Osamu Samura1, Akihiko Sekizawa2, Nobuhiro Suzumori3, Aiko Sasaki4, Seiji Wada4, Haruka Hamanoue5, Fumiki Hirahara5, Hideaki Sawai6, Hiroaki Nakamura7, Takahiro Yamada8, Kiyonori Miura9, Hideaki Masuzaki9, Setsuko Nakayama10, Takashi Okai10, Yoshimasa Kamei11, Akira Namba11, Jun Murotsuki12, Tomohiro Tanemoto1, Akimune Fukushima13, Kazufumi Haino14, Shinya Tairaku15, Keiichi Matsubara16, Kazuhisa Maeda17, Takashi Kaji18, Masanobu Ogawa19, Hisao Osada20, Haruki Nishizawa21, Yoko Okamoto22, Takeshi Kanagawa22,23, Aiko Kakigano23, Michihiro Kitagawa24, Masaki Ogawa25, Shunichiro Izumi26, Yukiko Katagiri27, Naoki Takeshita28, Yasuyo Kasai29, Katsuhiko Naruse30, Reiko Neki31, Hisashi Masuyama32, Maki Hyodo33, Yukie Kawano34, Takashi Ohba35, Kiyotake Ichizuka36, Yasuhiro Kido37, Toshiyuki Fukao38, Norio Miharu39, Takeshi Nagamatsu40, Atsushi Watanabe41, Naoki Hamajima42, Masaya Hirose43, Ayako Sanui44, Nahoko Shirato2, Junko Yotsumoto45, Miyuki Nishiyama4, Tatsuko Hirose2, Haruhiko Sago4. 1. Department of Obstetrics and Gynecology, Jikei University School of Medicine, Tokyo, Japan. 2. Department of Obstetrics and Gynecology, Showa University School of Medicine, Tokyo, Japan. 3. Division of Clinical and Molecular Genetics, Department of Obstetrics and Gynecology, Nagoya City University, Nagoya, Japan. 4. Center of Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Tokyo, Japan. 5. Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan. 6. Department of Obstetrics and Gynecology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan. 7. Department of Obstetrics, Osaka City General Hospital, Osaka City, Osaka, Japan. 8. Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan. 9. Department of Obstetrics and Gynecology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. 10. Maternal and Child Health Center, Aiiku Hospital, Tokyo, Japan. 11. Departments of Obstetrics and Gynecology, Saitama Medical University School of Medicine, Moroyama, Iruma, Saitama, Japan. 12. Department of Maternal and Fetal Medicine, Tohoku University Graduate School of Medicine, Miyagi Children's Hospital, Sendai, Miyagi, Japan. 13. Departments of Obstetrics and Gynecology, Iwate Medical University School of Medicine, Morioka, Iwate, Japan. 14. Department of Obstetrics and Gynecology, Niigata University Medical and Dental Hospital, Niigata, Japan. 15. Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan. 16. Department of Obstetrics and Gynecology, Ehime University School of Medicine, Matsuyama, Ehime, Japan. 17. Department of Obstetrics and Gynecology, Shikoku Medical Center for Children and Adults, Zentsuji, Kagawa, Japan. 18. Department of Obstetrics and Gynecology, University of Tokushima Faculty of Medicine, Tokushima, Japan. 19. Department of Obstetrics and Gynecology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan. 20. Department of Obstetrics and Gynecology, Chiba University Graduate School of Medicine, Chiba, Japan. 21. Department of Obstetrics and Gynecology, Fujita Health University, Toyoake, Aichi, Japan. 22. Department of Obstetrics, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Osaka, Japan. 23. Department of Obstetrics and Gynecology, Osaka University Faculty of Medicine, Suita, Osaka, Japan. 24. Sanno Hospital, Tokyo, Japan. 25. Perinatal Medical Center, Tokyo Women's Medical University Hospital, Tokyo, Japan. 26. Department of Obstetrics and Gynecology, Tokai University School of Medicine, Hiratsuka, Kanagawa, Japan. 27. Department of Obstetrics and Gynecology, Toho University Omori Medical Center, Tokyo, Japan. 28. Toho University Omori Medical Center, Tokyo, Japan. 29. Department of Obstetrics and Gynecology, Japanese Red Cross Medical Center, Tokyo, Japan. 30. Department of Obstetrics and Gynecology, Nara Medical University, Kashihara, Nara, Japan. 31. Department of Perinatology and Gynecology, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan. 32. Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Okayama, Japan. 33. Department of Obstetrics and Gynecology, Hiroshima University Graduate School of Medicine, Hiroshima, Japan. 34. Department of Molecular Pathology, Faculty of Medicine, Oita University, Oita, Japan. 