Chip-Based Digital PCR Approach Provides A Sensitive and Cost-Effective Single-Day Screening Tool for Common Fetal Aneuploidies-A Proof of Concept Study

Int J Mol Sci. 2019 Nov 4;20(21):5486. doi: 10.3390/ijms20215486.


In the prenatal period, the copy number aberrations of chromosomes 13, 18, 21, X and Y account for over 80% of the clinically significant chromosome abnormalities. Classical cytogenetic analysis is the gold standard in invasive prenatal diagnostics but the long test waiting time affects its clinical utility. Several molecular rapid tests have been developed and employed in clinical practice, however all have substantial drawbacks. The aim of the study was to design and evaluate an optimized tool for rapid molecular detection of fetal aneuploidies. We established a novel single-day method using a chip-based platform, the QuantStudio 3D Digital PCR system. In order to assess the clinical usefulness of our screening test, we analyzed 133 prenatal samples. The difference in distributions of euploid and aneuploid samples identified the ploidy of each of the target chromosomes with high precision. The distribution of the chromosome ratio for euploid and aneuploid samples showed a statistically significant result (p = 0.003 for trisomy 13, p = 0.001 for trisomies 18 and 21, Mann-Whitney U test). Our results suggest that this novel chip-based approach provides a tool for rapid, technically simple, cost-effective screening for common fetal aneuploidies.

Keywords: digital PCR; prenatal diagnosis; rapid aneuploidy screening.

MeSH terms

  • Adult
  • Aneuploidy*
  • Chromosome Disorders / diagnosis*
  • Chromosome Disorders / genetics
  • Costs and Cost Analysis
  • Female
  • Genetic Testing / economics
  • Genetic Testing / methods*
  • Genetic Testing / standards
  • Humans
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis / economics
  • Oligonucleotide Array Sequence Analysis / methods*
  • Oligonucleotide Array Sequence Analysis / standards
  • Polymerase Chain Reaction / economics
  • Polymerase Chain Reaction / methods
  • Polymerase Chain Reaction / standards
  • Pregnancy
  • Prenatal Diagnosis / economics
  • Prenatal Diagnosis / methods*
  • Prenatal Diagnosis / standards
  • Sensitivity and Specificity