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

• Published in: Prenatal diagnosis 2021-11, Vol.41 (12), p.1602-1610
• Main Authors: Chen, Min, Su, Fengxia, Wang, Jiayan, Zhou, Lijun, Liu, Qiang, Chai, Xianghua, Yuan, Yuying, Cen, Miaolan, Wu, Yujing, Wang, Yicong, Chen, Fang, Zhang, Yanyan, Chen, Dunjin, Gao, Ya
• Format: Article
• Language: English
• Subjects: Adult; Aneuploidy; Cell-Free Nucleic Acids - analysis; Cell-Free Nucleic Acids - blood; Deoxyribonucleic acid; DNA; Female; Fetal Death; Fetuses; Humans; Informed consent; Pregnancy; Pregnancy, Twin - blood; Pregnancy, Twin - metabolism; Pregnancy, Twin - physiology; Prenatal Diagnosis - methods; Prospective Studies; Reduction; Trisomy
• ISSN: 0197-3851; 1097-0223
• DOI: 10.1002/pd.5898

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. Key Points What's already known about this topic? The estimated prevalence of a cotwin's fetal demise in all twin pregnancies is 6.2%, although the prevalence might be underestimated. The deceased fetus releases residual cell‐free DNA (cfDNA) to the maternal circulation, leading to false‐positive findings of fetal aneuploidy on noninvasive prenatal testing (NIPT). However, the evidence is still needed to determine the implications of longitudinal residual cfDNA for NIPT use. What does this study add? The fetal fraction of the cfDNA of the deceased cotwin was persistent, peaking at 7–9 weeks after fetal demise, and then gradually declining to almost undetectable levels at 12–20 weeks after fetal demise. The persistent detection of fetal aneuploidy based on NIPT T‐scores lasted for up to 16 weeks after fetal demise.