Chromosomal microarray versus karyotyping for prenatal diagnosis

Ronald J. Wapner, Christa Lese Martin, Brynn Levy, Blake C. Ballif, Christine M. Eng, Julia M. Zachary, Melissa Savage, Lawrence D. Platt, Daniel Saltzman, William A. Grobman, Susan D. Klugman, Thomas Scholl, Joe Leigh Simpson, Kimberly McCall, Vimla S. Aggarwal, Brian Bunke, Odelia Nahum, Ankita Patel, Allen N. Lamb, Elizabeth A. ThomArthur L. Beaudet, David H. Ledbetter, Lisa G. Shaffer, Laird Jackson

Research output: Contribution to journalArticle

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Abstract

BACKGROUND:Chromosomal microarray analysis has emerged as a primary diagnostic tool for the evaluation of developmental delay and structural malformations in children. We aimed to evaluate the accuracy, efficacy, and incremental yield of chromosomal microarray analysis as compared with karyotyping for routine prenatal diagnosis. METHODS:Samples from women undergoing prenatal diagnosis at 29 centers were sent to a central karyotyping laboratory. Each sample was split in two; standard karyotyping was performed on one portion and the other was sent to one of four laboratories for chromosomal microarray. RESULTS:We enrolled a total of 4406 women. Indications for prenatal diagnosis were advanced maternal age (46.6%), abnormal result on Down's syndrome screening (18.8%), structural anomalies on ultrasonography (25.2%), and other indications (9.4%). In 4340 (98.8%) of the fetal samples, microarray analysis was successful; 87.9% of samples could be used without tissue culture. Microarray analysis of the 4282 nonmosaic samples identified all the aneuploidies and unbalanced rearrangements identified on karyotyping but did not identify balanced translocations and fetal triploidy. In samples with a normal karyotype, microarray analysis revealed clinically relevant deletions or duplications in 6.0% with a structural anomaly and in 1.7% of those whose indications were advanced maternal age or positive screening results. CONCLUSIONS:In the context of prenatal diagnostic testing, chromosomal microarray analysis identified additional, clinically significant cytogenetic information as compared with karyotyping and was equally efficacious in identifying aneuploidies and unbalanced rearrangements but did not identify balanced translocations and triploidies. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT01279733.)

Original languageEnglish (US)
Pages (from-to)2175-2184
Number of pages10
JournalNew England Journal of Medicine
Volume367
Issue number23
DOIs
StatePublished - Dec 6 2012

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Karyotyping
Microarray Analysis
Prenatal Diagnosis
Triploidy
Maternal Age
Aneuploidy
National Institute of Child Health and Human Development (U.S.)
Down Syndrome
Karyotype
Cytogenetics
Ultrasonography

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Wapner, R. J., Martin, C. L., Levy, B., Ballif, B. C., Eng, C. M., Zachary, J. M., ... Jackson, L. (2012). Chromosomal microarray versus karyotyping for prenatal diagnosis. New England Journal of Medicine, 367(23), 2175-2184. https://doi.org/10.1056/NEJMoa1203382

Chromosomal microarray versus karyotyping for prenatal diagnosis. / Wapner, Ronald J.; Martin, Christa Lese; Levy, Brynn; Ballif, Blake C.; Eng, Christine M.; Zachary, Julia M.; Savage, Melissa; Platt, Lawrence D.; Saltzman, Daniel; Grobman, William A.; Klugman, Susan D.; Scholl, Thomas; Simpson, Joe Leigh; McCall, Kimberly; Aggarwal, Vimla S.; Bunke, Brian; Nahum, Odelia; Patel, Ankita; Lamb, Allen N.; Thom, Elizabeth A.; Beaudet, Arthur L.; Ledbetter, David H.; Shaffer, Lisa G.; Jackson, Laird.

In: New England Journal of Medicine, Vol. 367, No. 23, 06.12.2012, p. 2175-2184.

