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Diana W. Bianchi - One of the best experts on this subject based on the ideXlab platform.
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review cell free Fetal DNA in the maternal circulation as an indication of placental health and disease
Placenta, 2014Co-Authors: Elizabeth S Taglauer, Louise Wilkinshaug, Diana W. BianchiAbstract:In human pregnancy, the constant turnover of villous trophoblast results in extrusion of apoptotic material into the maternal circulation. This material includes Cell-Free (cf) DNA, which is commonly referred to as “Fetal”, but is actually derived from the placenta. As the release of cf DNA is closely tied to placental morphogenesis, conditions associated with abnormal placentation, such as preeclampsia, are associated with high DNA levels in the blood of pregnant women. Over the past five years, the development and commercial availability of techniques of massively parallel DNA sequencing have facilitated noninvasive prenatal testing (NIPT) for Fetal trisomies 13, 18, and 21. Clinical experience accrued over the past two years has highlighted the importance of the Fetal fraction (ff) in cf DNA analysis. The ff is the amount of Cell-Free Fetal DNA in a given sample divided by the total amount of Cell-Free DNA. At any gestational age, ff has a bell-shaped distribution that peaks between 10 and 20% at 10–21 weeks. ff is affected by maternal body mass index, gestational age, Fetal aneuploidy, and whether the gestation is a singleton or multiple. In approximately 0.1% of clinical cases, the NIPT result and a subsequent diagnostic karyotype are discordant; confined placental mosaicism has been increasingly reported as an underlying biologic explanation. Cell-Free Fetal DNA is a new biomarker that can provide information about the placenta and potentially be used to predict clinical problems. Knowledge gaps still exist with regard to what affects production, metabolism, and clearance of feto-placental DNA.
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Cell-Free Fetal DNA levels in pregnancies conceived by IVF
Human Reproduction, 2005Co-Authors: Phillip D. Pan, Diana W. Bianchi, Jacob A Canick, Inga Peter, Geralyn Lambert-messerlian, Kirby L. JohnsonAbstract:BACKGROUND: Increased second-trimester levels of maternal serum HCG in IVF conceptions lead to an increased false-positive rate in Down syndrome screening. Increased levels of Cell-Free Fetal DNA (cffDNA) in maternal plasma have been correlated with increased HCG levels. Our aim was to determine whether cffDNA levels are elevated in IVF pregnancies compared with natural pregnancies. METHODS: Sixteen archived second-trimester serum samples from IVF pregnancies were matched with five control samples from naturally conceived pregnancies per case, all carrying a singleton male fetus. cffDNA concentrations were me asured by real-time PCR amplification of a Y chromosome sequence and compared with four standard second trimester serum screening markers (-fetoprotein, estriol, HCG and inhibin A). RESULTS: Mean cffDNA levels for cases and controls were 57.9 and 57.1 genome equivalents/ml, respectively (P = 0.95). Mean observed rank (from 1 to 6) of cffDNA was 3.625 in the IVF conceived group, compared with an expected value of 3.5 (P = 0.53). No significant correlations w ere observed between cffDNA and serum markers. CONCLUSIONS: IVF does not affect levels of cffDNA, which appears to be independent of traditional screening markers (e.g. HCG). Therefore, cffDNA can be used as an additional serum marker (e.g. Down syndrome screening) without adjustment for IVF pregnancies.
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Cell-Free Fetal DNA in the cerebrospinal fluid of women during the peripartum period
American Journal of Obstetrics and Gynecology, 2004Co-Authors: Robert M. Angert, Erik S. Leshane, Ralph W Yarnell, Kirby L. Johnson, Diana W. BianchiAbstract:Abstract Objective The purpose of this study was to determine whether Cell-Free Fetal DNA is detectable in the cerebrospinal fluid of women during pregnancy and after delivery. Study design Cerebrospinal fluid was collected from 39 women who underwent an indicated spinal anesthesia procedure. Twenty-six samples were from women who carried at least 1 male fetus, and 13 samples were from women with only a female fetus. DNA was analyzed with the use of real-time polymerase chain reaction for DYS-1 (which represented male Fetal DNA) and β-globin (which represented maternal and Fetal DNA). Results β-Globin DNA was detected in all cerebrospinal samples. DYS-1 gene sequences were detected in 4 cerebrospinal fluid samples from women who had male fetuses (2 samples were from women who underwent cesarean delivery of singleton pregnancies, 1 sample was from a triplet pregnancy, and 1 sample was from a woman after delivery). No male DNA was detected in the cerebrospinal fluid of women who carried female fetuses. Conclusion Male Fetal cells and/or Cell-Free Fetal DNA is detectable in the cerebrospinal fluid of some pregnant women or some women after delivery.
