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 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 High-throughput fetal fraction amplification increases analytical performance of noninvasive prenatal screening

2020 ◽  
Author(s):  
Noah C. Welker ◽  
Albert K. Lee ◽  
Rachel A. S. Kjolby ◽  
Helen Y. Wan ◽  
Mark R. Theilmann ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Prenatal Screening ◽  
Chromosomal Abnormalities ◽  
High Body Mass Index ◽  
Average Increase ◽  
Noninvasive Prenatal Screening ◽  
Maternal Cell ◽  
Key Driver ◽  
Fetal Fraction ◽  
Test Failure

Abstract Purpose The percentage of a maternal cell-free DNA (cfDNA) sample that is fetal-derived (the fetal fraction; FF) is a key driver of the sensitivity and specificity of noninvasive prenatal screening (NIPS). On certain NIPS platforms, >20% of women with high body mass index (and >5% overall) receive a test failure due to low FF (<4%). Methods A scalable fetal fraction amplification (FFA) technology was analytically validated on 1264 samples undergoing whole-genome sequencing (WGS)–based NIPS. All samples were tested with and without FFA. Results Zero samples had FF < 4% when screened with FFA, whereas 1 in 25 of these same patients had FF < 4% without FFA. The average increase in FF was 3.9-fold for samples with low FF (2.3-fold overall) and 99.8% had higher FF with FFA. For all abnormalities screened on NIPS, z-scores increased 2.2-fold on average in positive samples and remained unchanged in negative samples, powering an increase in NIPS sensitivity and specificity. Conclusion FFA transforms low-FF samples into high-FF samples. By combining FFA with WGS–based NIPS, a single round of NIPS can provide nearly all women with confident results about the broad range of potential fetal chromosomal abnormalities across the genome.

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