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Cell-free Fetal DNA (cell-free + fetal_dna)
Selected AbstractsCell-free fetal DNA (SRY locus) concentration in maternal plasma is directly correlated to the time elapsed from the onset of preeclampsia to the collection of bloodPRENATAL DIAGNOSIS, Issue 4 2004Antonio Farina MD Abstract Objective To determine (1) if fetal DNA (fDNA) in the maternal circulation in women affected by preeclampsia correlates with the time elapsed from the onset of symptoms to the time of blood collection, and (2) if the inclusion of this variable improves the discrimination between affected and unaffected patients by using fDNA distributions. Methods Plasma were collected from 34 women at 33.7 ± 3.9 weeks' gestation, affected by preeclampsia, and bearing a single male fetus. fDNA was extracted from 1.5-mL plasma samples, and the SRY and ,-globin gene were analyzed by real-time quantitative PCR. MoMs (multiple of the control median) were calculated by using a log equation of 102 normal cases. Log MoMs were then plotted against the time elapsed from onset of symptoms to blood collection (expressed in days) by means of a log-linear regression. Adjusted MoMs were then calculated. ROC curves were used to test the discrimination obtained by using adjusted MoMs. Results The median MoMs of controls and preeclamptic patients were 1.00 ± 1.53 and 2.62 ± 2.70 respectively. By plotting log MoM fDNA against the time elapsed from onset of symptoms to blood collection, we found a significant positive correlation, (p -value < 0.001, R2 = 0.55, F = 38.97, from 1 to 50 days). The adjusted median fDNA MoM was 2.66 ± 2.50. Areas under the curves, as estimated by ROC curves, were 76.7 for unadjusted and 85.5 for adjusted MoMs respectively (p -value = 0.02). Conclusions The effect of a further covariate showed that (1) fDNA passage from trophoblasts to maternal circulation for unit of time is proportional to the duration of the damage and that (2) increased discrimination can be obtained in comparison to normal subjects. Copyright © 2004 John Wiley & Sons, Ltd. [source] Recent advances in non-invasive prenatal DNA diagnosis through analysis of maternal bloodJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 6 2007Akihiko Sekizawa Abstract Prenatal diagnosis of aneuploidy and single-gene disorders is usually performed by collecting fetal samples through amniocentesis or chorionic villus sampling. However, these invasive procedures are associated with some degree of risk to the fetus and/or mother. Therefore, in recent years, considerable effort has been made to develop non-invasive prenatal diagnostic procedures. One potential non-invasive approach involves analysis of cell-free fetal DNA in maternal plasma or serum. Another approach utilizes fetal cells within the maternal circulation as a source of fetal DNA. At the present time, fetal gender and fetal RhD blood type within RhD-negative pregnant women can be reliably determined through analysis of maternal plasma. Furthermore, genetic alterations can be diagnosed in the maternal plasma when the mother does not have the alterations. However, the diagnosis of maternally inherited genetic disease and aneuploidy is limited using this approach. Non-invasive prenatal diagnosis through examination of intact fetal cells circulating within maternal blood can be used to diagnose a full range of genetic disorders. Since only a limited number of fetal cells circulate within maternal blood, procedures to enrich the cells and enable single cell analysis with high sensitivity are required. Recently, separation methods, including a lectin-based method and autoimage analyzing, have been developed, which have improved the sensitivity of genetic analysis. This progress has supported the possibility of non-invasive prenatal diagnosis of genetic disorders. In the present article, we discuss recent advances in the field of non-invasive prenatal diagnosis. [source] Noninvasive Prenatal Diagnosis: Past, Present, and FutureMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 6 2009Christian Litton MD Abstract The presence of fetal cells in the maternal circulation was first noted by Georg Schmorl when he documented the presence of multinucleated syncytial giant cells of placental origin in the lung tissue of women who had died from complications of eclampsia. In the intervening century, advances in cellular and molecular biology further elucidated both the physiology and pathophysiology of communication within the fetomaternal unit. This concept is at the foundation of the rapidly expanding field of noninvasive prenatal diagnosis. However, the clinical utility of this phenomenon had been limited until the presence of cell-free fetal DNA circulating in the maternal plasma was reported in 1997 and fetal messenger RNA was demonstrated to circulate in the maternal plasma in 2000. These circulating nucleic acids are found free-floating in the maternal plasma, unencumbered by a surrounding fetal cell. The analysis of these 3 fetal markers (fetal cells, cell-free fetal DNA, and fetal messenger RNA) for diagnostic and screening purposes