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Consequences of imprecision in fetal fraction estimation on performance of cell‐free DNA screening for Down syndrome
Author(s) -
Persson Fredrik,
Cuckle Howard S.
Publication year - 2022
Publication title -
prenatal diagnosis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.956
H-Index - 97
eISSN - 1097-0223
pISSN - 0197-3851
DOI - 10.1002/pd.6126
Subject(s) - prenatal screening , down syndrome , cell free fetal dna , medicine , statistics , fraction (chemistry) , prenatal diagnosis , fetus , mathematics , pregnancy , genetics , biology , chemistry , organic chemistry , psychiatry
Background There is a significant variability in reported fetal fraction (FF), a common cause for no‐calls in cell‐free (cf)DNA based non‐invasive prenatal screening. We examine the effect of imprecision in FF measurement on the performance of cfDNA screening for Down syndrome, when low FF samples are classified as no‐calls. Methods A model for the reported FF was constructed from the FF measurement precision and the underlying true FF. The model was used to predict singleton Down syndrome detection rates (DRs) for various FF cut‐offs and underlying discriminatory powers of the test. Results Increasing the FF cut‐off led to slightly increased apparent DR, when no‐calls are excluded, and an associated larger decrease in effective DR, when no‐calls are included. These effects were smaller for tests with higher discriminatory power and larger as maternal weight increased. Conclusions Most no‐calls due to a low reported FF have a true FF above the cut‐off. The discriminatory power of a test limits its effective DR and FF precision determines the tradeoff between apparent and effective DR when low FF is used to discard samples. Tests with high discriminatory power do not benefit from current FF measurements.