Accuracy of fetal fraction measurements in a single‐nucleotide polymorphism‐based noninvasive prenatal test

Abstract

AbstractBackgroundNoninvasive prenatal testing (NIPT) for fetal aneuploidy relies on the analysis of fetoplacental cell‐free DNA (cfDNA) found in maternal plasma. A minimum cfDNA fetal fraction (FF) is required for reliable test performance, but some methods may have suboptimal accuracy for FF measurement. This study investigated the accuracy of a single‐nucleotide polymorphism‐ (SNP‐) based NIPT method to assess FF.MethodsFF measurements using SNP‐based NIPT in consecutive samples from singleton male pregnancies were compared with FF measured using a “gold standard” Y‐chromosome method.ResultsIn a cohort of 106,846 samples, the SNP‐based FF method showed a standard deviation (SD) of 0.42%. Compared to the Y chromosome FF method, a correlation coefficient, r, of 0.995, and bias of 0.17% were observed. The SD was not substantially different across specific FF ranges or for samples with high‐risk NIPT results.ConclusionsThe SNP‐based NIPT method estimates FF with good accuracy, with a SD three to eight times better than other NIPT methods (0.42% vs. 1.3%–3.4%). FF is an important quality control parameter and should be routinely reported as part of NIPT.