High Risk Multiple Gestation Study

NCT02278874 | Completed

• 1 other identifier: 13-016B-NPT
• Study Type: observational
• Target: 99
• Locations: 1 country
• Sites: 4

Brief Summary

The objectives of the clinical study are to demonstrate the accuracy of our proprietary algorithm method to determine the genetic health of the developing fetuses in a multiple gestation pregnancy from a maternal blood sample. The long term goal of this study will be the development of a method of minimally invasive prenatal diagnosis that has a higher sensitivity and lower false positive rate in the intended population (e.g. multiple gestation pregnancies) than other currently available screening tests. This will result in fewer unnecessary amniocenteses and Chorionic Villus Sample (CVS) procedures, which are associated with a risk of miscarriage.

Conditions

Trisomy 13; Trisomy 18; Trisomy 21; Sex Chromosome Abnormalities

Keywords

Trisomy 13; Trisomy 18; Trisomy 21; Sex Chromosome Abnormalities; Monosomy X; XXX; XXY; XYY

Outcome Measures

Primary Outcomes (1)

• Screening capability of proprietary algorithm in the form of a risk results classified as positive result for aneuploidy, negative result for aneuploidy or 'no call.'

  The primary outcome will be to confirm the diagnostic capability of NATUS risk results (a risk score eg 1:100) classified as positive result for aneuploidy, negative result for aneuploidy or 'no call.' The outcome will be determined as a risk score given for samples collected. This outcome will be compared to the diagnostic testing results of ploidy status. The chromosomal status will be determined from the CVS or amniocentesis results, if available. A cheek swab or saliva sample will be collected from live-born children if there are no CVS or amniocentesis results. This will be used to determine the true ploidy status of the fetuses.

  4 years

Study Arms (1)

Multiple gestation high risk pregnancies

women pregnant with twins or triplets at high risk for aneuploidy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Pregnant Women

You may qualify if:

• Age 18 or older at enrollment
• Clinically confirmed multiple gestation pregnancy
• Pregnancy at high risk for genetic aneuploidy as defined below:
• Confirmed positive aneuploidy by invasive testing
• Non invasive prenatal testing "high risk" result
• Serum screening risk of greater than 1:100
• Ultrasound abnormalities indicative of aneuploidy
• Structural abnormality of the posterior fossa
• Holoprosencephaly
• Structural cardiac anomaly
• Omphalocele
• Nuchal translucency greater than or equal to 3.5 mm or a nuchal fold greater Hydrops of unknown etiology
• Age ≥ 38 years at delivery (if serum screening risk is not less than 1:100)
• Gestational age between ≥ 9 weeks, 0 days and ≤26 weeks 0 days by best obstetrical estimate
• Able to provide informed consent

You may not qualify if:

• Women carrying singleton pregnancy
• Surrogate or egg donor used

Sponsors & Collaborators

• Natera, Inc.: lead
• MOUNT SINAI HOSPITAL: collaborator
• Montefiore Medical Center: collaborator
• Long Island Jewish Medical Center: collaborator
• Tufts Medical Center: collaborator

Study Sites (4)

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Long Island Jewish Medical Center

Glen Cove, New York, 11542, United States

Location

Mt. Sinai Hospital

New York, New York, 10029, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

Related Publications (8)

• 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 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

• 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

• 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 BACKGROUND

• Bianchi DW, Platt LD, Goldberg JD, Abuhamad AZ, Sehnert AJ, Rava RP; MatErnal BLood IS Source to Accurately diagnose fetal aneuploidy (MELISSA) Study Group. Genome-wide fetal aneuploidy detection by maternal plasma DNA sequencing. Obstet Gynecol. 2012 May;119(5):890-901. doi: 10.1097/AOG.0b013e31824fb482.

  PMID: 22362253 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Canick JA, Kloza EM, Lambert-Messerlian GM, Haddow JE, Ehrich M, van den Boom D, Bombard AT, Deciu C, Palomaki GE. DNA sequencing of maternal plasma to identify Down syndrome and other trisomies in multiple gestations. Prenat Diagn. 2012 Aug;32(8):730-4. doi: 10.1002/pd.3892. Epub 2012 May 14.

  PMID: 22585317 BACKGROUND

Related Links

• Related Info

Biospecimen

Retention: SAMPLES WITH DNA

Maternal and Paternal blood samples CVS or Amniocentesis sample (optional) Child saliva sample (optional) \*Biospecimen retention is optional portion of consent form

MeSH Terms

Conditions

Trisomy 13 Syndrome; Trisomy 18 Syndrome; Down Syndrome; Sex Chromosome Aberrations; Turner Syndrome

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Chromosome Aberrations; Pathologic Processes; Pathological Conditions, Signs and Symptoms; 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; Endocrine System Diseases

Study Officials

• Joanne Stone, MD

  Mt. Sinai Hospital, New York

  PRINCIPAL INVESTIGATOR

• Peer Dar, MD

  Montefiore Medical Center

  PRINCIPAL INVESTIGATOR

• Rajeevi Madankumar, MD

  Long Island Jewish Medical Center

  PRINCIPAL INVESTIGATOR

• Errol Norwitz, MD, PhD

  Tufts Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 27, 2014
• First Posted: October 30, 2014
• Study Start: August 1, 2014
• Primary Completion: December 1, 2018
• Study Completion: March 1, 2019
• Last Updated: June 13, 2019

Record last verified: 2019-06

Locations

US (4)