Cell-free fetal DNA versus maternal serum screening for trisomy 21 in pregnant women with and without assisted reproduction technology: a prospective interventional study

Costa, Jean‐Marc; Letourneau, Alexandra; Favre, R.; Bidat, Laurent; Belaïsch-Allart, J.; Jouannic, Jean‐Marie; Quarello, E.; Sénat, Marie-Victoire; Broussin, B; Tsatsaris, Vassilis; Demain, Adèle; Kleinfinger, Pascale; Lohmann, Laurence; Agostini, Hélène; Bouyer, Jean; Benachi, Alexandra

doi:10.1038/gim.2018.4

Cited by 17 publications

(23 citation statements)

References 33 publications

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“…In some cases, cfDNA screening was performed for patients with ultrasound findings, as accepted by the American College of Obstetrics and Gynecology [ 20 ] and by the Society for Maternal–Fetal Medicine [ 21 ] and as a first-line screening test. Some of those patients were patients from the DEPOSA study as this study was prospective and interventional and results were given to the patients and used for clinical management [ 3 ].…”

Section: Methodsmentioning

confidence: 99%

Autoimmune disorders but not heparin are associated with cell-free fetal DNA test failure

Dabi¹,

Guterman²,

Jani³

et al. 2018

J Transl Med

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BackgroundRecent studies have suggested a possible association between heparin treatment at the time of cell-free DNA (cfDNA) testing and a non-reportable result. However, these studies lack of proper methodology and had a low level of proof to firmly incriminate heparin. Our objective was to investigate further the relationship between heparin treatment and cfDNA test results.MethodsTwo complementary approaches were used for the demonstration. First, we conducted a retrospective analysis of a cohort of patients with a singleton pregnancy, screened for aneuploidies by using cfDNA, but with a non-reportable cfDNA result. We included patients between 2013 and 2016 including the patients from the DEPOSA study as controls. CfDNA testing was performed by massive parallel sequencing by using a whole-genome approach. A multiple logistic regression was used to account for the influence of the variables included. Second, we performed in vitro experiments on mimic samples containing increased concentrations of heparin.ResultsOf 9867 singleton pregnancies tested during the inclusion period, 58 (0.59%) had a non-reportable result and were compared to 295 control patients. Fifteen (25.9%) and 20 (6.8%) patients were treated with heparin in the group with a non-reportable cfDNA result and with a successful assay, respectively. In multivariable analysis, an increased calculated risk at the first-trimester combined screening (OR 28.8 CI 9.76–85.15, p < 0.001), maternal weight (OR 1.03, CI 1.01–1.06, p = 0.01), and the presence of an autoimmune disease (OR 10.38, CI 1.62–66.53, p = 0.01) were the only characteristics associated with a non-reportable result. In vitro experiments showed that heparin had no impact on fetal fraction measurement or the final result, no matter what the dose tested.ConclusionsTreatment by heparin had no impact on cfDNA screening test for aneuploidies, while the presence of an autoimmune disorder is an independent predictor of a non-reportable result.

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Section: Methodsmentioning

confidence: 99%

Autoimmune disorders but not heparin are associated with cell-free fetal DNA test failure

Dabi¹,

Guterman²,

Jani³

et al. 2018

J Transl Med

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“…Interestingly, the occurrence of no results with the Harmony TM Prenatal Test was more pronounced in the subgroup of patients with IVF, while there was no difference between the 2 subpopulations of patients with the mother's weight ≥80 kg, who typically have a higher proportion of patients with a lower FF. Previous studies on singleton and twin pregnancies have shown that the GW-MPS method by Cerba testing leads to comparable no-result rates between IVF and non-IVF patients, whereas studies on singleton and twin pregnancies using the DANSR method showed a clearly significant difference in terms of no-result rates for IVF patients [4,16,27,28]. The increase in no-result rate with the DANSR method is not solely explained by a lower FF in this group.…”

