Z-score-based posttest risk as an alternative risk metric to positive predictive value following positive noninvasive prenatal screening.

Abstract

Noninvasive prenatal screening is a long-established and widely used methodology to screen pregnancies for the most common prenatal chromosomal aneuploidies. Since 2017, positive result reports have typically included a positive predictive value to assist informed clinical decision-making. Positive predictive value is calculated based on an assay's sensitivity and specificity for a particular condition, and for the purpose of noninvasive prenatal screening, the aneuploidy's prevalence by maternal age, sometimes further adjusted by gestational age, are included in the calculation. Considering the ubiquitous use of positive predictive value by major noninvasive prenatal screeningproviders in the US, it is important to consider its limitations and consequent clinical implications. Here we discuss how the calculation of positive predictive value for screen positive results precludes the ability of positive predictive value to act as a risk metric that is accurate for and specific to an individual pregnancy, and suggest posttest risk based on the amount of target chromosome excess (Z-score-based posttest risk) as an alternative metric for consideration.