Down’s syndrome (DS) is the most common genetic cause of developmental delay with an incidence of 1 in 800 live births, and is the predominant reason why women choose to undergo invasive prenatal diagnosis. However, as invasive tests are associated with around a 1% risk of miscarriage new non-invasive tests have been long sought after. Recently, the most promising approach for non-invasive prenatal diagnosis (NIPD) has been provided by the introduction of next generation sequencing (NGS) technologies. The clinical application of NIPD for DS detection is not yet applicable, as large scale validation studies in low-risk pregnancies need to be completed. Currently, prenatal screening is still the first line test for the detection of fetal aneuploidy. Screening cannot diagnose DS, but developing a more advanced screening program can help to improve detection rates, and therefore reduce the number of women offered invasive tests. This article describes how the prenatal screening program has developed since the introduction of maternal age as the original “screening” test, and subsequently discusses recent advances in detecting new screening markers with reference to both proteomic and bioinformatic techniques.
References
[1]
Ehrich, M.; Deciu, C.; Zwiefelhofer, T.; Tynan, J.A.; Cagasan, L.; Tim, R.; Lu, V.; McCullough, R.; McCarthy, E.; Nygren, A.O. Nonivasive detection of fetal trisomy 21 by sequencing of DNA in maternal blood: A study in a clinical setting. Am. J. Obstet. Gynecol. 2011, 204, 201–211.
[2]
Egan, J.F.; Benn, P.A.; Zelop, C.M.; Bolnick, A.; Gianferrari, E.; Borgida, A.F. Down syndrome births in the United States from 1989 to 2001. Am. J. Obstet. Gynecol. 2004, 191, 1044–1048, doi:10.1016/j.ajog.2004.06.050.
[3]
Morris, J.K.; Mutton, D.E.; Alberman, E. Revised estimates of the maternal age specific live birth prevalence of Down’s syndrome. J. Med. Screen 2002, 9, 2–6.
[4]
Crane, E.; Morris, J.K. Changes in maternal age in England and Wales—Implications for Down syndrome. Down Syndr. Res. Prac. 2006, 10, 41–43, doi:10.3104/reports.304.
[5]
McEwan, A.; Godfrey, A.; Wilkins, J. Screening for Down syndrome. Obstet. Gynaecol. Reprod. Med. 2012, 22, 70–75, doi:10.1016/j.ogrm.2012.01.006.
[6]
Rozenberg, P.; Bussières, L.; Chevret, S.; Bernard, J.P.; Malagrida, L.; Cuckle, H.; Chabry, C.; Durand-Zaleski, I.; Bidat, L.; Lacroix, I. Screening for Down syndrome using first-trimester combined screening followed by second trimester ultrasound examination in an unselected population. Gynecol. Obstet. Fertil. 2007, 35, 303–311, doi:10.1016/j.gyobfe.2007.02.004.
[7]
Morris, J.K.; Wald, N.J.; Watt, H.C. Fetal loss in Down syndrome pregnancies. Prenat. Diagn. 1999, 19, 142–145, doi:10.1002/(SICI)1097-0223(199902)19:2<142::AID-PD486>3.0.CO;2-7.
[8]
Chiu, R.W.K.; Cantor, C.R.; Lo, Y.M.D. Non-invasive prenatal diagnosis by single molecule counting technologies. Trends Genet. 2009, 25, 324–331, doi:10.1016/j.tig.2009.05.004.
[9]
Ferguson-Smith, M.A. Placental mRNA in maternal plasma: Prospects for fetal screening. Proc. Natl. Acad. Sci. USA 2003, 100, 4360–4362, doi:10.1073/pnas.0830966100.
[10]
Wald, N.J. Guidance on terminology. J. Med. Screen 2006, 13, 53, doi:10.1258/096914106776179818.
[11]
Buckley, F.; Buckley, S. Wrongful deaths and rightful lives—Screening for Down syndrome. Down Syndr. Res. Prac. 2008, 12, 79–86.
