2004
DOI: 10.1001/jama.291.9.1114
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Methods to Increase the Percentage of Free Fetal DNA Recovered From the Maternal Circulation

Abstract: RENATAL DIAGNOSIS IS USEFULfor managing a pregnancy with an identified fetal abnormality and may allow for planning and coordinating care during delivery and the neonatal period. 1 A variety of prenatal diagnostic tests are available but have limitations. Noninvasive tests such as maternal serum marker testing and ultrasound can be used to screen for the presence of chromosomal abnormalities but are not definitive. [2][3][4][5] On the other hand, invasive diagnostic tests (eg, amniocentesis, chorionic villus s… Show more

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Cited by 124 publications
(76 citation statements)
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“…To achieve a fractional fetal DNA concentration of 25%, methods are needed to allow the selective enrichment of fetal DNA (22) or the suppression of the maternal DNA background (11,23) The number of plasma DNA molecules that are present per unit volume of maternal plasma is limited (8). For example, in early pregnancy, the median maternal plasma concentration of an autosomal locus, the ␤-globin gene, has been shown to be 986 copies per milliliter, with contributions from both the fetus and mother (8).…”
Section: Discussionmentioning
confidence: 99%
“…To achieve a fractional fetal DNA concentration of 25%, methods are needed to allow the selective enrichment of fetal DNA (22) or the suppression of the maternal DNA background (11,23) The number of plasma DNA molecules that are present per unit volume of maternal plasma is limited (8). For example, in early pregnancy, the median maternal plasma concentration of an autosomal locus, the ␤-globin gene, has been shown to be 986 copies per milliliter, with contributions from both the fetus and mother (8).…”
Section: Discussionmentioning
confidence: 99%
“…Main disadvantages of this approach are: a) the currently used electrophoretic method is laborintensive and probably prone to contaminations and b) it is unknown if the provided DNA enrichment is enough satisfactory for the prenatal diagnosis of chromosomal aneuploidies [Lo, 2008]. In 2004, Dhallan's group proposed a specific blood processing protocol in which the addition of formaldehyde in maternal blood samples before centrifugation dramatically increased the percentage of fetal DNA recovered with the concurrent suppression of the maternal DNA background [Dhallan et al, 2004]. There are two speculations about the role of formaldehyde in increased yield of fetal DNA: a) prevention of maternal cell lysis and subsequent reduction of the amount of cfmDNA, and b) prevention of the degradation of cffDNA via its nuclease inhibitory effect [Dhallan et al, 2004].…”
Section: Fetal Dna Enrichment Methodsmentioning
confidence: 99%
“…In 2004, Dhallan's group proposed a specific blood processing protocol in which the addition of formaldehyde in maternal blood samples before centrifugation dramatically increased the percentage of fetal DNA recovered with the concurrent suppression of the maternal DNA background [Dhallan et al, 2004]. There are two speculations about the role of formaldehyde in increased yield of fetal DNA: a) prevention of maternal cell lysis and subsequent reduction of the amount of cfmDNA, and b) prevention of the degradation of cffDNA via its nuclease inhibitory effect [Dhallan et al, 2004]. The same research group supported that the application of this technique resulted in a significant increase in the proportion of cffDNA present from a maximum of about 6% to mean values of 20.2-25% in samples collected during various stages of gestation [Dhallan et al, 2004].…”
Section: Fetal Dna Enrichment Methodsmentioning
confidence: 99%
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“…Dhallan et al therefore reasoned that, if the maternal blood cells were stabilized through fixation with formaldehyde, the in vitro release of DNA from the maternal blood cells could be minimized 34 . However, several groups were unable to reproduce the data that Dhallan et al presented to support this line of reasoning 35,36 .…”
Section: Recent Advancesmentioning
confidence: 99%