Nobuhiro Suzumori1, Akihiko Sekizawa2, Eri Takeda3, Osamu Samura4, Aiko Sasaki5, Rina Akaishi5, Seiji Wada5, Haruka Hamanoue6, Fumiki Hirahara6, Hideaki Sawai7, Hiroaki Nakamura8, Takahiro Yamada9, Kiyonori Miura10, Hideaki Masuzaki10, Setsuko Nakayama11, Yoshimasa Kamei12, Akira Namba12, Jun Murotsuki13, Masayuki Yamaguchi14, Shinya Tairaku15, Kazuhisa Maeda16, Takashi Kaji17, Yoko Okamoto18, Masayuki Endo19, Masaki Ogawa20, Yasuyo Kasai21, Kiyotake Ichizuka22, Naoki Yamada23, Akinori Ida24, Norio Miharu25, Satoshi Kawaguchi26, Yasuyuki Hasuo27, Tetsuya Okazaki28, Mayuko Ichikawa29, Shunichiro Izumi30, Naohiko Kuno31, Junko Yotsumoto32, Miyuki Nishiyama5, Nahoko Shirato2, Tatsuko Hirose2, Haruhiko Sago5. 1. Department of Obstetrics and Gynaecology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; Division of Clinical and Molecular Genetics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. Electronic address: og.n.suz@med.nagoya-cu.ac.jp. 2. Department of Obstetrics and Gynaecology, Showa University School of Medicine, Tokyo, Japan. 3. Department of Obstetrics and Gynaecology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; Division of Clinical and Molecular Genetics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. 4. Department of Obstetrics and Gynaecology, Jikei University School of Medicine, Tokyo, Japan. 5. Centre for Maternal-Fetal, Neonatal and Reproductive Medicine, National Centre for Child Health and Development, Tokyo, Japan. 6. Department of Clinical Genetics, Yokohama City University Hospital, Yokohama, Japan. 7. Department of Obstetrics and Gynaecology, Hyogo College of Medicine, Nishinomiya, Japan. 8. Department of Obstetrics, Osaka City General Hospital, Osaka, Japan. 9. Clinical Genetics Unit, Kyoto University Hospital, Kyoto, Japan. 10. Department of Obstetrics and Gynaecology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. 11. Boshi-Aiikukai Maternal & Child Health Center, Aiiku Clinic, Tokyo, Japan. 12. Departments of Obstetrics and Gynaecology, Saitama Medical University School of Medicine, Saitama, Japan. 13. Department of Maternal and Fetal Medicine, Tohoku University Graduate School of Medicine, Miyagi Children's Hospital, Sendai, Japan. 14. Department of Obstetrics and Gynaecology, Niigata University Medical and Dental Hospital, Niigata, Japan. 15. Department of Obstetrics and Gynaecology, Kobe University Graduate School of Medicine, Kobe, Japan. 16. Department of Obstetrics and Gynaecology, Shikoku Medical Centre for Children and Adults, Kagawa, Japan. 17. Department of Obstetrics and Gynaecology, The University of Tokushima Faculty of Medicine, Tokushima, Japan. 18. Department of Obstetrics, Osaka Women's and Child's Hospital, Osaka, Japan. 19. Department of Obstetrics and Gynaecology, Osaka University Graduate School of Medicine, Osaka, Japan. 20. Department of Obstetrics and Gynaecology, Tokyo Women's Medical University, Tokyo, Japan. 21. Department of Obstetrics and Gynaecology, Japanese Red Cross Medical Centre, Tokyo, Japan. 22. Department of Obstetrics and Gynaecology, Showa University Northern Yokohama Hospital, Yokohama, Japan. 23. Departments of Obstetrics and Gynaecology, Mito Saiseikai General Hospital, Ibaraki, Japan. 24. Department of Obstetrics and Gynaecology, Kobe Adventist Hospital, Kobe, Japan. 25. Department of Obstetrics and Gynaecology, Chugokudenryoku Hospital, Hiroshima, Japan. 26. Department of Obstetrics and Gynaecology, Hokkaido University Hospital, Hokkaido, Japan. 27. Department of Obstetrics and Gynaecology, National Hospital Organization, Kyushu Medical Centre, Fukuoka, Japan. 28. Division of Clinical Genetics, Tottori University Hospital, Yonago, Japan. 29. Department of Obstetrics and Gynaecology, Nara Medical University, Nara, Japan. 30. Department of Obstetrics and Gynaecology, Tokai University, Isehara, Japan. 31. Department of Obstetrics and Gynaecology, AOI Nagoya Hospital, Nagoya, Japan. 32. Graduate School of Health and Welfare Sciences, International University of Health and Welfare, Tokyo, Japan.
Abstract
OBJECTIVE: Maternal characteristics and neonatal outcomes associated with cell-free DNA (cfDNA) results were analysed retrospectively to assess the details of false-positive and false-negative results after initial blood sampling in non-invasive prenatal testing (NIPT). STUDY DESIGN: A multicentre retrospective study was performed for women undergoing NIPT who received discordant cfDNA results between April 2013 and March 2018. The NIPT data obtained using massive parallel sequencing were studied in terms of maternal background, fetal fraction, z-scores, invasive procedure results and neonatal outcomes after birth. RESULTS: Of the 56,545 women who participated in this study, 54 false-positive (0.095 %) and three false-negative (0.006 %) cases were found. Seven of the 54 false-positive cases (13.0 %) had vanishing twin on ultrasonography. Among the 18 false-positive cases of trisomy 18, confined placental mosaicism (CPM) was confirmed in three cases (16.7 %), while CPM was present in one of the three false-negative cases of trisomy 21. CONCLUSION: These data suggest that the incidence of women with false-positive or false-negative results is relatively low, that such false results can often be explained, and that vanishing twin and CPM are potential causes of NIPT failure. Genetic counselling with regard to false results is important for clients prior to undergoing NIPT.
OBJECTIVE: Maternal characteristics and neonatal outcomes associated with cell-free DNA (cfDNA) results were analysed retrospectively to assess the details of false-positive and false-negative results after initial blood sampling in non-invasive prenatal testing (NIPT). STUDY DESIGN: A multicentre retrospective study was performed for women undergoing NIPT who received discordant cfDNA results between April 2013 and March 2018. The NIPT data obtained using massive parallel sequencing were studied in terms of maternal background, fetal fraction, z-scores, invasive procedure results and neonatal outcomes after birth. RESULTS: Of the 56,545 women who participated in this study, 54 false-positive (0.095 %) and three false-negative (0.006 %) cases were found. Seven of the 54 false-positive cases (13.0 %) had vanishing twin on ultrasonography. Among the 18 false-positive cases of trisomy 18, confined placental mosaicism (CPM) was confirmed in three cases (16.7 %), while CPM was present in one of the three false-negative cases of trisomy 21. CONCLUSION: These data suggest that the incidence of women with false-positive or false-negative results is relatively low, that such false results can often be explained, and that vanishing twin and CPM are potential causes of NIPT failure. Genetic counselling with regard to false results is important for clients prior to undergoing NIPT.