Maternal cell contamination (MCC) is the presence of a mother’s cells within a sample collected from a fetus. This mixing of maternal and fetal materials is a primary consideration in prenatal diagnostics. Because the inclusion of maternal cells can obscure or alter the results of genetic analysis, understanding MCC is necessary for ensuring the accuracy of tests that guide medical decisions during pregnancy.
Origins of Maternal Cell Contamination
Maternal cells can be introduced into a fetal sample through biological processes and collection procedures. While a small number of maternal cells can naturally cross the placenta during pregnancy, the most common source of contamination is the sampling process itself. Procedures designed to collect fetal cells carry an inherent risk of admixing maternal tissues with the fetal specimen.
During amniocentesis, a needle inserted through the mother’s abdomen can pass through maternal tissue, introducing her cells into the amniotic fluid. Chorionic villus sampling (CVS) involves taking a sample of placental tissue. This tissue is in direct contact with maternal tissue called the decidua, making it easy for some maternal material to be collected along with the fetal villi. For this reason, CVS samples are more prone to higher levels of contamination.
The physical characteristics of the sample may indicate a higher risk of contamination. A bloody sample of amniotic fluid or a chorionic villus sample that is not clean and white suggests the presence of maternal blood or tissue. Even in cord blood banking, where blood is collected from the umbilical cord after birth, MCC can occur if the collection is not performed carefully.
Consequences for Prenatal and Genetic Testing
The presence of maternal DNA in a fetal sample can alter genetic test results and lead to a misdiagnosis. If a fetus has a genetic abnormality, contamination with genetically normal maternal cells can mask the issue. This may cause a false-negative result, preventing parents and doctors from preparing for a condition the child will have.
A false-positive result can also occur. If the mother is a carrier for a genetic mutation the fetus has not inherited, her cells could lead to the incorrect conclusion that the fetus is affected. This may cause undue anxiety and lead to unnecessary invasive testing. The accuracy of tests for chromosomal disorders like Down syndrome is also compromised, as maternal cells can dilute the fetal cell population and interfere with chromosome counting.
Contamination also affects the determination of fetal sex. If the fetus is male (XY), a high level of the mother’s female (XX) cells can obscure the Y chromosome and produce an incorrect result. In research, MCC can invalidate findings by making it impossible to distinguish between fetal and maternal cellular activity. The reliability of molecular genetic testing for single-gene disorders is also threatened, as the maternal DNA can interfere with the analysis of the fetal gene sequences.
Identifying Maternal Cell Contamination in Samples
Laboratories use precise methods to detect and quantify MCC in a fetal sample. The most common technique is Short Tandem Repeat (STR) analysis. STRs are short, repeated segments of DNA that vary greatly between individuals, allowing technicians to identify the presence of two distinct DNA sources by comparing STR profiles from the mother and the fetus.
A blood sample from the mother is required for comparison. The laboratory amplifies specific STR markers from both the mother’s DNA and the DNA from the fetal sample. A pure fetal sample will have one set of markers inherited from the mother and one from the father. If maternal cells are present, the markers in the fetal sample will show a pattern skewed toward the mother’s profile, allowing the lab to detect contamination and estimate its percentage.
Other molecular techniques, such as quantitative Polymerase Chain Reaction (qPCR), can also quantify the amount of specific maternal DNA in the fetal sample. Advanced methods using next-generation sequencing can also estimate the percentage of contamination with high sensitivity. These detection methods are a standard part of the quality control process in prenatal diagnostic labs.
Strategies for Prevention and Handling
Preventing MCC begins with careful sample collection. During amniocentesis, clinicians often discard the first few milliliters of fluid, as this portion is most likely to contain maternal cells from the needle’s path. In chorionic villus sampling, technicians dissect the collected tissue under a microscope to manually remove any visible maternal decidua from the fetal villi.
Because some contamination may be unavoidable, laboratories establish thresholds for acceptable levels of MCC. These thresholds vary depending on the genetic test being performed and its sensitivity to contamination. Contamination levels below 5% are often considered acceptable for many analyses, while some tests can tolerate more.
If contamination is detected above the established threshold, the laboratory will not proceed with the diagnostic test. The lab will communicate this to the clinician, and the recommendation is to collect a new sample, which may involve a repeat amniocentesis or CVS. This process of prevention, detection, and management helps ensure that clinical decisions are based on accurate genetic information.