title: Chromosomal microarray versus karyotyping for prenatal diagnosis.
abstract: 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.).
authors.affiliation: Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, NY 10032, USA. rw2191@mail.cumc.columbia.edu
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Wapner
authors.forename: Christa Lese
authors.initials: CL
authors.lastname: Martin
authors.forename: Brynn
authors.initials: B
authors.lastname: Levy
authors.forename: Blake C
authors.initials: BC
authors.lastname: Ballif
authors.forename: Christine M
authors.initials: CM
authors.lastname: Eng
authors.forename: Julia M
authors.initials: JM
authors.lastname: Zachary
authors.forename: Melissa
authors.initials: M
authors.lastname: Savage
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Platt
authors.forename: Daniel
authors.initials: D
authors.lastname: Saltzman
authors.forename: William A
authors.initials: WA
authors.lastname: Grobman
authors.forename: Susan
authors.initials: S
authors.lastname: Klugman
authors.forename: Thomas
authors.initials: T
authors.lastname: Scholl
authors.forename: Joe Leigh
authors.initials: JL
authors.lastname: Simpson
authors.forename: Kimberly
authors.initials: K
authors.lastname: McCall
authors.forename: Vimla S
authors.initials: VS
authors.lastname: Aggarwal
authors.forename: Brian
authors.initials: B
authors.lastname: Bunke
authors.forename: Odelia
authors.initials: O
authors.lastname: Nahum
authors.forename: Ankita
authors.initials: A
authors.lastname: Patel
authors.forename: Allen N
authors.initials: AN
authors.lastname: Lamb
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Thom
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Beaudet
authors.forename: David H
authors.initials: DH
authors.lastname: Ledbetter
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Shaffer
authors.forename: Laird
authors.initials: L
authors.lastname: Jackson
mesh_terms: D000328:Adult; D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000175:diagnosis*; D002877:Chromosomes, Human / Q000235:genetics; D004314:Down Syndrome / Q000175:diagnosis; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D059785:Karyotype; D007621:Karyotyping; D008423:Maternal Age; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D016216:Ultrasonography, Prenatal