Fetal sex determination in twin pregnancies using non-invasive prenatal testing

Villela, Darine; Che, Huiwen; Ghelue, Marijke Van; Dehaspe, Luc; Brison, Nathalie; Bogaert, Kris Van Den; Devriendt, Koen; Lewi, Liesbeth; Bayindir, Baran; Vermeesch, Joris Robert

doi:10.1038/s41525-019-0089-4

Cited by 14 publications

(12 citation statements)

References 26 publications

(33 reference statements)

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“…Based on prior studies [ 3 , 9 ] and limited cases from the current study, singleton gestations affected with aneuploidy appear to be a suitable proxy for twin gestations in which both fetuses are affected with aneuploidy, either because the pregnancy is monochorionic, or because both placentas in a dichorionic gestation are impacted by the same aneuploidy. For trisomy 21, there was no significant difference noted between the MRs of affected singleton gestations and twin gestations in which both fetuses were affected.…”

Section: Discussionmentioning

confidence: 88%

“…This singleton group was assembled to biologically mimic the scenario of affected monochorionic twins. Both singleton gestations and monochorionic twins involve cfDNA analysis from a single placenta, and prior studies have demonstrated that monochorionic twin pregnancies behave similarly to singletons in the context of cfDNA screening [ 3 , 9 ]. By extension, in the rare circumstance that both placentas of a dichorionic pregnancy are affected with the same, non-mosaic aneuploidy (i.e.…”

Section: Methodsmentioning

confidence: 99%

“…Additionally, when Y chromosome material is detected in a multifetal gestation, the MR associated with the Y chromosome may be useful in predicting whether one or more fetuses are male. Prior studies have focused on similar data metrics to develop a fetal sex prediction model for twin gestations [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

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Application of mosaicism ratio to multifetal gestations

et al. 2021

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Mosaicism ratio, or MR, is a laboratory metric that can be calculated using massively parallel sequencing data from cell-free DNA (cfDNA) screening. MR compares the amount of cfDNA present from a particular chromosome or chromosomal region to the overall fetal fraction of the specimen. In singleton gestations, MR may be used to refine the positive predictive value of an abnormal cfDNA screening result by identifying cases that could be impacted by various biological factors, such as placental mosaicism or prior co-twin demise. The current study was designed to examine the behavior of mosaicism ratio (MR) in multifetal gestations. Multifetal cfDNA specimens with positive results for trisomies 21, 18, or 13 and confirmed diagnostic outcomes were compiled to examine MR of the aneuploid chromosome based on the number of affected fetuses/placentas. A second multifetal cohort was assembled to analyze the MR of the Y chromosome in cases with at least one male fetus. For aneuploid cases, the average MR of affected singletons (used as a biological proxy for two affected twins) was significantly higher than the average MR for twins in which one fetus was affected. The average MR of the aneuploid chromosome for one affected twin was 52%, 42%, and 48% of that of singleton gestations for trisomy 21, 18, and 13 cases, respectively. MR cutoffs of 0.7 for trisomy 21, and 0.5 for trisomies 18 and 13 may help predict whether one versus both twins are affected with aneuploidy when clinical concern arises. For male cases, the Y MR of XX/XY gestations was 48% of the Y MR for XY/XY gestations. Using a Y MR cutoff of 0.8 allowed determination of XX/XY versus XY/XY gestations with 92.3–94.9% accuracy. Based on the data presented, MR may have utility in the analysis and interpretation of cfDNA data from multifetal gestations.

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Section: Discussionmentioning

confidence: 88%

Section: Methodsmentioning

confidence: 99%

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Application of mosaicism ratio to multifetal gestations

et al. 2021

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“…Thirdly, in the prediction of monogenic disease, the FF is also a key parameter 5,6 to determine the statistical thresholds to ensure the statistical significance. Lastly, when FF is accurately known, a more powerful test to screen for fetal trisomy can be developed 28,33 and the fetal sex determination in twin pregnancies 34,35 also becomes a much simpler problem. The ability of measuring FF with high accuracy would make LDFF serve as a valuable tool to improve NIPT performance.…”

Section: Discussionmentioning

confidence: 99%

Estimation of cell-free fetal DNA fraction from maternal plasma based on linkage disequilibrium information

Liu

et al. 2021

npj Genom. Med.

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Cell-free fetal DNA fraction (FF) in maternal plasma is a key parameter affecting the performance of noninvasive prenatal testing (NIPT). Accurate quantitation of FF plays a pivotal role in these tests. However, there are few methods that could determine FF with high accuracy using shallow‐depth whole‐genome sequencing data. In this study, we hypothesized that the actual FF in maternal plasma should be proportional to the discrepancy rate between the observed genotypes and inferred genotypes based on the linkage disequilibrium rule in certain polymorphism sites. Based on this hypothesis, we developed a method named Linkage Disequilibrium information-based cell-free Fetal DNA Fraction (LDFF) to accurately quantify FF in maternal plasma. This method achieves a high performance and outperforms existing methods in the fetal DNA fraction estimation. As LDFF is a gender-independent method and developed on shallow-depth samples, it can be easily incorporated into routine NIPT test and may enhance the current NIPT performance.

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“…Villela et al employed NIPT for sex determination in twin pregnancies. Their analytical method exhibited 100% sensitivity and specificity when both twins were female, while the presence of a male co-twin declined the sensitivity and specificity to 98 and 95%, respectively [4]. More recently, Yang et al successfully applied NIPT for screening more than 400 twin pregnancies including both double chorionic dichorionic diamniotic (DCDA) and monochorionic diamniotic (MCDA).…”

Section: Introductionmentioning

confidence: 99%

Non-invasive prenatal test to screen common trisomies in twin pregnancies

Motevasselian

Gargari

Younesi³

et al. 2020

Mol Cytogenet

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Objectives: Recent years have witnessed a shift from invasive methods of prenatal screening to non-invasive strategies. Accordingly, non-invasive prenatal testing (NIPT) using cell-free fetal DNA in maternal plasma has gained a considerable deal of interest from both geneticists and obstetricians. Efficacy of this method in identification of common aneuploidies has been extensively assessed in singleton pregnancies. However, a limited number of studies have addressed the twin pregnancies. In this context, the present study is aimed at identification of the efficacy of NIPT in twin pregnancies. Methods: NIPT was performed on twin pregnancies to screen trisomies 13, 18 and 21. Pregnant women referring to Nilou Clinical Laboratory between March 2016 and December 2018 were included in this research. Results: In the current study, a total 356 twin pregnancies were screened in search for trisomies 13, 18 and 21. 6 cases exhibited positive NIPT results in which the presence of trisomies 13, 18 and 21 was confirmed by fetal karyotype in 1, 2 and 2 cases, respectively. One twin pregnancy showed normal karyotype. The combined false-positive rate for these trisomies was 0.28%. No false negative case was observed. The combined sensitivity and specificity of NIPT in twin pregnancies were 100 and 99.7%, respectively. Conclusion: The results of the current study verify the feasibility, sensitivity and specificity of NIPT in twin pregnancies.

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Fetal sex determination in twin pregnancies using non-invasive prenatal testing

Cited by 14 publications

References 26 publications

Application of mosaicism ratio to multifetal gestations

Application of mosaicism ratio to multifetal gestations

Estimation of cell-free fetal DNA fraction from maternal plasma based on linkage disequilibrium information

Non-invasive prenatal test to screen common trisomies in twin pregnancies

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