Placental, maternal, fetal and technical origins of false-positive cell-free DNA screening results.

Abstract

The introduction of non-invasive prenatal testing (NIPT) has resulted in substantial reductions to previously accepted false-positive rates of prenatal screening. Despite this, the possibility of false-positive results remains a challenging consideration in clinical practice, particularly in light of the increasing uptake of genome-wide NIPT, and the subsequent increased proportion of high-risk results attributable to various biological events besides fetal aneuploidy. Confined placental mosaicism (CPM), whereby chromosome anomalies exclusively affect the placenta, is perhaps the most widely accepted cause of false-positive NIPT. There remains, however, a substantial degree of ambiguity in the literature pertaining to the clinical ramifications of CPM and its potential association with placental insufficiency, and consequentially adverse pregnancy outcomes including fetal growth restriction. Other causes of false-positive NIPT include vanishing twin syndrome, in which the cell-free DNA from a demised aneuploidy affected twin triggers a high-risk result, technical failures, and maternal origins of abnormal cell-free DNA such as uterine fibroids or unrecognized mosaicisms. Most concerningly, maternal malignancies are also a documented cause of false-positive screening results. In this review, we compile what is currently known about the various causes of false-positive NIPT.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.