scholarly journals A multivariate modeling method for the prediction of low fetal fraction before noninvasive prenatal testing

2021 ◽  
Vol 104 (4) ◽  
pp. 003685042110523
Author(s):  
Liang Hu ◽  
Yuanyuan Pei ◽  
Xiaojin Luo ◽  
Lijuan Wen ◽  
Hui Xiao ◽  
...  
Keyword(s):  
Complete Blood Count ◽  
Factor Model ◽  
Cohort Analysis ◽  
Protein A ◽  
Prenatal Testing ◽  
Maternal Weight ◽  
Free T4 ◽  
Noninvasive Prenatal Testing ◽  
Predictive Method ◽  
Fetal Fraction

Objective: To investigate factors associated with fetal fraction and to develop a new predictive method for low fetal fraction before noninvasive prenatal testing. Methods: The study was a retrospective cohort analysis based on the results of noninvasive prenatal testing, complete blood count, thyroxin test, and Down's syndrome screening during the first or second trimester in 14,043 pregnant women. Random forests algorithm was applied to predict the low fetal fraction status (fetal fraction < 4%) through individual information and laboratory records. The performance of the model was evaluated and compared to predictions using maternal weight. Results: Of 14,043 cases, maternal weight, red blood cell, hemoglobin, and free T3 were significantly negatively correlated with fetal fraction while gestation age, free T4, pregnancy-associated plasma protein-A, alpha-fetoprotein, unconjugated estriol, and β-human chorionic gonadotropin were significantly positively correlated with fetal fraction. Compared to predictions using maternal weight as an isolated parameter, the model had a higher area under the curve of receiver operating characteristic and overall accuracy. Conclusions: The comprehensive predictive method based on combined multiple factors was more effective than a single-factor model in low fetal fraction status prediction. This method can provide more pretest quality control for noninvasive prenatal testing.

scholarly journals A comprehensive predictive method for low fetal fraction in noninvasive prenatal screening

2020 ◽  
Author(s):  
Liang Hu ◽  
Yuanyuan Pei ◽  
Xiaojin Luo ◽  
Lijuan Wen ◽  
Hui Xiao ◽  
...  
Keyword(s):  
Prenatal Screening ◽  
Complete Blood Count ◽  
Factor Model ◽  
Cohort Analysis ◽  
Maternal Weight ◽  
Test Quality ◽  
Free T4 ◽  
Noninvasive Prenatal Screening ◽  
Predictive Method ◽  
Fetal Fraction

Abstract Background The study was a retrospective cohort analysis based on the results of noninvasive prenatal screening (NIPS), complete blood count, thyroxin test and Down’s syndrome screening in first or second trimester from 14043 pregnant women. Random forests algorithm was applied to predict the low fetal fraction of cell free DNA (with FF lower than 10th percentile) through individual and laboratory information. Performance of the model was evaluated and compared to prediction using maternal weight.To investigate factors associated with lower FF in the NIPS and to develop a new predictive method for low FF before NIPS. Results Of 14043 cases, maternal weight, RBC, HGB and free T3 were significantly negative correlated with FF while gestation age, free T4, PAPP-A, AFP, uE3 and β-hCG were significantly positive correlated with FF. Compared to prediction using maternal weight as isolated parameter, the model has a higher area under curve(AUC) of Receiver Operating Characteristic (ROC) and overall accuracy. Conclusions The comprehensive predictive method based on combined multiple factors was more effective than single-factor model in low FF status prediction. This method can provide more information for clinical choice and pre-test quality control of NIPS.

scholarly journals An online tool for fetal fraction prediction based on direct size distribution analysis of maternal cell-free DNA

BioTechniques ◽  
2020 ◽  
Author(s):  
Luca Bedon ◽  
Josef Vuch ◽  
Simeone Dal Monego ◽  
Germana Meroni ◽  
Vanna Pecile ◽  
...  
Keyword(s):  
Size Distribution ◽  
Prenatal Testing ◽  
Distribution Analysis ◽  
Blood Draw ◽  
Noninvasive Prenatal Testing ◽  
Cell Free Dna ◽  
Maternal Cell ◽  
Fetal Dna ◽  
Free Dna ◽  
Fetal Fraction

The discovery of circulating fetal DNA in the plasma of pregnant women has greatly promoted advances in noninvasive prenatal testing. Screening performance is enhanced with higher fetal fraction and analysis of samples whose fetal DNA fraction is lower than 4% are unreliable. Although current approaches to fetal fraction measurement are accurate, most of them are expensive and time consuming. Here we present a simple and cost-effective solution that provides a quick and reasonably accurate fetal fraction by directly evaluating the size distribution of circulating DNA fragments in the extracted maternal cell-free DNA. The presented approach could be useful in the presequencing stage of noninvasive prenatal testing to evaluate whether the sample is suitable for the test or a repeat blood draw is recommended.