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evaluation of cell free Fetal DNA as a second trimester maternal serum marker of down syndrome pregnancy
Clinical Chemistry, 2003Co-Authors: Antonio Farina, Erik S. Leshane, Geralyn Lambertmesserlian, Jacob A Canick, Louis M Neveux, Glenn E Palomaki, Diana W. BianchiAbstract:Background: Second-trimester Cell-Free Fetal DNA (studied only in pregnancies with male fetuses) is higher in maternal serum samples from women carrying Down syndrome fetuses than in unaffected pregnancies. In this study we evaluated the potential performance of Fetal DNA as a screening marker for Down syndrome. Methods: Data on maternal serum Fetal DNA concentrations and the corresponding concentrations of the quadruple serum markers were available from 15 Down syndrome cases, each matched for gestational age and length of freezer storage, with 5 control samples. Analyte values were expressed as multiple(s) of the control or population median. Screening performance of Fetal DNA, both alone and when added to estimates of quadruple marker performance, was determined after modeling using univariate and multivariate gaussian distribution analysis. Results: The median Fetal DNA concentration in Down syndrome cases was 1.7 times higher than in controls. In univariate analysis, Fetal DNA gave a 21% detection rate at a 5% false-positive rate. When added to quadruple marker screening, Fetal DNA increased the estimated detection rate from 81% to 86% at a 5% false-positive rate. Conclusions: Cell-Free Fetal DNA, measured in maternal serum, can modestly increase screening performance above what is currently available in the second trimester. If and when maternal serum Fetal DNA can be measured in pregnancies with both male and female fetuses, the utility and cost-effectiveness of adding it as a Down syndrome screening marker should be assessed.
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maternal serum cell free Fetal DNA levels are increased in cases of trisomy 13 but not trisomy 18
Human Genetics, 2003Co-Authors: Tuangsit Wataganara, Erik S. Leshane, Antonio Farina, Jacob A Canick, Geralyn Messerlian, Diana W. BianchiAbstract:Cell-Free Fetal DNA in the maternal circulation is a potential noninvasive marker for Fetal aneuploidies. In previous studies with Y DNA as a Fetal-specific marker, levels of circulating Fetal DNA were shown to be elevated in women carrying trisomy 21 fetuses. The goal of this study was to determine whether Cell-Free Fetal DNA levels in the serum of pregnant women carrying fetuses with trisomies 13 or 18 are also elevated. Archived maternal serum samples from five cases of male trisomy 13 and five cases of male trisomy 18 were studied. Each case was matched for Fetal gender, gestational age, and duration of freezer storage to four or five control serum samples presumed to be euploid after newborn medical record review. Real-time quantitative polymerase chain reaction amplification of DYS1 was performed to measure the amount of male Fetal DNA present. Unadjusted median serum Fetal DNA concentrations were 97.5 GE/ml (genomic equivalents per milliliter; 29.2–187.0) for the trisomy 13 cases, 31.5 GE/ml (18.6–77.6) for the trisomy 18 cases, and 40.3 GE/ml (3.7–127.4) for the controls. Fetal DNA levels in trisomy 13 cases were significantly elevated (P=0.016) by analysis of variance of the ranks of values within each matched set. In contrast, Fetal DNA levels in trisomy 18 cases were no different from the controls (P=0.244). Second trimester maternal serum analytes currently used in screening do not identify fetuses at high risk for trisomy 13. Fetal DNA may facilitate noninvasive screening for trisomy 13 provided that a gender-independent Fetal DNA marker can be developed.
Mark Phillippe - One of the best experts on this subject based on the ideXlab platform.
