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NCT Number: NCT02381457

SNP-based Microdeletion and Aneuploidy RegisTry (SMART)

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.

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Key information

Conditions

22q11 Deletion Syndrome 1p36 Deletion Syndrome Abnormalities, Multiple Aneuploidy Angelman Syndrome Cardiovascular Abnormalities Cardiovascular Diseases Central Nervous System Diseases Chromosome 1p36 Deletion Syndrome Chromosome Aberrations Chromosome Disorders Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Craniofacial Abnormalities Cri-du-Chat Syndrome DiGeorge Syndrome Disorders of Sex Development Down Syndrome Endocrine System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genetic Diseases, Inborn Gonadal Disorders Gonadal Dysgenesis Heart Defects, Congenital Heart Diseases Hemic and Lymphatic Diseases Hypoparathyroidism Imprinting Disorders Intellectual Disability Lymphatic Abnormalities Lymphatic Diseases Male Urogenital Diseases Monosomy X Movement Disorders Musculoskeletal Abnormalities Musculoskeletal Diseases Nervous System Diseases Neurobehavioral Manifestations Neurologic Manifestations Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Parathyroid Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Prader-Willi Syndrome Sex Chromosome Aberrations Sex Chromosome Abnormalities Sex Chromosome Disorders Sex Chromosome Disorders of Sex Development Trisomy 13 Trisomy 13 Syndrome Trisomy 18 Trisomy 18 Syndrome Trisomy 21 Turner Syndrome Urogenital Abnormalities Urogenital Diseases

Age range

18 year–48 year

Sex eligibility

Female

Study type

Observational

Primary location

Royal Prince Alfred, Camperdown, New South Wales, Australia

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About this study

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 studies to further refine issues surrounding mosaicism as NIPT represents circulating placental DNA.
  • 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).
  • Investigate other risk factors that may impact risk assessment for microdeletions including sonographic findings consistent with 22q11.2 (cardiac anomalies and thymus size).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Primary outcomes

  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 outcomes

  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).

Sponsors and collaborators

Lead sponsor

Natera, Inc.

Industry

Collaborators

  • Children's Hospital of Philadelphia
  • George Washington University
  • Montefiore Medical Center
  • University of California, San Francisco

Registry information

Official study title

SNP-based Microdeletion and Aneuploidy RegisTry

Acronym: SMART

Important dates

Study start
2015
Primary completion
2020
Study completion
2020
First posted
Mar 6, 2015
Registry last updated
Jan 29, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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