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The Influence of Maternal Cell Contamination on Fetal Aneuploidy Detection Using Chip-Based Digital PCR Testing
Anna Nykel1, Rafał Woźniak2, Agnieszka Gach2
1Department of Genetics, Polish Mother's Memorial Hospital Research Institute, 93-338 Lodz, Poland.
Abstract:
Prenatal samples obtained by amniocentesis or chorionic villus sampling are at risk of maternal cell contamination (MCC). In traditional prenatal analysis, MCC is recommended to be assayed by special tests, such as the short tandem repeat analysis and, if detected at a high level, may result in failed analysis report. The objective of this study was to test the ability of chip-based digital PCR to detect fetal aneuploidies in the presence of MCC. To determine the level of accuracy of MCC detection, an aneuploid male sample was subjected to serial dilution with an euploid female sample. DNA was extracted from prenatal samples and analyzed with QuantStudio 3D Digital PCR. Digital PCR analysis allowed the detection of trisomy 21, trisomy 18, and X monosomy accurately in samples with 90%, 85%, and 92% of MCC, respectively. Moreover, our results indicated that digital PCR was able to accurately confirm the presence of Y chromosome at up to 95% contamination. The amniotic fluid and chorionic villus sampling (CVS) received in our clinical laboratory was subjected to further analysis of MCC based on the aneuploidy assessment algorithm, resulting in the identification of 10 contaminated samples and four cases of true fetal mosaicism. We conclude that chip-based digital PCR analysis enables the detection of fetal aneuploidy with high levels of accuracy, even in cases of significant MCC. Importantly, the algorithm eliminates the need for maternal DNA and additional MCC tests, which reduces costs and simplifies the diagnostic procedure. The method is easy to set up and suitable for routine clinical practice.
Insights
Chip-based digital PCR accurately detects fetal aneuploidies, even with high maternal cell contamination (MCC). This method simplifies prenatal testing by eliminating the need for additional MCC assays, reducing costs and improving efficiency.
Area of Science:
- Molecular Biology
- Genetics
- Prenatal Diagnostics
Background:
- Prenatal samples from amniocentesis or CVS risk maternal cell contamination (MCC).
- High MCC levels can lead to failed prenatal analysis reports.
- Traditional MCC detection methods are often complex and require additional testing.
Purpose of the Study:
- To evaluate chip-based digital PCR for detecting fetal aneuploidies in samples with MCC.
- To assess the accuracy of digital PCR in identifying specific aneuploidies (trisomy 21, 18, X monosomy) and Y chromosome presence under varying MCC levels.
Main Methods:
- Serial dilution of aneuploid male samples with euploid female samples to simulate MCC.
- DNA extraction from prenatal samples.
- Analysis using QuantStudio 3D Digital PCR for aneuploidy detection and MCC quantification.
Main Results:
- Accurate detection of trisomy 21, 18, and X monosomy with up to 90%, 85%, and 92% MCC, respectively.
- Accurate confirmation of Y chromosome presence with up to 95% MCC.
- Identification of 10 contaminated samples and four cases of true fetal mosaicism in clinical samples.
Conclusions:
- Chip-based digital PCR reliably detects fetal aneuploidies even with significant maternal cell contamination.
- The developed algorithm simplifies prenatal diagnostics by removing the need for separate maternal DNA testing and MCC assays.
- This method offers a cost-effective, efficient, and clinically applicable approach for routine prenatal testing.
