Is it time for prenatal chromosomal-microarray analysis to all women? A review of the diagnostic yield in structurally normal fetuses

Daum, Hagit; Stern, Shira; Shkedi‐Rafid, Shiri

doi:10.1097/gco.0000000000000690

Cited by 6 publications

(3 citation statements)

References 23 publications

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“…A 2020 study indicated that the frequency of pathogenic or likely pathogenic CNVs is 1.2% in all indications by prenatal SNP array [ 34 ]. A recent review summarized a total of 29,612 cases using array techniques in foetuses with abnormal structures and the rate of pathogenic or likely pathogenic CNVs was 0.4–2.5% [ 35 ]. In our study, we found a 1.4% increased diagnostic yield, which might have been missed if only conventional karyotyping had been performed.…”

Section: Discussionmentioning

confidence: 99%

Detection rates of abnormalities in over 10,000 amniotic fluid samples at a single laboratory

Kakongoma

et al. 2023

BMC Pregnancy Childbirth

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Background A growing number of cytogenetic techniques have been used for prenatal diagnosis. This study aimed to demonstrate the usefulness of karyotyping, BACs-on-Beads (BoBs) assay and single nucleotide polymorphism (SNP) array in prenatal diagnosis during the second trimester based on our laboratory experience. Methods A total of 10,580 pregnant women with a variety of indications for amniocentesis were enrolled in this retrospective study between January 2015 and December 2020, of whom amniotic fluid samples were analysed in 10,320 women. The main technical indicators of participants in the three different technologies were summarized, and cases of chromosome abnormalities were further evaluated. Results The overall abnormality detection rate of karyotyping among all the amniotic fluid samples was 15.4%, and trisomy 21 was the most common abnormality (20.9%). The total abnormality detection rate of the BoBs assay was 5.6%, and the diagnosis rate of microdeletion/microduplication syndromes that were not identified by karyotyping was 0.2%. The detection results of the BoBs assay were 100.0% concordant with karyotyping analysis in common aneuploidies. Seventy (87.5%) cases of structural abnormalities were missed by BoBs assay. The total abnormality detection rate of the SNP array was 21.6%. The detection results of common aneuploidies were exactly the same between SNP array and karyotyping. Overall, 60.1% of structural abnormalities were missed by SNP array. The further detection rate of pathogenic significant copy number variations (CNVs) by SNP was 1.4%. Conclusions Karyotyping analysis combined with BoBs assay or SNP array for prenatal diagnosis could provide quick and accurate results. Combined use of the technologies, especially with SNP array, improved the diagnostic yield and interpretation of the results, which contributes to genetic counselling. BoBs assay or SNP array could be a useful supplement to karyotyping.

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Section: Discussionmentioning

confidence: 99%

Detection rates of abnormalities in over 10,000 amniotic fluid samples at a single laboratory

Kakongoma

et al. 2023

BMC Pregnancy Childbirth

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“…50 Studies consistently show that pathogenic CNVs can be identified in 0.4 to 2.5% of structurally normal fetuses. 52,53 While CNVs may be associated with a wide variety of outcomes and varying penetrance and expressivity, a substantial proportion are associated with major neurodevelopmental impairment or physical/medical debility. However, the detection of variants of uncertain significance presents some challenges for the use of CMA, and it is essential that genetic counseling addresses this prospect before invasive testing.…”

