Interpreting False-Positive or Atypical Prenatal Cell-Free DNA Results

Cell-free DNA (cfDNA) screening is a highly accurate method of genetic screening that relies on the presence of placenta-derived DNA circulating in maternal plasma. The widespread availability of this screening, also known as non-invasive prenatal testing, has transformed prenatal genetic screening for fetal chromosome disorders, including trisomies 21, 18, and 13. Despite the increased accuracy of the cfDNA approach, false-positive results remain a possibility. Such results have distinct biological causes and clinical implications. In this article, we review the most common causes of false-positive screening results: confined placental mosaicism; vanishing twin syndrome; and maternal factors, including maternal mosaicism and malignancies. We also review unexplained false-positive and nonreportable cfDNA results and appropriate follow-up. Clinical vignettes demonstrate scenarios that nurses and other providers may encounter in the delivery of prenatal care.