Validation of Noninvasive Prenatal Testing for Fetal Aneuploidies and Microdeletions Down to 2% Fetal Fraction [20O]

2019 ◽  
Vol 133 (1) ◽  
pp. 167S-167S
Author(s):  
Yoshiko Mito ◽  
Jonathan McCafferty ◽  
Robert Calder ◽  
Xingwu Lu ◽  
Susan Gross ◽  
...  
Keyword(s):  
Prenatal Testing ◽  
Noninvasive Prenatal Testing ◽  
Fetal Aneuploidies ◽  
Fetal Fraction

scholarly journals Unexplained False Negative Results in Noninvasive Prenatal Testing: Two Cases Involving Trisomies 13 and 18

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
R. Hochstenbach ◽  
G. C. M. L. Page-Christiaens ◽  
A. C. C. van Oppen ◽  
K. D. Lichtenbelt ◽  
J. J. T. van Harssel ◽  
...  
Keyword(s):  
False Negative ◽  
Prenatal Testing ◽  
High Sensitivity ◽  
Trisomy 13 ◽  
Maternal Weight ◽  
Noninvasive Prenatal Testing ◽  
Root Cause ◽  
Negative Results ◽  
False Negative Results ◽  
Negative Case

Noninvasive prenatal testing (NIPT) validation studies show high sensitivity and specificity for detection of trisomies 13, 18, and 21. False negative cases have rarely been reported. We describe a false negative case of trisomy 13 and another of trisomy 18 in which NIPT was commercially marketed directly to the clinician. Both cases came to our attention because a fetal anatomy scan at 20 weeks of gestation revealed multiple anomalies. Karyotyping of cultured amniocytes showed nonmosaic trisomies 13 and 18, respectively. Cytogenetic investigation of cytotrophoblast cells from multiple placental biopsies showed a low proportion of nontrisomic cells in each case, but this was considered too small for explaining the false negative NIPT result. The discordant results also could not be explained by early gestational age, elevated maternal weight, a vanishing twin, or suboptimal storage or transport of samples. The root cause of the discrepancies could, therefore, not be identified. The couples involved experienced difficulties in accepting the unexpected and late-adverse outcome of their pregnancy. We recommend that all parties involved in caring for couples who choose NIPT should collaborate to clarify false negative results in order to unravel possible biological causes and to improve the process of patient care from initial counseling to communication of the result.

scholarly journals Adverse perinatal outcomes are more frequent in pregnancies with a low fetal fraction result on noninvasive prenatal testing

2016 ◽  
Vol 36 (3) ◽  
pp. 210-215 ◽  
Author(s):  
Iris Krishna ◽  
Martina Badell ◽  
Tammy L. Loucks ◽  
Michael Lindsay ◽  
Amber Samuel
Keyword(s):  
Perinatal Outcomes ◽  
Prenatal Testing ◽  
Noninvasive Prenatal Testing ◽  
Adverse Perinatal Outcomes ◽  
Fetal Fraction

scholarly journals Validation of Copy Number Variants Detection from Pregnant Plasma Using Low-Pass Whole-Genome Sequencing in Noninvasive Prenatal Testing-Like Settings

Diagnostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 569
Author(s):  
Michaela Hyblova ◽  
Maria Harsanyova ◽  
Diana Nikulenkov-Grochova ◽  
Jitka Kadlecova ◽  
Marcel Kucharik ◽  
...  
Keyword(s):  
Copy Number ◽  
Copy Number Variants ◽  
Prenatal Testing ◽  
Detection Algorithm ◽  
Detection Sensitivity ◽  
Clinical Settings ◽  
Noninvasive Prenatal Testing ◽  
Low Pass ◽  
Cnv Detection ◽  
Fetal Fraction

Detection of copy number variants as an integral part of noninvasive prenatal testing is increasingly used in clinical practice worldwide. We performed validation on plasma samples from 34 pregnant women with known aberrations using cell-free DNA sequencing to evaluate the sensitivity for copy number variants (CNV) detection using an in-house CNV fraction-based detection algorithm. The sensitivity for CNVs smaller than 3 megabases (Mb), larger than 3Mb, and overall was 78.57%, 100%, and 90.6%, respectively. Regarding the fetal fraction, detection sensitivity in the group with a fetal fraction of less than 10% was 57.14%, whereas there was 100% sensitivity in the group with fetal fraction exceeding 10%. The assay is also capable of indicating whether the origin of an aberration is exclusively fetal or fetomaternal/maternal. This validation demonstrated that a CNV fraction-based algorithm was applicable and feasible in clinical settings as a supplement to testing for common trisomies 21, 18, and 13.

Sign in / Sign up

Export Citation Format

Share Document