Detection Rates for Aneuploidy by First-Trimester and Sequential Screening

Baer, Rebecca J.; Flessel, Monica; Jelliffe‐Pawlowski, Laura L.; Goldman, Sara; Hudgins, Louanne; Hull, Andrew; Norton, Mary E.; Currier, Robert

doi:10.1097/aog.0000000000001040

Cited by 43 publications

(31 citation statements)

References 20 publications

(29 reference statements)

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“…Though seminal studies (eg, the FaSTER Trial) have characterized performance of non‐DNA screening for trisomy 21, herein we use Baer et al as our reference for non‐DNA screening performance because it reports sensitivity results for T13, T18, and T21, plus it involved greater than 10x more patients than the FaSTER Trial, greater than 90% of whom received integrated screening. Non‐DNA screening sensitivity for T21 and T18 was 92.9% and 93.2%, respectively, but together with the specificities (96.0% for T21, 99.6% for T18, calculated from Tables 2 and 3 in), the positive predictive values (PPV) for these trisomies are lackluster: 6.2% for T21 and 14.8% for T18 (calculated from Tables 2 and 3 in). For confirmed T13 cases, non‐DNA screening returned abnormal results in 80.4% of patients, making this number the effective sensitivity; however, because non‐DNA screening does not specifically identify T13 as the source of abnormality, specificity and PPV cannot be directly calculated.…”

Section: Introductionmentioning

confidence: 99%

“…Each year in the United States, millions of pregnant women undergo screening to detect fetal aneuploidy on chromosomes 13, 18, and 21. Depending on the tested population, the reported collective incidence of fetal trisomy on these chromosomes ranges from approximately 1 in 100 (1,2) to 1 in 250 . While some women opt for definitive diagnosis via chorionic villus sampling (CVS) or amniocentesis (these procedures are the recommended follow‐up for all screening modalities), these invasive procedures carry a risk of pregnancy loss (medical societies report an estimated rate of 0.1%‐0.3%), and in the case of amniocentesis, patients are tested relatively late in pregnancy (typically 15‐ to 20‐week gestation).…”

Section: Introductionmentioning

confidence: 99%

“…Non‐DNA screening sensitivity for T21 and T18 was 92.9% and 93.2%, respectively, but together with the specificities (96.0% for T21, 99.6% for T18, calculated from Tables 2 and 3 in), the positive predictive values (PPV) for these trisomies are lackluster: 6.2% for T21 and 14.8% for T18 (calculated from Tables 2 and 3 in). For confirmed T13 cases, non‐DNA screening returned abnormal results in 80.4% of patients, making this number the effective sensitivity; however, because non‐DNA screening does not specifically identify T13 as the source of abnormality, specificity and PPV cannot be directly calculated.…”

Section: Introductionmentioning

confidence: 99%

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Noninvasive prenatal screening for patients with high body mass index: Evaluating the impact of a customized whole genome sequencing workflow on sensitivity and residual risk

2019

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Objective Women with high body mass index (BMI) tend to have reduced fetal fraction (FF) during cell‐free DNA‐based noninvasive prenatal screening (NIPS), causing test failure rates up to 24.3% and prompting guidelines that recommend aneuploidy screening other than NIPS for patients with significant obesity. Because alternatives to NIPS are only preferable if they perform better, we compared the respective sensitivities at different BMI levels of traditional aneuploidy screening and a customized whole‐genome sequencing NIPS. Method The relationship between FF, aneuploidy, and BMI was quantified from 58 105 patients screened with a customized NIPS that does not fail samples because of low FF alone. Expected analytical sensitivity as a function of aneuploidy and BMI (eg, trisomy 18 sensitivity when BMI = 35) was determined by scaling the BMI‐ and aneuploidy‐specific FF distribution by the FF‐ and aneuploidy‐specific sensitivity calculated from empirically informed simulations. Results Across all classes of obesity and assuming zero FF‐related test failures, analytical sensitivity for the investigated NIPS exceeded that of traditional aneuploidy screening for trisomies 13, 18, and 21. Conclusion Relative to traditional aneuploidy screening, a customized NIPS with high accuracy at low FF and a low test‐failure rate is a superior screening option for women with high BMI.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Noninvasive prenatal screening for patients with high body mass index: Evaluating the impact of a customized whole genome sequencing workflow on sensitivity and residual risk

