Biological explanations for discordant noninvasive prenatal test results: Preliminary data and lessons learned

Wilkins‐Haug, Louise; Zhang, Chengsheng; Cerveira, Eliza; Ryan, Mallory; Mil-homens, Adam; Zhu, Qihui; Reddi, Honey V.; Lee, Charles; Bianchi, Diana W.

doi:10.1002/pd.5260

Cited by 20 publications

(18 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with reports of a range of biological factors (e.g. mosaicism) that can cause false NIPS results at any FF level 21,22 , the FF of FNs ranged from 3.4% to 20.0% and the FF of FPs ranged from 1.2% to 18.9% (Figure 2a). Because our calling algorithm does not fail samples because of low FF alone, we closely scrutinized the test performance specifically for those samples with FF < 4% using the updated algorithm.…”

supporting

confidence: 87%

Clinical experience across the fetal‐fraction spectrum of a non‐invasive prenatal screening approach with low test‐failure rate

Hancock

Ben‐Shachar

Adusei

et al. 2020

Ultrasound in Obstet & Gyne

View full text Add to dashboard Cite

What are the novel findings of this work? This study is the first to directly explore pregnancy outcomes following noninvasive prenatal screening (NIPS) on samples with low fetal fraction (FF). On most NIPS offerings, low-FF samples are failed, yet we find that a customized NIPS that does not fail samples based on FF has comparable sensitivity and specificity for high-and low-FF samples. What are the clinical implications of this work? Test failures due to low fetal fraction (FF) during noninvasive prenatal screening (NIPS) increase patient anxiety, lengthen the prenatal screening process, and complicate provider workflow. Our study shows that a customized NIPS based upon whole-genome sequencing performs comparably at high and low FF, rendering low-FF test failures unnecessary.

show abstract

supporting

confidence: 87%

Clinical experience across the fetal‐fraction spectrum of a non‐invasive prenatal screening approach with low test‐failure rate

Hancock

Ben‐Shachar

Adusei

et al. 2020

Ultrasound in Obstet & Gyne

View full text Add to dashboard Cite

show abstract

“…Thymic hypoplasia or aplasia may be diagnosed during ultrasound of the heart (Figure ) . Also, for women/couples who decline amniocentesis, cffDNA for fetal aneuploidy detection may be an option but it is not a diagnostic test . However, it should be noted that the 15% of smaller detections are unlikely to be detected by cffDNA screening.…”

Section: Other Genetic Syndromes Associated With Cardiac Anomaliesmentioning

confidence: 99%

“…[60][61][62][63] Also, for women/couples who decline amniocentesis, cffDNA for fetal aneuploidy detection may be an option but it is not a diagnostic test. 64 However, it should be noted that the 15% of smaller detections are unlikely to be detected by cffDNA screening. Thus, a significant proportion of these clinical cases would not be detected.…”

Section: Prenatal Ultrasound Findingsmentioning

confidence: 99%

Fetal cardiac abnormalities: Genetic etiologies to be considered

et al. 2019

Self Cite

View full text Add to dashboard Cite

Congenital heart diseases are a common prenatal finding. The prenatal identification of an associated genetic syndrome or a major extracardiac anomaly helps to understand the etiopathogenic diagnosis. Besides, it also assesses the prognosis, management, and familial recurrence risk while strongly influences parental decision to choose termination of pregnancy or postnatal care. This review article describes the most common genetic diagnoses associated with a prenatal finding of a congenital heart disease and a suggested diagnostic process.

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

Biological explanations for discordant noninvasive prenatal test results: Preliminary data and lessons learned

Cited by 20 publications

References 62 publications

Clinical experience across the fetal‐fraction spectrum of a non‐invasive prenatal screening approach with low test‐failure rate

Clinical experience across the fetal‐fraction spectrum of a non‐invasive prenatal screening approach with low test‐failure rate

Fetal cardiac abnormalities: Genetic etiologies to be considered

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

Contact Info

Product

Resources

About