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

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

[Article in German]

Author information

1
Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
2
Competence Centre on Health Technologies, Tartu, Estonia.
3
Department of Obstetrics and Gynaecology, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.
4
Institute of Bio- and Translational Medicine, University of Tartu, Tartu, Estonia.
5
Women's Clinic, Tartu University Hospital, Tartu, Estonia.
6
Institute of Genomics, University of Tartu, Tartu, Estonia.
7
Department of Clinical Genetics, Tartu University Hospital, Tartu, Estonia.
8
Center for Perinatal Care, Women's Clinic, East-Tallinn Central Hospital, Tallinn, Estonia.
9
Department of Clinical Genetics, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.
10
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
11
Centre for Human Genetics, University Hospital Leuven, Department of Human Genetics, KU Leuven, Leuven, Belgium.
12
Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
13
Molecular Neurology Research Program, University of Helsinki and Folkhälsan Institute of Genetics, Helsinki, Finland.
14
Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Abstract

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.

PMID:
31691324
DOI:
10.1002/pd.5578

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