BACKGROUND: Cell-free fetal nucleic acids (cffNA) can be detected in the 
maternal circulation during pregnancy, potentially offering an excellent method 
for early non-invasive prenatal diagnosis (NIPD) of the genetic status of a 
fetus. Using molecular techniques, fetal DNA and RNA can be detected from 5 
weeks gestation and are rapidly cleared from the circulation following birth.
METHODS: We searched PubMed systematically using keywords free fetal DNA and 
NIPD. Reference lists from relevant papers were also searched to ensure 
comprehensive coverage of the area.
RESULTS: Cell-free fetal DNA comprises only 3-6% of the total circulating 
cell-free DNA, therefore diagnoses are primarily limited to those caused by 
paternally inherited sequences as well as conditions that can be inferred by the 
unique gene expression patterns in the fetus and placenta. Broadly, the 
potential applications of this technology fall into two categories: first, high 
genetic risk families with inheritable monogenic diseases, including sex 
determination in cases at risk of X-linked diseases and detection of specific 
paternally inherited single gene disorders; and second, routine antenatal care 
offered to all pregnant women, including prenatal screening/diagnosis for 
aneuploidy, particularly Down syndrome (DS), and diagnosis of Rhesus factor 
status in RhD negative women. Already sex determination and Rhesus factor 
diagnosis are nearing translation into clinical practice for high-risk 
individuals.
CONCLUSIONS: The analysis of cffNA may allow NIPD for a variety of genetic 
conditions and may in future form part of national antenatal screening 
programmes for DS and other common genetic disorders.