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On the road to replacing invasive testing with cell‐based NIPT: Five clinical cases with aneuploidies, microduplication, unbalanced structural rearrangement, or mosaicism

Objective: Trophoblastic fetal cells harvested from maternal blood have the capacity to be used for copy number analyses in a cell‐based non‐invasive prenatal test (cbNIPT). Potentially, this will result in increased resolution for detection of subchromosomal aberrations due to high quality DNA not intermixed with maternal DNA. We present 5 selected clinical cases from first trimester pregnancies where cbNIPT was used to demonstrate a wide range of clinically relevant aberrations.

Method: Blood samples were collected from high risk pregnancies in gestational week 12 + 1 to 12 + 5. Fetal trophoblast cells were enriched and stained using fetal cell specific antibodies. The enriched cell fraction was scanned, and fetal cells were picked using a capillary‐based cell picking instrument. Subsequently, whole genome amplification (WGA) was performed on fetal cells, and the DNA was analyzed blindly by array comparative genomic hybridization (aCGH).

Results: We present 5 cases where non‐invasive cell‐based prenatal test results are compared with aCGH results on chorionic villus samples (CVS), demonstrating aneuploidies including mosa- icism, unbalanced translocations, subchromosomal deletions, or duplications.

Conclusion: Aneuploidy and subchromosomal aberrations can be detected using fetal cells harvested from maternal blood. The method has the future potential of being offered as a cell‐ based NIPT with large high genomic resolution.