Use of cell‐free non‐invasive prenatal testing in pregnancies affected by placental mosaicism

Objective To evaluate cell‐free non‐invasive prenatal testing (cfNIPT) in pregnancies affected by mosaicism. Method We assessed paired cfNIPT and chorionic villus sample (CVS) results from the same pregnancies in a case series of mosaicism detected in Central and North Denmark Regions from April 2014 to September 2018. Indications for the clinically obtained CVS, pregnancy markers and outcome were retrieved from The Danish Fetal Medicine Database. Results Mosaicisms in CVS involved common aneuploidy, n = 14; sex chromosomal aneuploidies, n = 14; rare autosomal trisomies (RATs), n = 16 and copy number variants (CNVs) >5Mb, n = 9. Overall, 24/53 (45.3%; CI 95%: 31.8%–59.4%) of cases with mosaicism were detected by cfNIPT; highest for RATs (56%) and lowest for CNVs (22%). CfNIPT more commonly detected high‐level than low‐level mosaic cases (p = 0.000). CfNIPT detected 7/16 (43.8%; CI 95%: 21%–69%) clinically significant mosaic cases, either true fetal mosaicism or confined placental mosaicisms with adverse pregnancy outcome. There was a trend toward a higher risk for adverse outcome in pregnancies where mosaicism was detected by cfNIPT compared to pregnancies where mosaicism was not detected by cfNIPT (p = 0.31). Conclusion CfNIPT has a low detection rate of mosaicism, including pregnancies with clinically significant mosaicism. However, abnormal cfNIPT results may be a predictor of adverse pregnancy outcomes. Key points What´s already known about this topic? The prevalence of mosaicism in chorionic villus samples is 2%–4% Fetoplacental mosaicism is one of the causes behind false results with cell‐free non‐invasive prenatal testing (cfNIPT) What does this study add? CfNIPT detects ∼50% of mosaic cases revealed in chorionic villus samples The detection rate of mosaicism by cfNIPT correlates with the level of mosaicism in chorionic villus samples In case of placental mosaicism, a positive cfNIPT result may be a predictor of adverse pregnancy outcome