[12]
Haddow, J.E.; Palomaki, G.E.; Knight, G.J.; Williams, J.; Pulkkinen, A.; Canick, J.A.; Saller, D.N.; Bowers, G.B. Prenatal screening for Down’s syndrome with use of maternal serum markers. N. Engl. J. Med. 1992, 327, 588–593, doi:10.1056/NEJM199208273270902.
[13]
Benacerraf, B.R.; Gelman, R.; Friholetto, F.D. Sonographic identification of second-trimester fetuses with Down’s syndrome. N. Engl. J. Med. 1987, 317, 1371–1376, doi:10.1056/NEJM198711263172203.
[14]
Merkatz, I.; Nitowsky, H.; Marci, J.; Johnson, W. An association between low maternal serum alpha-fetoprotein and fetal chromosomal abnormalities. Am. J. Obstet. Gynecol. 1984, 148, 886–894.
[15]
Cuckle, H.; Wald, N.; Lindenbaum, R. Maternal serum alpha-fetoprotein measurement: A screening test for Down syndrome. Lancet 1984, 1, 926–929, doi:10.1016/S0140-6736(84)92389-4.
[16]
Furhmann, W.; Wendt, P.; Weitzel, H. Maternal serum-AFP as screening test for Down syndrome. Lancet 1984, 2, doi:10.1016/S0140-6736(84)92389-4.
[17]
Gillespie, G.; Uversky, V. Structure and function of alpha-fetoprotein: A biophysical overview. Biochem. Biophys. Acta 2000, 1480, 41–56.
[18]
DiMaio, M.; Baumgarten, A.; Greenstein, R.; Mahoney, M. Screening for fetal Down’s syndrome in pregnancy by measuring maternal serum alpha-fetoprotein levels. N. Engl. J. Med. 1987, 6, 342–346.
[19]
Cole, L. New discoveries on the biology and detection of human chorionic gonadotrophin. Reprod. Biol. Endocrinol. 2009, 7, doi:10.1186/1477-7827-7-8.
[20]
Bogart, M.; Pandian, M.; Jones, O. Abnormal maternal serum chorionic gonadotropin levels in pregnancies with fetal chromosome abnormalities. Prenat. Diagn. 1987, 7, 623–630, doi:10.1002/pd.1970070904.
[21]
Agarwal, R. Prenatal diagnosis of chromosomal anomalies: Pictorial essay. Indian J. Radiol. Imaging 2003, 13, 173–188.
[22]
Canick, J.; Kellner, L. First trimester screening for aneuploidy: Serum biochemical markers. Semin. Perinatol. 1999, 5, 359–368, doi:10.1016/S0146-0005(99)80002-0.
[23]
Crossley, J.; Aitken, D.; Connor, J. Second-trimester unconjugated oestriol levels in maternal serum from chromosomally abnormal pregnancies using an optimized assay. Prenat. Diagn. 1993, 13, 271–280, doi:10.1002/pd.1970130406.
[24]
Ryall, R.; Staples, A.; Robertson, E.; Pollard, A. Improved performance in a prenatal screening programme for Down’s syndrome incorporating serum-free hCG subunit analyses. Prenat. Diagn. 1992, 12, 251–261, doi:10.1002/pd.1970120404.
[25]
Reynolds, T. The triple test as a screening technique for Down syndrome: Reliability and relevance. Int. J. Wom. Health 2010, 2010, 83–88, doi:10.2147/IJWH.S8548.
[26]
Aitken, D.A.; Wallace, E.M.; Crossley, J.A.; Swanston, I.A.; Pareren, Y.V.; Maarle, M.V.; Groome, N.P.; Macri, J.N.; Connor, M.J. Dimeric inhibin A as a marker for Down’s syndrome in early pregnancy. N. Engl. J. Med. 1996, 334, 1231–1236, doi:10.1056/NEJM199605093341904.
