Non-invasive Chromosomal Examination of Trisomy Study

NCT01511458 | Completed DMC

• 1 other identifier: TD007
• Study Type: observational
• Target: 18,955
• Locations: 6 countries
• Sites: 36

Brief Summary

The purpose of this blinded, multi-center, prospective, case-controlled study is to compare the Ariosa Harmony™ Prenatal Test for trisomy 21 detection with a standard first-trimester prenatal screening test consisting of serum screening (PAPP-A,free beta-hCG \[β-hCG\] or total hCG) and a nuchal translucency (NT) measurement (i.e. combined first trimester screening) in a general screened population. The performance characteristics of these two test modalities will be assessed relative to the clinical reference standard of genetic analysis of the fetus or phenotypic characterization and genetic analysis of the newborn.

Conditions

Trisomy 21

Keywords

Pregnancy; Fetal aneuploidy; Trisomy 21; Down Syndrome; Prenatal screening; Non-invasive prenatal testing; First trimester; Combined screening; Nuchal translucency; PAPP-A; hCG; cell free DNA; cf DNA; DNA; Performance characteristics of non-invasive first trimester screening; Harmony Prenatal Test

Outcome Measures

Primary Outcomes (1)

• Difference in sensitivity and specificity of Ariosa Harmony™ Prenatal Test (AUCt) and combined first-trimester screening for detection of T21.

  Enrollment to delivery

Study Arms (2)

Case

Patient with a trisomy 21 pregnancy confirmed by genetic testing.

Control

Patients without a trisomy 21 pregnancy confirmed by either genetic testing or a normal newborn phenotype.

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Pregnant women presenting for combined first trimester screening as part of routine prenatal care

You may qualify if:

• Subject is at least 18 years old and can provide informed consent.
• Subject is planning a hospital delivery.
• Subject has a singleton pregnancy with a documented gestational age between 10 weeks, 0 days, and 14 weeks, 2 days, inclusive, at the time of the study blood sample collection.
• Subject is planning to undergo combined first trimester prenatal screening that includes NT measurement, and when indicated, serum screening with total or free β-hCG and PAPP-A.

You may not qualify if:

• Subject has known aneuploidy.
• Subject has active or history of malignancy requiring major surgery and/or systemic chemotherapy.

Sponsors & Collaborators

• Roche Sequencing Solutions: lead
• Perinatal Quality Foundation: Nuchal Translucency Quality Review: collaborator

Study Sites (36)

Tucson Medical Center

Tucson, Arizona, 85712, United States

Location

East Bay Perinatal Associates

Oakland, California, 94609, United States

Location

Stanford University

Palo Alto, California, 94305-5317, United States

Location

Perinatal Diagnostic Center

Riverside, California, 92501, United States

Location

University of California San Diego

San Diego, California, 92037-1300, United States

Location

California Pacific Medical Center

San Francisco, California, 94118, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

The Institute of Prenatal Diagnosis and Reproductive Medicine

San Gabriel, California, 91776, United States

Location

Christiana Care Health System

Newark, Delaware, 19718, United States

Location

Altus Research

Lake Worth, Florida, 33461, United States

Location

Fetal Diagnostic Institute of the Pacific

Honolulu, Hawaii, 96814, United States

Location

Northshore University Health System

Evanston, Illinois, 60201, United States

Location

Norton Healthcare

Louisville, Kentucky, 40202, United States

Location

Brigham and Women's Hospital - Center for Fetal Medicine and Prenatal Genetics

Boston, Massachusetts, 02115, United States

Location

Minnesota Perinatal Associates

Minneapolis, Minnesota, 55407, United States

Location

Robert Wood Johnson School of Medicine

New Brunswick, New Jersey, 08901, United States

Location

St. Peters University Medical Center

New Brunswick, New Jersey, 08901, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Northwest Perinatal Center

Portland, Oregon, 97225, United States

Location

Oregon Health Sciences University

Portland, Oregon, 97239, United States

Location

Abington Memorial Hospital

Abington, Pennsylvania, 19001, United States

Location

Thomas Jefferson Univeristy Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Women's Health Care Group of Pennsylvania

