Tuesday, 10 November 2015

Advance in prenatal testing at Plymouth

Research into a simple, accurate and low risk blood test that can detect foetal blood group, sex, and genetic conditions in unborn babies has been published in the international scientific journal, Clinical Chemistry.

Kelly Silence, a PhD student in the School and lead author, writes "We have developed a highly sensitive and cost-effective test that enables rapid determination of fetal sex and RHD genotype from a maternal blood sample, which can be collected in the first trimester of pregnancy during the initial consultation. Developing non-invasive tests eradicates the need for invasive testing, such as CVS and amniocentesis, which are associated with a small but significant risk of miscarriage (1%).

Determining fetal sex is important for families at risk of X-linked genetic disorders and congenital adrenal hyperplasia (CAH), in which diagnosis can enable treatment to be targeted to female fetuses.
In addition, determining whether the fetus is positive or negative (for RHD) in mothers with a negative blood type, can enable treatment to be target to fetuses which are RHD positive, and thus at risk of developing haemolytic disease of the fetus and newborn (HDFN).

Currently, routine testing of fetal RHD status has been implemented in the Netherlands and Denmark using real-time PCR (qPCR). However, this approach can be associated with false negative results, especially if the level of cell-free fetal DNA (cffDNA) within the maternal circulation is low (<3%). False negative results can be detrimental, since treatment is not given, and thus fetus is at risk of developing HDFN.

By using droplet digital PCR (ddPCR) technology, we have identified an approach that enables accurate determination of fetal sex and RHD status, even when the cffDNA is present at <1%. This novel platform separates each sample into thousands of droplets (up to 20,000), which enables accurate detection of molecules present in low copy numbers.

Fetal aneuploidy is one of the most predominant reasons why women choose to undergo invasive testing, and although next generation sequencing techniques can determine fetal aneuploidy non-invasively with high sensitivity (>99%), these tests are too expensive for routine clinical testing (£400- £900). Our group has shown, using spike samples, that ddPCR can be used an alternative non-invasive test for a fraction of the cost (<£10). However, further analysis of clinical samples is required to determine the feasibility of this approach.

For more information see Clinical Chemistry publication entitled; ‘Fetal sex and RHD genotyping using droplet digital PCR demonstrates greater sensitivity compared to real-time PCR’ (http://www.ncbi.nlm.nih.gov/pubmed/26354802)". Links to press coverage are below.