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

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Raymond, Yvette
Fernando, Shavi
Menezes, Melody
Mol, Ben W
McLennan, Andrew
da Silva Costa, Fabricio
Hardy, Tristan
Rolnik, Daniel L
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2023
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Abstract

The introduction of noninvasive prenatal testing 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 considering the increasing uptake of genome-wide noninvasive prenatal testing, and the subsequent increased proportion of high-risk results attributable to various biological events besides fetal aneuploidy. Confined placental mosaicism, whereby chromosome anomalies exclusively affect the placenta, is perhaps the most widely accepted cause of false-positive noninvasive prenatal testing. There remains, however, a substantial degree of ambiguity in the literature pertaining to the clinical ramifications of confined placental mosaicism and its potential association with placental insufficiency, and consequentially adverse pregnancy outcomes including fetal growth restriction. Other causes of false-positive noninvasive prenatal testing 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 noninvasive prenatal testing.

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American Journal of Obstetrics and Gynecology

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© 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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Reproductive medicine

Cancer in pregnancy

Cell-free DNA Screening

Confined Placental Mosaicism

Genome-Wide Screening

Maternal Malignancy

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Raymond, Y; Fernando, S; Menezes, M; Mol, BW; McLennan, A; DA Silva Costa, F; Hardy, T; Rolnik, DL, Placental, maternal, fetal, and technical origins of false-positive cell-free DNA screening results, American Journal of Obstetrics and Gynecology, 2023

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