ABSTRACT
BACKGROUND
Genome-wide noninvasive prenatal testing identifies several rare autosomal trisomies
in the general obstetrical population, but its use is questioned by its low positive
predictive value. Furthermore, the origin of rare autosomal trisomies and the clinical
effect of reporting them has not been sufficiently investigated. In addition, professional
societies express their need for data assessing the clinical use of genome-wide noninvasive
prenatal testing for rare autosomal trisomies for years.
OBJECTIVE
This study aimed to investigate the origin of rare autosomal trisomies and the clinical
effect of disclosing rare autosomal trisomies in clinical settings.
STUDY DESIGN
Women who received noninvasive prenatal testing between March 2021 and March 2022
were prospectively enrolled. Clinical follow-up and cytogenetic and molecular investigations
were performed. Posthoc analysis was performed to investigate the association between
placental mosaicism and clinical outcomes.
RESULTS
Overall, 154 rare autosomal trisomies were identified in 89,242 pregnancies (0.17%)
through noninvasive prenatal testing. In the 120 cases in which cytogenetic and molecular
investigations were carried out, the rare autosomal trisomies were found to originate
from true fetal mosaicism (n=5), uniparental disomy (n=5), maternal mosaic trisomy
(n=3), maternal malignancy (n=1), and confined placental mosaicism (n=106). Clinical
follow-up showed that 40% of all rare autosomal trisomy cases had adverse perinatal
outcomes. In women with false-positive noninvasive prenatal testing results originating
from confined placental mosaicism, the frequency of adverse perinatal outcomes was
26%. More importantly, the placental mosaicism ratio revealed by noninvasive prenatal
testing was significantly higher in women who experienced adverse perinatal outcomes
than those who did not (0.688 vs 0.332; P<.001).
CONCLUSION
Women with noninvasive prenatal testing results indicative of rare autosomal trisomies
are at risk of adverse perinatal outcomes, and that risk can be stratified using chromosomes
and the mosaicism ratio revealed by noninvasive prenatal testing. Our data are valuable
for obstetrical caregivers advising a patient with a noninvasive prenatal testing
result indicative of a rare autosomal trisomy and a false-positive diagnosis and for
managing risks during pregnancy.
Keywords
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Article info
Publication history
Published online: October 28, 2022
Accepted:
October 24,
2022
Received:
October 20,
2022
Footnotes
J.X., N.S., J.P., J.L., S.L., J.S., and Z.P. are employed by BGI Genomics. The remaining authors report no conflict of interest.
This work was supported by the Subproject of the National Key R&D Program (grant number 2021YFC2701002), the National Natural Science Foundation of China (grant numbers 81801461, 81873836, and 81771594), the Natural Science Foundation of Hunan Province Science & Technology Department (grant number 2019JJ50681), and the Natural Science Foundation of Inner Mongolia Autonomous Region (grant number 2019MS08006). The funding bodies played no role in the design of this study; collection, analysis, and interpretation of data, and writing of the manuscript.
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