ArticleArchives of gynecology and obstetrics2025
Repeat cell-free DNA screening after initial false-positive results and term placental analysis for confined mosaicism: a prospective cohort study.
Article in Archives of gynecology and obstetrics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeFalse-positive prenatal cell-free DNA screening (cfDNA) results may arise from confined placental mosaicism (CPM). This cohort study examines the persistence of high-risk cfDNA in the third pregnancy trimester after exclusion of fetal involvement, and the concordance of these results with CPM in the postpartum placenta.
methodsPregnant individuals receiving a false-positive primary cfDNA result were recruited from Monash Health and Monash Ultrasound for Women in Melbourne, Australia, between August 2023 and December 2024. Participants underwent genome-wide repeat cfDNA screening (r-cfDNA) after 30 + 0 weeks' gestation. Placental samples were collected and cytogenetically analysed postpartum.
resultsThis cohort included 21 individuals, of which 33.3% (7/21) screened high-risk on r-cfDNA. There was no significant association between r-cfDNA and CPM in the postpartum placenta (p = 0.397), as five (5/12, 41.7%) cases involving CPM were screened 'low-risk'. Fetal-fraction was significantly lower (5.0% [IQR = 4.6-8.0%] vs. 9.0% [IQR = 7.0-13.5%], p = 0.025), and maternal BMI (Kg/m2) higher (29.0 [IQR = 25.7-31.2] vs. 23.3 [IQR = 22.0-24.9], p = 0.006), in false-positive cases not attributable to CPM detected by r-cfDNA or postpartum. High-risk r-cfDNA results were associated with smaller babies (median birthweight percentile = 12.3 [IQR = 4.4-21.7] vs. 31.9 [IQR = 21.5-55.5], p = 0.009), though the majority of outcomes were favorable.
conclusionHigh-risk r-cfDNA is not a sensitive predictor of CPM, though high mosaic ratios are associated with adverse obstetric outcomes. An alternative explanation for false-positive cfDNA besides CPM may be low fetal fraction, particularly in the context of high maternal BMI.
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