Chromosomal Microarray Analysis — Products of Conception

CPT Code(s): 81229, 88235, 88261, 88265

Ordering Recommendation: Chromosome abnormalities are estimated to be the cause of 15% to 60% of spontaneous abortions or may result in malformed fetuses or neonatal deaths. Analysis of fetal tissue/products of conception (POC) by Chromosomal Microarray (CMA) may identify the cause of the spontaneous abortion, malformation, or neonatal death. CMA may also help in assessing risk for additional pregnancy loss or having subsequent children with chromosome abnormalities, and may be important in managing future pregnancies. Indications for this test include fetal demise or stilbirth, pregnancy loss or termination in the presence of fetal anomalies, further characterization of fetal chromosomal abnormalities seen by conventional G-banded cytogenetic analysis, and analysis of specimens that fail to grow in culture. Traditional G-banded chromosome analysis for POC yields low resolution structural and numerical analysis of the chromosomes, while CMA provides high definition copy number analysis. Chromosome analysis can be ordered concurrently with CMA or CMA can be reflexed after normal chromosome results or a culture failure.

Synonyms: CMA, Chromosomal Microarray, SNP, Microarray, POC, Products of Conception

Methodology: Cytogenomic SNP microarray

Performed: Monday through Friday

Reported: 7-10 days

Collect: Preferred: Villi from placenta collected aseptically and placed in tissue transport media (provided upon request). Cartilage, membrane, tendon also accepted. Maternal cell contamination in fetal tissue/POC specimens can interfere with the interpretation, but it is minimized if fetal tissue is positively identified and sent for analysis. Whenever possible, maternal blood should accompany the POC sample for detection of maternal cell contamination (MCC): 3 ml whole blood in lavender top (EDTA) tube.

Specimen Volume: 3-10 mm³

Storage/Transport: Refrigerate (in transport media which can be provided or sterile screw-top container with sterile media).

Unacceptable Conditions: Frozen. Do not place tissue in fixative.

Parental Samples: Whenever possible, maternal blood should accompany the POC sample for detection of maternal cell contamination (MCC): 3 ml whole blood in lavender top (EDTA) tube.

Remarks: Physician/genetic counselor may be contacted if report exceeds 10 days.

Stability: Ambient: 24 hours; Refrigerated: 48 hours; Frozen: Unacceptable

Characteristics:

• Negative: “Normal Female/Male by CMA Analysis” indicating no clinically significant copy number changes or regions with absence of heterozygosity (AOH) were detected.

• Pathogenic or Uncertain Clinical Significance:

  • Identification of copy number variants (CNVs) including deletions ≥ 1 megabase (Mb) and duplications ≥ 2 Mb containing at least one exon of a gene. Smaller CNVs, minimally ≥25 kb with 25 probes for deletions or ≥50 kb with 50 probes for duplications, will be reported if of clearly established clinical significance.

  • Copy number changes of uncertain clinical significance have insufficient information currently available to fully interpret their clinical significance.

  • Large regions of Copy-neutral Absence of Heterozygosity (CN-AOH), indicated by stretches of continuously homozygous SNP markers, across a single chromosome suggestive of uniparental disomy. This may increase the risk of recessive conditions or imprinting disorders.

  • Large regions of CN-AOH across multiple chromosomes suggesting identical by descent. This may increase the risk of recessive conditions.

  • A report detailing interpretation of results will be provided.

Limitations:

• This assay does not detect balanced rearrangements, low-level mosaicism (<10%), or tetraploidy.

• The presence of maternal cell contamination could interfere with detection of small copy number changes and low-level mosaic chromosome aneuploidies.

• Microarray studies cannot differentiate free trisomies from unbalanced translocations or specify the location of a duplicated segment.