Prenatal Diagnosis of Chromosomal Abnormalities through Chorionic Villus Sampling and Amniocentesis

Benn, Peter

doi:10.1002/9781118981559.ch4

Cited by 15 publications

(20 citation statements)

References 582 publications

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“…We reviewed cytogenetic abnormalities detected in POCs referred to the TOMA laboratory between 1995 and 2015, including some data published previously. These results were merged with those in the literature to provide the spectrum of autosomal trisomies detected in early miscarriages.…”

Section: Methodsmentioning

confidence: 99%

Rare autosomal trisomies: comparison of detection through cell‐free DNA analysis and direct chromosome preparation of chorionic villus samples

Benn

Malvestiti²,

Grimi³

et al. 2019

Ultrasound in Obstet & Gyne

109

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Objective Direct chromosome preparations of chorionic villus samples (CVS) and cell‐free DNA (cfDNA) testing both involve analysis of the trophoblastic cell lineage. The aim of this study was to compare the spectrum of rare autosomal trisomies (RATs) detected by these two approaches and assess the available information on their clinical significance. Methods Data from 10 reports on genome‐wide cfDNA testing were pooled to determine which chromosomes were most frequently involved in RAT‐positive cases, and pregnancy outcome information was reviewed. CVS information was obtained from an updated database of 76 102 consecutive CVS analyses performed over a period of 18 years at TOMA laboratory, in which trophoblastic and mesenchymal layers were analyzed and amniotic fluid cell analysis was recommended for RAT‐positive cases. Chromosomes involved and presence of confined placental mosaicism, true fetal mosaicism and uniparental disomy (UPD) for imprinted chromosomes were assessed. Also evaluated were the frequency and types of RATs in products of conception. Results RATs were present in 634 of 196 662 (0.32%) cfDNA samples and 237 of 57 539 (0.41%) CVS trophoblast samples (P < 0.01). The frequency of RATs varied over 8‐fold between the cfDNA reports. Confirmation of abnormality through amniocentesis was more likely when RATs were ascertained through cfDNA (14 of 151; 9.3%) than through CVS trophoblasts (seven of 237; 3.0%) (P < 0.01). In cfDNA‐ascertained cases, trisomies 15, 16 and 22, which are associated with fetal loss, were identified proportionately more often. Of 151 cases with RAT identified by cfDNA and outcome information available, 41.1% resulted in normal live birth; 27.2% in fetal loss; 7.3% had phenotypic abnormality detected through ultrasound or other follow‐up evaluation; 2.0% had a clinically significant UPD; and 14.6% had fetal growth restriction or low birth weight. All autosomes were involved in trisomies in products of conception; the most common RATs detected were trisomies 16, 22 and 15 with a frequency of > 9% each. Conclusions Although there are strong parallels between RATs ascertained through cfDNA analysis and direct chromosome preparation of CVS, caution is needed in applying conclusions from CVS analysis to cfDNA testing, and vice versa. RATs identified through genome‐wide cfDNA tests have uncertain risks for fetal loss, growth restriction or fetal abnormality. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

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Section: Methodsmentioning

confidence: 99%

Rare autosomal trisomies: comparison of detection through cell‐free DNA analysis and direct chromosome preparation of chorionic villus samples

Benn

Malvestiti²,

Grimi³

et al. 2019

Ultrasound in Obstet & Gyne

109

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“…Incidence of chromosome abnormalities in newborns. Data is derived from 120,290 livebirths, for all maternal ages and is extracted from 15 publications as detailed elsewhere . The studies were conducted prior to the widespread use of prenatal screening and diagnosis.…”

Section: Additional Abnormalities Potentially Detectablementioning

confidence: 99%

“…A rare autosomal mosaicism was found in 0.26/1000 cases. Approximately 60% of the rare autosomal trisomies that are identified at the time of amniocentesis are not confirmed in follow‐up studies on fetal or newborn tissues and some additional cases appear to show a normal phenotype . Triploidy was present in 0.15/1000 cases but these are not expected to survive to term.…”