[27]
Brambati, B.; Macintosh, M.C.; Teisner, B.; Maguiness, S.; Shrimanker, K.; Lanzani, A.; Bonacchi, I.; Tului, L.; Chard, T.; Grudzinskas, J.G. Low maternal serum levels of pregnancy associated plasma protein a (PAPP-A) in the first trimester in association with abnormal fetal karyotype. Br. J. Obstet. Gynaecol. 1993, 100, 324–326, doi:10.1111/j.1471-0528.1993.tb12973.x.
[28]
Knight, G.; Palomaki, G.; Haddow, J.E. Pregnancy associated plasma protein A as a marker for Down syndrome in the second trimester of pregnancy. Prenat. Diagn. 1993, 13, 222–223, doi:10.1002/pd.1970130312.
[29]
Reis, F.; D’Antona, D.; Petraglia, F. Predictive value of hormone measurements in maternal and fetal complications of pregnancy. Endo Rev. 2002, 23, 230–257, doi:10.1210/er.23.2.230.
[30]
Nicolaides, K.H.; Azar, G.; Byrne, D.; Mansur, C.; Marks, K. Fetal nuchal translucency: Ultrasound screening for chromosomal defects in first trimester of pregnancy. BMJ 1992, 304, 867–869, doi:10.1136/bmj.304.6831.867.
[31]
Nicolaides, K.H.; Brizot, M.L.; Snijders, R.J. Fetal nuchal translucency: Ultrasound screening for chromosomal defects in first trimester of pregnancy. J. Obstet. Gynaecol. 1994, 101, 782–786, doi:10.1111/j.1471-0528.1994.tb11946.x.
[32]
Committee, T.N.S. National Down’s Syndrome Screening Program (DoSYSP). Available online: http://fetalanomaly.screening.nhs.uk/standardsandpolicies (accessed on 20 May 2013).
[33]
Chitty, L.S.; Pandya, P.P. Ultrasound screening for fetal abnormalities in the first trimester. Prenat. Diagn. 1997, 17, 1269–1281, doi:10.1002/(SICI)1097-0223(199712)17:13<1269::AID-PD3>3.0.CO;2-G.
Wald, N.; Hackshaw, A.K. Combining ultrasound and biochemistry in first trimester screening for Down’s syndrome. Prenat. Diagn. 1997, 17, 821–829, doi:10.1002/(SICI)1097-0223(199709)17:9<821::AID-PD154>3.0.CO;2-5.
[36]
Spencer, K.; Nicolaides, K.H. Screening for trisomy 21 in twins using first trimester ultrasound and maternal serum biochemistry in a one-stop clinic: A review of three years experience. Br. J. Obstet. Gynaecol. 2003, 110, 276–280, doi:10.1046/j.1471-0528.2003.02222.x.
[37]
Nicolaides, K.H.; Spencer, K.; Avqidou, K.; Faiola, S.; Falcon, O. Multicenter study of first-trimester screening for trisomy 21 in 75,821 pregnancies: Results and estimation of the potential impact of individual risk-orientated two-stage first-trimester screening. Ultrasound Obstet. Gynecol. 2005, 25, 221–226, doi:10.1002/uog.1860.
[38]
Jaques, A.M.; Halliday, J.L.; Francis, I.; Bonacquisto, L.; Forbes, R.; Cronin, A.; Sheffield, L.J. Follow up and evaluation of the victorian first-trimester combined screening programme for Down syndrome and trisomy 18. BJOG 2007, 114, 812–818, doi:10.1111/j.1471-0528.2007.01349.x.
[39]
Valinen, Y.; Rapakko, K.; Kokkonen, H.; Laitinen, P.; Tekay, A.; Ahola, T.; Ryynanen, M. Clinical first-trimester routine screening for Down syndrome in singleton pregnancies in northern Finland. Am. J. Obstet. Gynecol. 2007, 196, 278, doi:10.1016/j.ajog.2006.11.040.
[40]
Wald, N.J.; Huttly, W.J.; Murphy, K.W.; Ali, K.; Bestwick, J.P.; Rodeck, C.H. Antenatal screening for Down’s syndrome using the integrated test at two London hospitals. J. Med. Screen 2009, 16, 7–10, doi:10.1258/jms.2009.008094.
