Placental cytogenetic testing for confined placental mosaicism and obstetrical outcomes after discordant cell-free DNA screening results.

BACKGROUND

A false-positive cell-free DNA prenatal screening result may arise from confined placental mosaicism, however, the frequency and obstetrical ramifications of such cases are poorly understood.

OBJECTIVE

This study aimed to assess the prevalence of confined placental mosaicism among pregnancies with false-positive cell-free DNA results and the associated obstetrical outcomes.

STUDY

DESIGN

This was a prospective, matched-cohort study with a 1:2 ratio of cases with false-positive cell-free DNA results and controls with low-risk cell-free DNA results that were matched by maternal age and body mass index. Participants were recruited between November 2022 and March 2025 at Monash Health and Monash Ultrasound for Women in Melbourne, Australia. Cytogenetic testing was conducted on 4 biopsies per placenta to investigate confined placental mosaicism. The cases and matched controls were compared using trio matching identifiers as random effect in conditional logistic regression and linear mixed-effects modelling.

RESULTS

A total of 60 cases with false-positive cell-free DNA results were matched with 120 controls. Confined placental mosaicism was observed in 20 of the 60 cases (33.3%) and in none of the controls. The prevalence of confined placental mosaicism was highest among those with rare autosomal trisomy (57.9%; 11/19) and monosomy X (75.5%; 3/4) results. Confined placental mosaicism was also observed following common autosomal trisomy results (21.4%; 3/14) and subchromosomal copy number variants (15.8%; 3/19). The median birth weight percentile was significantly lower among instances of confirmed confined placental mosaicism (20.1; interquartile range, 9.9-48.5) than among matched controls (43.5; interquartile range, 17.1-66.1; P=.049); however, there were no statistically significant increases in small-for-gestational-age neonates or other adverse pregnancy outcomes.

CONCLUSION

Confined placental mosaicism is a frequent contributor to false-positive cell-free DNA results, most often for monosomy X and rare autosomal trisomy results. Although the birth weight median percentiles were lower, the outcomes of cell-free DNA-detected confined placental mosaicism in this average-risk cohort were predominantly favorable. El resumen está disponible en Español al final del artículo. VIDEO ABSTRACT.