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Cell-Free Fetal DNA Increases Prior to Labor at Term and in a Subset of Preterm Births.
Reproductive Sciences, 2020Co-Authors: Nardhy Gomez-lopez, Roberto Romero, George Schwenkel, Valeria Garcia-flores, Bogdan Panaitescu, Aneesha Varrey, Fatime Ayoub, Sonia S. Hassan, Mark PhillippeAbstract:Cell-Free Fetal DNA in the maternal circulation has been associated with the onset of labor at term. Moreover, clinical studies have suggested that Cell-Free Fetal DNA has value to predict pregnancy complications such as spontaneous preterm labor leading to preterm birth. However, a mechanistic link between Cell-Free Fetal DNA and preterm labor and birth has not been established. Herein, using an allogeneic mouse model in which a paternal green fluorescent protein (GFP) can be tracked in the fetuses, we established that Cell-Free Fetal DNA (Egfp) concentrations were higher in late gestation compared to mid-pregnancy and were maintained at increased levels during the onset of labor at term, followed by a rapid decrease after birth. A positive correlation between Cell-Free Fetal DNA concentrations and the number of GFP-positive pups was also observed. The increase in Cell-Free Fetal DNA concentrations prior to labor at term was not linked to a surge in any specific cytokine/chemokine; yet, specific chemokines (i.e., CCL2, CCL7, and CXCL2) increased as gestation progressed and maintained elevated levels in the postpartum period. In addition, Cell-Free Fetal DNA concentrations increased prior to systemic inflammation-induced preterm birth, which was associated with a strong cytokine response in the maternal circulation. However, Cell-Free Fetal DNA concentrations were not increased prior to intra-amniotic inflammation-induced preterm birth, but in this model, a mild inflammatory response was observed in the maternal circulation. Collectively, these findings suggest that an elevation in Cell-Free Fetal DNA concentrations in the maternal circulation precedes the physiological process of labor at term and the pathological process of preterm labor linked with systemic inflammation, but not that associated with intra-amniotic inflammation.
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Cell-Free Fetal DNA, Telomeres, and the Spontaneous Onset of Parturition
Reproductive Sciences, 2015Co-Authors: Mark PhillippeAbstract:Multiple previous reports have provided compelling support for the premise that spontaneous parturition is mediated by activation of inflammation-related signaling pathways leading to increased secretion of cytokines and chemokines, the influx of neutrophils and macrophages into the pregnant uterus, increased production of uterine activation proteins (eg, connexin-43, cyclo-oxygenase-2, oxytocin receptors, etc), activation of matrix metalloproteinases, and the release of uterotonins leading to cervical ripening, membrane rupture, and myometrial contractions. The missing link has been the Fetal/placental signal that triggers these proinflammatory events in the absence of microbial invasion and intrauterine infection. This article reviews the biomedical literature regarding the increase in Cell-Free Fetal DNA (cffDNA), which is released during apoptosis in the placenta and Fetal membranes at term, the ability of apoptosis modified vertebrate DNA to stimulate toll-like receptor-9 (TLR9) leading to increased release of cytokines and chemokines, and the potential “fail-safe” role for the anti-inflammatory cytokine IL-10. This article also reviews the literature supporting the key role that telomere loss plays in regard to increasing the ability of vertebrate (including placental) DNA to stimulate TLR9, and in regard to signaling the onset of apoptosis in the placenta and Fetal membranes, thereby providing a biologic clock that determines the length of gestation and the timing for the onset of parturition. In summary, this literature review provides a strong rationale for future research to test the hypothesis that telomere loss and increased cffDNA levels trigger the proinflammatory events leading to the spontaneous onset of parturition in mammals: the “cffDNA/telomere hypothesis.”