Wynnewood, Pennsylvania, 19096, United States

Location

Partners in Obstetrics and Gynecology

Pawtucket, Rhode Island, 02860, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

University Hospitals Leuven

Leuven, Belgium

Location

Early Risk Assessment Program - University of Alberta

Calgary, Alberta, T2N 4N1, Canada

Location

Ottawa Hospital and Research Institute

Ottawa, Ontario, ON1Kh8L6, Canada

Location

Mount Sinai University

Toronto, Ontario, M5G 1X5, Canada

Location

University of Toronto

Toronto, Ontario, M5G1X8, Canada

Location

University of Perugia

Perugia, 06132, Italy

Location

Leiden University Medical Center

Leiden, 2333, Netherlands

Location

Maastricht University Medical Center

Maastricht, 6202, Netherlands

Location

Sahlgrenska University Medical Center

Gothenburg, SE-41685, Sweden

Location

Karolinska University Hospital

Stockholm, 14186, Sweden

Location

Related Publications (20)

• American College of Obstetricians and Gynecologists. Guidelines for Perinatal Care, Sixth Edition, October 2007.

  BACKGROUND

• Nicolaides KH. A model for a new pyramid of prenatal care based on the 11 to 13 weeks' assessment. Prenat Diagn. 2011 Jan;31(1):3-6. doi: 10.1002/pd.2685. No abstract available.

  PMID: 21210474 BACKGROUND

• Malone FD, Canick JA, Ball RH, Nyberg DA, Comstock CH, Bukowski R, Berkowitz RL, Gross SJ, Dugoff L, Craigo SD, Timor-Tritsch IE, Carr SR, Wolfe HM, Dukes K, Bianchi DW, Rudnicka AR, Hackshaw AK, Lambert-Messerlian G, Wald NJ, D'Alton ME; First- and Second-Trimester Evaluation of Risk (FASTER) Research Consortium. First-trimester or second-trimester screening, or both, for Down's syndrome. N Engl J Med. 2005 Nov 10;353(19):2001-11. doi: 10.1056/NEJMoa043693.

  PMID: 16282175 BACKGROUND

• Nicolaides KH, Spencer K, Avgidou 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 Mar;25(3):221-6. doi: 10.1002/uog.1860.

  PMID: 15736186 BACKGROUND

• Cicero S, Rembouskos G, Vandecruys H, Hogg M, Nicolaides KH. Likelihood ratio for trisomy 21 in fetuses with absent nasal bone at the 11-14-week scan. Ultrasound Obstet Gynecol. 2004 Mar;23(3):218-23. doi: 10.1002/uog.992.

  PMID: 15027007 BACKGROUND

• Borrell A. The ductus venosus in early pregnancy and congenital anomalies. Prenat Diagn. 2004 Sep;24(9):688-92. doi: 10.1002/pd.958.

  PMID: 15386454 BACKGROUND

• Faiola S, Tsoi E, Huggon IC, Allan LD, Nicolaides KH. Likelihood ratio for trisomy 21 in fetuses with tricuspid regurgitation at the 11 to 13 + 6-week scan. Ultrasound Obstet Gynecol. 2005 Jul;26(1):22-7. doi: 10.1002/uog.1922.

  PMID: 15937972 BACKGROUND

• Sonek J, Borenstein M, Dagklis T, Persico N, Nicolaides KH. Frontomaxillary facial angle in fetuses with trisomy 21 at 11-13(6) weeks. Am J Obstet Gynecol. 2007 Mar;196(3):271.e1-4. doi: 10.1016/j.ajog.2006.10.891.

  PMID: 17346551 BACKGROUND

• ACOG Committee on Practice Bulletins. ACOG Practice Bulletin No. 77: screening for fetal chromosomal abnormalities. Obstet Gynecol. 2007 Jan;109(1):217-27. doi: 10.1097/00006250-200701000-00054.

