cfDNA Screen Assesses Fetal Risk for Recessive Disorders

A prospective, multisite study published in Obstetrics & Gynecology evaluated cell-free DNA (cfDNA) fetal risk assessment as a primary screen for autosomal recessive conditions in a large, general-risk pregnancy population. BillionToOne announced the publication and identified the tested approach as its Unity Fetal Risk Screen.

Conducted at nine US institutions, the analysis involved pregnant carriers with singleton pregnancies at a gestational age of at least 10 weeks whose partners’ carrier status was unknown at testing. The screen covered cystic fibrosis, spinal muscular atrophy, and beta and alpha hemoglobinopathies. Cases in which both partners were known carriers of the same condition were excluded from the primary analysis and assessed separately.

Investigators analyzed 2,403 cfDNA results from 2,212 pregnant carriers; 188 participants carried more than one condition. Fetal or neonatal outcomes were available for 2,369 results, or 98.6%. Outcomes were confirmed through prenatal or postnatal diagnostic testing, newborn screening, clinical records, or molecular testing.

Among results with known outcomes, 18 fetuses or neonates were affected. Seventeen had cfDNA fetal risk estimates of at least 1 in 4, and one had a lower-risk result. Sensitivity was 94.44%, specificity was 99.49%, positive predictive value was 58.62%, and negative predictive value was 99.96%; 1.3% of completed cfDNA tests received a fetal risk estimate of at least 1 in 4.

Investigators concluded that the findings support the possibility of cfDNA fetal risk assessment as a primary screen without requiring a partner sample. They also noted that the high-risk-couple sample was too small for an informative performance analysis and that low fetal fraction was associated with a higher no-result rate.

Sources: McElwee ER, Wynn J, Rego S, et al. A prospective, multi-site study of performance of cell-free DNA testing for recessive conditions in a large, general-risk pregnancy population. Obstet Gynecol. 2026;00:1-7. doi:10.1097/AOG.0000000000006403

BillionToOne. Largest prospective study in general-risk pregnancies strengthens evidence for cfDNA fetal risk assessment as a primary screen for recessive conditions. Press release. BillionToOne; August 18, 2026. Accessed August 20, 2026.