Karyotype versus microarray testing for genetic abnormalities after stillbirth

Uma M. Reddy, Grier P. Page, George 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

Research output: Contribution to journalArticle

107 Citations (Scopus)

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.)

Original languageEnglish (US)
Pages (from-to)2185-2193
Number of pages9
JournalNew England Journal of Medicine
Volume367
Issue number23
DOIs
StatePublished - Dec 6 2012

Fingerprint

Stillbirth
Genetic Testing
Karyotype
Microarray Analysis
National Institute of Child Health and Human Development (U.S.)
Aneuploidy
Single Nucleotide Polymorphism
Autopsy
Fetus
Databases

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Reddy, U. M., Page, G. P., Saade, G., Silver, R. M., Thorsten, V. R., Parker, C. B., ... Levy, B. (2012). Karyotype versus microarray testing for genetic abnormalities after stillbirth. New England Journal of Medicine, 367(23), 2185-2193. https://doi.org/10.1056/NEJMoa1201569

Karyotype versus microarray testing for genetic abnormalities after stillbirth. / Reddy, Uma M.; Page, Grier P.; Saade, George; Silver, Robert M.; Thorsten, Vanessa R.; Parker, Corette B.; Pinar, Halit; Willinger, Marian; Stoll, Barbara J.; Heim-Hall, Josefine; Varner, Michael W.; Goldenberg, Robert L.; Bukowski, Radek; Wapner, Ronald J.; Drews-Botsch, Carolyn D.; O'Brien, Barbara M.; Dudley, Donald J.; Levy, Brynn.

In: New England Journal of Medicine, Vol. 367, No. 23, 06.12.2012, p. 2185-2193.

Research output: Contribution to journalArticle

Reddy, UM, Page, GP, Saade, G, Silver, RM, Thorsten, VR, Parker, CB, Pinar, H, Willinger, M, Stoll, BJ, Heim-Hall, J, Varner, MW, Goldenberg, RL, Bukowski, R, Wapner, RJ, Drews-Botsch, CD, O'Brien, BM, Dudley, DJ & Levy, B 2012, 'Karyotype versus microarray testing for genetic abnormalities after stillbirth', New England Journal of Medicine, vol. 367, no. 23, pp. 2185-2193. https://doi.org/10.1056/NEJMoa1201569
Reddy, Uma M. ; Page, Grier P. ; Saade, George ; Silver, Robert M. ; Thorsten, Vanessa R. ; Parker, Corette B. ; Pinar, Halit ; Willinger, Marian ; Stoll, Barbara J. ; Heim-Hall, Josefine ; Varner, Michael W. ; Goldenberg, Robert L. ; Bukowski, Radek ; Wapner, Ronald J. ; Drews-Botsch, Carolyn D. ; O'Brien, Barbara M. ; Dudley, Donald J. ; Levy, Brynn. / Karyotype versus microarray testing for genetic abnormalities after stillbirth. In: New England Journal of Medicine. 2012 ; Vol. 367, No. 23. pp. 2185-2193.
@article{f36c8a3f64b34fbba621230946bf7b01,
title = "Karyotype versus microarray testing for genetic abnormalities after stillbirth",
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.)",
author = "Reddy, {Uma M.} and Page, {Grier P.} and George Saade and Silver, {Robert M.} and Thorsten, {Vanessa R.} and Parker, {Corette B.} and Halit Pinar and Marian Willinger and Stoll, {Barbara J.} and Josefine Heim-Hall and Varner, {Michael W.} and Goldenberg, {Robert L.} and Radek Bukowski and Wapner, {Ronald J.} and Drews-Botsch, {Carolyn D.} and O'Brien, {Barbara M.} and Dudley, {Donald J.} and Brynn Levy",
year = "2012",
month = "12",
day = "6",
doi = "10.1056/NEJMoa1201569",
language = "English (US)",
volume = "367",
pages = "2185--2193",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "23",

}

TY - JOUR

T1 - Karyotype versus microarray testing for genetic abnormalities after stillbirth

AU - Reddy, Uma M.

AU - Page, Grier P.

AU - Saade, George

AU - Silver, Robert M.

AU - Thorsten, Vanessa R.

AU - Parker, Corette B.

AU - Pinar, Halit

AU - Willinger, Marian

AU - Stoll, Barbara J.

AU - Heim-Hall, Josefine

AU - Varner, Michael W.

AU - Goldenberg, Robert L.

AU - Bukowski, Radek

AU - Wapner, Ronald J.

AU - Drews-Botsch, Carolyn D.

AU - O'Brien, Barbara M.

AU - Dudley, Donald J.

AU - Levy, Brynn

PY - 2012/12/6

Y1 - 2012/12/6

N2 - 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.)

AB - 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.)

UR - http://www.scopus.com/inward/record.url?scp=84870567269&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84870567269&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa1201569

DO - 10.1056/NEJMoa1201569

M3 - Article

VL - 367

SP - 2185

EP - 2193

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 23

ER -