2019

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“…They are further categorized as “Increased Risk or Screen Positive” or “Decreased Risk or Screen Negative” by the performing laboratory based on laboratory cut‐offs. Screen positive rate for each of the discussed serum screens is 5% (Baer et al, ). Screen positive rate does increase with increasing maternal age (Muller, Thalabard, Ngo, & Dommergues, ).…”

Section: Screening Testsmentioning

confidence: 99%

Current landscape of prenatal genetic screening and testing

Krstić

Običan

2019

Birth Defects Research

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Pregnant patients should be offered the option of prenatal genetic screening and diagnostic testing. The type of screening and testing offered to a patient may depend on various factors including but not limited to age, family history, fetal findings, exposures, and patient preferences. Prenatal screening is available for a variety of genetic conditions including aneuploidy, congenital abnormalities, and carrier status. Diagnostic testing options include karyotype, prenatal microarray, as well as next‐generation sequencing. The various options differ in methodology, accuracy, timing and indication for testing, and information they provide. Given that the technologies related to prenatal testing are rapidly evolving and improving, the array of available screening and testing modalities are increasing. This article reviews the current offerings in prenatal screening and diagnosis.

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“…However, a large retrospective cohort study of over 450,000 women in California participating in a state-wide prenatal screening program who received first trimester screening, second trimester screening, or both in an integrated risk assessment demonstrated that the program achieved high detection rates for trisomy 21 of 92%, for trisomy 18 of 93.2%, and for trisomy 13 of 80.4% while also detecting 80% of all chromosome abnormalities (including other trisomies, monosomy, translocations, additions, duplications, inversions, rings, polyploidy, triploidy, and other chromosome abnormalities). 64 Another study evaluated how many chromosome abnormalities were detected by diagnostic testing as compared with cfDNA screening among women who were identified as screen-positive by traditional screening. Over 1.3 million patients were screened in a state-wide screening program, and 68,990 (5.2%) were screen-positive.…”

Section: Complexities and Challenges Of Clinical Implementationmentioning

confidence: 99%

Cell-Free DNA Screening

Grace¹,

Hardisty²,

Dotters‐Katz³

et al. 2016

Obstetrical &Amp; Gynecological Survey

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Screening for fetal aneuploidy in pregnant women using cell-free DNA has increased dramatically since the technology became commercially available in 2011. Since that time, numerous trials have demonstrated high sensitivity and specificity to screen for common aneuploidies in high-risk populations. Studies assessing the performance of these tests in low-risk populations have also demonstrated improved detection rates compared with traditional, serum-based screening strategies. Concurrent with the increased use of this technology has been a decrease in invasive procedures (amniocentesis and chorionic villus sampling). As the technology becomes more widely understood, available, and utilized, challenges regarding its clinical implementation have become apparent. Some of these challenges include test failures, false-positive and false-negative results, limitations in positive predictive value in low-prevalence populations, and potential maternal health implications of abnormal results. In addition, commercial laboratories are expanding screening beyond common aneuploidies to include microdeletion screening and whole genome screening. This review article is intended to provide the practicing obstetrician with a summary of the complexities of cell-free DNA screening and the challenges of implementing it in the clinical setting. Target Audience Obstetricians and gynecologists, family physicians. Learning Objectives After completing this activity, the learner should be better able to understand the complexities of cell-free DNA screening and describe considerations involved in its clinical implementation.

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Detection Rates for Aneuploidy by First-Trimester and Sequential Screening

Abstract: II.

Cited by 43 publications

References 20 publications

Noninvasive prenatal screening for patients with high body mass index: Evaluating the impact of a customized whole genome sequencing workflow on sensitivity and residual risk

Noninvasive prenatal screening for patients with high body mass index: Evaluating the impact of a customized whole genome sequencing workflow on sensitivity and residual risk

Current landscape of prenatal genetic screening and testing

Cell-Free DNA Screening

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