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cell free Fetal DNA telomeres and the spontaneous onset of parturition
Reproductive Sciences, 2015Co-Authors: Mark PhillippeAbstract:Multiple previous reports have provided compelling support for the premise that spontaneous parturition is mediated by activation of inflammation-related signaling pathways leading to increased secretion of cytokines and chemokines, the influx of neutrophils and macrophages into the pregnant uterus, increased production of uterine activation proteins (eg, connexin-43, cyclo-oxygenase-2, oxytocin receptors, etc), activation of matrix metalloproteinases, and the release of uterotonins leading to cervical ripening, membrane rupture, and myometrial contractions. The missing link has been the Fetal/placental signal that triggers these proinflammatory events in the absence of microbial invasion and intrauterine infection. This article reviews the biomedical literature regarding the increase in Cell-Free Fetal DNA (cffDNA), which is released during apoptosis in the placenta and Fetal membranes at term, the ability of apoptosis modified vertebrate DNA to stimulate toll-like receptor-9 (TLR9) leading to increased ...
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cell free Fetal DNA a trigger for parturition
The New England Journal of Medicine, 2014Co-Authors: Mark PhillippeAbstract:Despite the importance of timing in parturition, little is known about its triggers. Emerging evidence supports an influential role for the level of Cell-Free Fetal DNA.
Antonio Farina - One of the best experts on this subject based on the ideXlab platform.
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Cell-Free Fetal DNA for the Prediction of Pre-Eclampsia at the First and Second Trimesters: A Systematic Review and Meta-Analysis.
Molecular Diagnosis & Therapy, 2016Co-Authors: Elena Contro, Dalila Bernabini, Antonio FarinaAbstract:Objective A systematic review and pooled analysis was carried out to estimate whether the increase in the quantity of Cell-Free Fetal DNA (cffDNA) before the onset of pre-eclampsia (PE) can predict the disease using real-time polymerase chain reaction (PCR).
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evaluation of cell free Fetal DNA as a second trimester maternal serum marker of down syndrome pregnancy
Clinical Chemistry, 2003Co-Authors: Antonio Farina, Erik S. Leshane, Geralyn Lambertmesserlian, Jacob A Canick, Louis M Neveux, Glenn E Palomaki, Diana W. BianchiAbstract:Background: Second-trimester Cell-Free Fetal DNA (studied only in pregnancies with male fetuses) is higher in maternal serum samples from women carrying Down syndrome fetuses than in unaffected pregnancies. In this study we evaluated the potential performance of Fetal DNA as a screening marker for Down syndrome. Methods: Data on maternal serum Fetal DNA concentrations and the corresponding concentrations of the quadruple serum markers were available from 15 Down syndrome cases, each matched for gestational age and length of freezer storage, with 5 control samples. Analyte values were expressed as multiple(s) of the control or population median. Screening performance of Fetal DNA, both alone and when added to estimates of quadruple marker performance, was determined after modeling using univariate and multivariate gaussian distribution analysis. Results: The median Fetal DNA concentration in Down syndrome cases was 1.7 times higher than in controls. In univariate analysis, Fetal DNA gave a 21% detection rate at a 5% false-positive rate. When added to quadruple marker screening, Fetal DNA increased the estimated detection rate from 81% to 86% at a 5% false-positive rate. Conclusions: Cell-Free Fetal DNA, measured in maternal serum, can modestly increase screening performance above what is currently available in the second trimester. If and when maternal serum Fetal DNA can be measured in pregnancies with both male and female fetuses, the utility and cost-effectiveness of adding it as a Down syndrome screening marker should be assessed.
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maternal serum cell free Fetal DNA levels are increased in cases of trisomy 13 but not trisomy 18
Human Genetics, 2003Co-Authors: Tuangsit Wataganara, Erik S. Leshane, Antonio Farina, Jacob A Canick, Geralyn Messerlian, Diana W. BianchiAbstract:Cell-Free Fetal DNA in the maternal circulation is a potential noninvasive marker for Fetal aneuploidies. In previous studies with Y DNA as a Fetal-specific marker, levels of circulating Fetal DNA were shown to be elevated in women carrying trisomy 21 fetuses. The goal of this study was to determine whether Cell-Free Fetal DNA levels in the serum of pregnant women carrying fetuses with trisomies 13 or 18 are also elevated. Archived maternal serum samples from five cases of male trisomy 13 and five cases of male trisomy 18 were studied. Each case was matched for Fetal gender, gestational age, and duration of freezer storage to four or five control serum samples presumed to be euploid after newborn medical record review. Real-time quantitative polymerase chain reaction amplification of DYS1 was performed to measure the amount of male Fetal DNA present. Unadjusted median serum Fetal DNA concentrations were 97.5 GE/ml (genomic equivalents per milliliter; 29.2–187.0) for the trisomy 13 cases, 31.5 GE/ml (18.6–77.6) for the trisomy 18 cases, and 40.3 GE/ml (3.7–127.4) for the controls. Fetal DNA levels in trisomy 13 cases were significantly elevated (P=0.016) by analysis of variance of the ranks of values within each matched set. In contrast, Fetal DNA levels in trisomy 18 cases were no different from the controls (P=0.244). Second trimester maternal serum analytes currently used in screening do not identify fetuses at high risk for trisomy 13. Fetal DNA may facilitate noninvasive screening for trisomy 13 provided that a gender-independent Fetal DNA marker can be developed.
