Reproduction, fetal medicine and genomics

2020 ◽  
pp. 175573802097470
Author(s):  
Tessa Homfray ◽  
Judith Hayward ◽  
Imran Rafi
Keyword(s):  
Primary Care ◽  
Recurrent Miscarriage ◽  
Genetic Disorder ◽  
Prenatal Testing ◽  
Antenatal Screening ◽  
Fetal Abnormality ◽  
Fetal Medicine ◽  
Non Invasive ◽  
Genomic Technologies ◽  
Increased Risk

Identification of a genetic disorder within a family raises the question of risk of the genetic disorder to other family members and future pregnancies. This question is particularly pertinent when considering reproductive risks and choices. Primary care is crucial in identifying and managing couples at increased risk of having an affected pregnancy, both pre-conceptually and in early pregnancy, before the first midwife appointment. Genomic technologies have an increasing role in antenatal screening programmes and antenatal testing; specifically non-invasive prenatal testing considered in this article. Infertility, recurrent miscarriage and fetal abnormality may all have an underlying genetic cause.

Factors Affecting Women's Knowledge of Antenatal Serum Screening

1997 ◽  
Vol 42 (4) ◽  
pp. 111-113 ◽  
Author(s):  
G.K. Grewal ◽  
H.J. Moss ◽  
D.A. Aitken ◽  
S. Bjornsson ◽  
A.D. Cameron ◽  
...  
Keyword(s):  
Spina Bifida ◽  
Fetal Anomaly ◽  
Antenatal Screening ◽  
Fetal Abnormality ◽  
Factors Affecting ◽  
Negative Results ◽  
Written Information ◽  
Superior Knowledge ◽  
Increased Risk ◽  
Positive Results

Antenatal screening for fetal anomaly is offered routinely in Glasgow. This study assessed pregnant women S knowledge of the test and implications of results. Questionnaires were completed by 574 women. Knowledge of the nature and uses of the test was superior to earlier studies Two-thirds knew that screening was undertaken for Down's syndrome, and 81% for spina bifida. The majority were aware of the sample used, ages invited and gestation at which it was undertaken. Knowledge of the likely results and implications was poorer. Three-quarters were unaware that 10% of results would suggest an increased risk. Half did not realise that positive results could occur without fetal abnormality, or negative results could be falsely reassuring. Socioeconomic deprivation was associated with poorer knowledge but not lower uptake. Written information was associated with superior knowledge and higher uptake. Leaflets should be provided prior to booking, at which time resultant queries can be answered.

scholarly journals Would I have Wanted to Know? A Qualitative Exploration of Women’s Attitudes, Beliefs and Concerns about Non-Invasive Prenatal Testing for de novo Genetic Conditions after having a Child with a de novo Genetic Disorder

OBM Genetics ◽  
2021 ◽  
Vol 05 (04) ◽  
pp. 1-1
Author(s):  
Sarah Long ◽  
◽  
Roanna Lobo ◽  
Peter O'Leary ◽  
Jan E. Dickinson ◽  
...  
Keyword(s):  
Personal Growth ◽  
De Novo ◽  
Genetic Disorder ◽  
Single Gene ◽  
Genetic Diagnosis ◽  
Prenatal Testing ◽  
Phenomenological Approach ◽  
Population Screening ◽  
Chromosomal Disorders ◽  
Non Invasive

Non-invasive prenatal testing (NIPT) for a panel of 25 single gene disorders became available in Western Australia in 2020 and potentially may be able to test for panels of hundreds of disorders as is the case with reproductive carrier screening. How this information would be used by parents in a population screening model is unknown. We used a phenomenological approach to explore retrospectively whether mothers of children with single gene or chromosomal disorders would have wanted to know about their child’s genetic diagnosis prior to delivery. Themes were identified such as having a child with a de novo disorder and effect on pregnancy outcomes in hypothetical situations, impact on family function, the diagnostic journey and personal growth. These themes related to both the concept of expanded NIPT (ENIPT) and the situation of having a child with a de novo genetic disorder that could now hypothetically be detected through ENIPT. Opinions were divided about whether participants would have wanted to know about their affected child’s condition, indicating any expanded NIPT testing panels would need to be offered in the context of an appropriate comprehensive counselling program. How this would be provided on a population screening level and the role of genetic counselling needs further exploration.

scholarly journals Estimation of Detection Rates of Aneuploidy in High-Risk Pregnancy Using an Approach Based on Nuchal Translucency and Non-Invasive Prenatal Testing: A Cohort Study

2015 ◽  
Vol 38 (4) ◽  
pp. 254-261 ◽  
Author(s):  
Asma Khalil ◽  
Negar Mahmoodian ◽  
Abhijit Kulkarni ◽  
Tessa Homfray ◽  
Aris Papageorghiou ◽  
...  
Keyword(s):  
Cohort Study ◽  
High Risk ◽  
Chorionic Villus ◽  
Prenatal Testing ◽  
Nuchal Translucency ◽  
Detection Rates ◽  
Non Invasive ◽  
Risk Pregnancy ◽  
Increased Risk ◽  
Clinically Significant

