Both intact fetal cells as well as cell-free fetal DNA are present in the 
maternal circulation and can be recovered for non-invasive prenatal genetic 
diagnosis. Although methods for enrichment and isolation of rare intact fetal 
cells have been challenging, diagnosis of fetal chromosomal aneuploidy including 
trisomy 21 in first- and second-trimester pregnancies has been achieved with a 
50-75% detection rate. Similarly, cell-free fetal DNA can be reliably recovered 
from maternal plasma and assessed by quantitative PCR to detect fetal trisomy 21 
and paternally derived single gene mutations. Real-time PCR assays are robust in 
detecting low-level fetal DNA concentrations, with sensitivity of approximately 
95-100% and specificity near 100%. Comparing intact fetal cell versus cell-free 
fetal DNA methods for non-invasive prenatal screening for fetal chromosomal 
aneuploidy reveals that the latter is at least four times more sensitive. These 
preliminary results do not support a relationship between frequency of intact 
fetal cells and concentration of cell-free fetal DNA. The above results imply 
that the concentration of fetal DNA in maternal plasma may not be dependent on 
circulating intact fetal cells but rather be a product of growth and cellular 
turnover during embryonic or fetal development.