The price of abandoning diagnostic testing for cell‐free fetal DNA screening

Evans, Mark I.; Evans, Slayton A.; Bennett, Terry Ann; Wapner, Ronald J.

doi:10.1002/pd.5226

Cited by 28 publications

(23 citation statements)

References 20 publications

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“…It thus remains a screening test requiring diagnostic testing for confirmation of positive results. Since the clinical implementation of cfDNA‐based NIPT, the number of Chorionic villus sampling (CVS)/amniocentesis procedures performed has decreased substantially over recent years . While this reduces the procedure‐related risk for pregnancy loss, it also leads to failure to diagnose clinically significant subchromosomal abnormalities such as deletion and duplication syndromes, easily detectable with chromosomal microarray (CMA), the current standard diagnostic test of DNA extracted from amniotic fluid or chorionic villi.…”

Section: Introductionmentioning

confidence: 99%

Reliable detection of subchromosomal deletions and duplications using cell‐based noninvasive prenatal testing

et al. 2018

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Objective To gather additional data on the ability to detect subchromosomal abnormalities of various sizes in single fetal cells isolated from maternal blood, using low‐coverage shotgun next‐generation sequencing for cell‐based noninvasive prenatal testing (NIPT). Method Fetal trophoblasts were recovered from approximately 30 mL of maternal blood using maternal white blood cell depletion, density‐based cell separation, immunofluorescence staining, and high‐resolution scanning. These trophoblastic cells were picked as single cells and underwent whole genome amplification for subsequent genome‐wide copy number analysis and genotyping to confirm the fetal origin of the cells. Results Applying our fetal cell isolation method to a series of 125 maternal blood samples, we detected on average 4.17 putative fetal cells/sample. The series included 15 cases with clinically diagnosed fetal aneuploidies and five cases with subchromosomal abnormalities. This method was capable of detecting findings that were 1 to 2 Mb in size, and all were concordant with the microarray or karyotype data obtained on a fetal sample. A minority of fetal cells showed evidence of genome degradation likely related to apoptosis. Conclusion We demonstrate that this cell‐based NIPT method has the capacity to reliably diagnose fetal chromosomal abnormalities down to 1 to 2 Mb in size.

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Section: Introductionmentioning

confidence: 99%

Reliable detection of subchromosomal deletions and duplications using cell‐based noninvasive prenatal testing

et al. 2018

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“…Since, currently, cfDNA testing is used most often for the detection of trisomies, as is the case in France, its efficiency regarding the detection of other abnormalities is seldom compared with that of invasive testing. Women might prefer invasive testing if they knew that it is no longer associated with an increased risk of miscarriage and that it can detect more pathogenic chromosomal abnormalities than can the cfDNA test.…”

Section: Discussionmentioning

confidence: 99%

“…Increasingly, women are seeking reassurance regarding all unbalanced chromosomal abnormalities (UBCA) that will have an impact on postnatal outcome, not only trisomies. Whilst cfDNA testing may increase the number of cases of trisomy detected, its exclusive use may reduce the detection of other types of abnormalitiy. A major reason for integrating cfDNA into screening strategies has been to avoid procedure‐related miscarriages, although the precise number of miscarriages avoided remains uncertain, and has not been taken into account systematically in economic models.…”

Section: Introductionmentioning

confidence: 99%

Cost‐effectiveness of five prenatal screening strategies for trisomies and other unbalanced chromosomal abnormalities: model‐based analysis

Bras

Salomon

Bussières

et al. 2019

Ultrasound in Obstet & Gyne

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Objective To evaluate the cost‐effectiveness of five prenatal screening strategies for trisomies (13/18/21) and other unbalanced chromosomal abnormalities (UBCA), following the introduction of cell‐free DNA (cfDNA) analysis. Methods A model‐based cost‐effectiveness analysis was performed to estimate prevalence, safety, screening‐program costs and healthcare costs of five different prenatal screening strategies, using a virtual cohort of 652 653 pregnant women in France. Data were derived from the French Biomedicine Agency and published articles. Uncertainty was addressed using one‐way sensitivity analysis. The five strategies compared were: (i) cfDNA testing for women with a risk following first‐trimester screening of ≥ 1/250; (ii) cfDNA testing for women with a risk of ≥ 1/1000 (currently recommended); (iii) cfDNA testing in the general population (regardless of risk); (iv) invasive testing for women with a risk of ≥ 1/250 (historical strategy); and (v) invasive testing for women with a risk of ≥ 1/1000. Results In our virtual population, at similar risk thresholds, cfDNA testing compared with invasive testing was cheaper but less effective. Compared with the historical strategy, cfDNA testing at the ≥ 1/1000 risk threshold was a more expensive strategy that detected 158 additional trisomies, but also 175 fewer other UBCA. Implementation of cfDNA testing in the general population would give an incremental cost‐effectiveness ratio of €9 166 689 per additional anomaly detected compared with the historical strategy. Conclusion Extending cfDNA to lower risk thresholds or even to all pregnancies would detect more trisomies, but at greater expense and with lower detection rate of other UBCA, compared with the historical strategy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

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“…The question that we believe all patients need to understand is: “If you’re going to be wrong, which way would you rather be wrong? Would you rather take a small risk (e.g., a 2% risk of having a baby with a serious problem vs. a 0.1–0.12% risk of having a complication from a procedure in experienced hands) because you wanted to know that” [ 14 , 15 , 16 ]? We tell them that essentially the middle does not count.…”

Section: Choicesmentioning

confidence: 99%

Understanding False Negative in Prenatal Testing

2021

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A false negative can happen in many kinds of medical tests, regardless of whether they are screening or diagnostic in nature. However, it inevitably poses serious concerns especially in a prenatal setting because its sequelae can mark the birth of an affected child beyond expectation. False negatives are not a new thing because of emerging new tests in the field of reproductive, especially prenatal, genetics but has occurred throughout the evolution of prenatal screening and diagnosis programs. In this paper we aim to discuss the basic differences between screening and diagnosis, the trade-offs and the choices, and also shed light on the crucial points clinicians need to know and be aware of so that a quality service can be provided in a coherent and sensible way to patients so that vital issues related to a false negative result can be appropriately comprehended by all parties.

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The price of abandoning diagnostic testing for cell‐free fetal DNA screening

Cited by 28 publications

References 20 publications

Reliable detection of subchromosomal deletions and duplications using cell‐based noninvasive prenatal testing

Reliable detection of subchromosomal deletions and duplications using cell‐based noninvasive prenatal testing

Cost‐effectiveness of five prenatal screening strategies for trisomies and other unbalanced chromosomal abnormalities: model‐based analysis

Understanding False Negative in Prenatal Testing

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