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Maternal serum Cell-Free Fetal DNA levels are increased in cases of trisomy 13 but not trisomy 18.
Human Genetics, 2003Co-Authors: Tuangsit Wataganara, Erik S. Leshane, Antonio Farina, Jacob A Canick, Geralyn Messerlian, Thomas H. Lee, Diana W. BianchiAbstract:Cell-Free Fetal DNA in the maternal circulation is a potential noninvasive marker for Fetal aneuploidies. In previous studies with Y DNA as a Fetal-specific marker, levels of circulating Fetal DNA were shown to be elevated in women carrying trisomy 21 fetuses. The goal of this study was to determine whether Cell-Free Fetal DNA levels in the serum of pregnant women carrying fetuses with trisomies 13 or 18 are also elevated. Archived maternal serum samples from five cases of male trisomy 13 and five cases of male trisomy 18 were studied. Each case was matched for Fetal gender, gestational age, and duration of freezer storage to four or five control serum samples presumed to be euploid after newborn medical record review. Real-time quantitative polymerase chain reaction amplification of DYS1 was performed to measure the amount of male Fetal DNA present. Unadjusted median serum Fetal DNA concentrations were 97.5 GE/ml (genomic equivalents per milliliter; 29.2–187.0) for the trisomy 13 cases, 31.5 GE/ml (18.6–77.6) for the trisomy 18 cases, and 40.3 GE/ml (3.7–127.4) for the controls. Fetal DNA levels in trisomy 13 cases were significantly elevated (P=0.016) by analysis of variance of the ranks of values within each matched set. In contrast, Fetal DNA levels in trisomy 18 cases were no different from the controls (P=0.244). Second trimester maternal serum analytes currently used in screening do not identify fetuses at high risk for trisomy 13. Fetal DNA may facilitate noninvasive screening for trisomy 13 provided that a gender-independent Fetal DNA marker can be developed.
Erik S. Leshane - One of the best experts on this subject based on the ideXlab platform.
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Cell-Free Fetal DNA in the cerebrospinal fluid of women during the peripartum period
American Journal of Obstetrics and Gynecology, 2004Co-Authors: Robert M. Angert, Erik S. Leshane, Ralph W Yarnell, Kirby L. Johnson, Diana W. BianchiAbstract:Abstract Objective The purpose of this study was to determine whether Cell-Free Fetal DNA is detectable in the cerebrospinal fluid of women during pregnancy and after delivery. Study design Cerebrospinal fluid was collected from 39 women who underwent an indicated spinal anesthesia procedure. Twenty-six samples were from women who carried at least 1 male fetus, and 13 samples were from women with only a female fetus. DNA was analyzed with the use of real-time polymerase chain reaction for DYS-1 (which represented male Fetal DNA) and β-globin (which represented maternal and Fetal DNA). Results β-Globin DNA was detected in all cerebrospinal samples. DYS-1 gene sequences were detected in 4 cerebrospinal fluid samples from women who had male fetuses (2 samples were from women who underwent cesarean delivery of singleton pregnancies, 1 sample was from a triplet pregnancy, and 1 sample was from a woman after delivery). No male DNA was detected in the cerebrospinal fluid of women who carried female fetuses. Conclusion Male Fetal cells and/or Cell-Free Fetal DNA is detectable in the cerebrospinal fluid of some pregnant women or some women after delivery.
