Clinical Trial: SNP-based Microdeletion and Aneuploidy RegisTry (SMART)
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational [Patient Registry]
Official Title: SNP-based Microdeletion and Aneuploidy RegisTry
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 Summary:
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:
- 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.
- 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.
- 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).
- Assess whether low fetal fraction is associated with specific ultrasound findings that may indicate aneuploidy (e.g. triploidy, trisomy 13 and 18).
- Investigate the relationship between NIPT and sonographic (nuchal translucency and anatomy survey) markers and serum markers from 1st and 2nd trimester aneuploidy screening.
- Determine sensitivity, specificity, and PPV for chromosomal aneuploidies and sex chromosome abnormalities.
- Perform detailed assessment of false positive aneuploidy samples to better understand sources of error, including placental
Sponsor: Natera, Inc.
Current Primary Outcome: 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.
Original Primary Outcome: Same as current
Current Secondary Outcome:
- 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.
- 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.
- 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).
- 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.
- 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).
Original Secondary Outcome: Same as current
Information By: Natera, Inc.
Dates:
Date Received: March 2, 2015
Date Started: April 2015
Date Completion: November 2017
Last Updated: April 19, 2016
Last Verified: April 2016
- Combined microdeletion syndrome screening test performance [ Time Frame: 3 years ]
