Prenatal Cytogenetic Diagnosis by Array-Based Copy Number Analysis

NCT ID: NCT01279733

Last Updated: 2012-08-22

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 4450 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2011-10-31

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.

Conditions

Genetic Diseases

Keywords

microarray

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Microarray Analysis

Microarray analysis

Intervention Type: 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.

Interventions

Microarray analysis

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.

Intervention Type: GENETIC

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Ronald J Wapner, MD

Professor of Obstetrics & Gynecology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ronald Wapner, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Columbia University Medical Center

New York, New York, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 23215555 (View on PubMed)

Other Identifiers

1R01HD055651-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AAAC8036

Identifier Type: -

Identifier Source: org_study_id