Experience with microarray-based comparative genomic hybridization for prenatal diagnosis in over 5000 pregnancies

Prenat Diagn. 2012 Oct;32(10):976-85. doi: 10.1002/pd.3945. Epub 2012 Aug 2.


Objective: To demonstrate the usefulness of microarray testing in prenatal diagnosis based on our laboratory experience.

Methods: Prenatal samples received from 2004 to 2011 for a variety of indications (n = 5003) were tested using comparative genomic hybridization-based microarrays targeted to known chromosomal syndromes with later versions of the microarrays providing backbone coverage of the entire genome.

Results: The overall detection rate of clinically significant copy number alterations (CNAs) among unbiased, nondemise cases was 5.3%. Detection rates were 6.5% and 8.2% for cases referred with abnormal ultrasounds and fetal demise, respectively. The overall rate of findings with unclear clinical significance was 4.2% but would reduce to 0.39% if only de novo CNAs were considered. In cases with known chromosomal rearrangements in the fetus or parent, 41.1% showed CNAs related to the rearrangements, whereas 1.3% showed clinically significant CNAs unrelated to the karyotype. Finally, 71% of the clinically significant CNAs found by microarray were below the resolution of conventional karyotyping of fetal chromosomes.

Conclusions: Microarray analysis has advantages over conventional cytogenetics, including the ability to more precisely characterize CNAs associated with abnormal karyotypes. Moreover, a significant proportion of cases studied by array will show a clinically significant CNA even with apparently normal karyotypes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormal Karyotype / embryology*
  • Chromosome Aberrations / embryology
  • Comparative Genomic Hybridization*
  • Female
  • Fetal Death / genetics
  • Humans
  • Karyotyping / methods
  • Microarray Analysis / methods
  • Pregnancy
  • Prenatal Diagnosis / methods*
  • Prospective Studies
  • Sequence Deletion / genetics
  • Ultrasonography, Prenatal