Temporal persistence of residual fetal cell-free DNA from a deceased cotwin after selective fetal reduction in dichorionic diamniotic twin pregnancies.

OBJECTIVES: To determine the temporal persistence of the residual cell-free DNA (cfDNA) of the deceased cotwin in maternal circulation after selective fetal reduction and evaluate its long persistence in noninvasive prenatal testing (NIPT). METHODS: Dichorionic diamniotic twins (N = 5) undergoing selective fetal reduction because of a trisomy were recruited. After informed consent, maternal blood was collected immediately before reduction and periodically after reduction until birth. The plasma cfDNA of each sample was sequenced and analyzed for fetal aneuploidy and fetal fractions. RESULTS: In all pregnancies, the fetal fraction of the cfDNA of the deceased fetus increased to peak at 7-9 weeks after fetal reduction, and subsequently decreased gradually to almost undetectable during the late third trimester. The NIPT T-scores persistently reflected the detection of fetal trisomy up to 16 (median 9.5) weeks after fetal reduction. CONCLUSIONS: Residual cfDNA from the deceased cotwin after selective reduction at 14-17 gestational weeks led to the persistent generation of false-positive NIPT results for up to 16 weeks postdemise. Thus, providing NIPT for pregnancies with a cotwin demise in early second trimester is prone to misleading results and not recommended.

FF-QuantSC: accurate quantification of fetal fraction by a neural network model.

BACKGROUND: Noninvasive prenatal testing (NIPT) is one of the most commonly employed clinical measures for screening of fetal aneuploidy. Fetal Fraction (ff) has been demonstrated to be one of the key factors affecting the performance of NIPT. Accurate quantification of ff plays vital role in NIPT. METHODS: In this study, we present a new approach, the accurate Quantification of Fetal Fraction with Shallow-Coverage sequencing of maternal plasma DNA (FF-QuantSC), for the estimation of ff in NIPT. The method employs neural network model and utilizes differential genomic patterns between fetal and maternal genomes to quantify ff. RESULTS: Our results show that the predicted ff by FF-QuantSC exhibit high correlation with the Y chromosome-based method on male pregnancies, and achieves the highest accuracy compared with other ff estimation approaches. We also demonstrate that the model generates statistically similar results on both male and female pregnancies. CONCLUSION: FF-QuantSC achieves high accuracy in ff quantification. The method is suitable for application in both male and female pregnancies. Since the method does not require additional information upon NIPT routines, it can be easily incorporated into current NIPT settings without causing extra costs. We believe that FF-QuantSC shall provide valuable additions to NIPT.