SNP-based Microdeletion and Aneuploidy RegisTry (SMART)

NCT02381457 | Completed

• 1 other identifier: 14-024-NPT
• Study Type: observational
• Target: 20,960
• Locations: 6 countries
• Sites: 21

Brief Summary

This multi-center prospective observational study is designed to track birth outcomes and perinatal correlates to the Panorama prenatal screening test in the general population among ten thousand women who present clinically and elect Panorama microdeletion and aneuploidy screening as part of their routine care. The primary objective is to evaluate the performance of Single Nucleotide Polymorphism (SNP)-based Non Invasive Prenatal Testing (NIPT) for 22q11.2 microdeletion (DiGeorge syndrome) in this large cohort of pregnant women. This will be done by performing a review of perinatal medical records and obtaining biospecimens after birth to perform genetic diagnostic testing for 22q11.2 deletion. Results from the follow-up specimens will be compared to those obtained by the Panorama screening test to determine test performance. Specific test performance parameters will include: PPV, specificity, and sensitivity.

Conditions

22q11 Deletion Syndrome; DiGeorge Syndrome; Trisomy 21; Trisomy 18; Trisomy 13; Monosomy X; Sex Chromosome Abnormalities; Cri-du-Chat Syndrome; Angelman Syndrome; Prader-Willi Syndrome; 1p36 Deletion Syndrome

Keywords

Microdeletion Syndrome; Aneuploidy; 22q; Non-Invasive Prenatal Screening; DiGeorge Syndrome

Outcome Measures

Primary Outcomes (1)

• 22q11.2 Snp-based non-invasive prenatal screening test performance, including positive predictive value (PPV), specificity, and sensitivity

  To determine in a prospective study the performance of SNP based NIPT for the 22q11.2 microdeletion (DiGeorge syndrome) in a large cohort of pregnant women clinically opting for this form of screening.

  3 years

Secondary Outcomes (5)

• Combined microdeletion syndrome screening test performance

  3 years

• No call rate

  3 years

• Low fetal fraction aneuploidy risk refinement

  3 years

• Placental mosaicism exploration

  3 years

• Placental complications exploration

  3 years

Study Arms (1)

Pregnancies undergoing prenatal microdeletion screening

Pregnant women undergoing non-invasive prenatal screening for microdeletion and aneuploidy syndromes. No drug will be administrated, this cohort will undergo a non invasive prenatal blood test and then follow up data and specimens will be collected for research analysis.

Eligibility Criteria

• Age: 18 Years - 48 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Pregnant women

You may qualify if:

• Singleton pregnancy
• Receiving Panorama prenatal screening test for both microdeletions (at least 22q11.2) and aneuploidy
• Planned hospital delivery
• Gestational age of ≥ 9 weeks, 0 days based on clinical information and evaluation.
• Able to provide informed consent

You may not qualify if:

• Received results of the Panorama test prior to enrollment
• Organ transplant recipient
• Egg donor used

Sponsors & Collaborators

• Natera, Inc.: lead
• George Washington University: collaborator
• University of California, San Francisco: collaborator
• Montefiore Medical Center: collaborator
• Children's Hospital of Philadelphia: collaborator

Study Sites (21)

University of California, San Francisco

San Francisco, California, 94158, United States

Location

Cooper University Hospital

Camden, New Jersey, 08103, United States

Location

Virtua

Mount Laurel, New Jersey, 08054, United States

Location

St. Peter's University

New Brunswick, New Jersey, 08901, United States

Location

Complete Women's Healthcare

Garden City, New York, 11530, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Madonna Perinatal

Mineola, New York, 11501, United States

Location

Long Island Jewish Medical Center

New Hyde Park, New York, 11040, United States

Location

New York University

New York, New York, 10016, United States

Location

Icahn School of Medicine Mt Sinai

New York, New York, 10029, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Montefiore Medical Center

New York, New York, 10461, United States

Location

Suffolk OB

Port Jefferson, New York, 11777, United States

Location

North Austin Maternal Fetal Medicine

Austin, Texas, 78758, United States

Location

Zeid Women's Health Center

Longview, Texas, 75601, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Royal Prince Alfred

Camperdown, New South Wales, 2050, Australia

Location

Royal College Surgeons in Ireland

Dublin, 1, Ireland

Location

Dexeus

Barcelona, 08028, Spain

Location

Sahlgrenska University Hospital

Gothenburg, SE-416 85, Sweden

Location

St. George University Hospital

London, SW17 0QT, United Kingdom

Location

Related Publications (25)

• American College of Obstetricians and Gynecologists Committee on Genetics. Committee Opinion No. 581: the use of chromosomal microarray analysis in prenatal diagnosis. Obstet Gynecol. 2013 Dec;122(6):1374-7. doi: 10.1097/01.AOG.0000438962.16108.d1.