Section: Cell-free Dna and Microarraymentioning

confidence: 99%

Prenatal Screening and Diagnosis: Time for a Paradigm Shift

Oyelese,

Schioppo,

O'Brien

2024

Am J Perinatol

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Recent advances in genetics and imaging have ushered in substantial breakthroughs in screening and diagnosis for chromosomal and structural abnormalities. Thus, it is imperative that healthcare providers caring for pregnant individuals should re-examine established practices in prenatal screening and diagnosis. In the past, screening for chromosomal abnormalities was based almost entirely on Down syndrome. Pregnant individuals aged > 35 were considered at “high risk” or of “advanced maternal age” based on age alone; however, the advent of tests with high sensitivity for prenatal detection of chromosomal abnormalities should lead to abandoning that concept, at least from the perspective of chromosomal abnormalities. Given that first-trimester and second-trimester screening will fail to detect between 5 and 20% of Down syndrome, in most situations, non-invasive testing with cell-free DNA should be the first-line screen for Down syndrome. The fact that over 99% of fetuses with Down syndrome will be detected prenatally with cell-free DNA gives other fetal chromosomal and structural abnormalities increasing prominence. Chromosomal microarray analysis (CMA) permits prenatal detection of several clinically important chromosomal aberrations that cannot be detected by karyotype and may exist in structurally normal fetuses with low-risk cell-free DNA screening. As such, CMA should be more readily conducted when invasive testing is performed, regardless of the presence of a structural abnormality. Isolated sonographic “soft markers” have no clinical significance in patients who have normal cell-free DNA screening, can cause unwarranted anxiety and a negative impact on pregnancy, and perhaps it is time to stop discussing them. Detailed first-trimester ultrasound allows early detection of several severe fetal anomalies, and therefore in settings with adequately trained personnel and resources, should be used more frequently. This Opinion traces the evolution of prenatal screening and diagnosis and advocates for a paradigm shift that aligns with recent developments in prenatal screening and diagnostic capabilities.

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“…CMA is currently recommended as the first‐tier test in pregnancies with fetal malformations 4,5,8 and adds a detection rate of 5%–7% over karyotyping 9,10 . In several countries, including Israel, CMA is the first‐tier test for all invasive prenatal diagnostic testing, including parental wishes in uneventful pregnancies, 1,11,12 with 0.4%–2.5% risk of pathogenic results 10,13,14 . Alongside the increased capacity of CMA to detect pathologic copy‐number variations (CNVs), it can also identify CNVs with variable expressivity and incomplete penetrance—often referred to as susceptibility loci (SL).…”

Section: Introductionmentioning

confidence: 99%

Women's attitudes towards disclosure of genetic information in pregnancy with varying levels of penetrance

Libman,

Macarov,

Friedlander

et al. 2024

Prenatal Diagnosis

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BackgroundChromosomal‐microarray‐analysis (CMA) may reveal susceptibility‐loci (SL) of varied penetrance for autism‐spectrum‐disorder (ASD) and other neurodevelopmental conditions. Attitudes of women/parents to disclosure of SL during pregnancy are understudied.MethodsA multiple‐choice questionnaire was distributed to postpartum women. Data were collected on women's interest to receive prenatal genetic information with various levels of penetrance.ResultsWomen's (n = 941) disclosure choices were dependent on the magnitude of risk: approximately 70% supported disclosure of either full or 40% penetrance, 53% supported disclosure at a 20% risk threshold, and 40% supported disclosure at 10% or less. Although most women supported, rejected or were indecisive about disclosure consistently across all risk levels, nearly one‐quarter (24%) varied their responses based on penetrance, and this was associated with religiosity, education, parity and concern about fetal health (p‐values <0.04). Among those who varied their choices, the risk threshold was lower among secular women (20%) than among ultraorthodox women (40%). In a multivariable analysis, ultraorthodox women were much less likely to vary their choices on ASD disclosure compared with secular women (aOR = 0.37, p < 0.001).ConclusionWomen's attitudes toward disclosure are influenced by the level of risk and their individual characteristics. We therefore encourage engaging women/couples in disclosure decisions regarding uncertain and probabilistic results from prenatal genomic tests.

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Is it time for prenatal chromosomal-microarray analysis to all women? A review of the diagnostic yield in structurally normal fetuses

Cited by 6 publications

References 23 publications

Detection rates of abnormalities in over 10,000 amniotic fluid samples at a single laboratory

Detection rates of abnormalities in over 10,000 amniotic fluid samples at a single laboratory

Prenatal Screening and Diagnosis: Time for a Paradigm Shift

Women's attitudes towards disclosure of genetic information in pregnancy with varying levels of penetrance

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