Free fetal dna

BACKGROUND: The risk of unexplained fetal death or stillbirth increases late in pregnancy suggesting that placental aging is an etiological factor. Aging is associated with oxidative damage to DNA, RNA and lipids. We hypothesized that placentas at more than 41 completed weeks of gestation (late-term) would show changes consistent with aging that would also be present in placentas associated with stillbirths. OBJECTIVE: We sought to determine whether placentas from late-term pregnancies and unexplained stillbirth show oxidative damage and other biochemical signs of aging...

OBJECTIVES: The primary aim was to compare the screening performance for Trisomy 21, of standard combined first trimester screening with referral to invasive testing at a cut-off at 1 in 300, with a contingent testing, consisting of referral to invasive testing at a 1 in 100 cut-off and referral to cell-free DNA (cfDNA) testing for a risk between 1 in 100 and 1 in 1000. METHODS: Singleton pregnant women with a combined first trimester risk ≥ 1 in 1000 were consecutively recruited from two Danish hospitals between August 2014 and May 2015...

OBJECTIVE: To estimate the risk for fetal trisomy 21 (T21) and other chromosomal abnormalities at 11-13 week's gestation using computational intelligence classification methods. METHODS: As a first step, we train the artificial neural networks with 72054 euploid pregnancies, 295 cases of T21 and 305 of other chromosomal abnormalities (OCA). Then, we sort the cases into two categories of "no-risk" and "risk". The cases of "no-risk" are no further examined, while the cases with "risk" are forwarded in Stage 2 for further examination where we classify them in three types of risk, namely "no-risk", "moderate-risk" and "high-risk"...

OBJECTIVE: Prenatal screening for trisomy 21 is a standard of care. Emerging cell-free fetal DNA (cffDNA) technologies can improve screening performance, but they are expensive. This study was conducted to propose a contingent screening model that would incorporate cffDNA technology, would remain affordable, and could be applied equitably in a publically funded system. METHODS: Using performance and cost parameters from published literature, four prenatal screening strategies were compared...

Although suggested that "fetal" cell-free DNA (cfDNA) is derived from trophoblast cells, the exact origin is unclear. The studies in this report sought to demonstrate that placental tissue releases cfDNA in parallel with cell death, that the size range of cfDNA is similar to that found in maternal plasma, and that the cfDNA fragments are able to stimulate a proinflammatory cytokine response. Placentas were harvested from near term pregnant CD-1 mice and cultured in DMEM/Ham's F12/FBS media in 8% or 21% O2. After centrifugation to remove cells and cellular debris, the cfDNA was extracted from the media and quantified by DNA spectrophotometry...

PurposeThe aim of this study was to assess the performance of a noninvasive prenatal screening (NIPS) assay for accurate fetal genotyping of pregnancies at genetic risk for autosomal recessive nonsyndromic hearing loss (ARNSHL).MethodsA total of 80 pregnant couples carrying known mutations in either the GJB2 or SLC26A4 genes associated with a risk for ARNSHL were recruited to the study. Fetal amniocyte samples were genotyped by invasive prenatal screening (IPS), whereas the cell-free fetal DNA present in maternal plasma samples was genotyped using a novel NIPS method based on circulating single-molecule amplification and resequencing technology (cSMART)...

AIMS: Thalassemia is a dangerous hematolytic genetic disease. In south China, ∼24% Chinese carry alpha-thalassemia or beta-thalassemia gene mutations. Given the fact that the invasive sampling procedures can only be performed by professionals in experienced centers, it may increase the risk of miscarriage or infection. Thus, most people are worried about the invasive operation. As such, a noninvasive and accurate prenatal diagnosis is needed for appropriate genetic counseling for families with high risks...

This paper contains a joint position of the Polish Gynecological Society and Polish Human Genetics Society on the cell-free fetal DNA testing in prenatal diagnosis. We present situations where the cell-free fetal DNA testing should be applied and cases in which performing of the test is not useful. We indicate what diagnostic steps should be performed before the test and how the test results should be interpreted and followed.

INTRODUCTION: Biological factors are known to influence the fetal fraction (FF) of cell-free DNA and may also influence the accuracy of non-invasive prenatal testing. MATERIAL AND METHODS: NIPT from 5,267 mixed risk women across three specialist clinics in Australia were analysed. Multivariable regression analysis was used to determine whether maternal characteristics, ultrasound and placental biomarkers affect FF and test accuracy. RESULTS: FF ranged from 4% - 37% (mean 11...

Non-invasive prenatal testing (NIPT) of cell-free DNA in maternal plasma, which is a mixture of maternal DNA and a low percentage of fetal DNA, can detect fetal aneuploidies using massively parallel sequencing. Because of the low percentage of fetal DNA, methods with high sensitivity and precision are required. However, sequencing variation lowers sensitivity and hampers detection of trisomy samples. Therefore, we have developed three algorithms to improve sensitivity and specificity: the chi-squared-based variation reduction (χ(2)VR), the regression-based Z-score (RBZ) and the Match QC score...

