Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Pregnancy and Childbirth
Published in: BMC Pregnancy and Childbirth 1/2014

Open Access 01-12-2014 | Study protocol

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

Authors: Melissa Hill, David Wright, Rebecca Daley, Celine Lewis, Fiona McKay, Sarah Mason, Nicholas Lench, Abigail Howarth, Christopher Boustred, Kitty Lo, Vincent Plagnol, Kevin Spencer, Jane Fisher, Mark Kroese, Stephen Morris, Lyn S Chitty

Published in: BMC Pregnancy and Childbirth | Issue 1/2014

Login to get access

Abstract

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
Appendix
Available only for authorised users
Literature
1.
Tabor A, Alfirevic Z: Update on procedure-related risks for prenatal diagnosis techniques. Fetal Diagn Ther. 2010, 27: 1-7.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMed
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-CrossRefPubMedPubMedCentral
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.CrossRef
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMedPubMedCentral
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, 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.CrossRefPubMed
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMed
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.CrossRefPubMed
18.
American College of Obstetricians and Gynecologists: Noninvasive prenatal testing for fetal aneuploidy. Committee Opinion No. 545. Obstet Gynecol. 2012, 120: 1532-1534.CrossRef
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.CrossRefPubMed
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMed
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-CrossRefPubMedPubMedCentral
23.
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMed
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-CrossRefPubMedPubMedCentral
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.CrossRefPubMed
35.
Myatt L, Clifton R, Roberts J, Spong C, Wapner R, Thorp J, 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.CrossRefPubMedPubMedCentral
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
39.
Deans Z, Newson AJ: Should non-invasiveness change informed consent procedures for prenatal diagnosis?. Health Care Anal. 2011, 19: 122-132.CrossRefPubMed
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.CrossRefPubMed
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.
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.CrossRefPubMed
45.
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.CrossRefPubMed
47.
48.
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.CrossRefPubMed
50.
51.
Braun V, Clarke V: Using thematic analysis in psychology. Qual Res Psychol. 2006, 3: 77-101.CrossRef
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMed
Metadata
Title
Evaluation of non-invasive prenatal testing (NIPT) for aneuploidy in an NHS setting: a reliable accurate prenatal non-invasive diagnosis (RAPID) protocol
Authors
Melissa Hill
David Wright
Rebecca Daley
Celine Lewis
Fiona McKay
Sarah Mason
Nicholas Lench
Abigail Howarth
Christopher Boustred
Kitty Lo
Vincent Plagnol
Kevin Spencer
Jane Fisher
Mark Kroese
Stephen Morris
Lyn S Chitty
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Pregnancy and Childbirth / Issue 1/2014
Electronic ISSN: 1471-2393
DOI
https://doi.org/10.1186/1471-2393-14-229

Other articles of this Issue 1/2014

BMC Pregnancy and Childbirth 1/2014 Go to the issue

Research article

Reproductive desire in women with HIV infection in Spain, associated factors and motivations: a mixed-method study

Research article

Intravenous ferric carboxymaltose for anaemia in pregnancy

Research article

Low birth weight at term and the presence of fine particulate matter and carbon monoxide in the Brazilian Amazon: a population-based retrospective cohort study

Research article

Diabetes in pregnancy among First Nations women in Alberta, Canada: a retrospective analysis

Research article

A comprehensive representation of the birth-experience: identification and prioritization of birth-specific domains based on a mixed-method design

Research article

Experiencing challenges when implementing Active Management of Third Stage of Labor (AMTSL): a qualitative study with midwives in Accra, Ghana