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.
Brief Title
SNP-based Microdeletion and Aneuploidy RegisTry (SMART)
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).
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).
Categories
Completion Date
Completion Date Type
Actual
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
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
* 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
Inclusion 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
* 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
Gender
Female
Gender Based
false
Keywords
Microdeletion Syndrome
Aneuploidy
22q
Non-Invasive Prenatal Screening
DiGeorge Syndrome
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
48 Years
Minimum Age
18 Years
NCT Id
NCT02381457
Org Class
Industry
Org Full Name
Natera, Inc.
Org Study Id
14-024-NPT
Overall Status
Completed
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
SNP-based Microdeletion and Aneuploidy RegisTry
Primary Outcomes
Outcome Description
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.
Outcome Measure
22q11.2 Snp-based non-invasive prenatal screening test performance, including positive predictive value (PPV), specificity, and sensitivity
Outcome Time Frame
3 years
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
3 years
Outcome Measure
Combined microdeletion syndrome screening test performance
Outcome Description
Determine the failure ('no call') rate for the NATUS method for 22q11.2 detection, as well as for aneuploidy.
Outcome Time Frame
3 years
Outcome Measure
No call rate
Outcome Description
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).
Outcome Time Frame
3 years
Outcome Measure
Low fetal fraction aneuploidy risk refinement
Outcome Description
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.
Outcome Time Frame
3 years
Outcome Measure
Placental mosaicism exploration
Outcome Description
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).
Outcome Time Frame
3 years
Outcome Measure
Placental complications exploration
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Study Population
Pregnant women
Std Ages
Adult
Maximum Age Number (converted to Years and rounded down)
48
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Peer Dar
Investigator Email
pdar@montefiore.org
Investigator Phone