International Society for Prenatal Diagnosis Position Statement: cell free (cf)<scp>DNA</scp> screening for Down syndrome in multiple pregnancies

Palomaki, Glenn E.; Chiu, Rossa W.K.; Pertile, Mark D.; Sistermans, Erik A.; Yaron, Yuval; Vermeesch, Joris Robert; Vora, Neeta L.; Best, Robert G.; Wilkins‐Haug, Louise

doi:10.1002/pd.5832

Cited by 46 publications

(56 citation statements)

References 65 publications

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“…These data included both monozygotic and dizygotic twins, various approaches to testing (mostly counting‐based NIPT), generally unspecified prior testing, various criteria for test referral and differences in the criteria for a sufficient fetal fraction. Overall, the observed performance for trisomy 21 screening in twin pregnancies has been comparable to that observed for singleton pregnancies, albeit with a higher proportion of cases that were not called due to concerns about low cf‐DNA fetal fraction 2,46 . Published data on the experience for NIPT for fetal trisomy 13 and trisomy 18 in twin pregnancies is scant but consistent with expectations for singleton pregnancies.…”

Section: Use Of Cf‐dna To Screen For Aneuploidysupporting

confidence: 59%

“…Overall, the observed performance for trisomy 21 screening in twin pregnancies has been comparable to that observed for singleton pregnancies, albeit with a higher proportion of cases that were not called due to concerns about low cf‐DNA fetal fraction. 2 , 46 Published data on the experience for NIPT for fetal trisomy 13 and trisomy 18 in twin pregnancies is scant but consistent with expectations for singleton pregnancies. As previously noted, there is a special concern for these latter aneuploidies because fetal fraction is often lower than normal.…”

Section: Use Of Cf‐dna To Screen For Aneuploidymentioning

confidence: 69%

“…NIPT in twin pregnancies is now endorsed by the International Society for Prenatal Diagnosis. 2 The American College of Obstetrics and Gynecology also notes that the testing can be offered. 13 This testing is therefore recognized as an option in the advancement of clinical management and care of twin pregnancies.…”

Section: Introductionmentioning

confidence: 99%

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Non‐invasive prenatal testing in the management of twin pregnancies

Benn

Rebarber

2021

Prenatal Diagnosis

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Twin pregnancies are common and associated with pregnancy complications and adverse outcomes. Prenatal clinical management is intensive and has been hampered by inferior screening and less acceptable invasive testing. For aneuploidy screening, meta-analyses show that non-invasive prenatal testing (NIPT) through analysis of cell-free DNA (cf-DNA) is superior to serum and ultrasound-based tests.The positive predictive value for NIPT is driven strongly by the discriminatory power of the assay and only secondarily by the prior risk. Uncertainties in a priori risks for aneuploidies in twin pregnancies are therefore of lesser importance with NIPT.Additional information on zygosity can be obtained using NIPT. Establishing zygosity can be helpful when chorionicity was not reliably established early in pregnancy or where the there is a concern for one versus two affected fetuses. In dizygotic twin pregnancies, individual fetal fractions can be measured to ensure that both values are satisfactory. Vanishing twins can be identified by NIPT. Although clinical utility of routinely detecting vanishing twins has not yet been demonstrated, there are individual cases where cf-DNA analysis could be helpful in explaining unusual clinical or laboratory observations. We conclude that cf-DNA analysis and ultrasound have synergistic roles in the management of multiple gestational pregnancies. Key PointsWhat's already known about this topic? � In singleton pregnancies, non-invasive prenatal testing (NIPT) for fetal aneuploidy is more effective than conventional serum and ultrasound-based screening tests.� NIPT is more complex in dizygotic twin pregnancies due to the presence of two fetal genotypes.� Overall fetal fraction is higher in twin pregnancies but the individual contribution for each fetus is lower. What does this study add?� A review of cell-free DNA testing in twin pregnancies.� Individual fetal fractions in dizygotic twin pregnancies can be measured.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Section: Use Of Cf‐dna To Screen For Aneuploidysupporting

confidence: 59%

Section: Use Of Cf‐dna To Screen For Aneuploidymentioning

confidence: 69%

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Non‐invasive prenatal testing in the management of twin pregnancies

Benn

Rebarber

2021

Prenatal Diagnosis

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“…National and International Scientific Societies worldwide are concordant in recommending not to offer cfDNA testing for MMs outside well-defined research protocols. [17][18][19][20][21] An important ethical concern is the kind of information that should accompany a negative test result, which was reported by all studies in more than 99% of the cases. Based on this review, parents demanding cfDNA testing for MMs should be informed that: (a) among cases with a positive test, the proportion of fetuses that are confirmed to be affected after diagnostic testing is on average 40% but this is likely to be lower in cases with no ultrasound anomalies; and (b) a negative test does not modify the risk for the examined MMs and therefore, the test report should express the result as "unchanged risk" because the DR is essentially unknown.…”

Section: Discussionmentioning

confidence: 99%

Cell‐free DNA analysis of maternal blood in prenatal screening for chromosomal microdeletions and microduplications: a systematic review

