title: Use of prenatal chromosomal microarray: prospective cohort study and systematic review and meta-analysis.
abstract: OBJECTIVE
  Chromosomal microarray analysis (CMA) is utilized in prenatal diagnosis to detect chromosomal abnormalities not visible by conventional karyotyping. A prospective cohort of women undergoing fetal CMA and karyotyping following abnormal prenatal ultrasound findings is presented in the context of a systematic review and meta-analysis of the literature describing detection rates by CMA and karyotyping.
  
  
  METHODS
  We performed a prospective cohort study of 243 women undergoing CMA alongside karyotyping when a structural abnormality was detected on prenatal ultrasound. A systematic review of the literature was also performed. MEDLINE (1970-Dec 2012), EMBASE (1980-Dec 2012) and CINAHL (1982-June 2012) databases were searched electronically. Selected studies included > 10 cases and prenatal CMA in addition to karyotyping. The search yielded 560 citations. Full papers were retrieved for 86, and 25 primary studies were included in the systematic review.
  
  
  RESULTS
  Our cohort study found an excess detection rate of abnormalities by CMA of 4.1% over conventional karyotyping when the clinical indication for testing was an abnormal fetal ultrasound finding; this was lower than the detection rate of 10% (95% CI, 8-13%) by meta-analysis. The rate of detection for variants of unknown significance (VOUS) was 2.1% (95% CI, 1.3-3.3%) when the indication for CMA was an abnormal scan finding. The VOUS detection rate was lower (1.4%; 95% CI, 0.5-3.7%) when any indication for prenatal CMA was meta-analyzed.
  
  
  CONCLUSIONS
  We present evidence for a higher detection rate by CMA than by karyotyping not just in the case of abnormal ultrasound findings but also in cases of other indications for invasive testing. It is likely that CMA will replace karyotyping in high-risk pregnancies.
authors.affiliation: School of Clinical and Experimental Medicine, College of Medicine and Dentistry, University of Birmingham, Edgbaston, Birmingham, UK.
authors.forename: S C
authors.initials: SC
authors.lastname: Hillman
authors.forename: D J
authors.initials: DJ
authors.lastname: McMullan
authors.forename: G
authors.initials: G
authors.lastname: Hall
authors.forename: F S
authors.initials: FS
authors.lastname: Togneri
authors.forename: N
authors.initials: N
authors.lastname: James
authors.forename: E J
authors.initials: EJ
authors.lastname: Maher
authors.forename: C H
authors.initials: CH
authors.lastname: Meller
authors.forename: D
authors.initials: D
authors.lastname: Williams
authors.forename: R J
authors.initials: RJ
authors.lastname: Wapner
authors.forename: E R
authors.initials: ER
authors.lastname: Maher
authors.forename: M D
authors.initials: MD
authors.lastname: Kilby
mesh_terms: D025063:Chromosome Disorders / Q000175:diagnosis*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping / Q000379:methods; D046228:Microarray Analysis / Q000379:methods*; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D011446:Prospective Studies; D016216:Ultrasonography, Prenatal / Q000379:methods