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.).
authors.affiliation: Pregnancy and Perinatology Branch, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD 20892-7510, USA.
authors.forename: Uma M
authors.initials: UM
authors.lastname: Reddy
authors.forename: Grier P
authors.initials: GP
authors.lastname: Page
authors.forename: George R
authors.initials: GR
authors.lastname: Saade
authors.forename: Robert M
authors.initials: RM
authors.lastname: Silver
authors.forename: Vanessa R
authors.initials: VR
authors.lastname: Thorsten
authors.forename: Corette B
authors.initials: CB
authors.lastname: Parker
authors.forename: Halit
authors.initials: H
authors.lastname: Pinar
authors.forename: Marian
authors.initials: M
authors.lastname: Willinger
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Stoll
authors.forename: Josefine
authors.initials: J
authors.lastname: Heim-Hall
authors.forename: Michael W
authors.initials: MW
authors.lastname: Varner
authors.forename: Robert L
authors.initials: RL
authors.lastname: Goldenberg
authors.forename: Radek
authors.initials: R
authors.lastname: Bukowski
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Wapner
authors.forename: Carolyn D
authors.initials: CD
authors.lastname: Drews-Botsch
authors.forename: Barbara M
authors.initials: BM
authors.lastname: O'Brien
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Dudley
authors.forename: Brynn
authors.initials: B
authors.lastname: Levy
mesh_terms: D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000175:diagnosis*; D002877:Chromosomes, Human / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D007621:Karyotyping; D020411:Oligonucleotide Array Sequence Analysis; D017384:Sequence Deletion; D050497:Stillbirth