Understanding how fetal DNA travels in a pregnant woman's blood could unlock the next generation of prenatal screening, according to a new paper published in Science Advances today.
An international team of scientists, led by Adelaide University , has reviewed decades of research to better understand where fetal DNA comes from, how it enters the bloodstream, and what structures it may be associated with once it is circulating in maternal blood.
The researchers challenge long-held assumptions about fetal DNA that could help improve the accuracy of non-invasive prenatal testing (NIPT).
NIPT is a widely used blood test that screens for genetic conditions during pregnancy, analysing small fragments of DNA from the placenta that circulate in the mother's bloodstream.
Since its introduction in 2011, millions of women around the world have used NIPT because it offers a safer alternative to invasive procedures such as amniocentesis.
In Australia, around 30% of families opt to pay $A500 for the test – often out of pocket.
Despite its success and popularity, NIPT still has limitations, according to lead author Adelaide University PhD candidate Kieran Sparkes from the Future Industries Institute .
"For most parents, a negative NIPT result provides reassurance about the health of their unborn baby. However, if NIPT does indicate a high risk for a chromosomal condition, parents have to wait over a month for confirmation and undergo an invasive diagnostic procedure," Sparkes said.
"High-risk NIPT results are rare, but in 47% of cases, a high-risk result turns out to be a false alarm, creating unnecessary stress as well as an unnecessary surgical operation.
"If we can better understand how fetal DNA is packaged and transported, we may be able to develop new ways to enrich and isolate it. That could improve test accuracy, reduce false results and potentially allow screening for a much broader range of genetic conditions."
The researchers found that while fetal DNA is generally believed to originate from the placenta, key questions remain unanswered about the exact cell types that release it and whether the DNA travels attached to biological particles such as extracellular vesicles or other molecular structures.
According to the authors, solving these questions could help scientists increase the proportion of fetal DNA available for testing, known as the "fetal fraction", which is one of the biggest challenges facing current prenatal screening technologies.
"Science and technology have advanced rapidly, but our biological understanding of fetal DNA has not kept pace," said Professor Benjamin Thierry, Director of the Precision Nanomedicine Program at Adelaide University.
"By uncovering the fundamental biology of fetal DNA, we can create new tools that make prenatal testing more reliable, more comprehensive and potentially more affordable."
The researchers believe that future advances could also allow prenatal tests to detect a wider range of genetic disorders from a simple blood sample and may even help identify pregnancy complications such as preeclampsia earlier.
The team says further research into the origins and structure of fetal DNA is now a critical priority if the full potential of prenatal genetic testing is to be realised.
'Reappraising the topology of cell-free fetal DNA in maternal blood towards improved prenatal genetic diagnostics' is published in Science Advances. DOI: 10.1126/sciadv.aef5425 . The research was funded by the Firefly Children's Foundation.