Section: Additional Abnormalities Potentially Detectablementioning

confidence: 99%

Expanding non‐invasive prenatal testing beyond chromosomes 21, 18, 13, X and Y

Benn

2016

Clinical Genetics

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Non-invasive prenatal testing (NIPT) based on cell-free DNA in maternal plasma is being expanded to include additional chromosome abnormalities beyond those involving chromosomes 21, 18, 13, X and Y. Review of population cytogenetic data provides insight into the likely number of additional abnormalities detectable. Additional clinically significant and cytogenetically recognizable abnormalities are present in less than 0.1% of newborns but clinically significant, or potentially significant, sub-microscopic imbalances are expected to be present in 1.7%. Cytogenetic studies on chorionic villus samples suggests that after excluding abnormalities involving chromosomes 21, 18, 13, X and Y, approximately 0.6% of NIPT results may be positive for an unbalanced abnormality attributable to mosaicism but most of these will not be confirmed at amniocentesis or in newborns. NIPT has also been developed for specific microdeletion syndromes and initial experience is now available. Laboratory procedures such as deeper sequencing and additional data analytics are rapidly evolving but even with existing protocols, it is already clear that NIPT does not necessarily need to be limited to trisomies 21, 18, 13 and the sex-chromosome abnormalities. Patient educational materials and genetic counseling services need to be available for women offered expanded NIPT.

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“…Women who are considering CVS and are concerned about the possible association of CVS with limb defects can be reassured that when the procedure is performed at or after 10 weeks of gestation, the risk is low and appears to be no greater than the risk among the general population (21). Another complication of CVS is vaginal spotting or bleeding, which may occur in up to 32% of patients after transcervical CVS (22); the incidence after transabdominal CVS is lower. The incidence of culture failure, amniotic fluid leakage, or infection after CVS is less than 0.5% (16,22,23).…”

Section: Invasive Prenatal Diagnostic Testing Techniquesmentioning

confidence: 99%

“…Another complication of CVS is vaginal spotting or bleeding, which may occur in up to 32% of patients after transcervical CVS (22); the incidence after transabdominal CVS is lower. The incidence of culture failure, amniotic fluid leakage, or infection after CVS is less than 0.5% (16,22,23).…”

Section: Invasive Prenatal Diagnostic Testing Techniquesmentioning

confidence: 99%

Practice Bulletin No. 162

2016

Obstetrics &Amp; Gynecology

242

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Prenatal genetic diagnostic testing is intended to determine, with as much certainty as possible, whether a specific genetic disorder or condition is present in the fetus. In contrast, prenatal genetic screening is designed to assess whether a patient is at increased risk of having a fetus affected by a genetic disorder. Originally, prenatal genetic testing focused primarily on Down syndrome (trisomy 21), but now it is able to detect a broad range of genetic disorders. Although it is necessary to perform amniocentesis or chorionic villus sampling (CVS) to definitively diagnose most genetic disorders, in some circumstances, fetal imaging with ultrasonography, echocardiography, or magnetic resonance imaging may be diagnostic of a particular structural fetal abnormality that is suggestive of an underlying genetic condition.The objective of prenatal genetic testing is to detect health problems that could affect the woman, fetus, or newborn and provide the patient and her obstetrician-gynecologist or other obstetric care provider with enough information to allow a fully informed decision about pregnancy management. Prenatal genetic testing cannot identify all abnormalities or problems in a fetus, and any testing should be focused on the individual patient's risks, reproductive goals, and preferences. It is important that patients understand the benefits and limitations of all prenatal screening and diagnostic testing, including the conditions for which tests are available and the conditions that will not be detected by testing. It also is important that patients realize that there is a broad range of clinical presentations, or phenotypes, for many genetic disorders and that results of genetic testing cannot predict all outcomes. Prenatal genetic testing has many benefits, including reassuring patients when results are normal, identifying disorders for which prenatal treatment may provide benefit, optimizing neonatal outcomes by ensuring the appropriate location for delivery and the necessary personnel to care for affected infants, and allowing the opportunity for pregnancy termination.The purpose of this Practice Bulletin is to review the current status of prenatal genetic diagnostic testing and the evidence supporting its use. For information regarding screening for fetal aneuploidy, refer to Practice Bulletin No. 163, Screening for Fetal Aneuploidy.

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Prenatal Diagnosis of Chromosomal Abnormalities through Chorionic Villus Sampling and Amniocentesis

Cited by 15 publications

References 582 publications

Rare autosomal trisomies: comparison of detection through cell‐free DNA analysis and direct chromosome preparation of chorionic villus samples

Rare autosomal trisomies: comparison of detection through cell‐free DNA analysis and direct chromosome preparation of chorionic villus samples

Expanding non‐invasive prenatal testing beyond chromosomes 21, 18, 13, X and Y

Practice Bulletin No. 162

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