  PMID: 24264715 BACKGROUND

• Pergament E, Cuckle H, Zimmermann B, Banjevic M, Sigurjonsson S, Ryan A, Hall MP, Dodd M, Lacroute P, Stosic M, Chopra N, Hunkapiller N, Prosen DE, McAdoo S, Demko Z, Siddiqui A, Hill M, Rabinowitz M. Single-nucleotide polymorphism-based noninvasive prenatal screening in a high-risk and low-risk cohort. Obstet Gynecol. 2014 Aug;124(2 Pt 1):210-218. doi: 10.1097/AOG.0000000000000363.

  PMID: 25004354 RESULT

• 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 RESULT

• 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 RESULT

• 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. 2011 Jul;57(7):1042-9. doi: 10.1373/clinchem.2011.165910. Epub 2011 Apr 25.

  PMID: 21519036 RESULT

• Benn P, Cuckle H, Pergament E. Genome-wide fetal aneuploidy detection by maternal plasma DNA sequencing. Obstet Gynecol. 2012 Jun;119(6):1270; author reply 1270-1. doi: 10.1097/AOG.0b013e318258c401. No abstract available.

  PMID: 22617594 RESULT

• 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 Mar;14(3):296-305. doi: 10.1038/gim.2011.73. Epub 2012 Feb 2.

  PMID: 22281937 RESULT

• 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 Apr;206(4):319.e1-9. doi: 10.1016/j.ajog.2012.01.030. Epub 2012 Jan 26.

  PMID: 22464072 RESULT

• Norton ME, Brar H, Weiss J, Karimi A, Laurent LC, Caughey AB, Rodriguez MH, Williams J 3rd, 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 Aug;207(2):137.e1-8. doi: 10.1016/j.ajog.2012.05.021. Epub 2012 Jun 1.

  PMID: 22742782 RESULT

• Nicolaides KH, Syngelaki A, Gil M, Atanasova V, Markova D. Validation of targeted sequencing of single-nucleotide polymorphisms for non-invasive prenatal detection of aneuploidy of chromosomes 13, 18, 21, X, and Y. Prenat Diagn. 2013 Jun;33(6):575-9. doi: 10.1002/pd.4103. Epub 2013 Apr 24.

  PMID: 23613152 RESULT

• Nicolaides KH, Syngelaki A, del Mar Gil M, Quezada MS, Zinevich Y. Prenatal detection of fetal triploidy from cell-free DNA testing in maternal blood. Fetal Diagn Ther. 2014;35(3):212-7. doi: 10.1159/000355655. Epub 2013 Oct 10.

  PMID: 24135152 RESULT

• Samango-Sprouse C, Banjevic M, Ryan A, Sigurjonsson S, Zimmermann B, Hill M, Hall MP, Westemeyer M, Saucier J, Demko Z, Rabinowitz M. SNP-based non-invasive prenatal testing detects sex chromosome aneuploidies with high accuracy. Prenat Diagn. 2013 Jul;33(7):643-9. doi: 10.1002/pd.4159. Epub 2013 Jun 20.

  PMID: 23712453 RESULT

• 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 Dec 6;367(23):2175-84. doi: 10.1056/NEJMoa1203382.

  PMID: 23215555 RESULT

• Wapner RJ, Babiarz JE, Levy B, Stosic M, Zimmermann B, Sigurjonsson S, Wayham N, Ryan A, Banjevic M, Lacroute P, Hu J, Hall MP, Demko Z, Siddiqui A, Rabinowitz M, Gross SJ, Hill M, Benn P. Expanding the scope of noninvasive prenatal testing: detection of fetal microdeletion syndromes. Am J Obstet Gynecol. 2015 Mar;212(3):332.e1-9. doi: 10.1016/j.ajog.2014.11.041. Epub 2014 Dec 2.

  PMID: 25479548 RESULT

• Vora NL, O'Brien BM. Noninvasive prenatal testing for microdeletion syndromes and expanded trisomies: proceed with caution. Obstet Gynecol. 2014 May;123(5):1097-1099. doi: 10.1097/AOG.0000000000000237.

  PMID: 24785862 RESULT

• Taglauer ES, Wilkins-Haug L, Bianchi DW. Review: cell-free fetal DNA in the maternal circulation as an indication of placental health and disease. Placenta. 2014 Feb;35 Suppl(Suppl):S64-8. doi: 10.1016/j.placenta.2013.11.014. Epub 2013 Dec 1.

  PMID: 24388429 RESULT

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  PMID: 9647154 RESULT

• Dar P, Curnow KJ, Gross SJ, Hall MP, Stosic M, Demko Z, Zimmermann B, Hill M, Sigurjonsson S, Ryan A, Banjevic M, Kolacki PL, Koch SW, Strom CM, Rabinowitz M, Benn P. Clinical experience and follow-up with large scale single-nucleotide polymorphism-based noninvasive prenatal aneuploidy testing. Am J Obstet Gynecol. 2014 Nov;211(5):527.e1-527.e17. doi: 10.1016/j.ajog.2014.08.006. Epub 2014 Aug 8.

