New approaches to prenatal screening for chromosomal abnormalities: Maternal blood DNA screening

Gennady T. Sukhikh; Сухих Геннадий Тихонович; Dmitry Yu. Trofimov; Трофимов Дмитрий Юрьевич; Ilya Yu. Barkov; Барков Илья Юрьевич; Andrey E. Donnikov; Донников Андрей Евгеньевич; Ekaterina S. Shubina; Шубина Екатерина Сергеевна; Dmitrii O. Korostin; Коростин Дмитрий Олегович; Alexey N. Ekimov; Екимов Алексей Николаевич; Andrey Y. Goltsov; Гольцов Андрей Юрьевич; Vladimir A. Bakharev; Бахарев Владимир Анатольевич; Nataliia A. Karetnikova; Каретникова Наталья Александровна; Pavel I. Borovikov; Боровиков Павел Игоревич; Nana K. Tetruashvili; Тетруашвили Нана Картлосовна; Lyudmila V. Kim; Ким Людмила Викторовна; Albina S. Gata; Гата Альбина Сергеевна; Stanislav V. Pavlovich; Павлович Станислав Владиславович; Konstantin G. Skryabin; Скрябин Константин Георгиевич; Egor B. Prokhorchuk; Прохорчук Егор Борисович; Alexander M. Mazur; Мазур Александр Михайлович; Katerina S. Pantyukh; Пантюх Катерина Сергеевна

doi:10.18565/aig.2016.8.72-78

New approaches to prenatal screening for chromosomal abnormalities: Maternal blood DNA screening

Authors: Sukhikh G.T.¹, Trofimov D.Y.², Barkov I.Y.², Donnikov A.E.², Shubina E.S.¹, Korostin D.O.², Ekimov A.N.², Goltsov A.Y.², Bakharev V.A.², Karetnikova N.A.², Borovikov P.I.¹, Tetruashvili N.K.², Kim L.V.¹, Gata A.S.², Pavlovich S.V.², Skryabin K.G.³, Prokhorchuk E.B.³, Mazur A.M.³, Pantyukh K.S.³
Affiliations:
1. Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia
2. Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
3. M.V. Lomonosov Moscow State University
Issue: No 8 (2016)
Pages: 72-78
Section: Articles
URL: https://journals.eco-vector.com/0300-9092/article/view/247777
DOI: https://doi.org/10.18565/aig.2016.8.72-78
ID: 247777

Cite item

Full Text

Open Access
Restricted Access

Access granted
Restricted Access

Subscription or Fee Access

Abstract
Full Text
About the authors
References
Supplementary files
Statistics

Abstract

Objective. The effectiveness of noninvasiveprenatal screening for fetal aneuploidies by maternal blood DNA-tests in clinical practice. Subjects and methods. The research was carried out at Kulakov Research Center for Obstetrics, Gynecology and Perinatology (Russia) and Lomonosov Moscow State University (Russia). Massive parallel sequencing and bioinformatics analysis of maternal peripheral blood free-cell DNA was performed. The research includes combined validation results of DNA screening for fetal aneuploidies of 529 pregnant women at 10-20th week of gestation (14 weeks median). The first group consists of 259 high-risk women, while the second group featured 270 women with different risk of fetal chromosomal abnormalities (177 low-risk and 93 high-risk). Reliability of results was assessed using data on fetal karyotype and pregnancy outcome. The obtained results were compared with literature. Results. Incidence of analyzed aneuploidies in the f irst group was 23.6%, while in the second it was only 4.1%, which is due to the peculiarities of group formation. The specificity and sensitivity of DNA screening come close to 100%. The highest PPV values are achieved for detection of aneuploidies for chromosomes 21 and 18. The PPV values for sex chromosomes and chromosome 13 are lower. DNA screening results can be unreliable when the cell-free fetal DNA fraction is below the sensitivity threshold of the method (about 4%). Validation results conform with published data and show that maternal blood DNA screening has a much higher specificity and sensitivity in chromosomes 21, 18, 13 and X aneuploidy detecting than the currently used combined screening. Conclusion. DNA screening can be recommended for prenatal aneuploidy screening for chromosomes 21, 18, 13 in most pregnant women. Determining of cell-free fetal DNA fraction is mandatory for the research. Positive DNA screening results require confirmation through invasive diagnostic methods.

