Low‐molecular‐weight heparin associated with reduced fetal fraction and subsequent false‐negative cell‐free DNA test result for trisomy 21

Ma, Gwo‐Chin; Wu, Wan‐Ju; Lee, Mei‐Hui; Lin, Yu-Hsiang; Chen, Ming

doi:10.1002/uog.17473

Cited by 32 publications

(19 citation statements)

References 11 publications

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“…A low percentage of placental DNA ("fetal fraction"), which is positively correlated with gestational age and the biochemical parameters PAPP-A and PIGF and negatively correlated with maternal body weight and age and reproductive measures, is often the cause [62 -64]. Treatment of pregnant women with heparin also often results in a reduced amount of placental DNA [65]. In the group of test failures, a significantly increased rate of fetuses with trisomy 13, trisomy 18 or a triploidy but not trisomy 21 can be observed [47,62] so that an early detailed fetal scan and if necessary a diagnostic procedure are indicated in these cases.…”

Section: Quality Parametersmentioning

confidence: 99%

DEGUM, ÖGUM, SGUM and FMF Germany Recommendations for the Implementation of First-Trimester Screening, Detailed Ultrasound, Cell-Free DNA Screening and Diagnostic Procedures

Kozlowski¹,

Burkhardt

Gembruch³

et al. 2018

Ultraschall in Med

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First-trimester screening between 11 + 0 and 13 + 6 weeks with qualified prenatal counseling, detailed ultrasound, biochemical markers and maternal factors has become the basis for decisions about further examinations. It detects numerous structural and genetic anomalies. The inclusion of uterine artery Doppler and PlGF screens for preeclampsia and fetal growth restriction. Low-dose aspirin significantly reduces the prevalence of severe preterm eclampsia. Cut-off values define groups of high, intermediate and low probability. Prenatal counseling uses detection and false-positive rates to work out the individual need profile and the corresponding decision: no further diagnosis/screening - cell-free DNA screening - diagnostic procedure and genetic analysis. In pre-test counseling it must be recognized that the prevalence of trisomy 21, 18 or 13 is low in younger women, as in submicroscopic anomalies in every maternal age. Even with high specificities, the positive predictive values of screening tests for rare anomalies are low. In the general population trisomies and sex chromosome aneuploidies account for approximately 70 % of anomalies recognizable by conventional genetic analysis. Screen positive results of cfDNA tests have to be proven by diagnostic procedure and genetic diagnosis. In cases of inconclusive results a higher rate of genetic anomalies is detected. Procedure-related fetal loss rates after chorionic biopsy and amniocentesis performed by experts are lower than 1 to 2 in 1000. Counseling should include the possible detection of submicroscopic anomalies by comparative genomic hybridization (array-CGH). At present, existing studies about screening for microdeletions and duplications do not provide reliable data to calculate sensitivities, false-positive rates and positive predictive values.

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Section: Quality Parametersmentioning

confidence: 99%

DEGUM, ÖGUM, SGUM and FMF Germany Recommendations for the Implementation of First-Trimester Screening, Detailed Ultrasound, Cell-Free DNA Screening and Diagnostic Procedures

Kozlowski¹,

Burkhardt

Gembruch³

et al. 2018

Ultraschall in Med

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show abstract

“…Several maternal medical conditions have been shown to either directly affect the interpretation of test results or contribute to test failure. These include vitamin B12 deficiency, 9 autoimmune disease, [10][11][12][13][14] and intrahepatic cholestasis of pregnancy (ICP). 15 These diseases and/or their treatments affect either the quantity or the quality of the circulating maternal DNA fragments, which comprise the majority of the blood sample.…”

Section: Maternal Medical Conditions That Can Affect Interpretation Omentioning

confidence: 99%

Cherchez la femme: maternal incidental findings can explain discordant prenatal cell-free DNA sequencing results

Bianchi

2018

Genetics in Medicine

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Circulating DNA fragments in a pregnant woman's plasma derive from three sources: placenta, maternal bone marrow, and fetus. Prenatal sequencing to noninvasively screen for fetal chromosome abnormalities is performed on this mixed sample; results can therefore reflect the maternal as well as the fetoplacental DNA. Although it is recommended that pretest counseling include the possibility of detecting maternal genomic imbalance, this seldom occurs. Maternal abnormalities that can affect a prenatal screening test result include disorders that affect the size and metabolism of DNA, such as B12 deficiency, autoimmune disease, and intrahepatic cholestasis of pregnancy. Similarly, maternal tumors, both benign and malignant, can release DNA fragments that contain duplications or deletions. Bioinformatics algorithms can subsequently interpret the raw sequencing data incorrectly, resulting in false-positive test reports of fetal monosomies or test failures. Maternal sex-chromosome abnormalities, both constitutional and somatic, can generate results that are discordant with fetal ultrasound examination or karyotype. Maternal copy-number variants and mosaicism for autosomal aneuploidies can also skew interpretation. A maternal etiology should therefore be considered in the differential diagnosis of prenatal cell-free DNA test failures, false-positive and false-negative sequencing results. Further study is needed regarding the clinical utility of reporting maternal incidental findings.

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“…We read with great interest the recent Letter to the Editor by Ma et al . in which the case of a patient treated with low‐molecular‐weight heparin (LMWH) for protein‐S deficiency is reported.…”

mentioning

confidence: 99%

“…We read with great interest the recent Letter to the Editor by Ma et al 1 in which the case of a patient treated with low-molecular-weight heparin (LMWH) for protein-S deficiency is reported. The patient had an initial non-invasive prenatal cell-free DNA (cfDNA) test for aneuploidy with a false-negative result due to low fetal fraction (1.6%).…”

mentioning

confidence: 99%

Re: Low‐molecular‐weight heparin associated with reduced fetal fraction and subsequent false‐ negative cell‐free DNA test result for trisomy 21

Dabi

Costa

Benachi

2018

Ultrasound in Obstet & Gyne

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Low‐molecular‐weight heparin associated with reduced fetal fraction and subsequent false‐negative cell‐free DNA test result for trisomy 21

Cited by 32 publications

References 11 publications

DEGUM, ÖGUM, SGUM and FMF Germany Recommendations for the Implementation of First-Trimester Screening, Detailed Ultrasound, Cell-Free DNA Screening and Diagnostic Procedures

DEGUM, ÖGUM, SGUM and FMF Germany Recommendations for the Implementation of First-Trimester Screening, Detailed Ultrasound, Cell-Free DNA Screening and Diagnostic Procedures

Cherchez la femme: maternal incidental findings can explain discordant prenatal cell-free DNA sequencing results

Re: Low‐molecular‐weight heparin associated with reduced fetal fraction and subsequent false‐ negative cell‐free DNA test result for trisomy 21

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