Evaluation of non-invasive prenatal testing (NIPT) for aneuploidy in an NHS setting: a reliable accurate prenatal non-invasive diagnosis (RAPID) protocol

BMC Pregnancy and Childbirth

Lyn S Chitty⁷  Stephen Morris⁶  Mark Kroese⁸  Jane Fisher¹  Kevin Spencer⁴  Vincent Plagnol⁵  Kitty Lo⁵  Christopher Boustred³  Abigail Howarth³  Nicholas Lench³  Sarah Mason³  Fiona McKay³  Celine Lewis⁹  Rebecca Daley⁷  David Wright²  Melissa Hill⁹ 

[1] Antenatal Results and Choices, London, UK;Centre for Medical Statistics & Bioinformatics, Plymouth University, Plymouth, UK;North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Foundation Trust, Level 5, York House, 37 Queen Square, London WC1N 3BH, UK;Clinical Biochemistry Department, Barking, Havering & Redbridge University Hospitals NHS Trust, Essex, UK;UCL Genetics Institute, London, UK;Research Department of Applied Health Research, University College London, London, UK;Fetal Medicine Unit, University College London Hospitals NHS Foundation Trust, London, UK;PHG Foundation, Cambridge, UK;Genetics and Genomic Medicine, UCL Institute of Child Health and Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK

关键词: Prenatal diagnosis;    Aneuploidy;    Cell-free fetal DNA;    Non-invasive prenatal testing;   

Others  :  1127170
DOI  :  10.1186/1471-2393-14-229

 received in 2014-07-03, accepted in 2014-07-11,  发布年份 2014

【 摘 要 】

Background

Non-invasive prenatal testing (NIPT) for aneuploidies is now available through commercial companies in many countries, including through private practice in the United Kingdom (UK). Thorough evaluation of service delivery requirements are needed to facilitate NIPT being offered more widely within state funded healthcare systems such as the UK’s National Health Service (NHS). Successful implementation will require the development of laboratory standards, consideration of stakeholder views, an analysis of costs and development of patient and health professional educational materials.

Methods/Design

NIPT will be offered in an NHS setting as a contingent screening test. Pregnant woman will be recruited through six maternity units in England and Scotland. Women eligible for Down’s syndrome screening (DSS) will be informed about the study at the time of booking. Women that choose routine DSS will be offered NIPT if they have a screening risk ≥1:1000. NIPT results for trisomy 21, 18, 13 will be reported within 7–10 working days. Data on DSS, NIPT and invasive testing uptake, pregnancy outcomes and test efficacy will be collected. Additional data will be gathered though questionnaires to a) determine acceptability to patients and health professionals, b) evaluate patient and health professional education, c) assess informed choice in women accepting or declining testing and d) gauge family expenses. Qualitative interviews will also be conducted with a sub-set of participating women and health professionals.

Discussion

The results of this study will make a significant contribution to policy decisions around the implementation of NIPT for aneuploidies within the UK NHS. The laboratory standards for testing and reporting, education materials and counselling strategies developed as part of the study are likely to underpin the introduction of NIPT into NHS practice.