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evaluation of cell free Fetal DNA as a second trimester maternal serum marker of down syndrome pregnancy
Clinical Chemistry, 2003Co-Authors: Antonio Farina, Erik S. Leshane, Geralyn Lambertmesserlian, Jacob A Canick, Louis M Neveux, Glenn E Palomaki, Diana W. BianchiAbstract:Background: Second-trimester Cell-Free Fetal DNA (studied only in pregnancies with male fetuses) is higher in maternal serum samples from women carrying Down syndrome fetuses than in unaffected pregnancies. In this study we evaluated the potential performance of Fetal DNA as a screening marker for Down syndrome. Methods: Data on maternal serum Fetal DNA concentrations and the corresponding concentrations of the quadruple serum markers were available from 15 Down syndrome cases, each matched for gestational age and length of freezer storage, with 5 control samples. Analyte values were expressed as multiple(s) of the control or population median. Screening performance of Fetal DNA, both alone and when added to estimates of quadruple marker performance, was determined after modeling using univariate and multivariate gaussian distribution analysis. Results: The median Fetal DNA concentration in Down syndrome cases was 1.7 times higher than in controls. In univariate analysis, Fetal DNA gave a 21% detection rate at a 5% false-positive rate. When added to quadruple marker screening, Fetal DNA increased the estimated detection rate from 81% to 86% at a 5% false-positive rate. Conclusions: Cell-Free Fetal DNA, measured in maternal serum, can modestly increase screening performance above what is currently available in the second trimester. If and when maternal serum Fetal DNA can be measured in pregnancies with both male and female fetuses, the utility and cost-effectiveness of adding it as a Down syndrome screening marker should be assessed.
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maternal serum cell free Fetal DNA levels are increased in cases of trisomy 13 but not trisomy 18
Human Genetics, 2003Co-Authors: Tuangsit Wataganara, Erik S. Leshane, Antonio Farina, Jacob A Canick, Geralyn Messerlian, Diana W. BianchiAbstract:Cell-Free Fetal DNA in the maternal circulation is a potential noninvasive marker for Fetal aneuploidies. In previous studies with Y DNA as a Fetal-specific marker, levels of circulating Fetal DNA were shown to be elevated in women carrying trisomy 21 fetuses. The goal of this study was to determine whether Cell-Free Fetal DNA levels in the serum of pregnant women carrying fetuses with trisomies 13 or 18 are also elevated. Archived maternal serum samples from five cases of male trisomy 13 and five cases of male trisomy 18 were studied. Each case was matched for Fetal gender, gestational age, and duration of freezer storage to four or five control serum samples presumed to be euploid after newborn medical record review. Real-time quantitative polymerase chain reaction amplification of DYS1 was performed to measure the amount of male Fetal DNA present. Unadjusted median serum Fetal DNA concentrations were 97.5 GE/ml (genomic equivalents per milliliter; 29.2–187.0) for the trisomy 13 cases, 31.5 GE/ml (18.6–77.6) for the trisomy 18 cases, and 40.3 GE/ml (3.7–127.4) for the controls. Fetal DNA levels in trisomy 13 cases were significantly elevated (P=0.016) by analysis of variance of the ranks of values within each matched set. In contrast, Fetal DNA levels in trisomy 18 cases were no different from the controls (P=0.244). Second trimester maternal serum analytes currently used in screening do not identify fetuses at high risk for trisomy 13. Fetal DNA may facilitate noninvasive screening for trisomy 13 provided that a gender-independent Fetal DNA marker can be developed.
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Maternal serum Cell-Free Fetal DNA levels are increased in cases of trisomy 13 but not trisomy 18.
