Discordant <scp>NIPT</scp> result in a viable trisomy‐21 pregnancy due to prolonged contribution to cf<scp>DNA</scp> by a demised trisomy‐14 cotwin

Hochstenbach, Ron; Elferink, Martin; Zon, Patrick H.A. van; Harssel, Jeske van; Schuring-Blom, Heleen; Page-Christiaens, G. C. M. L.

doi:10.1002/ccr3.1424

Cited by 11 publications

(19 citation statements)

References 10 publications

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“…The fetal demise of a cotwin has been known as an important factor in association with false-positive NIPT results. 11,[23][24][25][26] Substantial proportions of false-positive NIPT results ranging from an estimated 15% to 33% might be caused by unrecognized fetal demise. [27][28][29] Critical questions of NIPT clinical practice include how long the residual cfDNA from a deceased cotwin remains in the maternal circulation and if NIPT should be used when the fetal demise of a cotwin has been identified.…”

Section: Discussionmentioning

confidence: 99%

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

Chen

Wang

et al. 2021

Prenatal Diagnosis

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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 ¼ 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 PointsWhat'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.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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Section: Discussionmentioning

confidence: 99%

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

Chen

Wang

et al. 2021

Prenatal Diagnosis

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“…In three patients, the NIPT results showed evidence of aneuploidy that was not present following invasive sampling. Such results can be caused by confined placental mosaicism (CPM), undetected twin pregnancies with foetal demise or maternal aneuploidy (e.g., due to neoplasia) (26) or maternal copy-number variants. One such trisomy 18 result from our study was confirmed to be due to CPM.…”

Section: Cohortmentioning

confidence: 99%

Implementation of cell-free DNA-based non-invasive prenatal testing in a National Health Service Regional Genetics Laboratory

et al. 2019

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Background Non-invasive prenatal testing (NIPT) for the detection of foetal aneuploidy through analysis of cell-free DNA (cfDNA) in maternal blood is offered routinely by many healthcare providers across the developed world. This testing has recently been recommended for evaluative implementation in the UK National Health Service (NHS) foetal anomaly screening pathway as a contingent screen following an increased risk of trisomy 21, 18 or 13. In preparation for delivering a national service, we have implemented cfDNA-based NIPT in our Regional Genetics Laboratory. Here, we describe our validation and verification processes and initial experiences of the technology prior to rollout of a national screening service. Methods Data are presented from more than 1000 patients (215 retrospective and 840 prospective) from ‘high- and low-risk pregnancies’ with outcome data following birth or confirmatory invasive prenatal sampling. NIPT was by the Illumina Verifi® test. Results Our data confirm a high-fidelity service with a failure rate of ~0.24% and a high sensitivity and specificity for the detection of foetal trisomy 13, 18 and 21. Secondly, the data show that a significant proportion of patients continue their pregnancies without prenatal invasive testing or intervention after receiving a high-risk cfDNA-based result. A total of 46.5% of patients referred to date were referred for reasons other than high screen risk. Ten percent (76/840 clinical service referrals) of patients were referred with ultrasonographic finding of a foetal structural anomaly, and data analysis indicates high- and low-risk scan indications for NIPT. Conclusions NIPT can be successfully implemented into NHS regional genetics laboratories to provide high-quality services. NHS provision of NIPT in patients with high-risk screen results will allow for a reduction of invasive testing and partially improve equality of access to cfDNA-based NIPT in the pregnant population. Patients at low risk for a classic trisomy or with other clinical indications are likely to continue to access cfDNA-based NIPT as a private test.

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“…Fetal demise in a multifetal pregnancy can complicate aneuploidy screening as the cell-free DNA (cfDNA) from the non-viable conception may lead to a non-invasive prenatal testing result that is discordant with that of the viable fetus 1,2 . This poses a challenge for healthcare providers in identifying an appropriate prenatal genetic screening option in such cases.…”

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confidence: 99%

Cell‐free DNA analysis after reduction in multifetal pregnancy

Bevilacqua

Chen

Wang

et al. 2020

Ultrasound in Obstet & Gyne

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Discordant NIPT result in a viable trisomy‐21 pregnancy due to prolonged contribution to cfDNA by a demised trisomy‐14 cotwin

Cited by 11 publications

References 10 publications

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

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

Implementation of cell-free DNA-based non-invasive prenatal testing in a National Health Service Regional Genetics Laboratory

Cell‐free DNA analysis after reduction in multifetal pregnancy

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