Abstract
Some women undergoing noninvasive prenatal testing (NIPT) do not receive an informative result due to low fetal fraction (FF). A proportion of these are at increased risk for fetal trisomy 13, 18, or triploidy, while others have no change from their prior risk. Women with an initial uninformative NIPT need to be counseled about any such change in their risk for fetal abnormality and also the probability that a redraw will be informative. To help in the decision making, we reviewed a dataset of single nucleotide polymorphism‐based NIPT with uninformative results where a redraw was received. Risk for trisomy 13, 18, or triploidy was evaluated using a fetal fraction‐based risk (FFBR) algorithm. Risk‐unchanged women were further analyzed using a regression model to determine the likelihood of an informative redraw. Of 2,644 women with an uninformative NIPT and a redraw, 1,147 (43.4%) were high risk for trisomy 13, 18, or triploidy. 1,497 (56.6%) were risk unchanged and, of these, 975 (65.1%) cases had an informative redraw (i.e., risks were available for 2,122 (80%) of those initially classified as uninformative). The regression model for the risk‐unchanged cases provided a new table for predicting an informative redraw. Likelihood of a successful redraw was significantly (p < .001) dependent on the initial FF, maternal weight, and time between blood draws. We conclude that the FFBR algorithm and the predictive model for an informative redraw provide complementary additions in the management of women presented with an initially uninformative SNP‐based NIPT due to low FF. We suggest approaches for the counseling and follow‐up testing for women with an initially uninformative NIPT.
Highlights
We recently reported that fetal fraction (FF) could be used as a biomarker to identify the sub-group of women who do not receive a noninvasive prenatal testing (NIPT) result using a SNP-based NIPT but are at significantly increased risk for trisomy 18, trisomy 13, triploidy, and pregnancy loss (McKanna et al, 2019)
To calculate the net proportion of cases with a result of any type, we considered cases with a high fetal fraction-based risk (FFBR) score as informative and those cases with a result obtained from a follow-up plasma sample as informative
We show that using the FFBR algorithm materially reduces the proportion of women with entirely uninformative results
Summary
Noninvasive prenatal testing (NIPT) for fetal chromosome abnormalities, based on the analysis of cell-free DNA (cf-DNA) in maternal plasma, is widely available as a clinical service (Bianchi & Chiu, 2018; Cuckle, Benn, & Pergament, 2015). We recently reported that FF could be used as a biomarker to identify the sub-group of women who do not receive a NIPT result using a SNP-based NIPT but are at significantly increased risk for trisomy 18, trisomy 13, triploidy, and pregnancy loss (McKanna et al, 2019). Using a risk cutoff of 1 in 100 in this fetal fraction-based risk (FFBR) algorithm, 22% of the high-risk group had abnormal pregnancy outcomes This algorithm has been introduced into clinical practice, and instead of receiving an uninformative NIPT result, increased risk status for the relevant conditions is reported. These women can be promptly offered further counseling, ultrasound, and the option of diagnostic testing. We discuss the complex options and pathways for the clinical management of women with an initial no result with the goal of facilitating counseling
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