[41]
Benn, P.; Borell, A.; Chiu, R.; Cuckle, H.; Dugoff, L.; Faas, B.; Gross, S.; Johnson, J.; Maymon, R.; Norton, M.; et al. Position statement from the aneuploidy screening committee on behalf of the board of the international society for prenatal diagnosis, April 2013. Prenat. Diagn. 2013, 32, 1–2.
[42]
NHS Fetal Anomaly Screening Programme. Screening for Down’s syndrome: UK NSC Policy Recommendations 2011–2014 Model of Best Practice. Available online: http://www.fetalanomaly. screening.nhs.uk/getdata.php?id=11393 (accessed on 13 May 2013).
[43]
Fang, Y.M.V.; Benn, P.; Campbell, W.; Bolnick, J.; Prabulos, A.M.; Egan, J.F.X. Down syndrome screening in the united states in 2001 and 2007: A survey of maternal-fetal medicine specialists. Am. J. Obstet. Gynecol. 2009, 201, e91–e95.
[44]
Benn, P.; Borrell, A.; Crossley, J.; Cuckle, H.; Dugoff, L.; Gross, S.; Johnson, J.-A.; Maymon, R.; Odibo, A.; Schielen, P.; et al. Aneuploidy screening: A position statement from a committee on behalf of the board of the international society for prenatal diagnosis, January 2011. Prenat. Diagn. 2011, 31, 519–522.
[45]
Maslen, C.L.; Babcock, D.; Robinson, S.W.; Bean, L.J.; Dooley, K.J.; Willour, V.L.; Sherman, S.L. Creld1 mutations contribute to the occurrence of cardiac atrioventricular septal defects in Down syndrome. Am. J. Med. Genet. 2006, 140, 2501–2505.
[46]
Nyberg, D.; Souter, V. Sonographic markers of fetal trisomies: Second trimester. J. Ultrasound Med. 2001, 20, 655–674.
[47]
Stoll, C.; Dott, B.; Alembik, Y.; Roth, M. Evaluation of routine prenatal ultrasound examination in detecting fetal chromosomal abnormalities in a low risk population. Hum. Genet. 1993, 91, 37–41.
[48]
Hill, L. The sonographic detection of trisomies 13, 18 and 21. Clin. Obstet. Gynecol. 1996, 39, 831–850.
Cowans, N.; Stamatopoulou, A.; Torring, N.; Spencer, K. Early first trimester maternal serum placental growth factor in trisomy 21 pregnancies. Ultrasound Obstet. Gynecol. 2011, 37, 515–519.
[55]
Akinlade, F.; Cowans, N.; Kisanga, M.; Spencer, K. Maternal serum CA 19-9 and CA 15-3 levels in pregnancies affected by trisomy 21. Prenat. Diagn. 2012, 32, 644–648.
[56]
Kamyab, A.R.; Shahrokhi, F.; Shamsian, E.; Nosaied, M.H.; Dibajnia, P.; Hashemi, M.; Mahdian, R. Determination of sensitivity and specificity of a novel gene dosage assay for prenatal screening of trisomy 21 syndrome. Clin. Biochem. 2012, 45, 267–271.
[57]
Lim, J.H.; Kim, S.Y.; Park, S.Y.; Lee, S.Y.; Kim, M.J.; Han, Y.J.; Lee, S.W.; Chung, J.H.; Kim, M.Y.; Yang, J.H.; et al. Non-invasive epigenetic detection of fetal trisomy 21 in first trimester maternal plasma. PLoS One 2011, 6, doi:10.1371/journal.pone.0027709.
[58]
Du, Y.; Zhang, J.; Wang, H.; Yan, X.; Yang, Y.; Yang, L.; Luo, X.; Chen, Y.; Duan, T.; Ma, D. Hypomethylated dscr4 is a placenta-derived epigenetic marker for trisomy 21. Prenat. Diagn. 2011, 31, 207–214, doi:10.1002/pd.2684.
