"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," Sparkes said.

That 47% figure is the heart of the problem. Every high-risk result must be confirmed with an invasive procedure, which means false alarms expose families to weeks of anxiety and an avoidable surgery.

The packaging question

The researchers found that while fetal DNA is generally believed to originate from the placenta, key questions remain unanswered. Scientists still do not know exactly which cell types release the DNA, or whether it travels attached to biological particles such as extracellular vesicles — tiny membrane-bound sacs that cells use to transport molecules — or other molecular structures.

Answering these questions matters for a practical reason. If researchers can learn how fetal DNA is packaged and transported, they may find new ways to enrich and isolate it from the mother's own DNA. That could boost the "fetal fraction" — the proportion of DNA in a blood sample that actually comes from the fetus — which is one of the biggest challenges facing current prenatal screening technology.

A low fetal fraction makes tests harder to read and contributes to inaccurate results.

"Science and technology have advanced rapidly, but our biological understanding of fetal DNA has not kept pace," said 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."

What could come next

The researchers, who published as Kieran Sparkes et al. in Science Advances (DOI: 10.1126/sciadv.aef5425), caution that their paper is a review of existing evidence rather than a report of new experimental findings. The hypotheses it raises will need testing in future studies.

Still, the potential payoff is substantial. The team believes future advances could allow prenatal tests to detect a wider range of genetic disorders from a simple blood sample, and might even help identify pregnancy complications such as preeclampsia — a condition involving dangerously high blood pressure — earlier than is currently possible.

The researchers say further work on the origins and structure of fetal DNA is now a critical priority if the full potential of prenatal genetic testing is to be realized. For now, NIPT remains a screening tool, not a diagnosis, and high-risk results still require confirmatory testing. But a clearer picture of fetal DNA's journey through maternal blood could shrink that 47% false alarm rate — and the stress that comes with it.

Publication details: Kieran Sparkes et al., "Reappraising the topology of cell-free fetal DNA in maternal blood towards improved prenatal genetic diagnostics," Science Advances (2026). DOI: 10.1126/sciadv.aef5425.