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Pre-Implantation Genetic Testing for Aneuploidy on a Semiconductor Based Next-Generation Sequencing Platform
Published on: August 17, 2022
Neonatal cytogenetic validation demonstrates high accuracy of single-nucleotide polymorphism-based non-invasive
Shiho Uchida1, Yuki Mizuguchi2,3,4, Suguru Sato5
1Department of Obstetrics and Gynecology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Journal of Human Genetics
|June 4, 2026
Summary
Single-nucleotide polymorphism (SNP)-based non-invasive prenatal testing (NIPT) demonstrates high accuracy for fetal aneuploidy screening when confirmed by neonatal cytogenetics. Rare false negatives highlight the need for confirmation in cases with ultrasound abnormalities.
Area of Science:
- Genetics
- Prenatal Diagnostics
- Molecular Biology
Background:
- Non-invasive prenatal testing (NIPT) is crucial for fetal aneuploidy screening.
- Current evaluations often lack cytogenetic confirmation, limiting real-world performance data for SNP-based NIPT.
- Evidence on the analytical accuracy of SNP-based NIPT validated by postnatal cytogenetics is scarce.
Purpose of the Study:
- To evaluate the analytical accuracy of single-nucleotide polymorphism (SNP)-based NIPT.
- To assess performance using neonatal buccal mucosal fluorescence in situ hybridization (FISH) as a cytogenetic confirmation method.
- To determine sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for common trisomies.
Main Methods:
- Prospective analysis of clinical data from high-risk pregnant women undergoing SNP-based NIPT (2013-2022).
- Validation of positive NIPT results with amniocentesis.
- Systematic validation of negative NIPT results with postnatal buccal mucosal FISH.
- Calculation of accuracy metrics for trisomies 13, 18, and 21.
Main Results:
- High analytical accuracy was observed: Sensitivity (94.6%-100%), Specificity (99.9%), PPV (89.1%), and NPV (99.9%).
- Two false-negative cases (0.06%) were identified, linked to low-level mosaicism.
- SNP-based NIPT showed high performance, with 88.9% of initial 'no call' results becoming reportable after redraw.
Conclusions:
- SNP-based NIPT exhibits high analytical performance when validated with neonatal cytogenetic confirmation.
- Low-level mosaicism can lead to rare false-negative NIPT results, underscoring biological limitations.
- Cytogenetic confirmation remains essential, particularly when fetal ultrasound abnormalities are present.