35. Department of Obstetrics and Gynecology, Kumamoto University, Kumamoto, Japan. 36. Department of Obstetrics and Gynecology, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa, Japan. 37. Division of Clinical Genetics, Dokkyo Medical University Koshigaya Hospital, Mibu, Shimotsuga, Tochigi, Japan. 38. Department of Pediatrics, Graduate school of medicine, Gifu University, Gifu, Japan. 39. Department of Obstetrics and Gynecology, Chuden Hospital, Hiroshima, Japan. 40. Departments of Obstetrics and Gynecology, Tokyo University Hospital, Tokyo, Japan. 41. Division of Clinical Genetics, Nippon Medical School Hospital, Tokyo, Japan. 42. Department of Clinical Genetics, Nagoya City West Medical Center, Nagoya, Japan. 43. Departments of Obstetrics and Gynecology, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Hyogo, Japan. 44. Departments of Obstetrics and Gynecology, Fukuoka University Hospital, Fukuoka, Japan. 45. Departments of Genetic Counseling, Ochanomizu University, Tokyo, Japan.
Abstract
AIM: The purpose of this study was to report the 3-year experience of a nationwide demonstration project to introduce non-invasive prenatal testing (NIPT) of maternal plasma for aneuploidy, and review the current status of NIPT in Japan. METHODS: Tests were conducted to detect aneuploidy in high-risk pregnant women, and adequate genetic counseling was provided. The clinical data, test results, and pregnancy outcomes were recorded. We discuss the problems of NIPT on the basis of published reports and meta-analyses. RESULTS: From April 2013 to March 2016, 30 613 tests were conducted at 55 medical sites participating in a multicenter clinical study. Among the 30 613 women tested, 554 were positive (1.81%) and 30 021 were negative (98.1%) for aneuploidy. Of the 289, 128, and 44 women who tested positive for trisomies 21, 18, and 13, respectively, and underwent definitive testing, 279 (96.5%), 106 (82.8%), and 28 (63.6%) were determined to have a true-positive result. For the 13 481 women with negative result and whose progress could be traced, two had a false-negative result (0.02%). The tests were performed on the condition that a standard level of genetic counseling be provided at hospitals. CONCLUSION: Here, we report on the 3-year nationwide experience with NIPT in Japan. It is important to establish a genetic counseling system to enable women to make informed decisions regarding prenatal testing. Moreover, a welfare system is warranted to support women who decide to give birth to and raise children with chromosomal diseases.
AIM: The purpose of this study was to report the 3-year experience of a nationwide demonstration project to introduce non-invasive prenatal testing (NIPT) of maternal plasma for aneuploidy, and review the current status of NIPT in Japan. METHODS: Tests were conducted to detect aneuploidy in high-risk pregnant women, and adequate genetic counseling was provided. The clinical data, test results, and pregnancy outcomes were recorded. We discuss the problems of NIPT on the basis of published reports and meta-analyses. RESULTS: From April 2013 to March 2016, 30 613 tests were conducted at 55 medical sites participating in a multicenter clinical study. Among the 30 613 women tested, 554 were positive (1.81%) and 30 021 were negative (98.1%) for aneuploidy. Of the 289, 128, and 44 women who tested positive for trisomies 21, 18, and 13, respectively, and underwent definitive testing, 279 (96.5%), 106 (82.8%), and 28 (63.6%) were determined to have a true-positive result. For the 13 481 women with negative result and whose progress could be traced, two had a false-negative result (0.02%). The tests were performed on the condition that a standard level of genetic counseling be provided at hospitals. CONCLUSION: Here, we report on the 3-year nationwide experience with NIPT in Japan. It is important to establish a genetic counseling system to enable women to make informed decisions regarding prenatal testing. Moreover, a welfare system is warranted to support women who decide to give birth to and raise children with chromosomal diseases.