Prenatal Cytogenetic Diagnosis by Array-Based Copy Number Analysis

NCT01279733 | Completed

• 2 other identifiers: AAAC80361R01HD055651-01
• Study Type: observational
• Target: 4,450
• Locations: 1 country
• Sites: 1

Brief Summary

The main objective of the multi-centered collaborative study is to evaluate the accuracy, efficacy and clinical advantages of prenatal diagnosis using microarray analysis as compared with conventional karyotyping.

Conditions

Genetic Diseases

Keywords

microarray

Outcome Measures

Primary Outcomes (1)

• Detection rate of fetal cytogentic abnormalites between microarray copy number analysis and karyotype in prenatal samples

  This is a blinded prospective comparison of microarray copy number analysis to metaphase karyotyping for the detection of common fetal cytogentic abnormalites

  Up to 2.5 years after recruitment of 4400 patients.

Secondary Outcomes (2)

• The ability of microarray copy number analysis to identify clinically significant microdeletions and duplications not seen by standard karyotyping

  Up to 2.5 years .

• The rates of clinically significant copy number variants associated with specific prenatal conditions

  Up to 2.5 years after recruitment of 4400 patients.

Study Arms (1)

Microarray Analysis

Genetic: Microarray analysis

Interventions

Microarray analysis GENETIC

Microarray performed on prenatal specimen: Fluorescence in-situ hybridization (FISH) or other standardized tests such as qPCR or MLPA will be performed on the fetal sample to confirm abnormal MA findings of known and unknown clinical significance which are discordant with CC findings, including anomalies normally detected by karyotyping. Microarray analysis of DNA from parental blood samples will be used to determine whether CNVs detected in a fetal sample are also present in a healthy parent, in which case no further evaluation will take place, moreover any finding in a fetus which is duplicated in a parental microarray is considered to be confirmed.

Microarray Analysis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

A total of 4,400 prenatal diagnostic samples will be obtained from patients undergoing prenatal testing for standard indications. Patients will be recruited at participating prenatal diagnostic centers by designated study personnel; recruitment of patients will be initiated as a pilot study. These patients will not contribute to the final planned sample size of 4400 patients. Two sub-studies will then be initiated consisting of 250 (or more) patients enrolled with sufficient amniotic fluid sample and 250 (or more) patients with sufficient villus sample.

You may qualify if:

• Singleton pregnancy having either chorionic villus sampling in the first trimester or an amniocentesis procedure at or after 16 weeks of gestation performed for prenatal cytogenetic diagnosis
• Karyotyping to be performed at Genzyme Genetics Cytogenetics Laboratory
• Trained study personnel available
• Presenting at pre-specified sites using Genzyme Genetics for routine prenatal diagnostic services

You may not qualify if:

• Unavailability of one or both biologic parents to provide blood sample (e.g. egg or sperm donor, non-paternity)
• Patient refusal to allow follow-up through the neonatal period and up to age two if selected
• Participation in the study in a previous pregnancy
• Insufficient sample for microarray assay

Sponsors & Collaborators

• Columbia University: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

Related Publications (1)

• Wapner RJ, Martin CL, Levy B, Ballif BC, Eng CM, Zachary JM, Savage M, Platt LD, Saltzman D, Grobman WA, Klugman S, Scholl T, Simpson JL, McCall K, Aggarwal VS, Bunke B, Nahum O, Patel A, Lamb AN, Thom EA, Beaudet AL, Ledbetter DH, Shaffer LG, Jackson L. Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med. 2012 Dec 6;367(23):2175-84. doi: 10.1056/NEJMoa1203382.

  PMID: 23215555 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

* Additional 15 ml of amniotic fluid (minimum 10 ml) for amniocentesis * Blood sample (10 ml) from each parent will be obtained in case of a need to test for suspected familial copy number variants (CNVs) or discrepant results, and also to evaluate for maternal cell contamination (patient's blood sample). * 10 ml of amniotic fluid with suspended cells, (minimum 7 ml) * 5 mg of villi (minimum of 2mg)

MeSH Terms

Conditions

Genetic Diseases, Inborn

Interventions

Microarray Analysis

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Microchip Analytical Procedures; Investigative Techniques

Study Officials

• Ronald Wapner, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Obstetrics & Gynecology

Study Record Dates

• First Submitted: July 19, 2010
• First Posted: January 19, 2011
• Study Start: October 1, 2008
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: August 22, 2012

Record last verified: 2012-08

Locations

US (1)