  PMID: 17197615 BACKGROUND

• American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 88, December 2007. Invasive prenatal testing for aneuploidy. Obstet Gynecol. 2007 Dec;110(6):1459-67. doi: 10.1097/01.AOG.0000291570.63450.44.

  PMID: 18055749 BACKGROUND

• 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 Mar;204(3):205.e1-11. doi: 10.1016/j.ajog.2010.12.060. Epub 2011 Feb 18.

  PMID: 21310373 BACKGROUND

• 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 Aug 16;350(9076):485-7. doi: 10.1016/S0140-6736(97)02174-0.

  PMID: 9274585 BACKGROUND

• 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 Oct 21;105(42):16266-71. doi: 10.1073/pnas.0808319105. Epub 2008 Oct 6.

  PMID: 18838674 BACKGROUND

• Chiu RW, Chan KC, Gao Y, Lau VY, Zheng W, Leung TY, Foo CH, Xie B, Tsui NB, Lun FM, Zee BC, Lau TK, Cantor CR, Lo YM. Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma. Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20458-63. doi: 10.1073/pnas.0810641105. Epub 2008 Dec 10.

  PMID: 19073917 BACKGROUND

• Chiu RW, Sun H, Akolekar R, Clouser C, Lee C, McKernan K, Zhou D, Nicolaides KH, Lo YM. Maternal plasma DNA analysis with massively parallel sequencing by ligation for noninvasive prenatal diagnosis of trisomy 21. Clin Chem. 2010 Mar;56(3):459-63. doi: 10.1373/clinchem.2009.136507. Epub 2009 Dec 21.

  PMID: 20026875 BACKGROUND

• 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 Nov;13(11):913-20. doi: 10.1097/GIM.0b013e3182368a0e.

  PMID: 22005709 BACKGROUND

• Dhallan R, Guo X, Emche S, Damewood M, Bayliss P, Cronin M, Barry J, Betz J, Franz K, Gold K, Vallecillo B, Varney J. A non-invasive test for prenatal diagnosis based on fetal DNA present in maternal blood: a preliminary study. Lancet. 2007 Feb 10;369(9560):474-81. doi: 10.1016/S0140-6736(07)60115-9.

  PMID: 17292767 BACKGROUND

• Tong YK, Jin S, Chiu RW, Ding C, Chan KC, Leung TY, Yu L, Lau TK, Lo YM. Noninvasive prenatal detection of trisomy 21 by an epigenetic-genetic chromosome-dosage approach. Clin Chem. 2010 Jan;56(1):90-8. doi: 10.1373/clinchem.2009.134114. Epub 2009 Oct 22.

  PMID: 19850629 BACKGROUND

• Ghanta S, Mitchell ME, Ames M, Hidestrand M, Simpson P, Goetsch M, Thilly WG, Struble CA, Tomita-Mitchell A. Non-invasive prenatal detection of trisomy 21 using tandem single nucleotide polymorphisms. PLoS One. 2010 Oct 8;5(10):e13184. doi: 10.1371/journal.pone.0013184.

  PMID: 20949031 BACKGROUND

• Norton ME, Jacobsson B, Swamy GK, Laurent LC, Ranzini AC, Brar H, Tomlinson MW, Pereira L, Spitz JL, Hollemon D, Cuckle H, Musci TJ, Wapner RJ. Cell-free DNA analysis for noninvasive examination of trisomy. N Engl J Med. 2015 Apr 23;372(17):1589-97. doi: 10.1056/NEJMoa1407349. Epub 2015 Apr 1.

  PMID: 25830321 DERIVED

Related Links

• Click here for more information about Ariosa Diagnostics
• Click here to find more information about the Perinatal Quality Foundation

MeSH Terms

Conditions

Down Syndrome

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn

Study Officials

• Mary E. Norton, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Ronald Wapner, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2012
• First Posted: January 18, 2012
• Study Start: March 1, 2012
• Primary Completion: November 1, 2013
• Study Completion: May 1, 2014
• Last Updated: July 14, 2014

Record last verified: 2014-07

Locations

CA (4); BE (1); IT (1); US (26); SE (2); NL (2)