THE CELL-FREE DNA DETECTION AND ANALYSIS AS THE NEW NON-INVASIVE PRENATAL DIAGNOSTICS OPTION

Maja Milojković, Jelena Milenković

DOI Number
10.22190/FUMB170227003M
First page
006
Last page
010

Abstract


Screening procedures for chromosomal abnormalities in fetuses are a standard of care for pregnant women. Ultrasound and maternal serum analysis are traditional prenatal screening methods with detection rates between 75%-95%, and considerable false-negative and false-positive results. Also, both require follow up by invasive diagnostic tests in screen-positive cases, mostly amniocentesis and chorionic villi sampling, which are associated with notable risk of pregnancy loss. One of the innovative non-invasive prenatal testing (NIPT) options is the analysis of cell-free DNA (cfDNA) in plasma, which is detected in maternal circulation in a relatively high concentration. Commercial tests for cfDNA in maternal blood have recently become available. Cell-free DNA detection tests do not separate fetal from maternal DNA but use full cfDNA complement and analyze difference in total amount of sequenced DNA fragments, with the help of sophisticated data analysis software. It seems that cfDNA technology testing is highly accurate and has a very high sensitivity, so the difference compared to routine serum sample screening shows its significant superiority. However, cfDNA positive results still need confirmation by the invasive testing. The cell-free DNA analysis aims to become the first choice NIPT option due to its safety and high accuracy rate. The final goal is to develop the reliable method that could eventually replace invasive prenatal testing procedures.


Keywords

cfDNA, aneuploidy, prenatal diagnosis, amniocentesis, chorionic villi sampling, maternal-fetal exchange.

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References


Lo YM. Non-invasive prenatal diagnosis by massively parallel sequencing of maternal plasma DNA. Open Biol 2012; 2:120086.

Norwitz ER, Levy B. Noninvasive prenatal testing: the future is now. Rev Obstet Gynecol 2013; 6:48-62.

ACOG committee on practice bulletins. ACOG Practice Bulletin No. 77: screening for fetal chromosomal abnormalities. Obstet Gynecol 2007; 109:217-227.

ACOG committee on practice bulletins. ACOG Practice Bulletin No. 88, December 2007. Invasive prenatal testing for aneuploidy. Obstet Gynecol 2007; 110:1459-1467.

Driscoll DA, Gross, SJ. Professional Practice Guidelines Committee. Screening for fetal aneuploidy and neural tube defects. Genet Med 2009; 11:818-821.

ACOG committee on practice bulletins. ACOG Committee on Genetics. Committee Opinion No. 545: Noninvasiveprenatal testing for fetal aneuploidy. Obstet Gynecol 2012; 120:1532-1534.

Palomaki GE, Kloza EM, Lambert-Messerlian GM, Haddow JE, Neveux LM, Ehrich M, Van den Boom D, Bombard AT, Deciu C, Grody WW, Nelson SF Canick JA. DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study. Genet Med 2011; 13:913-920.

Cuckle H, Benn P, Wright D. Down syndrome screening in the first and/or second trimester: model predicted performance using meta-analysis parameters. Semin Perinatol 2005; 29:252257.

Nicolaides KH, Nuchal translucency and other firsttrimester sonographic markers of chromosomal abnormalities. Am J Obstet Gynecol 2004; 191:45-67.

Spencer K, Spencer CE, Power M, Dawson C, Nicolaides KH. Screening for chromosomal abnormalities in the first trimester using ultrasound and maternal serum biochemistry in a one-stop clinic: a review of three years prospective experience. BJOG 2003; 110:281-286.

Song K, Musci TJ, Caughey AB. Clinical utility and cost of non-invasive prenatal testing with cfDNA analysis in high-risk women based on a US population. J Matern Fetal Neonatal Med 2013; 26:1180-1185.

Coman D, Gardner RJ, Pertile MD, Kannu P. Trisomy 16 mosaicism at chorionic villus sampling and amniocentesis with a normal physical and intellectual outcome. Fetal Diagn Ther 2010; 28:117-118.

Hodor JG, Poggi SH, Spong CY, Goodwin KM, Vink JS, Pezzullo JC, Ghidini A. Risk of third-trimester amniocentesis: a case-control study. Am J Perinatol 2006; 23:177-180.