is now being developed. The scope of noninvasive prenatal diagnosis is not limited to only the diagnosis of fetal genetic traits and aneuploidies. Recently, researchers have focused their investigations on the role of cell-free fetal DNA and fetal messenger RNA in preeclampsia, intrauterine growth restriction, and preterm labor. These biomarkers, the result of inherent placental dysfunction or the byproducts of placental trophoblastic apoptosis, may allow for improvements in the diagnosis and management of high-risk pregnancies. Mt Sinai J Med 76:521-528, 2009. © 2009 Mount Sinai School of Medicine [source] Fetal sex determination using circulating cell-free fetal DNA (ccffDNA) at 11 to 13 weeks of gestationPRENATAL DIAGNOSIS, Issue 10 2010Ranjit Akolekar Abstract Objective To examine the performance of a mass spectrometry-based detection platform using three Y-chromosome sequences for fetal sex determination from circulating cell-free fetal DNA (ccffDNA) in maternal blood in the first trimester of pregnancy. Methods We extracted ccffDNA for the determination of fetal sex from stored maternal plasma obtained at 11 to 13 weeks' gestation from singleton pregnancies with documented fetal gender. Mass spectrometry was used to examine 236 specimens for the presence of three Y-chromosome sequences (SRY, DBY and TTTY2). The sample was classified as male, female or inconclusive depending on the detection of three, one/none and two sequences, respectively. Results Three (1.3%) of the 236 cases were classified as invalid due to the absence of a well-defined spectral peak for TGIF and 22 (9.3%) were reported as inconclusive. In the 211 cases with a valid result, the fetal sex was correctly identified in 90 of 91 male babies and 119 of 120 female babies giving an accuracy of 99.1% and sensitivity and specificity for prediction of male fetuses of 98.9 and 99.2%, respectively. Conclusion Fetal sex determination can be accurately determined from maternal ccffDNA in the first trimester of pregnancy using mass spectrometry analysis. Copyright © 2010 John Wiley & Sons, Ltd. [source] Management of red cell alloimmunisation in pregnancy: the non-invasive monitoring of the diseasePRENATAL DIAGNOSIS, Issue 7 2010Sebastian Illanes Abstract Haemolytic disease of the fetus and newborn (HDFN) due to red cell alloimmunization was a significant cause of fetal and neonatal morbidity and mortality until the introduction of anti-D immunoglobulin, which has dramatically changed the incidence of the disease. However, it is still a major problem in affected pregnancies. The emphasis of current clinical management has shifted from an invasive approach to non-invasive monitoring of the disease. The key elements of the modern management are determining which fetuses are at risk of HDFN with the use of cell-free fetal DNA in maternal plasma (fetal RHD genotype) and the follow-up of antigen positive fetuses by Doppler ultrasonography to detect anaemia severe enough to need treatment. When anaemia is suspected, an invasive approach is still required in a timely manner for confirmation of the degree of anaemia and to administer blood transfusions. This non-invasive approach prevents unnecessary administration of human-derived blood products, with the consequent ethical and cost implications and most importantly avoids iatrogenic conversion of mild to severe disease by avoiding need for techniques such as amniocentesis. The potential problem of the non-invasive approach is the reduction in the total number of invasive procedures, with the subsequent difficulty of maintaining the skills required to perform them. Copyright © 2010 John Wiley & Sons, Ltd. [source] Comparison of activin A and cell-free fetal DNA levels in maternal plasma from patients at high risk for preeclampsiaPRENATAL DIAGNOSIS, Issue 13 2006Claude Henri Diesch Abstract Objectives We examined the concentration of activin A in a prospective manner before the clinical manifestation of preeclampsia and compared the data with those of cell-free fetal DNA in the maternal plasma. Methods The levels of activin A were analysed by enzyme-linked immunosorbent assay (ELISA) for pregnant women: (1) with preeclampsia (n = 34) in the third-trimester and normal controls (n = 44); and (2) at-risk of preeclampsia in the second-trimester (n = 15) as indicated by uterine artery Doppler and normal controls (n = 68). Correlation between activin A level and cell-free fetal DNA level was examined using the Spearman rank test. Results The level of plasma activin A was significantly higher in the preeclamptic samples (12.056 vs 7.068 ng/mL, p = 0.000). The increase in the activin A concentration was observed prior to the onset of preeclampsia (3.483 vs 1.324 ng/mL, p = 0.000). This increase in activin A correlated significantly with the increased level of cell-free fetal DNA, in the maternal circulation prior to the onset of preeclampsia (r = 0.977, p = 0.000). Conclusion Our data suggest that circulatory activin A could be an independent biomarker for the early identification and monitoring of preeclampsia. Copyright © 2006 John Wiley & Sons, Ltd. [source] | ||||||||||