Establishment of a diagnostic and management method for fetal circulatory insufficiency in twin-to-twin transfusion syndrome

• Project/Area Number: 16K11114
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Toho University
• Principal Investigator: Nakata Masahiko 東邦大学, 医学部, 教授 (10294646)
• Co-Investigator(Kenkyū-buntansha): 日根 幸太郎 東邦大学, 医学部, 助教 (50729308) ; 大路 斐子 東邦大学, 医学部, 助教 (90385641) ; 與田 仁志 東邦大学, 医学部, 教授 (90589053)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 双胎間輸血症候群 / 超音波ドプラ法 / 超音波2Dトラッキング法 / 胎児循環 / 胎児心不全 / 超音波パルスドプラ法 / NT-proBNP / Fractional Shortening / Fractional shortening / アルドステロン / 胎児・新生児学 / 超音波診断学 / 産科学

Outline of Final Research Achievements

To establish a diagnostic and management method for fetal circulatory insufficiency in twin-to-twin transfusion syndrome (TTTS), we validated the evaluation of fetal cardiac diastolic function using the ultrasound pulsed doppler method. The results showed that the Dual-gate Doppler evaluation of fetal left and right ventriclar E/e' was useful to assess the circadian function in the recipient twin in the early onset of TTTS.
We also demonstrated for the first time that an ultrasound 2D tracking system can be used to measure fractional shortening of the ventricle, which is an indicator of fetal contractility. It is hoped that this time the same method will be applied clinically.

Academic Significance and Societal Importance of the Research Achievements

双胎間輸血症候群は一絨毛膜双胎の約10％に発症する生命予後ないし神経学的発達予後の不良の疾患である。本研究では、双胎間輸血症候群の認められる胎児循環不全の早期診断法の探索と胎児循環の定量的な評価法の確立を目的として遂行され、Dual-gate Doppler法によるE/e'の測定や2Dトラッキング法によるfractional shorteningの計測が有用であることが世界で初めて明らかとなった。

