Prenatal Cytogenetic Diagnosis by Array-Based Copy Number Analysis

Prenatal Cytogenetic Diagnosis by Array-Based Copy Number Analysis

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.

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.

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