Optimal Detection of Fetal Chromosomal Abnormalities by Massively Parallel DNA Sequencing of Cell-Free Fetal DNA from Maternal Blood

Sehnert, Amy J.; Rhees, Brian; Comstock, David; Feo, Eileen de; Heilek, Gabrielle; Burke, John M.; Rava, Richard P.

doi:10.1373/clinchem.2011.165910

Cited by 269 publications

(310 citation statements)

References 12 publications

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“…The number of reads e.g. for chromosome 13 varies significantly from sequencing run to sequencing run and also shows a detectable intra-run variation [13,14]. One major cause for these intra-and inter-run variabilities is fragment size-and guanosin-cytosin (GC) -bias, defined as the preferential amplification and sequencing of shorter and GC-rich templates [9,15].…”

Section: Methods Of Niptmentioning

confidence: 99%

Current status of non-invasive prenatal testing (NIPT): genetic counseling, dominant methods and overall performance

Harasim¹,

Rost

Klein³

2016

LaboratoriumsMedizin

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Abstract:The introduction of non-invasive prenatal testing (NIPT) into prenatal care represents a paradigm shift. With the absence of any intervention risk in contrast to invasive diagnostic procedures, NIPT has been widely adopted for the detection of fetal trisomy 13, 18 and 21. Additionally, fetal sex chromosome aneuploidy testing and sex determination are available, but can be compromised by both, medical and legal factors. Available validation studies were predominantly based on patients with a high a priori aneuploidy risk, determined by trimester screening or invasive diagnostics. In this review, we discuss the interpretation of NIPT results in context of patient specific risk constellations, the available performance data and dominant methodical approaches of NIPT including necessary content of genetic counseling.

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Section: Methods Of Niptmentioning

confidence: 99%

Current status of non-invasive prenatal testing (NIPT): genetic counseling, dominant methods and overall performance

Harasim¹,

Rost

Klein³

2016

LaboratoriumsMedizin

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“…11 Gestational age, maternal weight, and maternal age were assumed to have a reasonably normal distribution. This was also true for the z-scores in euploid singleton (and twin) pregnancies, which are expected to be normally distributed with a mean of 0 and standard deviation of 1.…”

Section: Brief Reportmentioning

confidence: 99%

Maternal plasma DNA testing for aneuploidy in pregnancies achieved by assisted reproductive technologies

Lambert-Messerlian

Kloza

Williams

et al. 2014

Genetics in Medicine

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Advances in molecular technologies have resulted in the introduction of next-generation sequencing of maternal plasma DNA for prenatal identification of Down syndrome and other common trisomies. 1,2 Circulating cell-free (ccf) DNA of placental/fetal origin 3 in the maternal circulation is thought to be released by apoptotic cells of the placenta, 4 and the success of next-generation sequencing is dependent on the percentage of fetal (placental) DNA present in maternal plasma (the fetal fraction). The higher the fetal fraction, the more easily a trisomy or other aneuploidy can be detected. On average, 13% of ccf DNA in maternal plasma is of fetal (placental) origin, and fetal fractions of less than 4% may not be sufficient for reliable testing. 1 First and second trimester maternal serum marker levels are known to be altered in pregnancies conceived using assisted reproductive technologies (ART) versus those conceived naturally (controls). [5][6][7][8][9][10] In particular, secretory products of the placenta, such as human chorionic gonadotropin and inhibin A, are 10-30% higher in pregnancies from ART relative to control pregnancies. The cause of the increased secretion is not known. Regardless, serum marker levels can be adjusted so that screening performance in ART pregnancies is comparable with that of controls. Given that a portion of ccf DNA also is released by placental cells, albeit by a different mechanism, we sought to explore the possibility that the levels of ccf DNA also differed between ART and control pregnancies. If ART pregnancies were to release at least as much fetal-specific ccf DNA into maternal blood as do naturally conceived pregnancies, this could reassure clinicians that next-generation testing in ART pregnancies would perform at least as well as in naturally conceived pregnancies. In addition, we examined the chromosome-specific z-score and the final interpretation of the testing in the ART and control pregnancies. MATERIALS AND METHODSSamples for this study were selected from among those reported earlier as part of a multicenter international clinical validation of a next-generation sequencing test for Down syndrome. 1Purpose: We sought to compare measurements of circulating cellfree DNA as well as Down syndrome test results in women with naturally conceived pregnancies with those conceived using assisted reproductive technologies.Methods: Data regarding assisted reproductive technologies were readily available from seven enrollment sites participating in an external clinical validation trial of nested case/control design. Measurements of circulating cell-free fetal and total DNA, fetal fraction (ratio of fetal to total DNA), chromosome-specific z-scores, and karyotype results were available for analysis.Results: Analyses were restricted to 632 euploid (5.2% assisted reproductive technologies) and 73 Down syndrome (13.7% assisted reproductive technologies), including 16 twin pregnancies. No differences were found for fetal or total circulating cell-free DNA, or for the fetal fraction in ...

