Maternal Cell Contamination (MCC) occurs when a sample intended for fetal analysis inadvertently contains the mother’s cells or DNA. This issue primarily arises in prenatal testing, where the goal is to obtain a pure sample of fetal genetic material to accurately assess the developing baby’s health. The presence of maternal genetic information introduces a confounding variable that can compromise the accuracy of the final test results. Laboratories must account for MCC as a potential source of error to ensure reliable diagnostic information.
How Maternal Cells Enter the Sample
Maternal cells infiltrate fetal samples through biological pathways and collection processes. During invasive procedures, such as Chorionic Villus Sampling (CVS), the chorionic villi are collected. This tissue is often surrounded by the mother’s decidua, the maternal tissue layer of the placenta. It is difficult to completely dissect the fetal villi away from the maternal decidual cells, which introduces maternal genetic material directly into the sample. The risk of MCC in CVS is estimated to be around 1–2%.
Amniocentesis, the collection of amniotic fluid, is also susceptible to MCC, primarily through maternal blood cells. The needle used to collect the fluid may pick up small amounts of maternal peripheral blood as it passes through the uterine wall, or maternal blood may be present in the amniotic fluid itself due to minor bleeding. Uncultured amniocytes, the cells collected directly from the fluid, carry a higher risk of MCC due to this potential for maternal blood contamination.
Why Contamination Affects Test Results
The presence of maternal DNA directly interferes with the analysis, leading to skewed or misleading results. MCC can cause both false-negative and false-positive results, which impacts clinical decision-making. A false-negative result occurs when the mother’s normal genetic material dilutes or masks a true fetal abnormality, making the fetus appear healthy when it is not. Conversely, if the mother carries a genetic condition, a false-positive result can occur when maternal cells incorrectly attribute the mother’s condition to the fetus.
In molecular testing for single-gene disorders, if the fetus has a recessive mutation, the mother’s normal DNA can suppress the fetal mutation’s signal. In sex determination, if the fetus is female (XX), contamination might misinterpret the ratio of X chromosomes if the mother has a sex chromosome abnormality, such as mosaicism. For non-invasive prenatal testing (NIPT), the presence of maternal cells from a mother with an undiagnosed condition, such as a tumor shedding cancerous DNA, can lead to confusing results by introducing abnormal DNA that is not fetal in origin.
Identifying and Preventing Maternal Cell Contamination
Clinical and laboratory strategies are in place to minimize and detect maternal cell contamination. Prevention begins with careful technique during sample collection, such as meticulous dissection of the chorionic villi to remove the surrounding maternal decidua. Laboratories often require a simultaneously collected maternal peripheral blood sample, which serves as a control for later contamination testing.
Detection of MCC is often performed using genetic techniques such as short tandem repeat (STR) analysis. This method compares repetitive DNA sequences in the fetal sample with those in the maternal control sample. If the fetal sample contains alleles that match the mother’s unique alleles but are not expected in the fetus, it confirms the presence of maternal DNA. Many laboratories aim to detect at least a 10% level of contamination.
If MCC is detected, the laboratory may attempt to culture the cells, as this process can sometimes selectively grow the fetal cells, reducing maternal contaminants. If the contamination level is too high for a reliable result, the clinician may recommend a repeat procedure, such as performing an amniocentesis after a high-MCC CVS result. Alternatively, results may be interpreted with caution and a clear disclaimer. Testing for MCC is a standard quality assurance measure.