Keywords

pregnancy, DNA-screening, trisomy, aneuploidy, Down syndrome, Edwards syndrome, Patau syndrome, trisomy 21, trisomy 18, trisomy 13, prenatal diagnosis, invasive prenatal diagnosis, noninvasive prenatal screening, NIPS, NIPT, cell-free fetal DNA

Full Text

References

Жученко Л.А., Андреева Е.Н., Воскобоева Е.Ю., Давыдова О.Н., Калашникова Е.А., Кокаровцева С.Н., Лагкуева Ф.К., Одегова Н.О., Серкова ТН.А., Степнова С.В., Судакова Е.В., Цветкова Т.Г. Реализация мероприятий Национального проекта «Пренатальная (дородовая) диагностика нарушений развития ребенка» в Московской области. Российский вестник акушера-гинеколога. 2013; 13(4): 6-12. [Zhuchenko L.A., Andreeva E.N., Voskoboeva E.Yu., Davyidova O.N., Kalashnikova E.A., Kokarovtseva S.N., Lagkueva F.K., Odegova N.O., Serkova N.A., Stepnova S.V., Sudakova E.V., Tsvetkova T.G. Implementation of activities of the National Project „Prenatal (antenatal) diagnosis of child development disorders” in the Moscow region. Rossiyskiy vestnik akushera-ginekologa. 2013; 13(4): 6-12. (in Russian)]
Сухих Г.Т., Каретникова Н.А., Баранова Е.Е., Шубина Е.С., Коростин Д.О., Екимов А.Н., Парсаданян Н.Г., Гус А.И., Бахарев В.А., Трофимов Д.Ю., Воеводин С.М., Тетруашвили Н.К. Неинвазивная пренатальная диагностика анеуплоидий методом высокопроизводительного секвенирования (NGS) в группе женщин высокого риска. Акушерство и гинекология. 2015; 4: 5-10. [Sukhikh G.T., Karetnikova N.A., Baranova E.E., Shubina E.S., Korostin D.O., Ekimov A.N., Parsadanyan N.G., Gus A.I., Bakharev V.A., Trofimov D.Yu., Voevodin S.M., Tetruashvili N.K. Noninvasive prenatal diagnosis of aneuploidies by next-generation sequencing (NGS) in a group of high-risk women. Akusherstvo i ginekologiya/Obstetrics and Gynecology. 2015; (4): 5-10. (in Russian)
Norton M.E., Brar H., Weiss J., Karimi A., Laurent L.C., Caughey A.B. et al. Non-Invasive Chromosomal Evaluation (NICE) Study: results of a multicenter prospective cohort study for detection of fetal trisomy 21 and trisomy 18. Am. J. Obstet. Gynecol. 2012; 207(2): 137. e1-8.
Dar P., Curnow K.J., Gross S.J., Hall M.P., Stosic M., Demko Z. et al. Clinical experience and follow-up with large scale single-nucleotide polymorphism-based noninvasive prenatal aneuploidy testing. Am. J. Obstet. Gynecol. 2014; 211(5): 527. e1-527. e17.
Bhatt S., Parsa S., Snyder H., Taneja P., Halks-Miller M., Seltzer W., DeFeo E. Clinical laboratory experience with noninvasive prenatal testing: update on clinically relevant metrics. ISPD 2014 poster.
Palomaki G.E., Kloza E.M., Lambert-Messerlian G.M., Haddow J.E., Neveux L.M., Ehrich M. et al. DNA sequencing of maternal plasma to detect Down syndrome: An international clinical validation study. Genet. Med. 2011; 13(11): 913-20.
Palomaki G.E., Deciu C., Kloza E.M., Lambert-Messerlian G.M., Haddow J.E., Neveux L.M. et al. DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as down syndrome: an international collaborative study. Genet. Med. 2012; 14(3): 296-305.
Nicolaides K.H., Musci T.J., Struble C.A., Syngelaki A., Gil M.M. Assessment of fetal sex chromosome aneuploidy using directed cell-free DNA analysis. Fetal Diagn. Ther. 2014; 35(1): 1-6.
Porreco R.P., Garite T.J., Maurel K., Marusiak B., Ehrich M., van den Boom D. et al. Noninvasive prenatal screening for fetal trisomies 21, 18, 13 and the common sex chromosome aneuploidies from maternal blood using massively parallel genomic sequencing of DNA. Am. J. Obstet. Gynecol. 2014; 211(4): 365. e1-12.
Jiang F., Ren J., Chen F., Zhou Y., Xie J., Dan S. et al. Noninvasive Fetal Trisomy (NIFTY) test: an advanced noninvasive prenatal diagnosis methodology for fetal autosomal and sex chromosomal aneuploidies. BMC Medical Genomics. 2012; 5: 57.
Fleiss J.L. Statistical methods for rates and proportions. 2nd ed. New York: John Wiley & Sons; 1981.
Ижевская В.Л. Старые заботы и новые этические проблемы в пренатальной диагностике. Медицинская генетика. 2015; 14(4): 67. [Izhevskaya V.L. Old concerns and new ethical issues in prenatal diagnostics. Meditsinskaya genetika. 2015; 14(4): 67. (in Russian)]

Supplementary files

Supplementary Files

Action

1. JATS XML

Download

Username
Password
Remember me

Forgot password?	Register

Username
Password
Remember me

Forgot password?	Register

New approaches to prenatal screening for chromosomal abnormalities: Maternal blood DNA screening

Full Text

Abstract

Keywords

Full Text

About the authors

References

Supplementary files

This website uses cookies