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SNP-based Microdeletion and Aneuploidy RegisTry (SMART) (SMART)

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ClinicalTrials.gov Identifier: NCT02381457
Recruitment Status : Completed
First Posted : March 6, 2015
Last Update Posted : January 29, 2021
Sponsor:
Collaborators:
George Washington University
University of California, San Francisco
Montefiore Medical Center
Children's Hospital of Philadelphia
Information provided by (Responsible Party):
Natera, Inc.

Study Description
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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.

Condition or disease
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

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).
Study Design
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Study Type : Observational [Patient Registry]
Actual Enrollment : 20960 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 2 Years
Official Title: SNP-based Microdeletion and Aneuploidy RegisTry
Actual Study Start Date : April 2015
Actual Primary Completion Date : June 2020
Actual Study Completion Date : June 2020

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Group/Cohort
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.


Outcome Measures
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Primary Outcome Measures :
  1. 22q11.2 Snp-based non-invasive prenatal screening test performance, including positive predictive value (PPV), specificity, and sensitivity [ Time Frame: 3 years ]
    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.


Secondary Outcome Measures :
  1. Combined microdeletion syndrome screening test performance [ Time Frame: 3 years ]
    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. No call rate [ Time Frame: 3 years ]
    Determine the failure ('no call') rate for the NATUS method for 22q11.2 detection, as well as for aneuploidy.

  3. Low fetal fraction aneuploidy risk refinement [ Time Frame: 3 years ]
    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), or whether low fetal fraction is associated with specific ultrasound findings that may indicate aneuploidy (e.g. triploidy, trisomy 13 and 18).

  4. Placental mosaicism exploration [ Time Frame: 3 years ]
    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.

  5. Placental complications exploration [ Time Frame: 3 years ]
    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).


Biospecimen Retention:   Samples With DNA
  • Maternal residual blood sample
  • Placental tissue
  • Child dried blood spot
  • Child buccal sample

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 48 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Pregnant women
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02381457


Locations
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Sponsors and Collaborators
Natera, Inc.
George Washington University
University of California, San Francisco
Montefiore Medical Center
Children's Hospital of Philadelphia
Investigators
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Principal Investigator: Peer Dar, MD Montefiore Medical Center
Principal Investigator: Mary Norton, MD University of California, San Francisco
More Information
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Additional Information:

Publications of Results:

Other Publications:

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Responsible Party: Natera, Inc.
ClinicalTrials.gov Identifier: NCT02381457    
Other Study ID Numbers: 14-024-NPT
First Posted: March 6, 2015    Key Record Dates
Last Update Posted: January 29, 2021
Last Verified: January 2021
Keywords provided by Natera, Inc.:
Microdeletion Syndrome
Aneuploidy
22q
Non-Invasive Prenatal Screening
DiGeorge Syndrome
Additional relevant MeSH terms:
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DiGeorge Syndrome
22q11 Deletion Syndrome
Prader-Willi Syndrome
Down Syndrome
Angelman Syndrome
Trisomy 13 Syndrome
Cri-du-Chat Syndrome
Trisomy 18 Syndrome
Chromosome Disorders
Syndrome
Aneuploidy
Trisomy
Chromosome Aberrations
Monosomy
Sex Chromosome Aberrations
 Disease
Pathologic Processes
Congenital Abnormalities
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Abnormalities, Multiple
Genetic Diseases, Inborn
Obesity
Overnutrition
Nutrition Disorders
Chromosome Duplication
Movement Disorders
Central Nervous System Diseases