Use of prenatal chromosomal microarray: prospective cohort study and systematic review and meta-analysis

Hillman, Sarah; McMullan, Dominic; Hall, Gillian; Togneri, Fiona S.; James, Nathan T.; Maher, E. J.; Meller, Christian; Williams, Denise; Wapner, Ronald J.; Maher, ER; Kilby, Mark D.

doi:10.1002/uog.12464

Cited by 263 publications

(264 citation statements)

References 34 publications

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“…Our results are slightly lower than those observed in a recent meta-analysis that found a 10% increased diagnostic yield of chromosomal microarrays over karyotyping (95% confidence interval: 8-13%) in the presence of ultrasound anomalies. 27 Several recent large-scale prospective studies found rates between 6 and 8% in the presence of ultrasound anomalies. 6,7,28 However, we demonstrate that arrays provide additional information over karyotyping in 3.9% of patients.…”

Section: Discussionmentioning

confidence: 99%

“…Rates of VOUS ranged from 0.39 to 4.2% depending on whether de novo imbalances were included or not. 6,7,27,28 The risk of detecting a pathogenic CNV in the absence of any ultrasound anomalies has been estimated to be between 0.5 and 1.7% in several studies that have included the use of chromosomal microarrays for general screening. [28][29][30] Hillman et al 27 comment in their meta-analysis the high degree of heterogeneity in results of different array studies, which may be due to a number of factors including the type of cohort studied and the type of platform used.…”

Section: Discussionmentioning

confidence: 99%

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A prospective study of the clinical utility of prenatal chromosomal microarray analysis in fetuses with ultrasound abnormalities and an exploration of a framework for reporting unclassified variants and risk factors

Brady

Chiaie

Christenhusz

et al. 2014

Genetics in Medicine

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Original research article INTRODUCTIONConventional karyotyping has been considered the gold standard for routine prenatal genetic diagnosis for many decades now, allowing for microscopic visualization and inspection of chromosomes and thus detection of numerical and structural chromosomal rearrangements. The main limitations are the resolution achieved by G-banding, which is limited to 5-10 Mb at best, and the requirement for cultured cells, needing a minimum of 8-10 days. The introduction of targeted methods of analysis such as fluorescence in situ hybridization (FISH) and multiplex ligation-dependent probe amplification (MLPA) overcome the time constraints and resolution limitations inherent to karyotyping but do not provide a genome-wide analysis.1 More recently, molecular karyotyping using genomic microarrays has reached mainstream use in the postnatal diagnostic setting, providing a genome-wide screen for genomic imbalances at a far superior resolution to karyotyping.2 A number of studies have demonstrated the feasibility of prenatal diagnosis by genomic arrays using a variety of platforms, 3-7 but challenges remain in applying high-resolution genomic arrays to prenatal diagnosis. 6,8,9 One of the major ethical issues often raised is how to deal with variants of uncertain significance (VOUS) or risk loci, the detection of which leads to additional challenges for genetic counseling of parents. Furthermore, array analysis may reveal an imbalance for known "risk loci" where the future penetrance is uncertain or may be associated with variable expression. The penetrance risks for a number of recurrent copy-number variations (CNVs) have been estimated based on the frequencies in patients and controls. [10][11][12] However, although it is possible to calculate a populationbased risk, it is impossible in the prenatal setting to predict the phenotypic outcome in the child. Purpose:To evaluate the clinical utility of chromosomal microarrays for prenatal diagnosis by a prospective study of fetuses with abnormalities detected on ultrasound. Methods: Patients referred for prenatal diagnosis due to ultrasound anomalies underwent analysis by array comparative genomic hybridization as the first-tier diagnostic test.Results: A total of 383 prenatal samples underwent analysis by array comparative genomic hybridization. Array analysis revealed causal imbalances in a total of 9.6% of patients (n = 37). Submicroscopic copy-number variations were detected in 2.6% of patients (n = 10/37), and arrays added valuable information over conventional karyotyping in 3.9% of patients (n = 15/37). We highlight a novel advantage of arrays; a 500-kb paternal insertional translocation is the likely driver of a de novo unbalanced translocation, thus improving recurrence risk calculation in this family. Variants of uncertain significance were revealed in 1.6% of patients (n = 6/383). Conclusion:We demonstrate the added value of chromosomal microarrays for prenatal diagnosis in the presence of ultrasound anomalies. We advocate reporting back on...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A prospective study of the clinical utility of prenatal chromosomal microarray analysis in fetuses with ultrasound abnormalities and an exploration of a framework for reporting unclassified variants and risk factors

Brady

Chiaie

Christenhusz

et al. 2014

Genetics in Medicine

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“…in those with structural anomalies). Increasingly, it is thought that in 'high' risk groups, such as those in which karyotyping is undertaken because of the presence of a fetal anomaly, as reported in our prospective cohort 1 , there is to be an advantage in detecting 'pathological' copy number variants (CNVs). However, when the prior probability of pathologic CNV detection is low, the health economic analysis indicates that alternative karyotyping strategies (using targeted fluorescent in-situ hybridization) should be explored and compared to CMA technology.…”

Section: Replymentioning

confidence: 93%

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Kilby

Hillman

Maher

et al. 2014

Ultrasound in Obstet & Gyne

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“…At present, chromosomal microarray analysis is recommended instead of, or as an adjunct to, conventional karyotyping, as it allows genome-wide analysis at a much higher resolution (up to 1 kilobase (kb)), revealing clinically significant unbalanced submicroscopic aberrations [1][2][3] . However, these techniques all require fetal tissue obtained by an invasive diagnostic procedure, i.e.…”

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confidence: 99%

Clinical Utility of Noninvasive Prenatal Testing in Pregnancies With Ultrasound Anomalies

Beulen

Faas

Feenstra

et al. 2017

Obstetrical &Amp; Gynecological Survey

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Use of prenatal chromosomal microarray: prospective cohort study and systematic review and meta-analysis

Abstract: Objectives MEDLINE (1970-Dec 2012, EMBASE (1980-Dec 2012 and CINAHL (1982-June 2012

Cited by 263 publications

References 34 publications

A prospective study of the clinical utility of prenatal chromosomal microarray analysis in fetuses with ultrasound abnormalities and an exploration of a framework for reporting unclassified variants and risk factors

A prospective study of the clinical utility of prenatal chromosomal microarray analysis in fetuses with ultrasound abnormalities and an exploration of a framework for reporting unclassified variants and risk factors

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Clinical Utility of Noninvasive Prenatal Testing in Pregnancies With Ultrasound Anomalies

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