Clinical trial NCT02381457: SNP-based Microdeletion and Aneuploidy RegisTry (SMART)
Official title: SNP-based Microdeletion and Aneuploidy RegisTry
Study type: OBSERVATIONAL
Overall status: COMPLETED
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
Lead sponsor: Natera, Inc.
Sponsor class: INDUSTRY
Collaborators: name: George Washington University
name: University of California, San Francisco
name: Montefiore Medical Center
name: Children's Hospital of Philadelphia
First posted: 2015-03-06
Enrollment: 20960
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 48
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Pregnant women

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).

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

Primary outcomes:
measure: 22q11.2 Snp-based non-invasive prenatal screening test performance, including positive predictive value (PPV), specificity, and sensitivity
timeFrame: 3 years
Secondary outcomes:
measure: Combined microdeletion syndrome screening test performance
timeFrame: 3 years
measure: No call rate
timeFrame: 3 years
measure: Low fetal fraction aneuploidy risk refinement
timeFrame: 3 years
measure: Placental mosaicism exploration
timeFrame: 3 years
measure: Placental complications exploration
timeFrame: 3 years
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Mount Laurel
country: United States
facility: Virtua
state: New Jersey
city: New Brunswick
country: United States
facility: St. Peter's University
state: New Jersey
city: Garden City
country: United States
facility: Complete Women's Healthcare
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: Mineola
country: United States
facility: Madonna Perinatal
state: New York
city: New Hyde Park
country: United States
facility: Long Island Jewish Medical Center
state: New York
city: New York
country: United States
facility: New York University
state: New York
city: New York
country: United States
facility: Icahn School of Medicine Mt Sinai
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: New York
country: United States
facility: Montefiore Medical Center
state: New York
city: Port Jefferson
country: United States
facility: Suffolk OB
state: New York
city: Austin
country: United States
facility: North Austin Maternal Fetal Medicine
state: Texas
city: Longview
country: United States
facility: Zeid Women's Health Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Camperdown
country: Australia
facility: Royal Prince Alfred
state: New South Wales
city: Dublin
country: Ireland
facility: Royal College Surgeons in Ireland
city: Barcelona
country: Spain
facility: Dexeus
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital
city: London
country: United Kingdom
facility: St. George University Hospital
Study officials:
affiliation: Montefiore Medical Center
name: Peer Dar, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Mary Norton, MD
role: PRINCIPAL_INVESTIGATOR
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