Chitty, L.S.; van der Schoot, C.E.; Hahn, S.; Avent, N.D. SAFE-the special non-invasive advances in fetal and neonatal evaluation network: Aims and achievements. Prenat. Diagn. 2008, 28, 83–88, doi:10.1002/pd.1929.
[61]
Shipp, T.; Benacerraf, B. Second trimester ultrasound screening for chromosomal abnormalities. Prenat. Diagn. 2002, 22, 296–307, doi:10.1002/pd.307.
[62]
Cicero, S.; Curcio, P.; Papageorghiou, A.; Sonek, J.; Nicolaides, K. Absence of nasal bone in fetuses with trisomy 21 at 11–14 weeks of gestation: An observational study. Lancet 2001, 358, 1665–1667, doi:10.1016/S0140-6736(01)06709-5.
[63]
Donaldson, K.; Turner, S.; Morrison, L.; Liitte, P.; Nilsson, C.; Cuckle, H. Maternal serum placental growth factor and α-fetoprotein testing in first trimester screening for Down syndrome. Prenat. Diagn. 2013, 33, 457–461.
[64]
Wang, M.; Lu, S.; Zhu, Y.; Li, H. Adam12 is an effective marker in the second trimester of pregnancy for prenatal screening of Down syndrome. Prenat. Diagn. 2010, 30, 561–564.
[65]
Chim, S.S.; Tong, Y.K.; Chiu, R.W.; Lau, T.K.; Leung, T.Y.; Chan, L.Y.S.; Oudejans, C.B.M.; Ding, C.; Lo, Y.M. Detection of the placental epignetic signature of the maspin gene in maternal plasma. Proc. Natl. Acad. Sci. USA 2005, 11, 14753–14758.
[66]
Kang, Y.; Dong, X.; Zhou, Q.; Zhang, Y.; Cheng, Y.; Hu, R.; Su, C.; Jin, H.; Liu, X.; Ma, D.; et al. Identification of novel candidate maternal serum protein markers for Down syndrome by integrated proteomic and bioinformatic analysis. Prenat. Diagn. 2012, 32, 284–292, doi:10.1002/pd.3829.
[67]
Avent, N.D. Maternal plasma biomarkers for Down syndrome: Present and future. Drugs Today 2013, 49, 145–152.
[68]
Honda, H.; Miharu, N.; Ohashi, Y.; Samura, O.; Kinutani, M.; Hara, T.; Ohama, K. Fetal gender determination in early pregnancy through qualitative and quantitative analysis of fetal DNA in maternal serum. Hum. Genet. 2002, 110, 75–79, doi:10.1007/s00439-001-0649-3.
[69]
Bianchi, D.W.; Avent, N.D.; Costa, J.M.; van der Schoot, C.E. Noninvasive prenatal diagnosis of fetal rhesus D: Ready for prime(r) time. Obstet. Gynecol. 2005, 106, 841–844, doi:10.1097/01.AOG.0000179477.59385.93.
[70]
Lo, Y.M.D.; Hjelm, M.; Fidler, C.; Sargent, I.L.; Murphy, M.F.; Chamberlain, P.F.; Poon, P.M.K.; Redman, C.W.G.; Wainscoat, J.S. Prenatal diagnosis of fetal rhd status by molecular analysis of maternal plasma. N. Engl. J. Med. 1998, 339, 1734–1738.
[71]
Satio, H.; Sekizawa, A.; Morimoto, T. Prenatal DNA diagnosis of a single-gene disorder from maternal plasma. Lancet 2000, 356, doi:10.1016/S0140-6736(00)02767-7.
[72]
Sehnert, A.J.; Rhees, B.; Comstock, D.; de Feo, E.; Heilek, G.; Burke, J.; Rava, R.P. Optimal detection of fetal chromosomal abnormalities by massively parallel DNA sequencing of cell-free fetal DNA from maternal blood. Clin. Chem. 2011, 57, 1042–1049, doi:10.1373/clinchem.2011.165910.