  PMID: 25111587 RESULT

• Amos-Landgraf JM, Ji Y, Gottlieb W, Depinet T, Wandstrat AE, Cassidy SB, Driscoll DJ, Rogan PK, Schwartz S, Nicholls RD. Chromosome breakage in the Prader-Willi and Angelman syndromes involves recombination between large, transcribed repeats at proximal and distal breakpoints. Am J Hum Genet. 1999 Aug;65(2):370-86. doi: 10.1086/302510.

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• Tranquilli AL, Emanuelli M. The thrombophilic fetus. Med Hypotheses. 2006;67(5):1226-9. doi: 10.1016/j.mehy.2006.04.046. Epub 2006 Jul 11.

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• Faiz AS, Ananth CV. Etiology and risk factors for placenta previa: an overview and meta-analysis of observational studies. J Matern Fetal Neonatal Med. 2003 Mar;13(3):175-90. doi: 10.1080/jmf.13.3.175.190.

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• Norton ME, MacPherson C, Demko Z, Egbert M, Malone F, Wapner RJ, Roman AS, Khalil A, Faro R, Madankumar R, Strong N, Haeri S, Silver R, Vohra N, Hyett J, Martin K, Rabinowitz M, Jacobsson B, Dar P. Obstetrical, perinatal, and genetic outcomes associated with nonreportable prenatal cell-free DNA screening results. Am J Obstet Gynecol. 2023 Sep;229(3):300.e1-300.e9. doi: 10.1016/j.ajog.2023.03.026. Epub 2023 Mar 23.

  PMID: 36965866 DERIVED

• Dar P, Jacobsson B, MacPherson C, Egbert M, Malone F, Wapner RJ, Roman AS, Khalil A, Faro R, Madankumar R, Edwards L, Haeri S, Silver R, Vohra N, Hyett J, Clunie G, Demko Z, Martin K, Rabinowitz M, Flood K, Carlsson Y, Doulaveris G, Malone C, Hallingstrom M, Klugman S, Clifton R, Kao C, Hakonarson H, Norton ME. Cell-free DNA screening for trisomies 21, 18, and 13 in pregnancies at low and high risk for aneuploidy with genetic confirmation. Am J Obstet Gynecol. 2022 Aug;227(2):259.e1-259.e14. doi: 10.1016/j.ajog.2022.01.019. Epub 2022 Jan 25.

  PMID: 35085538 DERIVED

• Dar P, Jacobsson B, Clifton R, Egbert M, Malone F, Wapner RJ, Roman AS, Khalil A, Faro R, Madankumar R, Edwards L, Strong N, Haeri S, Silver R, Vohra N, Hyett J, Demko Z, Martin K, Rabinowitz M, Flood K, Carlsson Y, Doulaveris G, Daly S, Hallingstrom M, MacPherson C, Kao C, Hakonarson H, Norton ME. Cell-free DNA screening for prenatal detection of 22q11.2 deletion syndrome. Am J Obstet Gynecol. 2022 Jul;227(1):79.e1-79.e11. doi: 10.1016/j.ajog.2022.01.002. Epub 2022 Jan 13.

  PMID: 35033576 DERIVED

Related Links

• 1p36 Deletion Syndrome
• Angelman Syndrome
• Cri-du-chat Syndrome

Biospecimen

Retention: SAMPLES WITH DNA

* Maternal residual blood sample * Placental tissue * Child dried blood spot * Child buccal sample

MeSH Terms

Conditions

22q11 Deletion Syndrome; DiGeorge Syndrome; Down Syndrome; Trisomy 18 Syndrome; Trisomy 13 Syndrome; Turner Syndrome; Sex Chromosome Aberrations; Cri-du-Chat Syndrome; Angelman Syndrome; Prader-Willi Syndrome; Chromosome 1p36 Deletion Syndrome; Aneuploidy

Condition Hierarchy (Ancestors)

Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Lymphatic Abnormalities; Lymphatic Diseases; Hemic and Lymphatic Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Hypoparathyroidism; Parathyroid Diseases; Endocrine System Diseases; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Gonadal Dysgenesis; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Sex Chromosome Disorders of Sex Development; Male Urogenital Diseases; Sex Chromosome Disorders; Gonadal Disorders; Chromosome Aberrations; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Movement Disorders; Central Nervous System Diseases; Imprinting Disorders; Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Study Officials

• Peer Dar, MD

  Montefiore Medical Center

  PRINCIPAL INVESTIGATOR

• Mary Norton, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2015
• First Posted: March 6, 2015
• Study Start: April 1, 2015
• Primary Completion: June 1, 2020
• Study Completion: June 1, 2020
• Last Updated: January 29, 2021

Record last verified: 2021-01

Locations

GB (1); IE (1); AU (1); ES (1); SE (1); US (16)