title: Fetal cell-free DNA fraction in maternal plasma is affected by fetal trisomy.
abstract: The purpose of this noninvasive prenatal testing (NIPT) study was to compare the fetal fraction of singleton gestations by gestational age, maternal characteristics and chromosome-specific aneuploidies as indicated by z-scores. This study was a multicenter prospective cohort study. Test data were collected from women who underwent NIPT by the massively parallel sequencing method. We used sequencing-based fetal fraction calculations in which we estimated fetal DNA fraction by simply counting the number of reads aligned within specific autosomal regions and applying a weighting scheme derived from a multivariate model. Relationships between fetal fractions and gestational age, maternal weight and height, and z-scores for chromosomes 21, 18 and 13 were assessed. A total of 7740 pregnant women enrolled in the study, of which 6993 met the study criteria. As expected, fetal fraction was inversely correlated with maternal weight (P<0.001). The median fetal fraction of samples with euploid result (n=6850) and trisomy 21 (n=70) were 13.7% and 13.6%, respectively. In contrast, the median fetal fraction values for samples with trisomies 18 (n=35) and 13 (n=9) were 11.0% and 8.0%, respectively. The fetal fraction of samples with trisomy 21 NIPT result is comparable to that of samples with euploid result. However, the fetal fractions of samples with trisomies 13 and 18 are significantly lower compared with that of euploid result. We conclude that it may make detecting these two trisomies more challenging.
authors.affiliation: Japan NIPT consortium, Tokyo, Japan.|Division of Clinical and Molecular Genetics, Department of Obstetrics and Gynecology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Suzumori
authors.affiliation: Department of Occupational and Environmental Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ebara
authors.affiliation: Japan NIPT consortium, Tokyo, Japan.|Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Japan NIPT consortium, Tokyo, Japan.|Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Samura
authors.affiliation: Japan NIPT consortium, Tokyo, Japan.|Department of Genetic Counseling, Ochanomizu University, Tokyo, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Yotsumoto
authors.affiliation: Japan NIPT consortium, Tokyo, Japan.|Center of Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Nishiyama
authors.affiliation: Japan NIPT consortium, Tokyo, Japan.|Department of Obstetrics and Gynecology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Kiyonori
authors.initials: K
authors.lastname: Miura
authors.affiliation: Japan NIPT consortium, Tokyo, Japan.|Department of Obstetrics and Gynecology, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Sawai
authors.affiliation: Japan NIPT consortium, Tokyo, Japan.|Department of Maternal and Fetal Medicine, Tohoku University Graduate School of Medicine, Miyagi-Children's Hospital, Sendai, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Murotsuki
authors.affiliation: Japan NIPT consortium, Tokyo, Japan.|Sanno Hospital, Tokyo, Japan.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Kitagawa
authors.affiliation: Japan NIPT consortium, Tokyo, Japan.|Department of Obstetrics and Gynecology, Saitama Medical University, Saitama, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Kamei
authors.affiliation: Japan NIPT consortium, Tokyo, Japan.|Department of Obstetrics and Gynecology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Masuzaki
authors.affiliation: Japan NIPT consortium, Tokyo, Japan.|Department of Obstetrics and Gynecology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Fumiki
authors.initials: F
authors.lastname: Hirahara
authors.affiliation: Sequenom Laboratories, San Diego, CA, USA.
authors.forename: Juan-Sebastian
authors.initials: JS
authors.lastname: Saldivar
authors.affiliation: Sequenom Laboratories, San Diego, CA, USA.
authors.forename: Nilesh
authors.initials: N
authors.lastname: Dharajiya
authors.affiliation: Japan NIPT consortium, Tokyo, Japan.|Center of Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sago
authors.affiliation: Japan NIPT consortium, Tokyo, Japan.|Department of Obstetrics and Gynecology, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Sekizawa
mesh_terms: D000328:Adult; D001835:Body Weight; D004247:DNA / Q000097:blood / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D005820:Genetic Testing / Q000379:methods; D005865:Gestational Age; D006801:Humans; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods; D015203:Reproducibility of Results; D014314:Trisomy / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D004247:DNA