Chromosomal microarray versus karyotyping for prenatal diagnosis
Open accessAbstract
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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- Authors
- Wapner, R. J., Martin, C. L., Levy, B., Ballif, B. C., Eng, C. M., Zachary, J. M., Savage, M., Platt, L. D., Saltzman, D., Grobman, W. A., Klugman, S., Scholl, T., Simpson, J. L., McCall, K., Aggarwal, V. S., Bunke, B., Nahum, O., Patel, A., Lamb, A. N., Thom, E. A., Beaudet, A. L., Ledbetter, D. H., Shaffer, L. G., & Jackson, L.
- Affiliations
- Columbia University Irving Medical Center (US)
- Emory University (US)
- Genome Canada (CA)
- Baylor College of Medicine (US)
- George Washington University (US)
- Northwestern University (US)
- Albert Einstein College of Medicine (US)
- Sequenom (United States) (US)
- Florida International University (US)
- Drexel University (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2012-12-06
- Volume
- 367
- Issue
- 23
- Pages
- 2175-2184
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC3549418
- OpenAlex
- W2144967747
- Cited by
- 1,412
- References
- 34
- Citations by year
- 2026: 64 · 2025: 85 · 2024: 113 · 2023: 118 · 2022: 131 · 2021: 111 · 2020: 99 · 2019: 103 · 2018: 144 · 2017: 94 · 2016: 87 · 2015: 88 · 2014: 103 · 2013: 68 · 2012: 3
- FWCI
- 73.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000150)
- National Center for Advancing Translational Sciences
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (RC2HD064525, R01HD055651)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Screening and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- chromosomal microarray analysis, karyology, prenatal diagnosis, fetal aneuploidy, unbalanced chromosomal rearrangements, balanced translocation, Down syndrome screening, advanced maternal age, structural anomalies, diagnostic yield
- MeSH terms
- Adult, Chromosome Aberrations, Chromosomes, Human, Down Syndrome, Female, Fetal Diseases, Genetic Testing, Humans, Karyotyping, Maternal Age, Pregnancy, Prenatal Diagnosis, Ultrasonography, Prenatal, Oligonucleotide Array Sequence Analysis, Chromosome Disorders, Karyotype
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