Wapner RJ, Martin CL, Levy B, Ballif BC, Eng CM, Zachary JM, Savage M, Platt LD, Saltzman D, Grobman WA, Klugman S, Scholl T, Simpson JL, McCall K, Aggarwal VS, Bunke B, Nahum O, Patel A, Lamb AN, Thom EA, Beaudet AL, Ledbetter DH, Shaffer LG, Jackson L. Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med 2012; 367: 2175-2184.

Choy KW, Kwok YK, Cheng YK, Wong KM, Wong HK, Leung KO, Suen KW, Adler K, Wang CC, Lau TK, Schermer MJ, Lao TT, Leung TY. Diagnostic accuracy of the BACs-on-Beads™ assay versus karyotyping for prenatal detection of chromosomal abnormalities: a retrospective consecutive case series. BJOG 2014; 121:1245-1252.

Wright CF, Burton H. The use of cell-free fetal nucleic acids in maternal blood for non-invasive prenatal diagnosis. Hum Reprod Update 2009; 15:139-151.

Mujezinovic F, Alfirevic Z., Procedure-related complications of amniocentesis and chorionic villous sampling: a systematic review. Obstet Gynecol 2007; 110:687-694.

Odibo AO, Gray DL, Dicke JM, Stamilio DM, Macones GA, Crane JP. Revisiting the fetal loss rate after second-trimester genetic amniocentesis: a single center’s 16-year experience. Obstet Gynecol 2008; 111:589-595.

Akolekar R, Beta J, Picciarelli G, Ogilvie C, D'antonio F. Procedure-related risk of miscarriage following amniocentesis and chorionic villus sampling: a systematic review and meta-analysis. Ultrasound Obstet Gynecol 2015; 45:16-26.

Tepperberg J, Pettenati MJ, Rao PN, Lese CM, Rita D, Wyandt H, Gersen S, White B, Schoonmaker MM. Prenatal diagnosis using interphase fluorescence in situ hybridization (FISH): 2-year multi-center retrospective study and review of the literature. Prenat Diagn 2001; 21:293-301.

Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, Church DM, Crolla JA, Eichler EE, Epstein CJ, Faucett WA, Feuk L, Friedman JM, Hamosh A, Jackson L, Kaminsky EB, Kok K, Krantz ID, Kuhn RM, Lee C, Ostell JM, Rosenberg C, Scherer SW, Spinner NB, Stavropoulos, DJ, Tepperberg JH, Thorland EC, Vermeesch JR, Waggoner DJ, Watson MS, Martin CL, Ledbetter DH. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 2012; 86:749-764.

Wapner R. A multicenter, prospective, masked comparison of chromosomal microarray with standard karyotyping for routine and high risk prenatal diagnosis. Am J Obstet Gynecol 2012; 206:S2.

Klonisch T, Drouin R. Fetal-maternal exchange of multipotent stem/progenitor cells: microchimerism in diagnosis and disease. Trends Mol Med 2009; 15:510-518.

Dawe GS, Tan XW, Xiao ZC. Cell Migration from Baby to Mother. Cell Adh Migr 2007; 1:19-27.

Engelhardt B. Molecular mechanisms involved in T cell migration across the blood brain barrier. J Neural Transm 2006; 113:477-485.

Guetta E, Simchen MJ, Mammon-Daviko K, Gordon D, Aviram-Goldring A, Rauchbach N, Barkai G. Analysis of fetal blood cells in the maternal circulation: challenges, ongoing efforts, and potential solutions. Stem Cells Dev 2004; 13:93-99.

O’Donoghue K, Chan J, De La Fuente J, Kennea N, Sandison A, Anderson JR, Roberts IA, Fisk NM. Microchimerism in female bone marrow and bone decades after fetal mesenchymal stem cell trafficking in pregnancy. Lancet 2004; 364:179-182.

Gussin HAE, Elias S. Culture of fetal cells from maternal blood for prenataldiagnosis. Hum Reprod Up 2002; 8:523-527.

Lo YM, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman CW, Wainscoat JS, Presence of fetal DNA in maternal plasma and serum. Lancet 1997; 350:485-487.

