Salt Lake City – September 11, 2026 -- A decade-long study by ARUP Laboratories found that 50% of pregnancies with atypical prenatal cell-free DNA (cfDNA) screening results carried at least one clinically significant abnormality confirmed by follow-up testing, reshaping how providers should respond to inconclusive genetic screens.
ARUP analyzed over 200 atypical cfDNA cases spanning more than 10 years
Researchers reviewed more than 10 years of data and over 200 cases where atypical cfDNA screening results were followed by additional prenatal, postnatal, or maternal testing. The findings, published in Genetics in Medicine, the official journal of the American College of Medical Genetics and Genomics (ACMG), represent what ARUP describes as the largest study of its kind on atypical cfDNA findings.
Follow-up testing confirmed abnormalities in 102 of 204 atypical cases
Of the 204 atypical cfDNA cases studied, 102 yielded at least one abnormal diagnostic result. Among these, 55 were classified as pathogenic, 18 as variants of uncertain significance, and eight as likely benign. Copy number variations were the most frequent diagnostic finding, alongside aneuploidy and chromosome rearrangements.
Maternal genetic findings emerged as a distinct and frequent category
The study identified a notably high rate of maternal genetic anomalies detected through cfDNA screening that were unrelated to the fetus. Lauren Wallace, MS, LCGC, a co-author and former maternal-fetal medicine genetic counselor, said these maternal findings tend to be more benign than fetal-related results and could serve as an intermediary testing step before invasive procedures such as chorionic villus sampling or amniocentesis.
Rising atypical result rates increase pressure on clinical decision-making
Katie Rudd, PhD, FACMG, ARUP medical director of Cytogenetics and Genomic Microarray, said atypical cfDNA results have increased in frequency, likely driven by improving screening technology and expanded testing access. She noted the uncertainty of these results has historically left both providers and patients without a clear path forward, a gap this study aims to close by showing atypical findings carry meaningful diagnostic value rather than warranting dismissal.