Section: Uninformative Cfdna Testingmentioning

confidence: 56%

Cell-Free DNA Analysis in Maternal Blood: Differences in Estimates between Laboratories with Different Methodologies Using a Propensity Score Approach

et al. 2018

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Objectives: To evaluate the failure rate and performance of cell-free DNA (cfDNA) testing, mainly in terms of detection rates for trisomy 21, performed by 2 laboratories using different analytical methods. Methods: cfDNA testing was performed on 2,870 pregnancies with the Harmony^TM Prenatal Test using the targeted digital analysis of selected regions (DANSR) method, and on 2,635 pregnancies with the “Cerba test” using the genome-wide massively parallel sequencing (GW-MPS) method, with available outcomes. Propensity score analysis was used to match patients between the 2 groups. A comparison of the detection rates for trisomy 21 between the 2 laboratories was made. Results: In all, 2,811 patients in the Harmony group and 2,530 patients in the Cerba group had no trisomy 21, 18, or 13. Postmatched comparisons of the patient characteristics indicated a higher no-result rate in the Harmony group (1.30%) than in the Cerba group (0.75%; p = 0.039). All 41 cases of trisomy 21 in the Harmony group and 93 cases in the Cerba group were detected. Conclusions: Both methods of cfDNA testing showed low no-result rates and a comparable performance in detecting trisomy 21; yet GW-MPS had a slightly lower no-result rate than the DANSR method.

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“…Wong [13] et al found that amyloid precursor protein (APP) in DS placentas at RNA and protein levels had significant overexpression by qPCR, western blot, and immunohistochemistry. In this study, we reported on 7 proteins (OGDHL, SAP, ApoE, NAP1L1, Tβ10, Complement factor B, and ERO1L), that have been proven to be differentially expressed in umbilical cord blood from a pregnancy with a DS foetus [10]. The expression of each candidate protein markers are shown in Fig.…”

Section: Discussionmentioning

confidence: 94%

“…Thus, we chose umbilical cord blood to investigate DS biomarkers because it may transfer proteins and growth factors into the maternal circulation system. The current study found that cell-free foetal DNA (cf-DNA) can be used to screen pregnant women with trisomy 21 with a lower false positive rate than maternal serum screening (MSS), which means better accuracy for detecting DS [10].…”

Section: Introductionmentioning

confidence: 95%

Verification of foetal Down syndrome biomarker proteins in maternal plasma and applications in prenatal screening for Down syndrome

Sui¹,

Gan²,

Gong³

et al. 2018

transl med commun

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Background: Down Syndrome (DS) has a very high morbidity, according to statistics, the incidence rate of DS is as high as 1:700 among the new born babies. At present, there are still no effective prevention or treatment methods for the disease. We used a Western Blot technique to validate differentially expressed proteins between DS foetal umbilical cord blood plasma and healthy foetal peripheral blood plasma from pregnant women to identify new prenatal diagnostic biomarkers for down syndrome (DS) and establish a new non-invasive prenatal diagnosis method.Methods: We collected maternal peripheral blood (8 with foetal DS and 8 from normal foetuses) from April 2013 to January 2014, and separated the plasma. We combined the clinical characteristics and clinical differentially expressed proteins between DS foetal umbilical cord blood plasma and healthy foetal umbilical cord blood plasma to identify specific protein marker candidates and prepared monoclonal antibodies, which were then used for Western Blot technique to analyse the candidate markers.Results: In the DS foetal maternal plasma, serum amyloid P-component, Apolipoprotein E, Nucleosome assembly protein 1-like 1, Complement factor B,ERO1-like protein alpha, 2-oxoglutarate dehydrogenase-like, and Thymosin beta 10 were up-regulated proteins compared to the healthy control group, and the DS group showed higher expression, which agreed with the results from the DS foetal umbilical cord blood plasma. Conclusion:The up-regulated amyloid P-component, Apolipoprotein E, Nucleosome assembly protein 1-like 1, Complement factor B, ERO1-like protein alpha, 2-oxoglutarate dehydrogenase-like, Thymosin beta 10 all are upregulation, all of them have potential to be prenatal diagnosis biomarkers for DS, and these biomarkers can further reveal the pathogenesis of DS.

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Cell-free fetal DNA versus maternal serum screening for trisomy 21 in pregnant women with and without assisted reproduction technology: a prospective interventional study

Abstract: cfDNA achieved better performance than MSS in both spontaneous and ART pregnancies, thus decreasing the number of invasive procedures. Our findings suggest that cfDNA should be considered for primary screening, especially in pregnancies obtained after ART.

Cited by 17 publications

References 33 publications

Autoimmune disorders but not heparin are associated with cell-free fetal DNA test failure

Autoimmune disorders but not heparin are associated with cell-free fetal DNA test failure

Cell-Free DNA Analysis in Maternal Blood: Differences in Estimates between Laboratories with Different Methodologies Using a Propensity Score Approach

Verification of foetal Down syndrome biomarker proteins in maternal plasma and applications in prenatal screening for Down syndrome

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