Prenatal Cytogenetic Diagnosis by Array-Based Copy Number Analysis (Microarray)

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

• The ability of microarray copy number analysis to identify clinically significant microdeletions and duplications not seen by standard karyotyping [ Time Frame: 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
  
  
• The rates of clinically significant copy number variants associated with specific prenatal conditions [ Time Frame: 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.
  
  

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.