NIHR Portfolio Number

13865

【 授权许可】

   
2014 Hill et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Tabor A, Alfirevic Z: Update on procedure-related risks for prenatal diagnosis techniques. Fetal Diagn Ther 2010, 27:1-7.
• [2]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.
• [3]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 U S A 2008, 105:16266-16271.
• [4]Lo YM, Chiu RW, Lo YMD, Chiu RWK: Noninvasive prenatal diagnosis of fetal chromosomal aneuploidies by maternal plasma nucleic acid analysis. Clin Chem 2008, 54:461-466.
• [5]Chiu RW, Akolekar R, Zheng YW, Leung TY, Sun H, Chan KC, Lun FM, Go AT, Lau ET, To WW, Leung WC, Tang RY, Au-Yeung SK, Lam H, Kung YY, Zhang X, van Vugt JM, Minekawa R, Tang MH, Wang J, Oudejans CB, Lau TK, Nicolaides KH, Lo YM: Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study. BMJ 2011, 342:c7401.
• [6]Sehnert AJ, Rhees B, Comstock D, de Feo E, Heilek G, Burke J, Rava RP: Optimal detection of fetal chromosomal abnormalities by massively parallel DNA sequencing of cell-free fetal DNA from maternal blood. Clin Chem 2012, 57:1042-1049.
• [7]Ehrich M, Deciu C, Zwiefelhofer T, Tynan JA, Cagasan L, Tim R, Lu V, McCullough R, McCarthy E, Nygren AO, Dean J, Tang L, Hutchison D, Lu T, Wang H, Angkachatchai V, Oeth P, Cantor CR, Bombard A, van den Boom D: Noninvasive detection of fetal trisomy 21 by sequencing of DNA in maternal blood: a study in a clinical setting. Am J Obstet Gynecol 2011, 204(205):e201-211.
• [8]Palomaki GE, Kloza EM, Lambert-Messerlian GMH 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. Genet Med 2011, 13:913-920.
• [9]Ashoor G, Syngelaki A, Wagner M, Birdir C, Nicolaides KH: 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(322):e321-325.
• [10]Bianchi DW, Platt LD, Goldberg JD, Abuhamad AZ, Sehnert AJ, Rava RP: Genome-wide fetal aneuploidy detection by maternal plasma DNA sequencing. Obstet Gynecol 2012, 119:890-901.
• [11]Palomaki GE, Deciu C, Kloza EM, Lambert-Messerlian GM, Haddow JE, Neveux LM, Ehrich M, van den Boom D, Bombard AT, Grody WW, Nelson SF, Canick JA: DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study. Genet Med 2012, 14:296-305.
• [12]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):e311-319.
• [13]Norton ME, Brar H, Weiss J, Karimi A, Laurent LC, Caughey AB, Rodriguez MH, Williams J III, Mitchell ME, Adair CD, Lee H, Jacobsson B, Tomlinson MW, Oepkes D, Hollemon D, Sparks AB, Oliphant A, Song K: 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(137):e131-138.
• [14]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.
• [15]Futch T, Spinosa J, Bhatt S, de Feo E, Rava RP, Sehnert AJ: Initial clinical laboratory experience in noninvasive prenatal testing for fetal aneuploidy from maternal plasma DNA samples. Prenat Diagn 2013, 33:569-574.
• [16]Liang D, Lv W, Wang H, Xu L, Liu J, Li H, Hu L, Peng Y, Wu L: Non-invasive prenatal testing of fetal whole chromosome aneuploidy by massively parallel sequencing. Prenat Diagn 2013, 33:409-415.
• [17]Benn P, Borrell A, Cuckle H, Dugoff L, Gross S, Johnson JA, Maymon R, Odibo A, Schielen P, Spencer K, Wright D, Yaron Y: 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, 24 October 2011. Prenat Diagn 2012, 32:1-2.
• [18]American College of Obstetricians and Gynecologists: Noninvasive prenatal testing for fetal aneuploidy. Committee Opinion No. 545. Obstet Gynecol 2012, 120:1532-1534.
• [19]Gregg AR, Gross SJ, Best RG, Monaghan KG, Bajaj K, Skotko BG, Thompson BH, Watson MS: ACMG statement on noninvasive prenatal screening for fetal aneuploidy. Genet Med 2013, 15:395-398.
• [20]Srinivasan A, Bianchi DW, Huang H, Sehnert AJ, Rava RP: Non-invasive detection of fetal subchromosome abnormalities via deep sequencing of maternal plasma. Am J Hum Genet 2013, 92:167-176.
• [21]Lau TK, Jiang FM, Stevenson RJ, Lo TK, Chan LW, Chan MK, Lo PS, Wang W, Zhang HY, Chen F, Choy KW: Secondary findings from non-invasive prenatal testing for common fetal aneuploidies by whole genome sequencing as a clinical service. Prenat Diagn 2013, 33:602-608.
• [22]Yu SC, Jiang P, Choy KW, Chan KC, Won HS, Leung WC, Lau ET, Tang MH, Leung TY, Lo YM, Chiu RW: Noninvasive prenatal molecular karyotyping from maternal plasma. PLoS One 2013, 8:e60968.
• [23]RAPID Website. [http://www.rapid.nhs.uk webcite]
• [24]Chitty LS, Hill M, White H, Wright D, Morris S: Non-invasive prenatal testing for aneuploidy-ready for prime time? Am J Obstet Gynecol 2012, 206:269-275.
• [25]Deans Z, Newson AJ: Ethical considerations for choosing between possible models for using NIPD for aneuploidy detection. J Med Ethics 2012, 38:614-618.
• [26]Hill M, Fisher J, Chitty LS, Morris S: Women's and health professionals' preferences for prenatal tests for Down syndrome: a discrete choice experiment to contrast noninvasive prenatal diagnosis with current invasive tests. Genet Med 2012, 14:905-913.
• [27]Lewis C, Hill M, Silcock C, Daley R, Chitty L: Non-invasive prenatal testing for trisomy 21: a cross-sectional survey of service users' views and likely uptake. BJOG 2014, 121:582-594.
