Placental mosaicism for structural chromosomal variants: follow-up of 251 Danish cases (1983-2021)

Mosaicism, the presence of two or more chromosomally different cell lines in the same tissue, is detected in 2-4 % of chorionic villus samples (CVS). Its detection presents clinical challenges, as follow-up examinations are required to separate true fetal mosaicism (TFM) from confined placental mosaicism (CPM). While mosaicism involving autosomal trisomies is well studied, data on structural chromosomal variants (SV's) are limited. This study estimates risk of TFM and adverse outcomes in CPM cases when SV mosaicism is detected in CVS.

We performed a nationwide retrospective descriptive study of all pregnancies in Denmark from 1983 to 2021 with SV mosaicism involving an autosome, detected by chorionic villus sampling (CVS). We used two nationwide registries: Danish Cytogenetic Central Registry and Danish Fetal Medicine Database.

Of 90,973 CVS's, 302 involved mosaic SV's and 251 had follow-up. TFM was confirmed in 28 %. In CPM cases (n = 181), 6 % had a birth weight <2.3-percentile and 9 % were born preterm (<37 weeks), which was not significantly different from the general population. Pregnancies tested due to high-risk screening, advanced maternal age or abnormal ultrasound had a higher risk of TFM (31 %, 30 % and 33 %, respectively) compared to those tested due to family history of chromosomal or monogenic disease (11 %).

Mosaicism for an SV detected in CVS is associated with a high risk of TFM. CPM involving SV's does not generally appear to increase the risk of adverse outcomes, although a modestly elevated risk of preterm birth was observed in cases with overall chromosomal gains.