Current relevance of non-invasive prenatal study of cell-free fetal DNA in the mother’s blood and prospects for its application in mass screening of pregnant women in the Russian Federation

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Abstract

This review article offers an analysis of application of cell-free fetal DNA non-invasive prenatal screening test for chromosome abnormalities in the mother’s blood in different countries. The diagnostic capacities of the method, its limitations, execution models and ethical aspects pertinent to its application are discussed. The data for the discordant results is shown and analyzed. The advantages of the genome-wide variant of cell-free fetal DNA analysis and the problems concerning its application in the mass screening are described. The main suggestion is to implement the contingent cell-free fetal DNA testing model for the common trisomies (for the chromosomes 21, 18 and 13) into the prenatal diagnostic screening programs in the Russian Federation. This novel model is based on the results of the mass combined first trimester prenatal screening in four federal subjects of the country completed by 2019 and is offered as an additional screening in the mid-level risk group (with cut-off from 1 : 100 to 1 : 500 or from 1 : 100 to 1 : 1000) defined according to the first trimester prenatal screening results. The basic requirements for the implementation of the contingent model in the Russian Federation are stated.

About the authors

Elena A. Kalashnikova

Russian Medical Academy of Continuous Professional Education; Fetal Medicine Association “National Society of Prenatal Medicine”

Author for correspondence.
Email: elenakalash@yandex.ru
ORCID iD: 0000-0002-7861-6273

MD, PhD, Assistant Professor

Russian Federation, Moscow

Andrey S. Glotov

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott

Email: anglotov@mail.ru
ORCID iD: 0000-0002-7465-4504

PhD, DSci (Biology)

Russian Federation, Saint-Petersburg

Elena N. Andreyeva

Russian Medical Academy of Continuous Professional Education; Fetal Medicine Association “National Society of Prenatal Medicine”

Email: e.n.andreeva@mail.ru
ORCID iD: 0000-0002-5649-0534

MD, PhD, Assistant Professor

Russian Federation, Moscow

Ilya Yu. Barkov

National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov

Email: i@barkov.ru
ORCID iD: 0000-0001-6297-2073

MD, PhD

Russian Federation, Moscow

Galina Yu. Bobrovnik

The Family Planning and Reproduction Center of the Moscow City Health Department; Fetal Medicine Association “National Society of Prenatal Medicine”

Email: bobrovnik852@yandex.ru

 

 

Russian Federation, Moscow

Elena V. Dubrovina

The Family Planning and Reproduction Center of the Moscow City Health Department; Fetal Medicine Association “National Society of Prenatal Medicine”

Email: e.v.dubrovina@yandex.ru
ORCID iD: 0000-0002-2179-639X

 

 

Russian Federation, Moscow

Lyudmila A. Zhuchenko

Russian Medical Academy of Continuous Professional Education; Fetal Medicine Association “National Society of Prenatal Medicine”

Email: mrrcm@mail.ru
ORCID iD: 0000-0003-4918-2995

MD, PhD, DSci (Medicine)

Russian Federation, Moscow

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Supplementary files

Supplementary Files
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2. Fig. 1. Discordant results of non-invasive prenatal testing (cited from [33]). NIPT — non-invasive prenatal testing; CNV — copy number variations of DNA regions; Tr21, 18, 13, 9, 22 — trisomies for chromosomes 21, 18, 13, 9, and 22, respectively

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3. Fig. 2. Clinical significance, confirmed data, sensitivity of screening tests. Tr21, Tr18, and Tr13 — trisomies for chromosomes 21, 18, and 13, respectively; FPR — false positive results

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4. Fig. 3. The number of chromosomal abnormalities revealed during early prenatal screening within the designated risk groups in four constituent entities of the Russian Federation in 2018. The abscissa presents the intervals of risk groups between the borders. CA — chromosomal abnormalities; Tr21, Tr18, and Tr13 — trisomies for chromosomes 21, 18, and 13, respectively

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5. Fig. 4. Possible cohort models of the use of non-invasive prenatal testing (NIPT) in early prenatal screening: a — in the moderate risk group 1:101–1:500; b — in the moderate risk group 1:101–1:1,000

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6. Fig. 5. Schematic model of contingent prenatal screening of chromosomal abnormalities with the technology of non-invasive prenatal testing. NIPT — non-invasive prenatal testing; CPS — coccygeal-parietal size; FCA (CM) — fetal congenital abnormalities (congenital malformations); NFT — nuchal fold thickness; IPD — invasive prenatal diagnostics; CA — chromosomal abnormalities; US — ultrasound examination

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