BACKGROUND: Non-invasive prenatal testing (NIPT) by massively parallel 
sequencing is a useful clinical test for the detection of common fetal 
aneuploidies. While the accuracy of aneuploidy detection can approach 100%, 
results discordant with the fetus are occasionally reported. In this study we 
investigated the basis of a discordant T21 positive and T18 negative NIPT result 
associated with a T18 fetus confirmed by karyotyping.
METHODS: Massively parallel sequencing was used to detect fetal DNA in maternal 
circulating plasma. The parental origin and nature of the fetal and placental 
aneuploidies were investigated by quantitative fluorescent PCR of short tandem 
repeat (STR) sequences and by copy number variation (CNV) sequencing.
RESULTS: There was no evidence of T21 maternal mosaicism, T21 microchimerism or 
a vanishing twin to explain the discordant NIPT result. However, examination of 
multiple placental biopsies showed both T21 and T18 mosaicism, including one 
confined region with a significantly higher proportion of T21 cells. Based on 
fetal DNA fractions and average mosaicism levels, the effective T21 and T18 
fetal DNA fractions should have been sufficient for the detection of both 
trisomies.
CONCLUSIONS: In this pregnancy, we speculate that confined placental region(s) 
with higher proportions of T21 cells were preferentially releasing fetal DNAs 
into the maternal circulation. This study highlights placental mosaicism as a 
significant risk factor for discordant NIPT results.