Karyotype versus microarray testing for genetic abnormalities after stillbirth - PubMed (original) (raw)

Comparative Study

. 2012 Dec 6;367(23):2185-93.

doi: 10.1056/NEJMoa1201569.

Grier P Page, George R Saade, Robert M Silver, Vanessa R Thorsten, Corette B Parker, Halit Pinar, Marian Willinger, Barbara J Stoll, Josefine Heim-Hall, Michael W Varner, Robert L Goldenberg, Radek Bukowski, Ronald J Wapner, Carolyn D Drews-Botsch, Barbara M O'Brien, Donald J Dudley, Brynn Levy; NICHD Stillbirth Collaborative Research Network

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Comparative Study

Karyotype versus microarray testing for genetic abnormalities after stillbirth

Uma M Reddy et al. N Engl J Med. 2012.

Abstract

Background: Genetic abnormalities have been associated with 6 to 13% of stillbirths, but the true prevalence may be higher. Unlike karyotype analysis, microarray analysis does not require live cells, and it detects small deletions and duplications called copy-number variants.

Methods: The Stillbirth Collaborative Research Network conducted a population-based study of stillbirth in five geographic catchment areas. Standardized postmortem examinations and karyotype analyses were performed. A single-nucleotide polymorphism array was used to detect copy-number variants of at least 500 kb in placental or fetal tissue. Variants that were not identified in any of three databases of apparently unaffected persons were then classified into three groups: probably benign, clinical significance unknown, or pathogenic. We compared the results of karyotype and microarray analyses of samples obtained after delivery.

Results: In our analysis of samples from 532 stillbirths, microarray analysis yielded results more often than did karyotype analysis (87.4% vs. 70.5%, P<0.001) and provided better detection of genetic abnormalities (aneuploidy or pathogenic copy-number variants, 8.3% vs. 5.8%; P=0.007). Microarray analysis also identified more genetic abnormalities among 443 antepartum stillbirths (8.8% vs. 6.5%, P=0.02) and 67 stillbirths with congenital anomalies (29.9% vs. 19.4%, P=0.008). As compared with karyotype analysis, microarray analysis provided a relative increase in the diagnosis of genetic abnormalities of 41.9% in all stillbirths, 34.5% in antepartum stillbirths, and 53.8% in stillbirths with anomalies.

Conclusions: Microarray analysis is more likely than karyotype analysis to provide a genetic diagnosis, primarily because of its success with nonviable tissue, and is especially valuable in analyses of stillbirths with congenital anomalies or in cases in which karyotype results cannot be obtained. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.).

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Figure 1

Figure 1. Performance of Karyotype and Microarray Analyses in Samples Obtained after Delivery in 532 Stillbirths

On the left, karyotype results (blue) are categorized as failed, normal, or abnormal, as compared with findings from the same cases on microarray analysis (orange). On the right, the microarray results are categorized as failed, normal, abnormal, or variants of unknown significance (VOUS), with the corresponding karyotype results in the same cases. CNV denotes copy-number variant.

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References

    1. MacDorman MF, Kirmeyer S. Fetal and perinatal mortality, United States, 2005. Natl Vital Stat Rep. 2009;57(8):1–19. - PubMed
    1. Smith GC, Fretts RC. Stillbirth. Lancet. 2007;370:1715–1725. - PubMed
    1. Pauli RM, Reiser CA, Lebovitz RM, Kirkpatrick SJ. Wisconsin Stillbirth Service Program: I. Establishment and assessment of a community-based program for etiologic investigation of intrauterine deaths. Am J Med Genet. 1994;50:116–134. - PubMed
    1. Korteweg FJ, Bouman K, Erwich JJ, et al. Cytogenetic analysis after evaluation of 750 fetal deaths: proposal for diagnostic workup. Obstet Gynecol. 2008;111:865–874. - PubMed
    1. Parker CB, Hogue CJR, Koch MA, et al. Stillbirth Collaborative Research Network: design, methods and recruitment experience. Paediatr Perinat Epidemiol. 2011;25:425–435. - PMC - PubMed

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