Creating basis for introducing non-invasive prenatal testing in the Estonian public health setting

Prenat Diagn. 2019 Dec;39(13):1262-1268. doi: 10.1002/pd.5578. Epub 2019 Nov 6.
[Article in German]


Objective: The study aimed to validate a whole-genome sequencing-based NIPT laboratory method and our recently developed NIPTmer aneuploidy detection software with the potential to integrate the pipeline into prenatal clinical care in Estonia.

Method: In total, 424 maternal blood samples were included. Analysis pipeline involved cell-free DNA extraction, library preparation and massively parallel sequencing on Illumina platform. Aneuploidies were determined with NIPTmer software, which is based on counting pre-defined per-chromosome sets of unique k-mers from sequencing raw data. SeqFF was implemented to estimate cell-free fetal DNA (cffDNA) fraction.

Results: NIPTmer identified correctly all samples of non-mosaic trisomy 21 (T21, 15/15), T18 (9/9), T13 (4/4) and monosomy X (4/4) cases, with the 100% sensitivity. However, one mosaic T18 remained undetected. Six false-positive (FP) results were observed (FP rate of 1.5%, 6/398), including three for T18 (specificity 99.3%) and three for T13 (specificity 99.3%). The level of cffDNA of <4% was estimated in eight samples, including one sample with T13 and T18. Despite low cffDNA level, these two samples were determined as aneuploid.

Conclusion: We believe that the developed NIPT method can successfully be used as a universal primary screening test in combination with ultrasound scan for the first trimester fetal examination.

Publication types

  • Validation Study

MeSH terms

  • Aneuploidy*
  • Estonia
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Noninvasive Prenatal Testing / methods
  • Noninvasive Prenatal Testing / statistics & numerical data*
  • Pregnancy
  • Public Health
  • Sex Chromosome Aberrations*
  • Software*