Maternal Cell Contamination Analysis for Prenatal or Cord Blood Genetic Testing

Indications for Testing

MCC testing is generally required when molecular testing or chromosomal microarray analysis (CMA) is performed for:

• Prenatal testing of a sample from an ongoing pregnancy (i.e., amniocentesis, CVS)
• Testing of POC, including placental and/or fetal tissues

MCC testing may be recommended when molecular or CMA testing is performed for:

• Umbilical cord blood testing at delivery
• Percutaneous umbilical blood sampling in utero

Though not typically required, MCC studies may be recommended by the laboratory for chromosome analysis (karyotype) in the context of an XX result, depending on factors such as time in culture and assessment of the specimen for evidence of maternal cells (e.g., the presence of blood in AF or excess maternal decidua in a CVS or POC sample).

Laboratory Testing

Risk for MCC

MCC can occur due to the inability to separate villi from maternal decidua in a placental biopsy from an ongoing pregnancy or POC sample. MCC can also occur by introduction of maternal blood cells to a fetal specimen through an invasive procedure, such as amniocentesis or umbilical cord sampling. For CVS and POC testing, the laboratory performs a morphologic assessment of the specimen followed by manual dissection to clean and remove maternal decidua from fetal villi. Occasionally, MCC occurs due to receipt of a suboptimal specimen, maternal cell outgrowth in culture, or inability to distinguish fetal from maternal tissues. For AF and cord blood samples, MCC can occur during the amniocentesis procedure or cord blood collection when maternal blood cells may inadvertently be drawn into the needle used for the procedure or may be unavoidably present in the amniotic cavity as a result of maternal bleeding. It is important to note that the presence of maternal cells in cord blood cannot be determined by morphologic assessment of the specimen alone. In some cases, MCC is suspected due to a discordant sex chromosome complement or a result unlikely to represent the fetal genotype. Although umbilical cord blood sampling is widely utilized and performed effectively, in some cases MCC may only be ruled out by STR testing.

Laboratory Analysis and Detection of Maternal Cell Contamination

MCC studies are performed by comparing STRs from prenatal/fetal and maternal DNA. STRs are a collection of repetitive DNA sequences that uniquely identify an individual.  The presence of maternal alleles in a prenatal specimen confirms the presence of MCC. Quantification of the percentage of MCC is performed by the laboratory to determine accuracy and limitations of the result obtained/provided; the laboratory may also provide follow-up recommendations, including additional or repeat testing. Generally, MCC of 10% or greater is detectable by most laboratories.

Both false-negative results (e.g., when maternal cells are in excess such that a fetus’ abnormal genetic makeup is not detected) and false-positive results (e.g., when the mother carries a genetic variant that is detected during testing of an unaffected fetus) can occur due to MCC.  An accurate understanding of the biologic relationships of the pregnancy is important for interpreting results of MCC studies; if the pregnancy is carried by a surrogate or a gamete donor was used, this should be reported to the testing laboratory.  Similarly, a pregnancy with multiple gestations should be disclosed. 

It is important that backup cultures be available for follow-up testing if MCC is detected. Backup cultures should remain available until testing is completed and results are reported. 

Testing prenatal tissues may include culturing that will generally increase test turnaround times. In cases with detectable MCC, the laboratory may issue a test result with a caveat or disclaimer that urges caution in interpretation of the results or recommends repeat testing of a new specimen.