[73]
Dan, S.; Chen, F.; Choy, K.W.; Jiang, F.; Lin, J.; Xuan, Z.; Wang, W.; Chen, S.; Li, X.; Jiang, H.; et al. Prenatal detection of aneuploidy and imbalanced chromosomal parallel sequencing. PLoS One 2011, 7, doi:10.1371/journal.pone.0027835.
[74]
Papageorgiou, E.A.; Patsalis, P.C. Non-invasive prenatal diagnosis of aneuploidies: New technologies and clinical applications. Genom. Med. 2012, 4, doi:10.1016/j.tig.2009.05.004.
[75]
Hulten, M.; Dhanjal, S.; Pertl, B. Rapid and simple prenatal diagnosis of common chromosome disorders: Advantages and disadvantages of the molecular methods fish and QF-PCR. Reproduction 2003, 126, 279–297, doi:10.1530/rep.0.1260279.
[76]
Shaffer, L.; Bui, T. Molecular cytogenetic and rapid aneuploidy detection methods in prenatal diagnosis. Am. J. Med. Genet. 2007, 145, 87–98, doi:10.1002/ajmg.c.30114.
[77]
Zimmermann, B.; Holzgreve, W.; Wenzel, F.; Hahn, S. Novel real-time quantitative PCR test for trisomy 21. Clin. Chem. 2002, 48, 362–363.
[78]
Vogelstein, B.; Kinzler, K. Digital PCR. Proc. Natl. Acad. Sci. USA 1999, 96, 9236–9261, doi:10.1073/pnas.96.16.9236.
[79]
White, R.; Blainey, P.; Fan, H.; Quake, S. Digital PCR provides sensitive and absolute calibration for high throughput sequencing. BMC 2009, 10, 116, doi:10.1186/1471-2164-10-116.
[80]
Fan, H.C.; Blumenfeld, Y.J.; El-Sayed, Y.Y.; Chueh, J.; Quake, S.R. Microfluidic digital PCR enables rapid prenatal diagnosis of fetal aneuploidy. Am. J. Med. Genet. 2009, 200, e541–e547.
[81]
Zimmermann, B.G.; Grill, S.; Holzgreve, W.; Zhong, X.Y.; Jackson, L.G.; Hahn, S. Digital PCR: A powerful new tool for noninvasive prenatal diagnosis? Prenat. Diagn. 2008, 28, 1087–1093, doi:10.1002/pd.2150.
[82]
Lun, F.M.; Chiu, R.W.; Chan, K.C.; Leung, T.Y.; Lau, T.K.; Lo, Y.M. Microfluidics digital PCR reveals a higher than expected fraction of fetal DNA in maternal plasma. Clin. Chem. 2008, 54, 1664–1672, doi:10.1373/clinchem.2008.111385.
[83]
Lo, Y.M.D.; Lun, F.M.; Chan, K.C.; Tsui, N.B.Y.; Chong, K.C.; Lau, T.K.; Leung, T.Y.; Zee, T.Y.; Cantor, C.R.; Chiu, R.W. Digital PCR for the molecular detection of fetal chromosomal aneuploidy. Proc. Natl. Acad. Sci. USA 2007, 104, 13116–13121, doi:10.1073/pnas.0705765104.
[84]
Lo, Y.M.; Chan, K.C.; Chiu, R.W. Nonivasive fetal trisomy 21 detection using chromosom selective sequencing: A variation of the molecular counting theme. Expert Rev. Mol. Diagn. 2012, 12, 329–331, doi:10.1586/erm.12.24.
[85]
Evans, M.I.; Wright, D.A.; Pergament, E.; Cuckle, H.S.; Nicolaides, K.H. Digital PCR for noninvasive detection of aneuploidy: Power analysis equations for feasibility. Fetal Diagn. Ther. 2012, 31, 244–247, doi:10.1159/000337544.
[86]
Sonek, J.; Molina, F.; Hiett, A.K.; Glover, M.; McKenna, D.; Nicolaides, K. Paper abstracts of the ISPD 16th international conference on prenatal diagnosis and therapy. Prenat. Diagn. 2012, 32, 1–128.
