Fetal Fraction and Noninvasive Prenatal Testing: What Clinicians Need to Know

Hui, Lisa; Bianchi, Diana W.

doi:10.1097/01.ogx.0000669280.20035.ca

Cited by 18 publications

(35 citation statements)

References 69 publications

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“…In their recent review, Hui and Bianchi suggested that clinicians do not need to know the details behind the biological and technological reasons for cfDNA test failure, but they do need to have a "plan B" prepared for affected patients in their clinical practice. 27 Although waiting before redrawing a fresh sample will increase the probability of obtaining a result, the clinical utility of doing so must be considered. Redraws only resolve some of the cases and significantly increase turnaround time.…”

Section: Discussionmentioning

confidence: 99%

Factors associated with test failure in pregnant women undergoing cell-free DNA-based testing for fetal trisomy

Chang

Zhou

et al. 2021

J Med Screen

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Objective To investigate the factors associated with cell-free DNA test failure, and the optimal subsequent management of these pregnancies. Methods This was a retrospective study of 27,363 singleton pregnancies undergoing cell-free DNA testing. Women with cell-free DNA test failure were divided into a high-risk group and a low-risk group according to their indications. The subsequent management and pregnancy outcomes of these women were followed up. Results The rate of cell-free DNA test failure at the first sampling was 1.49%, and 78.4% of failures were due to a low fetal fraction. Of the 66 women who refused any subsequent management, an adverse pregnancy outcome was seen in 5 cases, all belonging to the high-risk group. Of the 13 low-risk women who chose second-trimester maternal serum screening, all obtained a low-risk maternal serum screening result and an unaffected pregnancy outcome. A redraw was chosen by 171 women, which yielded a result in 75.4% and their pregnancy outcomes were unaffected; 42 women had an uninformative result again and received an amniocentesis. As 158 women had an amniocentesis after the first sampling, this procedure was offered in 200 cases altogether. Abnormal genetic testing results were shown in six (3%, 6/200) cases, all in the high-risk group. Conclusions High-risk pregnant women with cell-free DNA test failure are at increased risk of adverse pregnancy outcomes. A second sampling for cell-free DNA test or maternal serum screening might be suggested to low-risk women. Invasive prenatal diagnosis should be offered to the high-risk patients, especially those with a second cell-free DNA test failure.

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Section: Discussionmentioning

confidence: 99%

Factors associated with test failure in pregnant women undergoing cell-free DNA-based testing for fetal trisomy

Chang

Zhou

et al. 2021

J Med Screen

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“…9 Obese pregnant women are at higher risk of test failure due to LFF, probably due to dilution because of an increased circulating volume or by higher release of maternal cfDNA into the systemic circulation through apoptosis of adipose cells. 6,10,11 Other maternal factors such as ethnicity and smoking have too been found to influence fetal fraction. 6,12 Fetal aneuploidy has also been associated with LFF.…”

Section: Introductionmentioning

confidence: 99%

Association between low fetal fraction in cell‐free DNA testing and adverse pregnancy outcome: A systematic review

et al. 2021

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Objective Low fetal fraction (LFF) in prenatal cell‐free DNA (cfDNA) testing is an important cause of test failure and no‐call results. LFF might reflect early abnormal placentation and therefore be associated with adverse pregnancy outcome. Here, we review the available literature on the relationship between LFF in cfDNA testing and adverse pregnancy outcome. Method A systematic literature search was conducted in MEDLINE and EMBASE up to November 1, 2020. Results Five studies met the criteria for inclusion; all were retrospective observational cohort studies. The cohort sizes ranged from 370 to 6375 pregnancies, with all tests performed in the first trimester or early second trimester. A 4% cutoff for LFF was used in two studies, two studies used the 5th and 25th percentiles, respectively, and one study used a variety of cutoff values for LFF. LFF in prenatal cfDNA testing was observed to be associated with hypertensive disease of pregnancy, small for gestational age neonates, and preterm birth. Conflicting results were found regarding the association between LFF and gestational diabetes mellitus. Conclusions LFF in cfDNA testing is associated with adverse pregnancy outcome,specifically pregnancy‐related hypertensive disorders, preterm birth, and impaired fetal growth related to placental dysfunction. Since the available evidence is limited, a large prospective cohort study on the relationship between fetal fraction and pregnancy outcomes is needed.

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“…The 'fetal fraction' (FF) is the proportion of total maternal plasma cfDNA that arises from the fetoplacental unit, that is FF = cffDNA/(cffDNA + maternal plasma cfDNA). The FF is an important quality control metric in NIPT and is routinely calculated by most laboratories during the clinical workflow (Hui and Bianchi 2020). Nomenclature for cfDNA in prenatal testing is summarized in Fig.…”

Section: Prenatal Testingmentioning

confidence: 99%

Towards systematic nomenclature for cell-free DNA

et al. 2020

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Cell-free DNA (cfDNA) has become widely recognized as a promising candidate biomarker for minimally invasive characterization of various genomic disorders and other clinical scenarios. However, among the obstacles that currently challenge the general progression of the research field, there remains an unmet need for unambiguous universal cfDNA nomenclature. To address this shortcoming, we classify in this report the different types of cfDNA molecules that occur in the human body based on its origin, genetic traits, and locality. We proceed by assigning existing terms to each of these cfDNA subtypes, while proposing new terms and abbreviations where clarity is lacking and more precise stratification would be beneficial. We then suggest the proper usage of these terms within different contexts and scenarios, focusing mainly on the nomenclature as it relates to the domains of oncology, prenatal testing, and post-transplant surgery surveillance. We hope that these recommendations will serve as useful considerations towards the establishment of universal cfDNA nomenclature in the future. In addition, it is conceivable that many of these recommendations can be transposed to cell-free RNA nomenclature by simply exchanging “DNA” with “RNA” in each acronym/abbreviation. Similarly, when describing DNA and RNA collectively, the suffix can be replaced with “NAs” to indicate nucleic acids.

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Fetal Fraction and Noninvasive Prenatal Testing: What Clinicians Need to Know

Cited by 18 publications

References 69 publications

Factors associated with test failure in pregnant women undergoing cell-free DNA-based testing for fetal trisomy

Factors associated with test failure in pregnant women undergoing cell-free DNA-based testing for fetal trisomy

Association between low fetal fraction in cell‐free DNA testing and adverse pregnancy outcome: A systematic review

Towards systematic nomenclature for cell-free DNA

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