Sifakis S, Koukou Z. Spandidos DA. Cell-free fetal DNA and pregnancy-related complications (review). Mol Med Rep 2015; 11:2367-2372.

Ariga H, Ohto H, Busch MP, Imamura S, Watson R, Reed W, Lee TH., Kinetics of fetal cellular and cell-free DNA in the maternal circulation during and after pregnancy: implications for noninvasive prenatal diagnosis. Transfusion 2001; 41: 1524-1530.

Invernizzi P, Biondi ML, Battezzati PM, Perego F, Selmi C, Cecchini F, Podda M, Simoni G. Presence of fetal DNA in maternal plasma decades after pregnancy. Hum Genet 2002; 110:587-591.

Hahn S, Huppertz B. Holzgreve W, Fetal cells and cell-free fetal nucleic acids in maternal blood: new tools to study abnormal placentation? Placenta 2005; 26:515-526.

Fan HC, Blumenfeld YJ, Chitkara U, Hudgins L. Quake, SR, Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood. Proc Natl Acad Sci USA 2008; 105:16266-16271.

Sparks AB, Struble CA, Wang ET, Song K, Oliphant A. Noninvasive prenatal detection and selective analysis of cell-free DNA obtained from maternal blood: evaluation for trisomy 21 and trisomy 18. Am J Obstet Gynecol 2012; 206:319.e1-9.

Chiu RWK, Chan KC, Gao Y, Lau VYM, Zheng W, Leung TY, Foo CHF, Xie B, Tsui NBY, Lun FMF, Zee BCY, Lau TK, Cantor CR, Lo YMD. Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma. Proc Natl Acad Sci USA 2008; 105:20458-20463.

Chen EZ, Chiu RW, Sun H, Akolekar R, Chan AKC, Leung TY, Jiang P, Zheng YWL, Lun FMF, Chan LYS, Jin Y, Go ATJI, Lau ET, To WWK, Leung WC, Tang RYK, Au-Yeung SKC, Lam H, Kung YY, Zhang X, Van Vugt JMG, Minekawa R, Tang MHY, Wang J, Oudejans CBM, Lau TK, Nicolaides KH, Lo YMD. Noninvasive prenatal diagnosis of fetal trisomy 18 and trisomy 13 by maternal plasma DNA sequencing. PLoS One 2011; 6:e21791.

Ashoor G, Syngelaki A, Wang E, Struble C, Oliphant A, Song K, Nicolaides KH. Trisomy 13 detection in the first trimester of pregnancy using a chromosome-selective cell-free DNA analysis method. Ultrasound Obstet Gynecol 2013; 41:21-25.

Zimmermann B, Hill M, Gemelos G, Demko Z, Banjevic M, Baner J, Ryan A, Sigurjonsson S, Chopra N, Dodd M, Levy B, Rabinowitz M. Noninvasive prenatal aneuploidy testing at chromosomes 13, 18, 21, X, and Y, using targeted sequencing at polymorphic loci. Prenat Diagn 2012; 32:1233-1241.

Grati FR, Barlocco A, Grimi B, Milani S, Frascoli G, Di Meco AM, Liuti R, Trotta A, Chinetti S, Dulcetti F, Ruggeri AM, De Toffol S, Clementi M, Maggi F, Simoni G. Chromosome abnormalities investigated by non-invasive prenatal testing account for approximately 50% of fetal unbalances associated with relevant clinical phenotypes. Am J Med Genet A 2010; 152A:1434-1442.

Hall MP, Panorama™ Non-Invasive Prenatal Screening for Microdeletion Syndromes. Nat-MD-WhitePaper-V5-NL-(4/1/14), 2014, Available from: http://www.lifelabs.com/files/WhitePaper-Microdeletion.pdf

Jansen MW, Korver-Hakkennes K, van Leenen D, Visser W, in 't Veld PA, de Groot CJ, Wladimiroff JW. Signifcantly higher number of fetal cells in the maternal circulation of women with pre-eclampsia. Prenat Diagn 2001; 21:1022-1026.




DOI: https://doi.org/10.22190/FUMB170227003M

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