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. 2020 Jan;40(2):179-184.
doi: 10.1002/pd.5609. Epub 2019 Nov 21.

Cell-free DNA fetal fraction in twin gestations in single-nucleotide polymorphism-based noninvasive prenatal screening

Herman Hedriana  1 , Kimberly Martin  2 , Daniel Saltzman  3 , Paul Billings  2 , Zachary Demko  2 , Peter Benn  4
Affiliations

Cell-free DNA fetal fraction in twin gestations in single-nucleotide polymorphism-based noninvasive prenatal screening

Herman Hedriana et al. Prenat Diagn. 2020 Jan.

Abstract

Objectives: The performance of noninvasive prenatal screening (NIPS) for fetal aneuploidy in twin pregnancies is dependent on the amount of placentally derived cell-free DNA, the "fetal fraction (FF)," present in maternal plasma. We report FF values in monozygotic (MZ) and dizygotic (DZ) pregnancies.

Methods: We reviewed FF in pregnancies at 10 to 20 completed weeks gestational age based on single-nucleotide polymorphism (SNP)-based NIPS where zygosity was routinely established in twin pregnancies. The cohort included 121 446 (96.3%) singleton, 1454 (1.2%) MZ, and 3161 (2.5%) DZ pregnancies. For DZ twins, individual FFs were measured.

Results: Combined FF for DZ and MZ fetuses were 35% and 26% greater than singletons, respectively. The individual FF contributions from each fetus in DZ twins were, on average, 32% less than singletons. FF in DZ twin pairs were moderately correlated (Pearson correlation coefficient.66). When a threshold of 2.8% FF was applied to define uninterpretable results, 1.7% (2102/121 446) of singletons, 0.8% (11/1454) of MZ pairs, and 5.6% (178/3161) of DZ pairs were uninterpretable.

Conclusion: For optimal aneuploidy NIPS in twin pregnancies, zygosity should be established and in DZ twins FF for both fetuses should be determined to identify those cases where results can be reliably interpreted.

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Conflict of interest statement

Zachary Demko and Paul Billings are employees of Natera, Inc and hold stock in the company. Kimberly Martin and Peter Benn are consultants to Natera and hold stock options. Herman Hedriana is a former employee of Natera and does not own stock or hold stock options. Daniel Salzman serves on the advisory board of Natera; he is not an employee and does not receive any financial compensation from Natera.

Figures

Figure 1
Figure 1
Mean fetal fraction (FF) in singletons and twins according to gestational age and maternal weight. A, Gestational age and B, maternal weight
See this image and copyright information in PMC

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