Research output: Contribution to journalArticle

Wapner, RJ, Martin, CL, Levy, B, Ballif, BC, Eng, CM, Zachary, JM, Savage, M, Platt, LD, Saltzman, D, Grobman, WA, Klugman, SD, Scholl, T, Simpson, JL, McCall, K, Aggarwal, VS, Bunke, B, Nahum, O, Patel, A, Lamb, AN, Thom, EA, Beaudet, AL, Ledbetter, DH, Shaffer, LG & Jackson, L 2012, 'Chromosomal microarray versus karyotyping for prenatal diagnosis', New England Journal of Medicine, vol. 367, no. 23, pp. 2175-2184. https://doi.org/10.1056/NEJMoa1203382
Wapner RJ, Martin CL, Levy B, Ballif BC, Eng CM, Zachary JM et al. Chromosomal microarray versus karyotyping for prenatal diagnosis. New England Journal of Medicine. 2012 Dec 6;367(23):2175-2184. https://doi.org/10.1056/NEJMoa1203382
Wapner, Ronald J. ; Martin, Christa Lese ; Levy, Brynn ; Ballif, Blake C. ; Eng, Christine M. ; Zachary, Julia M. ; Savage, Melissa ; Platt, Lawrence D. ; Saltzman, Daniel ; Grobman, William A. ; Klugman, Susan D. ; Scholl, Thomas ; Simpson, Joe Leigh ; McCall, Kimberly ; Aggarwal, Vimla S. ; Bunke, Brian ; Nahum, Odelia ; Patel, Ankita ; Lamb, Allen N. ; Thom, Elizabeth A. ; Beaudet, Arthur L. ; Ledbetter, David H. ; Shaffer, Lisa G. ; Jackson, Laird. / Chromosomal microarray versus karyotyping for prenatal diagnosis. In: New England Journal of Medicine. 2012 ; Vol. 367, No. 23. pp. 2175-2184.
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abstract = "BACKGROUND:Chromosomal microarray analysis has emerged as a primary diagnostic tool for the evaluation of developmental delay and structural malformations in children. We aimed to evaluate the accuracy, efficacy, and incremental yield of chromosomal microarray analysis as compared with karyotyping for routine prenatal diagnosis. METHODS:Samples from women undergoing prenatal diagnosis at 29 centers were sent to a central karyotyping laboratory. Each sample was split in two; standard karyotyping was performed on one portion and the other was sent to one of four laboratories for chromosomal microarray. RESULTS:We enrolled a total of 4406 women. Indications for prenatal diagnosis were advanced maternal age (46.6{\%}), abnormal result on Down's syndrome screening (18.8{\%}), structural anomalies on ultrasonography (25.2{\%}), and other indications (9.4{\%}). In 4340 (98.8{\%}) of the fetal samples, microarray analysis was successful; 87.9{\%} of samples could be used without tissue culture. Microarray analysis of the 4282 nonmosaic samples identified all the aneuploidies and unbalanced rearrangements identified on karyotyping but did not identify balanced translocations and fetal triploidy. In samples with a normal karyotype, microarray analysis revealed clinically relevant deletions or duplications in 6.0{\%} with a structural anomaly and in 1.7{\%} of those whose indications were advanced maternal age or positive screening results. CONCLUSIONS:In the context of prenatal diagnostic testing, chromosomal microarray analysis identified additional, clinically significant cytogenetic information as compared with karyotyping and was equally efficacious in identifying aneuploidies and unbalanced rearrangements but did not identify balanced translocations and triploidies. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT01279733.)",
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T1 - Chromosomal microarray versus karyotyping for prenatal diagnosis

AU - Wapner, Ronald J.

AU - Martin, Christa Lese

AU - Levy, Brynn

AU - Ballif, Blake C.

AU - Eng, Christine M.

AU - Zachary, Julia M.

AU - Savage, Melissa

AU - Platt, Lawrence D.

AU - Saltzman, Daniel

AU - Grobman, William A.

AU - Klugman, Susan D.

AU - Scholl, Thomas

AU - Simpson, Joe Leigh

AU - McCall, Kimberly

AU - Aggarwal, Vimla S.

AU - Bunke, Brian

AU - Nahum, Odelia

AU - Patel, Ankita

AU - Lamb, Allen N.

AU - Thom, Elizabeth A.

AU - Beaudet, Arthur L.

AU - Ledbetter, David H.

AU - Shaffer, Lisa G.

AU - Jackson, Laird

PY - 2012/12/6

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N2 - BACKGROUND:Chromosomal microarray analysis has emerged as a primary diagnostic tool for the evaluation of developmental delay and structural malformations in children. We aimed to evaluate the accuracy, efficacy, and incremental yield of chromosomal microarray analysis as compared with karyotyping for routine prenatal diagnosis. METHODS:Samples from women undergoing prenatal diagnosis at 29 centers were sent to a central karyotyping laboratory. Each sample was split in two; standard karyotyping was performed on one portion and the other was sent to one of four laboratories for chromosomal microarray. RESULTS:We enrolled a total of 4406 women. Indications for prenatal diagnosis were advanced maternal age (46.6%), abnormal result on Down's syndrome screening (18.8%), structural anomalies on ultrasonography (25.2%), and other indications (9.4%). In 4340 (98.8%) of the fetal samples, microarray analysis was successful; 87.9% of samples could be used without tissue culture. Microarray analysis of the 4282 nonmosaic samples identified all the aneuploidies and unbalanced rearrangements identified on karyotyping but did not identify balanced translocations and fetal triploidy. In samples with a normal karyotype, microarray analysis revealed clinically relevant deletions or duplications in 6.0% with a structural anomaly and in 1.7% of those whose indications were advanced maternal age or positive screening results. CONCLUSIONS:In the context of prenatal diagnostic testing, chromosomal microarray analysis identified additional, clinically significant cytogenetic information as compared with karyotyping and was equally efficacious in identifying aneuploidies and unbalanced rearrangements but did not identify balanced translocations and triploidies. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT01279733.)

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