Premium
Creating basis for introducing non‐invasive prenatal testing in the Estonian public health setting
Author(s) -
Žilina Olga,
Rekker Kadri,
Kaplinski Lauris,
Sauk Martin,
Paluoja Priit,
Teder Hindrek,
Ustav EvaLiina,
Tõnisson Neeme,
Reimand Tiia,
Ridnõi Konstantin,
Palta Priit,
Vermeesch Joris Robert,
Krjutškov Kaarel,
Kurg Ants,
Salumets Andres
Publication year - 2019
Publication title -
prenatal diagnosis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.956
H-Index - 97
eISSN - 1097-0223
pISSN - 0197-3851
DOI - 10.1002/pd.5578
Subject(s) - cell free fetal dna , massive parallel sequencing , trisomy , ion semiconductor sequencing , prenatal screening , prenatal diagnosis , aneuploidy , medicine , obstetrics , dna sequencing , fetus , chromosome , biology , pregnancy , genetics , dna , gene
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.