When a cell-free DNA (cfDNA) test yields an inconclusive result, several approaches can be considered, as there is no single standardized protocol. A common first step is to repeat the cfDNA test by submitting a new sample.
Alternatively, if not already performed, a standard serum screening test or a targeted ultrasound (detailed anomaly scan) may be recommended. For pregnancies already categorized as high-risk, an inconclusive cfDNA result might prompt consideration of an invasive diagnostic procedure, such as chorionic villus sampling (CVS), amniocentesis, or cordocentesis, depending on the gestational age.
Inconclusive cfDNA results can stem from various factors. Potential causes for false-positive results (indicating a condition that is not present) include confined placental mosaicism, vanishing twin syndrome, maternal mosaicism, maternal malignancy, or technical issues. Conversely, false-negative results (failing to detect an existing condition) may be attributed to confined placental mosaicism, borderline low fetal fraction, or technical problems.