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“…8,9 Recently, several studies have validated a technology known as mass genomic sequencing, quantifying millions of DNA fragments in biological samples and providing results within days with high accuracy to detect T13/18 and T21 in early gestational age (less than 10 weeks). 4,[10][11][12] Others have demonstrated a detection rate of over 98% with a false positive rate of less than 0.5%. [13][14][15][16][17][18][19][20] Thus, non-invasive prenatal testing (NIPT) seems to be the most effective screening method in women at high risk 21 and is already available at private laboratories in Brazil for tracking autosomal and sexual aneuploidies.…”

Section: Introductionmentioning

confidence: 99%

Intrauterine death in singleton pregnancies with trisomy 21, 18, 13 and monosomy X

Goulart

Liao

Carvalho

et al. 2016

Rev. Assoc. Med. Bras.

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Paulo (HC-FMUSP), which included 92 singleton pregnancies with prenatal diagnosis of trisomy of chromosome 21 (T21), 18, 13 (T13/18) and monosomy X (45X), with diagnosis performed until the 26th week of pregnancy. The aim of the study was to describe the frequency and to investigate predictors of spontaneous fetal death (FD). Diagnosis (T21, n=36; T13/18, n=25; 45X, n=31) was made at a mean gestational age of 18.3±3.7 weeks, through chorionic villus biopsy (n=22,24%), amniocentesis (n=66, 72%) and cordocentesis (n=4, 4%). Major malformations were present in 45 (49%); with hydrops in 32 (35%) fetuses, more frequently in 45X [n=24/31, 77% vs. T21 (n=6/36, 17%) and T13/18 (n=2/25, 8%), p<0.001]. Specialized fetal echocardiography was performed in 60% (55/92). Of these, 60% (33/55) showed changes in heart morphology and/or function. Fetuses with T13/18 had a higher incidence of cardiac anomalies [60 vs. 25% (T21) and 29% (45X), p= 0.01]. FD occurred in 55 (60%) gestations, being more frequent in 45X [n=26/31, 84% vs. T21 (n=13/36, 36%) and T13/18 (n=16/25, 64%), p<0.01]. Stepwise analysis showed a correlation between hydrops and death in fetuses with T21 (LR= 4.29; 95CI=1.9-8.0, p<0.0001). In fetuses with 45X, the presence of echocardiographic abnormalities was associated with lower risk of FD (LR= 0.56; p=0.005). No predictive factors were identified in the T13/18 group. Intra-uterine lethality of aneuploid fetuses is high. Occurrence of hydrops increases risk of FD in pregnancies with T21. In pregnancies with 45X, the occurrence of echocardiographic changes reduces this risk.

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Optimal Detection of Fetal Chromosomal Abnormalities by Massively Parallel DNA Sequencing of Cell-Free Fetal DNA from Maternal Blood

Abstract: BACKGROUND:Massively parallel DNA sequencing of cell-free fetal DNA from maternal blood can detect fetal chromosomal abnormalities. Although existing algorithms focus on the detection of fetal trisomy 21 (T21), these same algorithms have difficulty detecting trisomy 18 (T18).

Cited by 269 publications

References 12 publications

Current status of non-invasive prenatal testing (NIPT): genetic counseling, dominant methods and overall performance

Current status of non-invasive prenatal testing (NIPT): genetic counseling, dominant methods and overall performance

Maternal plasma DNA testing for aneuploidy in pregnancies achieved by assisted reproductive technologies

Intrauterine death in singleton pregnancies with trisomy 21, 18, 13 and monosomy X

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