Innovative method for reducing uninformative calls in non-invasive prenatal testing

TL;DR

This paper introduces a supplementary method analyzing DNA fragment length profiles to reduce uninformative results in non-invasive prenatal testing, aiming to decrease retests and improve diagnostic accuracy.

Contribution

A novel analysis of circulating cell-free DNA length profiles is proposed to complement traditional z-scores in NIPT, reducing uninformative calls and identifying maternal aberrations.

Findings

Substantial reduction in uninformative results when combining methods

Method helps identify maternal aberrations, lowering false positives/negatives

Complementary approach improves overall NIPT reliability

Abstract

Non-invasive prenatal testing or NIPT is currently among the top researched topic in obstetric care. While the performance of the current state-of-the-art NIPT solutions achieve high sensitivity and specificity, they still struggle with a considerable number of samples that cannot be concluded with certainty. Such uninformative results are often subject to repeated blood sampling and re-analysis, usually after two weeks, and this period may cause a stress to the future mothers as well as increase the overall cost of the test. We propose a supplementary method to traditional z-scores to reduce the number of such uninformative calls. The method is based on a novel analysis of the length profile of circulating cell free DNA which compares the change in such profiles when random-based and length-based elimination of some fragments is performed. The proposed method is not as accurate as the standard z-score; however, our results suggest that combination of these two independent methods correctly resolves a substantial portion of healthy samples with an uninformative result. Additionally, we discuss how the proposed method can be used to identify maternal aberrations, thus reducing the risk of false positive and false negative calls. Keywords: Next-generation sequencing, Cell-free DNA, Uninformative result, Method, Trisomy, Prenatal testing