Familiari

Boito

Rembouskos³

et al. 2021

Prenatal Diagnosis

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Background and aim of the study: Scientific Societies do not recommend the use of cell-free DNA (cfDNA) testing as a first-tier screening for microdeletion and microduplication syndromes (MMs). The aim of this study was to review the current available literature on the performance of cell-free DNA as a screening for MMs.Methods: Medline, Embase and the Cochrane Library were searched electronically from 2000 to January 2020 and articles reporting the diagnostic performance of cfDNA screening for MMs in large (>5000 cases) series were included. Betweenstudy heterogeneity and random effect model for screen positive rate (SPR), false positive rate (FPR) and positive predictive value (PPV) were calculated. Results:We identified 42 papers, seven included, for a total of 474,189 pregnancies and 210 cases of MMs. Diagnostic verification of positive cases was available overall in 486 (71.68 %) of 678 cases. The weighted pooled SPR, FPR and PPV were 0.19% (95% CI = 0.09-0.33), 0.07 (95% CI = 0.02-0.15) and 44.1 (95% CI = 31.49-63.07).In conclusion, the pooled PPV of cfDNA testing in screening for MMs was about 40%, ranging from 29% to 91%, for an overall FPR <0.1%. Conclusions:No confirmatory analysis was available in cases that did not undergo invasive testing, which were the vast majority of cases with a negative test, and therefore, the DR and the negative predictive value cannot be determined. K E Y W O R D Scell-free DNA, fetal cells, fetal diseases, fetal genetic analysis, genetic counseling, nucleic acids & proteins, noninvasive prenatal testing, fetal medicine and diagnostic procedures, whole genome sequencing Key PointsWhat's already known about this topic? � Cell-free DNA (cfDNA) as screening test for microduplication (MMs) is burdened by a high variability of positive predictive value (PPV) which is far from being considered acceptable. Scientific Societies worldwide are concordant in recommending not to offer cfDNA testing for MMs outside well-defined research protocols.

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“…5 Given the implementation challenges, and the lack of sufficient validation data related to the accuracy of NIPT in twin pregnancies, uniform recommendations are not available. [6][7][8][9] Nevertheless, an accurate NIPT for twin pregnancies is highly desired, as the accuracy of combined nuchal translucency and first trimester serum screening is limited in twin gestations, with a pooled sensitivity of 89.3% and a pooled specificity of 94.6% for the detection of trisomy 21. 10 Our objective was to evaluate the accuracy and diagnostic value of genome-wide NIPT for the detection of fetal aneuploidies in multiple gestations, with a specific focus on dichorionic-diamniotic twins.…”

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confidence: 99%

Performance and Diagnostic Value of Genome-Wide Noninvasive Prenatal Testing in Multiple Gestations

Riel

Brison

Baetens

et al. 2021

Obstetrics &Amp; Gynecology

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To evaluate the accuracy and diagnostic value of genome-wide noninvasive prenatal testing (NIPT) for the detection of fetal aneuploidies in multiple gestations, with a focus on dichorionic-diamniotic twin pregnancies. METHODS:We performed a retrospective cohort study including data from pregnant women with a twin or higher-order gestation who underwent genome-wide NIPT at one of the eight Belgian genetic centers between November 1, 2013, and March 1, 2020. Chorionicity and amnionicity were determined by ultrasonography. Follow-up invasive testing was carried out in the event of positive NIPT results. Sensitivity and specificity were calculated for the detection of trisomy 21, 18, and 13 in the dichorionic-diamniotic twin cohort.RESULTS: Unique NIPT analyses were performed for 4,150 pregnant women with a multiple gestation and an additional 767 with vanishing gestations. The failure rate in multiple gestations excluding vanishing gestations ranged from 0% to 11.7% among the different genetic centers. Overall, the failure rate was 4.8%, which could be reduced to 1.2% after single resampling. There were no common fetal trisomies detected among the 86 monochorionic-monoamniotic and 25 triplet cases. Two monochorionic-diamniotic twins had an NIPT result indicative of a trisomy 21, which was confirmed in both fetuses. Among 2,716 dichorionic-diamniotic twin gestations, a sensitivity of 100% (95% CI 74.12-100%) and a specificity of 100% (95% CI 99.86-100%) was reached for trisomy 21 (n512). For trisomy 18 (n53), the respective values were 75% (95% CI 30.06-95.44%) sensitivity and 100% (95% CI 99.86-100%) specificity, and for trisomy 13 (n52), 100% (95% CI 20.65-100%) sensitivity and 99.96% (95% CI 99.79-99.99%) specificity. In the vanishing gestation group, 28 NIPT results were positive for trisomy 21, 18, or 13, with only five confirmed trisomies.CONCLUSION: Genome-wide NIPT performed accurately for detection of aneuploidy in dichorionic-diamniotic twin gestations.

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International Society for Prenatal Diagnosis Position Statement: cell free (cf)DNA screening for Down syndrome in multiple pregnancies

Cited by 46 publications

References 65 publications

Non‐invasive prenatal testing in the management of twin pregnancies

Non‐invasive prenatal testing in the management of twin pregnancies

Cell‐free DNA analysis of maternal blood in prenatal screening for chromosomal microdeletions and microduplications: a systematic review

Performance and Diagnostic Value of Genome-Wide Noninvasive Prenatal Testing in Multiple Gestations

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