Prevalence of mosaicism in uncultured chorionic villus samples after chromosomal microarray and clinical outcome in pregnancies affected by confined placental mosaicism

Objective To evaluate the prevalence of mosaicism in chorionic villus sampling (CVS) samples after chromosomal microarray (CMA) and clinical outcome of pregnancies affected by confined placental mosaicism. Method We retrieved all results from CMA, array-based comparative genomic hybridization, on CVS samples from January 2011 to November 2017 from Central and North Denmark Regions. Mosaic results from uncultured chorionic villi, cytotrophoblasts and mesenchymal cells, after CVS and follow-up on amniocytes, fetal tissue, or postnatal blood were studied and matched with clinical data from The Danish Fetal Medicine Database. Results Prevalence of mosaicism was 93 out of 2,288 (4.1%) CVS samples of which 17 (18.3%) concerned submicroscopic copy number variations (CNVs) <10 Mb. Follow-up analyses were performed in 62 cases. True fetal mosaicism (TFM) was confirmed in 18.4% (7/38) when mosaicism involved whole chromosome aneuploidy and in 25.0% (6/24), when involving a CNV (P = .59). Median birth weight z-score was higher in cases of confined placental mosaicism for a CNV (0.21) than cases involving whole chromosomes (-0.74) (P = .02). Conclusion Prevalence of mosaicism in CVS samples is higher after CMA on uncultured tissue than after conventional karyotyping on cultured tissue. The risk of TFM is equally high in cases of mosaicism for CNVs and whole chromosomes.