title: Diagnostic utility of microarray testing in pregnancy loss.
abstract: OBJECTIVE
  To determine the frequency of clinically significant chromosomal abnormalities identified by chromosomal microarray in pregnancy losses at any gestational age and to compare microarray performance with that of traditional cytogenetic analysis when testing pregnancy losses.
  
  
  METHODS
  Among 535 fetal demise specimens of any gestational age, clinical microarray-based comparative genomic hybridization (aCGH) was performed successfully on 515, and a subset of 107 specimens underwent additional single nucleotide polymorphism (SNP) analysis.
  
  
  RESULTS
  Overall, clinically significant abnormalities were identified in 12.8% (64/499) of specimens referred with normal or unknown karyotypes. Detection rates were significantly higher with earlier gestational age. In the subset with normal karyotype, clinically significant abnormalities were identified in 6.9% (20/288). This detection rate did not vary significantly with gestational age, suggesting that, unlike aneuploidy, the contribution of submicroscopic chromosomal abnormalities to fetal demise does not vary with gestational age. In the 107 specimens that underwent aCGH and SNP analysis, seven cases (6.5%) had abnormalities of potential clinical significance detected by the SNP component, including female triploidy. aCGH failed to yield fetal results in 8.3%, which is an improvement over traditional cytogenetic analysis of fetal demise specimens.
  
  
  CONCLUSIONS
  Both the provision of results in cases in which karyotype fails and the detection of abnormalities in the presence of a normal karyotype demonstrate the increased diagnostic utility of microarray in pregnancy loss. Thus, chromosomal microarray testing is a preferable, robust method of analyzing cases of pregnancy loss to better delineate possible genetic etiologies, regardless of gestational age.
authors.affiliation: Signature Genomic Laboratories, PerkinElmer, Inc., Spokane, WA, USA.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: J A
authors.identifier: http://orcid.org/0000-0001-5664-7987
authors.initials: JA
authors.lastname: Rosenfeld
authors.affiliation: St. Vincent Hospital, Indianapolis, IN, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Tucker
authors.affiliation: St. Vincent Hospital, Indianapolis, IN, USA.
authors.forename: L F
authors.initials: LF
authors.lastname: Escobar
authors.affiliation: Signature Genomic Laboratories, PerkinElmer, Inc., Spokane, WA, USA.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: N J
authors.initials: NJ
authors.lastname: Neill
authors.affiliation: Signature Genomic Laboratories, PerkinElmer, Inc., Spokane, WA, USA.
authors.forename: B S
authors.initials: BS
authors.lastname: Torchia
authors.affiliation: Signature Genomic Laboratories, PerkinElmer, Inc., Spokane, WA, USA.
authors.forename: L D
authors.initials: LD
authors.lastname: McDaniel
authors.affiliation: Signature Genomic Laboratories, PerkinElmer, Inc., Spokane, WA, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Schultz
authors.affiliation: The Prenatal Diagnosis and Medical Genetics Program, Mount Sinai Hospital, University of Toronto, Ontario, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Chong
authors.affiliation: The Prenatal Diagnosis and Medical Genetics Program, Mount Sinai Hospital, University of Toronto, Ontario, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Chitayat
mesh_terms: D000022:Abortion, Spontaneous / Q000235:genetics*; D000782:Aneuploidy; D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000175:diagnosis / Q000235:genetics; D055028:Comparative Genomic Hybridization / Q000379:methods; D020732:Cytogenetic Analysis / Q000379:methods; D005260:Female; D005333:Fetus; D006801:Humans; D007621:Karyotyping / Q000379:methods; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods; D050497:Stillbirth / Q000235:genetics*; D057885:Triploidy
keywords: chromosomal microarray; fetal demise; miscarriage; prenatal diagnosis; stillbirth