SNP-based Microdeletion and Aneuploidy RegisTry (SMART)

NCT ID: NCT02381457

Last Updated: 2021-01-29

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 20960 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2020-06-30

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.

Detailed Description

The primary objective is 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. Specific test performance parameters will include: positive predictive value (PPV), specificity, and sensitivity.

Secondary objectives include:

1. Determine the test performance (PPV, specificity) of SNP based NIPT for detecting other microdeletion syndromes available in the Panorama microdeletion panel (e.g., 1p36 deletion, Cri-du-chat, Prader-Willi, and Angelman) individually and all combined (including 22q11.2). Given the incidences of <1:5000, the confidence intervals are expected to be large.

2. Determine the failure ('no call') rate for the Next-generation Aneuploidy Test Using SNPs (NATUS) method for 22q11.2 detection, as well as for aneuploidy.

3. Determine whether a more precise risk for aneuploidy can be generated in the setting of low fetal fraction by incorporating maternal BMI (adjusted fetal fraction percentile).

4. Assess whether low fetal fraction is associated with specific ultrasound findings that may indicate aneuploidy (e.g. triploidy, trisomy 13 and 18).

5. Investigate the relationship between NIPT and sonographic (nuchal translucency and anatomy survey) markers and serum markers from 1st and 2nd trimester aneuploidy screening.

6. Determine sensitivity, specificity, and PPV for chromosomal aneuploidies and sex chromosome abnormalities.

7. Perform detailed assessment of false positive aneuploidy samples to better understand sources of error, including placental studies to further refine issues surrounding mosaicism as NIPT represents circulating placental DNA.

8. Investigate any relationships between circulating placental DNA (fetal fraction) or other test parameters including potential genotypic markers, and outcomes related to abnormal placentation (including but not limited to preeclampsia, small for gestational age and morbidly adherent placenta).

9. Investigate other risk factors that may impact risk assessment for microdeletions including sonographic findings consistent with 22q11.2 (cardiac anomalies and thymus size).

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 48 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

George Washington University

OTHER

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: collaborator

Montefiore Medical Center

OTHER

Sponsor Role: collaborator

Children's Hospital of Philadelphia

OTHER

Sponsor Role: collaborator

Natera, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peer Dar, MD

Role: PRINCIPAL_INVESTIGATOR

Montefiore Medical Center

Mary Norton, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

University of California, San Francisco

San Francisco, California, United States

Cooper University Hospital

Camden, New Jersey, United States

Virtua

Mount Laurel, New Jersey, United States

St. Peter's University

New Brunswick, New Jersey, United States

Complete Women's Healthcare

Garden City, New York, United States

North Shore University Hospital

Manhasset, New York, United States

Madonna Perinatal

Mineola, New York, United States

Long Island Jewish Medical Center

New Hyde Park, New York, United States

New York University

New York, New York, United States

Icahn School of Medicine Mt Sinai

New York, New York, United States

Columbia University

New York, New York, United States

Montefiore Medical Center

New York, New York, United States

Suffolk OB

Port Jefferson, New York, United States

North Austin Maternal Fetal Medicine

Austin, Texas, United States

Zeid Women's Health Center

Longview, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Royal Prince Alfred

Camperdown, New South Wales, Australia

Royal College Surgeons in Ireland

Dublin, , Ireland

Dexeus

Barcelona, , Spain

Sahlgrenska University Hospital

Gothenburg, , Sweden

St. George University Hospital

London, , United Kingdom

Countries

United States; Australia; Ireland; Spain; Sweden; United Kingdom

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Related Links

http://www.ncbi.nlm.nih.gov/books/NBK1191/

1p36 Deletion Syndrome

http://www.ncbi.nlm.nih.gov/books/NBK1144/

Angelman Syndrome

http://www.omim.org/entry/123450?search=number%3A%28123450%29&highlight=123450.

Cri-du-chat Syndrome

Other Identifiers

14-024-NPT

Identifier Type: -

Identifier Source: org_study_id