Prenatal Cytogenetic Diagnosis by Array-Based Copy Number Analysis

Completed

• Conditions: Genetic Diseases
• Interventions: Genetic: Microarray analysis

• Registration Number: NCT01279733
• Lead Sponsor: Columbia University

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.

Detailed Description

Specifically, the aims are as follows:

1. Demonstrate the performance of microarray analysis as a clinical method for prenatal cytogenetic diagnosis with regard to:

1. Accuracy in the detection of the common autosomal and sex chromosomal aneuploid (trisomies, 13,18,21, 45,X, 47,XXY, etc.)

2. Ability of microarray to diagnose less common, but clinically significant, cytogenetic aneusomies (e.g. DiGeorge, Williams, Smith- Magenis, Prader-Willi syndrome, etc.) currently not detected by conventional karyotype.

3. Evaluation of the utility of microarray in specific clinical scenarios such as ultrasound detection of congenital anomalies and fetal growth disorders.

2. Evaluate the appropriate construction of prenatal diagnostic microarray devices to allow maximal detection of clinically relevant information with minimal detection of unexpected and difficult to interpret findings which have no clinical significance but might provoke patient anxiety.

3. Evaluate the feasibility and cost-effectiveness of using microarrays as a primary prenatal diagnostic tool.

4. Evaluate approaches to integrate microarray into clinical prenatal cytogenetic diagnostic practice.

5. Develop a prenatal diagnostic tissue repository (TDR) to facilitate the further development of microarray technology. This will be used to investigate the molecular etiologies of specific fetal anomalies and to test newer technologies, such as higher resolution microarrays.

Study Timeline

• Study Start: 2008-10
• Study First Submitted: 2010-07-19
• Study First Submitted QC: 2011-01-18
• Study First Posted: 2011-01-19
• Primary Completion: 2011-10
• Study Completion: 2011-10
• Status Verified: 2012-08
• Last Update Submitted: 2012-08-21
• Last Update Posted: 2012-08-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 4450

Inclusion Criteria

1. 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
2. Karyotyping to be performed at Genzyme Genetics Cytogenetics Laboratory
3. Trained study personnel available
4. Presenting at pre-specified sites using Genzyme Genetics for routine prenatal diagnostic services

Read More

Exclusion Criteria

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

Read More

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Microarray Analysis	Microarray analysis	-

Primary Outcome Measures

Name	Time	Method
Detection rate of fetal cytogentic abnormalites between microarray copy number analysis and karyotype in prenatal samples	Up to 2.5 years after recruitment of 4400 patients.	This is a blinded prospective comparison of microarray copy number analysis to metaphase karyotyping for the detection of common fetal cytogentic abnormalites

Secondary Outcome Measures

Name	Time	Method
The rates of clinically significant copy number variants associated with specific prenatal conditions	Up to 2.5 years after recruitment of 4400 patients.	THe frequency of clinically significant copy number variants in cases with fetal anomalies, advanced maternal age, positve serum screening, and fetal growth disorders will be determined.
The ability of microarray copy number analysis to identify clinically significant microdeletions and duplications not seen by standard karyotyping	Up to 2.5 years .	This outcome will identify the frequency of clinically significant microdeletions and microduplications that are identified on microarray CNA that were not seen on the clinical karyotype. Only copy number variants over 1 Mb in the backbone and those in predesignated critical regions will be included

Trial Locations

Locations (1)

Columbia University Medical Center; 🇺🇸 New York, New York, United States