Human Genetics, 2003Co-Authors: Tuangsit Wataganara, Erik S. Leshane, Antonio Farina, Jacob A Canick, Geralyn Messerlian, Thomas H. Lee, Diana W. BianchiAbstract:Cell-Free Fetal DNA in the maternal circulation is a potential noninvasive marker for Fetal aneuploidies. In previous studies with Y DNA as a Fetal-specific marker, levels of circulating Fetal DNA were shown to be elevated in women carrying trisomy 21 fetuses. The goal of this study was to determine whether Cell-Free Fetal DNA levels in the serum of pregnant women carrying fetuses with trisomies 13 or 18 are also elevated. Archived maternal serum samples from five cases of male trisomy 13 and five cases of male trisomy 18 were studied. Each case was matched for Fetal gender, gestational age, and duration of freezer storage to four or five control serum samples presumed to be euploid after newborn medical record review. Real-time quantitative polymerase chain reaction amplification of DYS1 was performed to measure the amount of male Fetal DNA present. Unadjusted median serum Fetal DNA concentrations were 97.5 GE/ml (genomic equivalents per milliliter; 29.2–187.0) for the trisomy 13 cases, 31.5 GE/ml (18.6–77.6) for the trisomy 18 cases, and 40.3 GE/ml (3.7–127.4) for the controls. Fetal DNA levels in trisomy 13 cases were significantly elevated (P=0.016) by analysis of variance of the ranks of values within each matched set. In contrast, Fetal DNA levels in trisomy 18 cases were no different from the controls (P=0.244). Second trimester maternal serum analytes currently used in screening do not identify fetuses at high risk for trisomy 13. Fetal DNA may facilitate noninvasive screening for trisomy 13 provided that a gender-independent Fetal DNA marker can be developed.
Jacob A Canick - One of the best experts on this subject based on the ideXlab platform.
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Cell-Free Fetal DNA levels in pregnancies conceived by IVF
Human Reproduction, 2005Co-Authors: Phillip D. Pan, Diana W. Bianchi, Jacob A Canick, Inga Peter, Geralyn Lambert-messerlian, Kirby L. JohnsonAbstract:BACKGROUND: Increased second-trimester levels of maternal serum HCG in IVF conceptions lead to an increased false-positive rate in Down syndrome screening. Increased levels of Cell-Free Fetal DNA (cffDNA) in maternal plasma have been correlated with increased HCG levels. Our aim was to determine whether cffDNA levels are elevated in IVF pregnancies compared with natural pregnancies. METHODS: Sixteen archived second-trimester serum samples from IVF pregnancies were matched with five control samples from naturally conceived pregnancies per case, all carrying a singleton male fetus. cffDNA concentrations were me asured by real-time PCR amplification of a Y chromosome sequence and compared with four standard second trimester serum screening markers (-fetoprotein, estriol, HCG and inhibin A). RESULTS: Mean cffDNA levels for cases and controls were 57.9 and 57.1 genome equivalents/ml, respectively (P = 0.95). Mean observed rank (from 1 to 6) of cffDNA was 3.625 in the IVF conceived group, compared with an expected value of 3.5 (P = 0.53). No significant correlations w ere observed between cffDNA and serum markers. CONCLUSIONS: IVF does not affect levels of cffDNA, which appears to be independent of traditional screening markers (e.g. HCG). Therefore, cffDNA can be used as an additional serum marker (e.g. Down syndrome screening) without adjustment for IVF pregnancies.
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evaluation of cell free Fetal DNA as a second trimester maternal serum marker of down syndrome pregnancy
Clinical Chemistry, 2003Co-Authors: Antonio Farina, Erik S. Leshane, Geralyn Lambertmesserlian, Jacob A Canick, Louis M Neveux, Glenn E Palomaki, Diana W. BianchiAbstract:Background: Second-trimester Cell-Free Fetal DNA (studied only in pregnancies with male fetuses) is higher in maternal serum samples from women carrying Down syndrome fetuses than in unaffected pregnancies. In this study we evaluated the potential performance of Fetal DNA as a screening marker for Down syndrome. Methods: Data on maternal serum Fetal DNA concentrations and the corresponding concentrations of the quadruple serum markers were available from 15 Down syndrome cases, each matched for gestational age and length of freezer storage, with 5 control samples. Analyte values were expressed as multiple(s) of the control or population median. Screening performance of Fetal DNA, both alone and when added to estimates of quadruple marker performance, was determined after modeling using univariate and multivariate gaussian distribution analysis. Results: The median Fetal DNA concentration in Down syndrome cases was 1.7 times higher than in controls. In univariate analysis, Fetal DNA gave a 21% detection rate at a 5% false-positive rate. When added to quadruple marker screening, Fetal DNA increased the estimated detection rate from 81% to 86% at a 5% false-positive rate. Conclusions: Cell-Free Fetal DNA, measured in maternal serum, can modestly increase screening performance above what is currently available in the second trimester. If and when maternal serum Fetal DNA can be measured in pregnancies with both male and female fetuses, the utility and cost-effectiveness of adding it as a Down syndrome screening marker should be assessed.