Objectives: The aim was to investigate aneuploidy detection using an approach based on nuchal translucency (NT) and non-invasive prenatal testing (NIPT). Methods: This was a cohort study including 5,306 high-risk pregnancies with NT measurements and chorionic villus samples (CVS) tested for full karyotype. Results: The fetal karyotype was normal in 4,172 (78.6%) cases and abnormal in 1,134 (21.4%), including 1,009 with a likely clinically significant adverse outcome. Universal CVS with full karyotyping would lead to the diagnosis of all clinically significant abnormalities. A policy of relying solely on NIPT would have led to the diagnosis of 88.9% of clinically significant abnormalities. A strategy whereby NIPT is the main method, with CVS reserved for cases with NT ≥3.0 mm, would require CVS in 21.7% of cases, identify 94.8% of significant abnormalities and avoid miscarriage in 41 pregnancies compared to CVS for all. Conclusions: A policy of NIPT for increased-risk cases and CVS with full karyotype if the NT was ≥3.0 mm reduced the risk of miscarriage yet still identified 95% of clinically significant aneuploidy.

scholarly journals Strategy for Use of Genome-Wide Non-Invasive Prenatal Testing for Rare Autosomal Aneuploidies and Unbalanced Structural Chromosomal Anomalies

2020 ◽  
Vol 9 (8) ◽  
pp. 2466
Author(s):  
Pascale Kleinfinger ◽  
Laurence Lohmann ◽  
Armelle Luscan ◽  
Detlef Trost ◽  
Laurent Bidat ◽  
...  
Keyword(s):  
Prenatal Testing ◽  
Diagnostic Procedures ◽  
Screening Strategy ◽  
Maternal Serum ◽  
Chromosomal Anomalies ◽  
Maternal Serum Screening ◽  
Non Invasive ◽  
Genome Wide ◽  
A Genome ◽  
Increased Risk

Atypical fetal chromosomal anomalies are more frequent than previously recognized and can affect fetal development. We propose a screening strategy for a genome-wide non-invasive prenatal test (NIPT) to detect these atypical chromosomal anomalies (ACAs). Two sample cohorts were tested. Assay performances were determined using Cohort A, which consisted of 192 biobanked plasma samples—42 with ACAs, and 150 without. The rate of additional invasive diagnostic procedures was determined using Cohort B, which consisted of 3097 pregnant women referred for routine NIPT. Of the 192 samples in Cohort A, there were four initial test failures and six discordant calls; overall sensitivity was 88.1% (37/42; CI 75.00–94.81) and specificity was 99.3% (145/146; CI 96.22–99.88). In Cohort B, there were 90 first-pass failures (2.9%). The rate of positive results indicating an anomaly was 1.2% (36/3007) and 0.57% (17/3007) when limited to significant unbalanced chromosomal anomalies and trisomies 8, 9, 12, 14, 15, 16, and 22. These results show that genome-wide NIPT can screen for ACAs with an acceptable sensitivity and a small increase in invasive testing, particularly for women with increased risk following maternal serum screening and by limiting screening to structural anomalies and the most clinically meaningful trisomies.

Prenatal diagnosis of fetal abnormality: the decision to terminate the pregnancy and the psychological consequences

2002 ◽  
Vol 13 (4) ◽  
pp. 213-247 ◽  
Author(s):  
Helen Statham
Keyword(s):  
Prenatal Screening ◽  
Genetic Disorders ◽  
Genetic Disorder ◽  
Psychological Consequences ◽  
Maternal Condition ◽  
Fetal Abnormality ◽  
Structural Anomaly ◽  
Increased Risk ◽  
History Of ◽  
Low Risk Women

In the absence of any prenatal screening, some two percent of babies will be born with a structural anomaly; a further 1 in 700–800 will be born with Down's syndrome, with similar numbers having other chromosomal and serious genetic disorders. The prevalence of abnormalities in early pregnancy is higher because abnormal fetuses are more likely to miscarry than normal ones. A small number of women enter pregnancy at increased risk of conceiving a baby with an abnormality. They may have a maternal condition such as diabetes, need medication for conditions such as epilepsy, or have a family history of a genetic disorder (www3.ncbi.nlm.nih.gov/Omim/searchomim.html). Most abnormalities, however, occur in healthy, low-risk women.