[87]
Fan, H.C.; Blumenfeld, Y.J.; Chitkara, U.; Hudgins, L.; Quake, S.R. Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood. Proc. Natl. Acad. Sci. USA 2008, 105, 16266–16271.
[88]
Ashoor, G.; Syngelaki, A.; Wagner, M.; Birdir, C.; Nicolaides, K. Chromosome-selective sequencing of maternal plasma cell-free DNA for first trimester detection of trisomy 21 and trisomy 18. Am. J. Obstet. Gynecol. 2012, 206, e321–e325.
Jensen, T.; Zwiefelhofer, T.; Tim, R.; Dzakula, Z.; Kim, S.; Mazloom, A.; Zhu, Z.; Tynan, J.; Lu, T.; McLennan, G. High-throughput massively parallel sequencing for fetal aneuploidy detection from maternal plasma. PLoS One 2013, 8, doi:10.1371/journal.pone.0057381.
[93]
Sparks, A.B.; Struble, C.A.; Wang, E.T.; Song, K.; Oliphant, A. Nonivasive 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, e311–e319.
[94]
Norton, M.E.; Brar, H.; Weiss, J.; Karimi, A.; Laurent, L.C.; Caughey, A.B.; Rodriguez, H.; Williams, J.I.; Mitchell, M.E.; Adair, C.D. 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, e131–e138.
Boon, E.M.J.; Faas, B.H.W. Benefits and limitations of whole genome versus targeted approaches for noninvasive prenatal testing for fetal aneuploidies. Prenat. Diagn. 2013, doi:10.1002/pd.4111.
[97]
Chitty, L.S.; Hill, L.; White, H.; Wright, D.; Morris, S. Noninvasive prenatal testing for aneuploidy-ready for prime time? Am. J. Obstet. Gynecol. 2012, 206, 269–275, doi:10.1016/j.ajog.2012.02.021.
[98]
GenomeWeb. Aria Kicks off Clinical Trial for Non-Invasive Down Syndrome Test. Available online: http://www.genomeweb.com/mdx/aria-kicks-clinical-trial-non-invasive-down-syndrome-test (accessed on 12 May 2013).
[99]
Liu, L.; Li, Y.; Li, S.; Hu, N.; He, Y.; Pong, R.; Lin, D.; Lu, L.; Law, M. Comparison of next-generation sequencing systems. J. Biomed. Biotechnol. 2012, doi:10.1155/2012/251364.
Pareek, C.S.; Smoczynski, R.; Trefyn, A. Sequencing technologies and genome sequencing. J. Appl. Genet. 2011, 52, 413–435, doi:10.1007/s13353-011-0057-x.
[102]
Benn, P.; Borrell, A.; Cuckle, H.; Dugoff, L.; Gross, S.; Johnson, J.A.; Maymon, R.; Odibo, A.; Schielen, P.; Spencer, K. Prenatal detection of Down syndrome using massively parallel sequencing (MPS): A rapid response statement from a committee on behalf of the board of the international society for prenatal diagnosis. Prenat. Diagn. 2012, 32, 1–2.
[103]
Hui, L. Non-invasive prenatal testing for fetal aneuploidy: Charting the course from clinical validation to clinical utility. Ultrasound Obstet. Gynecol. 2013, 41, 2–6, doi:10.1002/uog.12360.
[104]
Jiang, K. Competition intensifies over market for DNA-based prenatal tests. Nat. Med. 2013, 19, doi:10.1038/nm0413–1381.
[105]
Perkel, J. Finding the true $1,000 genome. BioTechniques 2013, 54, 71–74.
[106]
Nicolaides, K.; Syngelaki, A.; Ashoor, G.; Birdir, C.; Touzet, G. Noninvasive prenatal testing for fetal trisomies in a routinely screened first-trimester population. Am. J. Obstet. Gynecol. 2012, 207, e371–e376.
[107]
Anderson, C.; Brown, C. Fetal chromosome abnormalities: Antenatal screening and diagnosis. Am. Fam. Physic. 2009, 79, 117–123.
