 26, 2019 9AM)

Prospective head-to-head comparison of accuracy of two sequencing platforms for screening for fetal aneuploidy by cell-free DNA: the PEGASUS study.
Rousseau François et al. European journal of human genetics : EJHG 2019 Jun (Posted: Jun 25, 2019 0PM)

The study compared clinical validity of two non-invasive prenatal screening (NIPS) methods for fetal trisomies 13, 18, 21, and monosomy X. We recruited prospectively 2203 women at high risk of fetal aneuploidy and 1807 at baseline risk. Both sequencing platforms showed equivalent and excellent clinical validity

New Noninvasive Genetic Tests for IVF Embryos Are in Development
D Hernandez, Wall Street Journal, June 25, 2019 (Posted: Jun 25, 2019 0PM)

Scientists are developing more accurate and less invasive ways to test whether embryos made through in vitro fertilization procedures might have genetic abnormalities. The new tests could help the growing numbers of people pursuing IVF to make sure any embryo used is free from the genetic defects that can lead to miscarriage or devastating inherited diseases.

Validation of concurrent preimplantation genetic testing for polygenic and monogenic disorders, structural rearrangements, and whole and segmental chromosome aneuploidy with a single universal platform.
Treff Nathan R et al. European journal of medical genetics 2019 Apr (Posted: May 01, 2019 9AM)

Validation of Extensive Next-Generation Sequencing Method for Monogenic Disorder Analysis on Cell Free Fetal DNA: Noninvasive Prenatal Diagnosis.
Dello Russo Claudio et al. The Journal of molecular diagnostics : JMD 2019 Apr (Posted: May 01, 2019 9AM)

Impact of introduction of non-invasive prenatal testing on uptake of genetic testing in fetuses with central nervous system anomalies.
Al Toukhi Samar et al. Prenatal diagnosis 2019 Apr (Posted: May 01, 2019 9AM)

Identifying occult maternal malignancies from 1.93 million pregnant women undergoing noninvasive prenatal screening tests.
Ji Xing et al. Genetics in medicine : official journal of the American College of Medical Genetics 2019 Apr (Posted: Apr 15, 2019 8AM)

No US commercial laboratories fully meet guidance for noninvasive prenatal screening
Mass General Hospital, April 2, 2019 (Posted: Apr 03, 2019 10AM)

From diagnostic yield to clinical impact: a pilot study on the implementation of prenatal exome sequencing in routine care.
de Koning Maayke A et al. Genetics in medicine : official journal of the American College of Medical Genetics 2019 Mar (Posted: Mar 29, 2019 9AM)

Noninvasive Prenatal Testing for Trisomies 21, 18, and 13, Sex Chromosome Aneuploidies, and Microdeletions: A Health Technology Assessment.
et al. Ontario health technology assessment series 2019 19(4) 1-166 (Posted: Mar 12, 2019 11AM)

Towards a gamete matching platform: using immunogenetics and artificial intelligence to predict recurrent miscarriage
A Mora-Sanchez, et al, NPJ Digital Medicine, March 2019 (Posted: Mar 12, 2019 9AM)

Estimating yields of prenatal carrier screening and implications for design of expanded carrier screening panels
MH Guo et al, Genetics in Medicine, March 8, 2019 (Posted: Mar 08, 2019 0PM)

Clinical utility of noninvasive prenatal screening for expanded chromosome disease syndromes
D Liang et al, Genetics in Medicine, March 4, 2019 (Posted: Mar 04, 2019 1PM)

Pregnant women want physicians' advice on receiving fetal genomic information,
Physicians will need more training as new testing technologies are adopted Brand (Posted: Feb 26, 2019 2PM)

Feasibility of couple-based expanded carrier screening offered by general practitioners
J Shuurmans et al, Eur J Hum Genetics, February 11, 2019 (Posted: Feb 14, 2019 8AM)

Expanded reproductive carrier screening—how can we do the most good and cause the least harm?
MB Delatycki et al, Eur J Hum Genetics, February 13, 2019 (Posted: Feb 14, 2019 8AM)