What Potent Blood: Non-Invasive Prenatal Genetic Diagnosis and the Transformation of Modern Prenatal Care

2007 ◽  
Vol 33 (1) ◽  
pp. 9-53 ◽  
Author(s):  
Carolyn Jacobs Chachkin
Keyword(s):  
Genetic Disorders ◽  
Genetic Disorder ◽  
Genetic Material ◽  
Genetic Diagnosis ◽  
Prenatal Testing ◽  
Maternal Blood ◽  
Non Invasive ◽  
Tay Sachs Disease ◽  
Promising Solution ◽  
Low Levels

What potent blood hath modest May,What fiery force the earth renews,The wealth of forms, the flush of hues ….—Ralph Waldo EmersonSomeday soon, virtually any pregnant woman will be able to learn — with 98-99% accuracy — whether her fetus has contracted a serious genetic disorder by undergoing nothing more than an inexpensive, non-invasive blood test. For years, scientists have sought a method of prenatal testing that could boast both high levels of accuracy and low levels of risk. The most promising solution lies in an exciting recent discovery: tiny quantities of fetal cells and DNA cross over into the mother's bloodstream during pregnancy. If the fetal genetic material can be successfully isolated from the maternal blood, it can be used to diagnose a number of genetic disorders, such as Down Syndrome, cystic fibrosis, Tay-Sachs disease, and sickle cell anemia. Indeed, researchers have spent the last decade developing ways to accomplish this.

Amniotic fluid stem cells and the cell source repertoire for non-invasive prenatal testing

2021 ◽  
Author(s):  
Margit Rosner ◽  
Thomas Kolbe ◽  
Viktor Voronin ◽  
Markus Hengstschläger
Keyword(s):  
Stem Cells ◽  
Amniotic Fluid ◽  
False Negative ◽  
Prenatal Testing ◽  
Chorionic Villus Sampling ◽  
Amniotic Fluid Stem Cells ◽  
Non Invasive ◽  
Increased Risk ◽  
Cell Free Fetal Dna ◽  
Cell Source

AbstractCell-free fetal DNA (cffDNA)-based non-invasive prenatal testing (NIPT) is considered to be a very promising screening tool for pregnant women with an increased risk of fetal aneuploidy. Already millions of women worldwide underwent NIPT. However, due to the observed false-positive and false-negative results, this screening approach does not fulfil the criteria of a diagnostic test. Accordingly, positive results still require risk-carrying invasive prenatal testing, such as amniocentesis or chorionic villus sampling (CVS), for confirmation. Such hurdles need to be overcome before NIPT could become a diagnostic approach widely used in the general population. Here we discuss new evidence that besides the placenta amniotic fluid stem cells (AFSCs) could also represent an origin of cffDNA in the mother’s blood. A comprehensive picture of the involved cell source repertoire could pave the way to more reliable interpretations of NIPT results and ameliorate counselling of advice-seeking patients. Graphical abstract

scholarly journals Discordant structural chromosomal aberrations in chorionic villi and amniotic fluid leading to a formation of an isochromosome 21: a case report

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Eini Westenius ◽  
Maria Pettersson ◽  
Erik Björck
Keyword(s):  
Amniotic Fluid ◽  
Chromosomal Aberrations ◽  
Trisomy 21 ◽  
Chorionic Villus ◽  
Prenatal Testing ◽  
Chorionic Villus Sampling ◽  
Chorionic Villi ◽  
Non Invasive ◽  
Increased Risk ◽  
A Cell

Abstract Background Fetoplacental discrepancies occur in approximately 1–2% of analyzed prenatal cases. They are typically due to confined placental mosaicism, where an aberration is observed in the placental cells but not found in the fetal cells. Confined placental mosaicism usually involves aneuploidies and more sparsely structural chromosomal aberrations. To the best of our knowledge, this is the first reported case of a discrepancy in the analyses of chorionic villus sampling and amniocentesis involving two different structural chromosomal aberrations of chromosome 21. Case presentation We report a 33-year-old woman who was referred for a non-invasive prenatal testing due to an increased risk of trisomy 21 gleaned from a combined ultrasound and blood test. The non-invasive prenatal testing showed an increased risk of trisomy 21 with a normalized coverage signal that did not match the fetal cell-free DNA fraction. Rapid aneuploidy detection performed on uncultured chorionic villi indicated mosaicism for trisomy 21. The follow-up analyses revealed discordant chromosomal aberrations: 46,XY,der(21)t(10;21)(p11.21;q10) in the analysis of the chorionic villus sampling and 46,XY, + 21,der(21;21)(q10;q10) in the analysis of the amniocentesis. Thus, the analyses indicated mosaicism for a cell line containing trisomy 21 and a cell line containing a partially duplicated short arm of chromosome 10 in the chorionic villi and complete trisomy 21 resulting from an isochromosome 21 in the amniotic fluid. The analyses of the lymphocytes and the fibroblasts of the woman were normal. Conclusions We propose a multiple-step mechanism as a possible theoretical explanation for the formation of these discordant structural chromosomal aberrations in the chorionic villi and amniotic fluid. With this case report, we want to highlight the importance of understanding the possible underlying embryological mechanisms when interpreting results from different prenatal analyses.

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