Massively parallel sequencing (MPS) technology has become increasingly available and has been widely used to screen for trisomies 21, 18, and 13 in singleton pregnancies. This study assessed the performance of MPS testing of cell-free fetal DNA (cffDNA) from maternal plasma for trisomies 21, 18, and 13 in twin pregnancies. Ninety-two women with twin pregnancies were recruited. The results were identified through karyotypes of amniocentesis or clinical examination and follow-up of the neonates. Fluorescent in-situ hybridization was used to examine the placentas postnatally in cases of false-positive results...

Clinical observations and animal experiments have shown that higher fetal DNA in maternal plasma could participate on the pathogenesis of preeclampsia. The understudied factor that could participate in interindividual variability in cell-free DNA is enzymatic activity of deoxyribonuclease (DNase). We have found that healthy pregnant animals have higher plasma DNase activity than healthy pregnant women. Injection of cell-free fetal DNA into pregnant animals had no effect on DNase activity. Interspecies differences in DNase activity should be considered in animal experiments focusing on the role of fetal DNA in preeclampsia and cell-free DNA in other disease models...

NIPT - implentation, counselling and ethical issues It is today possible to analyze cell-free fetal DNA from a blood sample from the pregnant woman, i.e. non-invasive prenatal testing, NIPT. Thus, by a simple blood test from the mother you can detect trisomy 13, 18 and 21 in the fetus with high accuracy. However, NIPT is not a diagnostic test and a positive result should be confirmed by an invasive test, like chorionic villus sampling or amniocentesis. There are national guidelines from the Swedish Society of Obstetrics and Gynaecology (SFOG) on how to implement and use NIPT for trisomies in the Swedish health care...

The optimal management of the D-negative pregnant woman is now based on the non-invasive antenatal prediction of fetal D-blood group by cell-free DNA (cfDNA) in maternal plasma, with targeted prophylaxis for women carrying RHD-positive fetuses. This provides the optimal care for D-negative pregnant women and has been adopted as the standard approach in a growing number of countries around the world. This paper is the result of a consensus meeting of the Canadian National Rh Working Group, an interdisciplinary group formed to review the current status of fetal RHD genotyping based on cfDNA in Canada...

BACKGROUND: The availability of non-invasive prenatal testing (NIPT) for aneuploidies is expanding rapidly throughout the world. Training health professionals to offer NIPT in a way that supports informed choice is essential for implementation. The aim of this study was to develop and evaluate a training package for health professionals to support the introduction of NIPT into clinical practice. METHODS: Training on NIPT was offered to health professionals, primarily midwives, involved in Down syndrome screening and testing in eight hospitals located in England and Scotland as part of a research study evaluating the implementation of NIPT in the UK National Health Service...

The discovery of cell-free DNA fetal (cff DNA) in maternal plasma during pregnancy provides a novel perspective for the development of non‑invasive prenatal diagnosis (NIPD). Against the background of maternal DNA, the use of the relatively low concentration of cff DNA is limited in NIPD. Therefore, in order to overcome the complication of the background of maternal DNA and expand the scope of cff DNA application in clinical practice, it is necessary to identify novel universal fetal‑specific DNA markers...

OBJECTIVE: In this study, we expanded conventional cell-free fetal DNA (cfDNA)-based non-invasive prenatal testing (NIPT) to cover the entire genome. We aimed to compare the performance of the two tests in a large general population of pregnant women, in order to assess the clinical utility of the genome-wide screening. METHOD: Genome-wide cfDNA analysis was offered to 12 114 pregnant women undergoing NIPT for common fetal aneuploidy. Sequencing data were analyzed using an algorithm optimized to identify aneuploidies and subchromosomal aberrations...

OBJECTIVES: To investigate fetal cases identified at our institution to determine whether an enlarged cavum septi pellucidi or cavum vergae is associated with other fetal abnormalities and whether its presence warrants more detailed investigation of the fetus. METHODS: In a retrospective study, 15 high- and low-risk patients undergoing prenatal sonography who had an enlarged cavum septi pellucidi or cavum vergae identified were reviewed. Data were collected for the sonographic study indication, gestation age at diagnosis of a prominent cavum, and associated anomalies...

OBJECTIVE: Aim of the study was to assess the percentage and type of anomalies (structural and chromosomal) that can be detected at an early scan performed at 12-13 weeks' gestation, as opposed to the present screening policy (20 -week scan). METHODS: Sonographers accredited for the nuchal translucency (NT) measurement were asked, after additional training, to participate into the study. The early scans were performed according to a protocol, in six ultrasound practices and 2 referral centers in the Northeast of the Netherlands...

OBJECTIVE: To review clinical validation or implementation studies of maternal blood cell-free (cf) DNA analysis and define the performance of screening for fetal trisomies 21, 18 and 13 and sex chromosome aneuploidies. DATA SOURCES: Searches of PubMed, Embase and the Cochrane library were performed to identify all peer-reviewed articles on cfDNA testing in screening for aneuploidies between January 2011, when the first such study was published and 31 December 2016...