Cell‐free fetal DNA analysis in maternal plasma as screening test for trisomies 21, 18 and 13 in twin pregnancy

Conte, G.; Letourneau, Alexandra; Jani, Jacques; Kleinfinger, Pascale; Lohmann, Laurence; Costa, Jean Marc; Benachi, Alexandra

doi:10.1002/uog.18838

Cited by 42 publications

(31 citation statements)

References 31 publications

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“…The search identified 329 potentially relevant citations, but 322 were excluded because they were non-relevant publications, conference abstracts rather than peer-reviewed papers, review articles or opinions, studies not on twins, case-control studies, or studies on clinical implementation of cfDNA testing in screening for aneuploidies in which pregnancy outcome data were provided for fewer than 85% of the study population, proof-of-principle studies reporting laboratory techniques rather than clinical validation of a predefined method of maternal blood cfDNA analysis (Figure 1). In total, 9 relevant studies were identified 4,5,[17][18][19][20][21][22][23] but two of these 4,5 were excluded from the meta-analysis because their data are included in the updated Fetal Medicine Foundation results presented above. The characteristics of our current study and the seven ones identified by the literature search are summarized in Table 1.…”

Section: Data Sourcesmentioning

confidence: 99%

Screening for Trisomies by cfDNA Testing of Maternal Blood in Twin Pregnancy: Update of the Fetal Medicine Foundation Results and Meta-analysis

Gil

Galeva

Jani

et al. 2019

Obstetrical &Amp; Gynecological Survey

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Objective: To report on the routine clinical implementation of cell-free (cf)DNA analysis of maternal blood for trisomies 21, 18 and 13 in twin pregnancies and to define the performance of the test by combining our results with those arising from systematic review of the literature. Methods:The data for the study were derived from prospective screening for trisomies 21, 18 and 13 in twin pregnancies at 10 +0 -14 +1 weeks' gestation. Two populations were included; first self-referred women to the Fetal Medicine Centre in London or Brugmann University Hospital in Brussels and second, women selected for the cfDNA test after routine first-trimester combined testing in one of two National Health Service hospitals in England. This dataset was used to determine the performance of screening for the three trisomies. Search of Medline, Embase, CENTRAL (The Cochrane Library), ClinicalTrials.gov and ICTRP (World Health Organization) was carried out to identify all peer-reviewed publications on clinical validation or implementation of maternal cfDNA testing for trisomies 21, 18 and 13 in twin pregnancies. Meta-analysis was then performed using our data and data from the studies identified by the literature search.Results: In our dataset of 997 twin pregnancies with a cfDNA result and known outcome, the test classified correctly 16 (94.1%) of the 17 cases of trisomy 21, 9 (90.0%) of 10 of trisomy 18, 1 (50.0%) of 2 of trisomy 13 and 963 (99.5%) of 968 cases without any of the three trisomies. The literature search identified 7 relevant studies, excluding our papers because their data are included in the current study. In the combined total of our study and the 7 studies identified by the literature search there were 56 trisomy 21 and 3,718 non-trisomy 21 twin pregnancies; the pooled weighted detection rate (DR) and false positive rate (FPR) were 98.2% (95% CI 83.2, 99.8%) and 0.05% (95% CI 0.01, 0.26%), respectively. In the combined total of 18 cases of trisomy 18 and 3,143 non-trisomy 18 pregnancies the pooled weighted DR and FPR were 88.9% (95% CI 64.8, 97.2%) and 0.03% (95% CI 0.00, 0.33%), respectively. For trisomy 13, there were only 3 affected cases and 2 (66.7%) of these were detected by the cfDNA test at FPR of 0.19% (5/2,569).Conclusions: Performance of cfDNA testing for trisomies 21 in twin pregnancies is similar to that reported for singleton pregnancies. The number of cases of trisomies 18 and 13 is too small for accurate assessment of predictive performance of the cfDNA test.

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Section: Data Sourcesmentioning

confidence: 99%

Screening for Trisomies by cfDNA Testing of Maternal Blood in Twin Pregnancy: Update of the Fetal Medicine Foundation Results and Meta-analysis

Gil

Galeva

Jani

et al. 2019

Obstetrical &Amp; Gynecological Survey

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“…In singletons, the sensitivity of cfDNA screening for trisomy 21 is 99%, with a FPR less than 0.02%. [10] While there is still limited data available for performance of cfDNA screening in twins, and relatively no data for higher order multiples, in 10 published twin cohorts [23–32] the sensitivity for trisomy 21 was 92–100% with a FPR less than 0.5%. The improved sensitivity and lower FPR of cfDNA screening for Trisomy 21, compared to conventional screening in multiple gestation pregnancies, positions cfDNA as a valuable screening alternative.…”

Section: Introductionmentioning

confidence: 99%

A new era in aneuploidy screening: cfDNA testing in >30,000 multifetal gestations: Experience at one clinical laboratory

et al. 2019

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Since introducing cell-free DNA screening, Sequenom Laboratories has analyzed over 1 million clinical samples. More than 30,000 of these samples were from multifetal gestations (including twins, triplets and higher-order multiples). The clinical laboratory experience with the first 30,000 multifetal samples will be discussed. Maternal plasma samples from multifetal gestations were subjected to DNA extraction and library preparation followed by massively parallel sequencing. Sequencing data were analyzed to identify autosomal trisomies and other subchromosomal events. Fetal fraction requirements were adjusted in proportion to fetal number. Outcome data, when voluntarily received from the ordering provider, were collected from internal case notes. Feedback was received in 50 cases. The positivity rate in multifetal samples for trisomy 21 was 1.50%, 0.47% for trisomy 18, and 0.21% for trisomy 13. Average total sample fetal fraction was 12.2% at a mean gestational age of 13 weeks 6 days. Total non-reportable rate was 5.95%. Estimated performance based on ad hoc clinical feedback demonstrates that possible maximum sensitivity and specificity meet or exceed the original performance from clinical validation studies. Cell-free DNA (cfDNA) screening provides certain advantages over that of conventional screening in multifetal gestations and is available in higher-order multiples.

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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: 59%

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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Cell‐free fetal DNA analysis in maternal plasma as screening test for trisomies 21, 18 and 13 in twin pregnancy

Cited by 42 publications

References 31 publications

Screening for Trisomies by cfDNA Testing of Maternal Blood in Twin Pregnancy: Update of the Fetal Medicine Foundation Results and Meta-analysis

Screening for Trisomies by cfDNA Testing of Maternal Blood in Twin Pregnancy: Update of the Fetal Medicine Foundation Results and Meta-analysis

A new era in aneuploidy screening: cfDNA testing in >30,000 multifetal gestations: Experience at one clinical laboratory

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

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