SNP-based Microdeletion and Aneuploidy RegisTry (SMART)
- Conditions
- 22q11 Deletion SyndromeAngelman SyndromeDiGeorge SyndromeTrisomy 18Cri-du-Chat SyndromeTrisomy 21Trisomy 13Monosomy XSex Chromosome AbnormalitiesPrader-Willi Syndrome
- Registration Number
- NCT02381457
- Lead Sponsor
- Natera, Inc.
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 20960
- 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
- Received results of the Panorama test prior to enrollment
- Organ transplant recipient
- Egg donor used
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 22q11.2 Snp-based non-invasive prenatal screening test performance, including positive predictive value (PPV), specificity, and sensitivity 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
Name Time Method No call rate 3 years Determine the failure ('no call') rate for the NATUS method for 22q11.2 detection, as well as for aneuploidy.
Low fetal fraction aneuploidy risk refinement 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).
Combined microdeletion syndrome screening test performance 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.
Placental complications exploration 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).
Placental mosaicism exploration 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.
Trial Locations
- Locations (21)
Royal Prince Alfred
🇦🇺Camperdown, New South Wales, Australia
Sahlgrenska University Hospital
🇸🇪Gothenburg, Sweden
University of California, San Francisco
🇺🇸San Francisco, California, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
St. George University Hospital
🇬🇧London, United Kingdom
Virtua
🇺🇸Mount Laurel, New Jersey, United States
North Shore University Hospital
🇺🇸Manhasset, 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
Cooper University Hospital
🇺🇸Camden, New Jersey, United States
Madonna Perinatal
🇺🇸Mineola, New York, United States
Long Island Jewish Medical Center
🇺🇸New Hyde Park, New York, United States
Suffolk OB
🇺🇸Port Jefferson, New York, United States
St. Peter's University
🇺🇸New Brunswick, New Jersey, United States
Columbia University
🇺🇸New York, New York, United States
Dexeus
🇪🇸Barcelona, Spain
Royal College Surgeons in Ireland
🇮🇪Dublin, Ireland
North Austin Maternal Fetal Medicine
🇺🇸Austin, Texas, United States
Complete Women's Healthcare
🇺🇸Garden City, New York, United States
Zeid Women's Health Center
🇺🇸Longview, Texas, United States
Montefiore Medical Center
🇺🇸New York, New York, United States