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maternal serum cell free Fetal DNA levels are increased in cases of trisomy 13 but not trisomy 18
Human Genetics, 2003Co-Authors: Tuangsit Wataganara, Erik S. Leshane, Antonio Farina, Jacob A Canick, Geralyn Messerlian, Diana W. BianchiAbstract:Cell-Free Fetal DNA in the maternal circulation is a potential noninvasive marker for Fetal aneuploidies. In previous studies with Y DNA as a Fetal-specific marker, levels of circulating Fetal DNA were shown to be elevated in women carrying trisomy 21 fetuses. The goal of this study was to determine whether Cell-Free Fetal DNA levels in the serum of pregnant women carrying fetuses with trisomies 13 or 18 are also elevated. Archived maternal serum samples from five cases of male trisomy 13 and five cases of male trisomy 18 were studied. Each case was matched for Fetal gender, gestational age, and duration of freezer storage to four or five control serum samples presumed to be euploid after newborn medical record review. Real-time quantitative polymerase chain reaction amplification of DYS1 was performed to measure the amount of male Fetal DNA present. Unadjusted median serum Fetal DNA concentrations were 97.5 GE/ml (genomic equivalents per milliliter; 29.2–187.0) for the trisomy 13 cases, 31.5 GE/ml (18.6–77.6) for the trisomy 18 cases, and 40.3 GE/ml (3.7–127.4) for the controls. Fetal DNA levels in trisomy 13 cases were significantly elevated (P=0.016) by analysis of variance of the ranks of values within each matched set. In contrast, Fetal DNA levels in trisomy 18 cases were no different from the controls (P=0.244). Second trimester maternal serum analytes currently used in screening do not identify fetuses at high risk for trisomy 13. Fetal DNA may facilitate noninvasive screening for trisomy 13 provided that a gender-independent Fetal DNA marker can be developed.
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Maternal serum Cell-Free Fetal DNA levels are increased in cases of trisomy 13 but not trisomy 18.
Human Genetics, 2003Co-Authors: Tuangsit Wataganara, Erik S. Leshane, Antonio Farina, Jacob A Canick, Geralyn Messerlian, Thomas H. Lee, Diana W. BianchiAbstract:Cell-Free Fetal DNA in the maternal circulation is a potential noninvasive marker for Fetal aneuploidies. In previous studies with Y DNA as a Fetal-specific marker, levels of circulating Fetal DNA were shown to be elevated in women carrying trisomy 21 fetuses. The goal of this study was to determine whether Cell-Free Fetal DNA levels in the serum of pregnant women carrying fetuses with trisomies 13 or 18 are also elevated. Archived maternal serum samples from five cases of male trisomy 13 and five cases of male trisomy 18 were studied. Each case was matched for Fetal gender, gestational age, and duration of freezer storage to four or five control serum samples presumed to be euploid after newborn medical record review. Real-time quantitative polymerase chain reaction amplification of DYS1 was performed to measure the amount of male Fetal DNA present. Unadjusted median serum Fetal DNA concentrations were 97.5 GE/ml (genomic equivalents per milliliter; 29.2–187.0) for the trisomy 13 cases, 31.5 GE/ml (18.6–77.6) for the trisomy 18 cases, and 40.3 GE/ml (3.7–127.4) for the controls. Fetal DNA levels in trisomy 13 cases were significantly elevated (P=0.016) by analysis of variance of the ranks of values within each matched set. In contrast, Fetal DNA levels in trisomy 18 cases were no different from the controls (P=0.244). Second trimester maternal serum analytes currently used in screening do not identify fetuses at high risk for trisomy 13. Fetal DNA may facilitate noninvasive screening for trisomy 13 provided that a gender-independent Fetal DNA marker can be developed.