OBJECTIVE: To report the full cohort of identifiable anomalies, regardless of known clinical significance, in a large-scale cohort of postmiscarriage products-of-conception samples analyzed using a high-resolution single-nucleotide polymorphism (SNP)–based microarray platform. High-resolution chromosomal microarray analysis allows for the identification of visible and submicroscopic cytogenomic imbalances; the specific use of SNPs permits detection of maternal cell contamination, triploidy, and uniparental disomy.
METHODS: Miscarriage specimens were sent to a single laboratory for cytogenomic analysis. Chromosomal microarray analysis was performed using a SNP-based genotyping microarray platform. Results were evaluated at the cytogenetic and microscopic (greater than 10 Mb) and submicroscopic (less than 10 Mb) levels. Maternal cell contamination was assessed using information derived from fetal and maternal SNPs.
RESULTS: Results were obtained on 2,389 of 2,392 specimens (99.9%) that were less than 20 weeks of gestation. Maternal cell contamination was identified in 528 (22.0%) specimens. The remaining 1,861 specimens were considered to be of true fetal origin. Of these, 1,106 (59.4%) showed classical cytogenetic abnormalities: aneuploidy accounted for 945 (85.4%), triploidy for 114 (10.3%), and structural anomalies or tetraploidy for the remaining 47 (4.2%). Of the 755 (40.6%) cases considered normal at the cytogenetic level, SNP chromosomal microarray analysis revealed a clinically significant copy number change or whole-genome uniparental disomy in 12 (1.6%) and three (0.4%) cases, respectively.
CONCLUSION: Chromosomal microarray analysis of products-of-conception specimens yields a high diagnostic return. Using SNPs extends the scope of detectable genomic abnormalities and facilitates reporting “true” fetal results. This supports the use of SNP chromosomal microarray analysis for cytogenomic evaluation of miscarriage specimens when clinically indicated.
LEVEL OF EVIDENCE: III
Chromosomal microarray analysis with single-nucleotide polymorphisms expands diagnostic yield in studies of products of conception and produces a result that accurately reflects the genomic fetal status.
Department of Pathology and Cell Biology, Columbia University, New York, New York; the Departments of Statistics, Genetic Counseling, Research and Development, and Operations, Natera Inc., San Carlos, and the Reproductive Endocrinology and Infertility Division, Stanford University, Palo Alto, California.
Corresponding author: Brynn Levy, MSc(Med), PhD, Columbia University, 3959 Broadway, CHC Room 406b, New York, NY 10032; e-mail: firstname.lastname@example.org.
Funded by the private investors of Natera Inc.
Presented in part at the 62nd annual meeting of the American Society of Human Genetics, November 6–10, 2012, San Francisco, California.
Financial Disclosure Dr. Levy is a paid consultant for Natera Inc. Dr. Sigurjonsson, Ms. Pettersen, Ms. Maisenbacher, Dr. Hall, Dr. Demko, Ms. Tao, and Dr. Rabinowitz are employees of Natera Inc. and hold stock or options to hold stock in the company. The other authors did not report any potential conflicts of interest.