Noninvasive Prenatal Whole Genome Sequencing: Pregnant Women's Views and Preferences.
Sullivan Haley K et al. Obstetrics and gynecology 2019 Feb (Posted: Feb 12, 2019 10AM)

The uptake of pan-ethnic expanded carrier screening is higher when offered during preconception or early prenatal genetic counseling.
Larsen Dana et al. Prenatal diagnosis 2019 Feb (Posted: Feb 12, 2019 10AM)

Prenatal exome sequencing analysis in fetal structural anomalies detected by ultrasonography (PAGE): a cohort study.
Lord Jenny et al. Lancet (London, England) 2019 Jan (Posted: Feb 05, 2019 11AM)

Introduction of genomics into prenatal diagnostics.
Talkowski Michael E et al. Lancet (London, England) 2019 Jan (Posted: Feb 05, 2019 11AM)

Whole-exome sequencing in the evaluation of fetal structural anomalies: a prospective cohort study.
Petrovski Slavé et al. Lancet (London, England) 2019 Jan (Posted: Feb 05, 2019 11AM)

Prospective parents should be prepared for a surge in genetic data- The growing capabilities of prenatal diagnostics are expanding the need for counselling.
Nature editorial, January 29, 2019 (Posted: Jan 29, 2019 6PM)

Non-invasive prenatal sequencing for multiple Mendelian monogenic disorders using circulating cell-free fetal DNA
J Xhang et al, Nature Medicine, January 29, 2019 (Posted: Jan 29, 2019 6PM)

A safe prenatal genetic test is gaining popularity with young moms-to-be and their doctors
SE Richards, Washington Post, January 5, 2019 (Posted: Jan 09, 2019 1PM)

The Power of Preimplantation Genetic Testing
S Karipcin, US News, January 3, 2019 (Posted: Jan 04, 2019 9AM)

Identifying the genetic causes for prenatally diagnosed structural congenital anomalies (SCAs) by whole-exome sequencing (WES)
GKC Leung et al, BMC Medical Genomics, October 25, 2018 (Posted: Oct 30, 2018 0PM)

Use of a novel computerized decision aid for aneuploidy screening: a randomized controlled trial.
Carlson Laura M et al. Genetics in medicine : official journal of the American College of Medical Genetics 2018 Sep (Posted: Sep 19, 2018 9AM)

The epidemic of abnormal copy number variant cases missed because of reliance upon noninvasive prenatal screening.
Evans Mark I et al. Prenatal diagnosis 2018 Sep 38(10) 730-734 (Posted: Sep 12, 2018 9AM)

Effect of Cell-Free DNA Screening vs Direct Invasive Diagnosis on Miscarriage Rates in Women With Pregnancies at High Risk of Trisomy 21: A Randomized Clinical Trial.
Malan Valérie et al. JAMA 2018 Aug 320(6) 557-565 (Posted: Aug 22, 2018 11AM)

Do patients who achieve pregnancy using IVF-PGS do the recommended genetic diagnostic testing in pregnancy?
Kimelman Dana et al. Journal of assisted reproduction and genetics 2018 Aug (Posted: Aug 22, 2018 11AM)

Clinical and Economic Impact of Adopting Noninvasive Prenatal Testing as a Primary Screening Method for Fetal Aneuploidies in the General Pregnancy Population.
Kostenko Emilia et al. Fetal diagnosis and therapy 2018 Aug 1-11 (Posted: Aug 22, 2018 11AM)

Sequencing of Circulating Cell-free DNA during Pregnancy.
Bianchi Diana W et al. The New England journal of medicine 2018 Aug (5) 464-473 (Posted: Aug 02, 2018 8AM)

Fetal DNA sequencing potentially could reduce need for invasive prenatal diagnostic procedures
NIH, August 1, 2018 Brand (Posted: Aug 02, 2018 8AM)

Noninvasive Prenatal Genetic Screening Using Cell-free DNA
MA Allyse et al, JAMA< July 30, 2018 (Posted: Jul 30, 2018 1PM)

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Disclaimer: Articles listed in Hot Topics of the Day are selected by Public Health Genomics Branch to provide current awareness of the scientific literature and news. Inclusion in the update does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the Clips, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.
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