• [28]Sayres LC, Allyse M, Norton ME, Cho MK: Cell-free fetal DNA testing: a pilot study of obstetric healthcare provider attitudes toward clinical implementation. Prenat Diagn 2011, 31:1070-1076.
• [29]Tischler R, Hudgins L, Blumenfeld YJ, Greely HT, Ormond KE: Noninvasive prenatal diagnosis: pregnant women's interest and expected uptake. Prenat Diagn 2011, 31:1292-1299.
• [30]Sayres LC, Allyse M, Goodspeed TA, Cho MK: Demographic and experiential correlates of public attitudes towards cell-free fetal DNA screening. J Genet Couns 2014. Apr 14 [Epub ahead of print]
• [31]Allyse M, Sayres LC, Goodspeed TA, Cho MK: Attitudes towards non-invasive prenatal testing for aneuploidy among US adults of reproductive age. J Perinatol 2014, 34:429-34.
• [32]Chetty S, Garabedian MJ, Norton ME: Uptake of noninvasive prenatal testing (NIPT) in women following positive aneuploidy screening. Prenat Diagn 2013, 33:542-546.
• [33]Morris S, Karlsen S, Chung N, Hill M, Chitty LS: Model-based analysis of costs and outcomes of non-invasive prenatal testing for Down’s syndrome using cell free fetal DNA. Plos One 2014, 9:e93559.
• [34]Nicolaides KH: A model for a new pyramid of prenatal care based on the 11 to 13 weeks' assessment. Prenat Diagn 2011, 31:3-6.
• [35]Myatt L, Clifton R, Roberts J, Spong C, Wapner R, Thorp J Jr, Mercer B, Peaceman A, Ramin S, Carpenter M, Sciscione A, Tolosa J, Saade G, Sorokin Y, Anderson G: Can changes in angiogenic biomarkers between the first and second trimesters of pregnancy predict development of pre-eclampsia in a low-risk nulliparous patient population? BJOG 2013, 120:1183-91.
• [36]Donalson K, Turner S, Morrison L, Liitti P, Nilsson C, Cuckle H: Maternal serum placental growth factor and alpha-fetoprotein testing in first trimester screening for Down syndrome. Prenat Diagn 2013, 33:457-461.
• [37]Kooij L, Tymstra T, Berg P, Kooij L, Tymstra T, Berg P: The attitude of women toward current and future possibilities of diagnostic testing in maternal blood using fetal DNA. Prenat Diagn 2009, 29:164-168.
• [38]de Jong A, Dondorp WJ, de Die-Smulders CE, Frints SG, de Wert GM: Non-invasive prenatal testing: ethical issues explored. Eur J Hum Genet 2010, 18:272-277.
• [39]Deans Z, Newson AJ: Should non-invasiveness change informed consent procedures for prenatal diagnosis? Health Care Anal 2011, 19:122-132.
• [40]van den Heuvel A, Chitty L, Dormandy E, Newson A, Deans Z, Attwood S, Haynes S, Marteau TM: Will the introduction of non-invasive prenatal diagnostic testing erode informed choices? An experimental study of health care professionals. Patient Educ Couns 2010, 78:24-28.
• [41]Silcock C, Liao L-M, Hill M, Chitty LS: Will the introduction of non-invasive prenatal testing for Down's syndrome undermine informed choice? Health Expect 2014. [Epud ahead of print]
• [42]Lo KK, Boustred C, Chitty LS, Plagnol V: RAPIDR: an analysis package for non-invasive prenatal testing of aneuploidy. Bioinformatics 2014. doi:10.1093/bioinformatics/btu419
• [43]Illumina. [http://www.verifitest.com/ webcite]
• [44]Lewis C, Silcock C, Chitty LS: Non-invasive prenatal testing for Down's syndrome: pregnant women's views and likely uptake. Public Health Genomics 2013, 16:223-232.
• [45]Marteau TM, Dormandy E, Michie S: A measure of informed choice. Health Expect 2001, 4:99-108.
• [46]van den Berg M, Timmermans DR, ten Kate LP, van Vugt JM, van der Wal G: Informed decision making in the context of prenatal screening. Patient Educ Couns 2006, 63:110-117.
• [47]O'Connor A: User Manual – Decisional Conflict Scale (16 item statement format) [document on the Internet]. Ottawa: Ottawa Hospital Research Institute; Available from http://decisionaid.ohri.ca/docs/develop/User_Manuals/UM_Decisional_Conflict.pdf webcite 1993 (updated 2010): Accessed January 2014
• [48]O'Connor AM: Validation of a decisional conflict scale. Med Decis Making 1995, 15:25-30.
• [49]Marteau TM, Bekker H: The development of a six-item short-form of the state scale of the Spielberger State-Trait Anxiety Inventory (STAI). Br J Clin Psychol 1992, 31:301-306.
• [50]O'Connor A: User Manual – Decisional Regret Scale [document on the Internet]. Ottawa: Ottawa Hospital Research Institute; Available from https://decisionaid.ohri.ca/docs/develop/User_Manuals/UM_Regret_Scale.pdf webcite. 1996 (updated 2003): Accessed January 2014
• [51]Braun V, Clarke V: Using thematic analysis in psychology. Qual Res Psychol 2006, 3:77-101.
• [52]Lewis C, Hill M, Skirton H, Chitty LS: Non-invasive prenatal diagnosis for fetal sex determination: benefits and disadvantages from the service users' perspective. Eur J Hum Genet 2012, 20:1127-1133.
• [53]Hill M, Karunaratna M, Lewis C, Forya F, Chitty L: Views and preferences for the implementation of non-invasive prenatal diagnosis for single gene disorders from health professionals in the United Kingdom. Am J Med Genet A 2013, 161A:1612-1618.