Reappraising the topology of cell-free fetal DNA in maternal blood toward improved prenatal genetic diagnostics.

Authors

Kieran Sparkes, Marnie Winter, Gustaaf A Dekker, Lawrence Chamley, Martin J Larsen, Benjamin Thierry

Published in

Science advances. Volume 12. Issue 40. Pages eaef5425. Oct 02, 2026. Epub Oct 02, 2026.

Abstract

Noninvasive prenatal testing (NIPT) is a pregnancy screening test that analyses cell-free fetal DNA (cffDNA) in maternal plasma to detect fetal genetic abnormalities during pregnancy. Earlier and safer detection of fetal genetic abnormalities facilitated by NIPT has markedly transformed maternal-fetal medicine. However, NIPT is currently limited to be only a screening test due to fundamental biological bottlenecks, namely, the small proportion of cffDNA compared to cell-free maternal DNA in maternal plasma, the challenge to reliably distinguish between fetal and maternal DNA, and discordance between cffDNA and the true fetal genotype. Despite millions of NIPT being conducted each year, the exact origin and structural topology of cffDNA remain unexpectedly unclear. Elucidating the origin and structure of cffDNA could unlock new technological advances that address the current bottlenecks limiting NIPT toward realizing the full potential of state-of-the-art sequencing approaches for NIPT. In this Review, we critically discuss current cffDNA knowledge, including its origin, release into maternal blood circulation, and structures relevant to contemporary NIPT.

PMID:
42826178
Bibliographic data and abstract were imported from PubMed on 03 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.