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.