Research Products

• [Journal Article] Feasibility of automated fetal fractional shortening measurement with two‐dimensional tracking and construction of a reference range for normal fetuses (2019)
  • Author(s): Sumito Nagasaki, Masahiko Nakata, Mayumi Takano, Kento Usui, Junya Sakuma, Eijiro Hayata, Mineto Morita
  • Journal Title: Journal of Medical Ultrasonics Volume: 46 Issue: 4 Pages: 462-272
  • DOI: 10.1007/s10396-019-00957-z
  • Peer Reviewed
• [Journal Article] Reproducibility of automated fetal heart rate measurement using a novel technique with two-dimensional tracking (2019)
  • Author(s): Nagai R, Miyashita S, Murata S, Takahashi Y, Tajima A, Nagasaki S, Takano M, Nakata M
  • Journal Title: J Med Ultrason Volume: 46 Issue: 1 Pages: 105-111
  • DOI: 10.1007/s10396-018-0893-y
  • Peer Reviewed
• [Journal Article] Diagnosis of umbilical cord entanglement in a monochorionic diamniotic twin pregnancy with spontaneous septostomy of the dividing membranes using dual-gate Doppler imaging. (2018)
  • Author(s): Ito A, Nakata M, Oji A, Takano M, Umemura N, Nagasaki S, Maemura T, Morita M
  • Journal Title: Journal of Medical Ultrasonics Volume: 45 Issue: 1 Pages: 189-192
  • DOI: 10.1007/s10396-017-0793-6
  • Peer Reviewed
• [Journal Article] Assessment of diastolic function of normal fetal heart using the Dual gate Doppler method. (2017)
  • Author(s): Takano M, Nakata M, Nagasaki S, Ueyama R, Morita M.
  • Journal Title: Ultrasound in Obstetrics and Gynecology Volume: - Issue: 2 Pages: 238-242
  • DOI: 10.1002/uog.18821
  • Peer Reviewed
• [Journal Article] 注目のTopics TTTSに対する胎児鏡下レーザー治療 今後の展開 吻合血管を考慮した凝固法 (2017)
  • Author(s): 中田雅彦, 早田英二郎
  • Journal Title: Fetal & Neonatal Medicine Volume: 9 Pages: 22-24
• [Journal Article] Fetoscopic laser photocoagulation for amniotic fluid discordance bordering on twin-twin transfusion syndrome: Feasibility, perinatal and long-term outcomes (2017)
  • Author(s): Ozawa K, Sugibayashi R, Wada S, Sumie M, Ishii K, Nakata M, Murakoshi T, Ito Y, Sago H
  • Journal Title: The Journal of Obstetrics and Gynaecology Research Volume: 43 Issue: 8 Pages: 1256-1262
  • DOI: 10.1111/jog.13349
  • Peer Reviewed
• [Presentation] Postoperative cerebroplacental ratio can predict subsequent fetal demise of donor or smaller twin after fetoscopic laser surgery (2018)
  • Author(s): Masahiko Nakata
  • Organizer: 28th World congress of international society of ultrasound in obstetrics and gynecology
  • Int'l Joint Research
• [Presentation] Dual gate Doppler法を用いたE/e'による胎児心拡張能の評価に関する検討 (2018)
  • Author(s): 鷹野真由実, 中田雅彦, 長崎澄人, 上山怜, 片桐由起子, 森田峰人, 与田仁志
  • Organizer: 第24回日本胎児心臓病学会
• [Presentation] Low cerebroplacental ratio can predict subsequent fetal demise of donor or smaller twin with abnormal umbilical artery flow after fetoscopic laser surgery (2017)
  • Author(s): Nakata M, Takano M, Nagasaki S, Ueyama R, Hayata E, Oji A, Maemura T
  • Organizer: The 27th World Congress on Ultrasound in Obstetrics and Gynecology
  • Int'l Joint Research
• [Presentation] Novel technique to assess fetal fractional shortening by two-dimensional tracking. (2017)
  • Author(s): Sumito Nagasaki, Masahiko Nakata, Mayumi Takano, Rei Ueyama, Mineto Morita
  • Organizer: The 27th World Congress on Ultrasound in Obstetrics and Gynecology
  • Int'l Joint Research
• [Presentation] Fetal E/e' by dual gate Doppler method in Twin-twin transfusion syndrome and relationship with amniotic fluid brain-type natriuretic peptide (2017)
  • Author(s): Takano M, Nakata M, Nagasaki S, Ueyama R, Oji A, Maemura T, Morita M
  • Organizer: The 27th World Congress on Ultrasound in Obstetrics and Gynecology
  • Int'l Joint Research
• [Presentation] 胎児鏡下胎盤吻合血管レーザー凝固術を施行したTTTS,selective IUGR症例における羊水中のNT-pro BNPの検討 (2017)
  • Author(s): 鷹野真由実, 中田雅彦, 佐久間淳也, 梅村なほみ, 長崎澄人, 上山怜, 大路斐子, 荒井博子, 前村俊満, 片桐由起子, 与田仁志, 森田峰人
  • Organizer: 第53回日本周産期・新生児医学会総会および学術集会
• [Presentation] 胎児鏡下胎盤吻合血管レーザー凝固術を施行したTTTS症例におけるDual gate Dopplerを用いたE/e'の評価 (2017)
  • Author(s): 鷹野真由実, 中田雅彦, 佐久間淳也, 梅村なほみ, 長崎澄人, 上山怜, 大路斐子, 荒井博子, 前村俊満, 片桐由起子, 与田仁志, 森田峰人
  • Organizer: 第53回日本周産期・新生児医学会総会および学術集会
• [Presentation] 2Dトラッキング法によるAutoFSを用いた胎児心収縮能の検討 (2017)
  • Author(s): 長崎澄人, 鷹野真由実, 梅村なほみ, 上山怜, 荒井博子, 片桐由起子, 与田仁志, 中田雅彦, 森田峰人
  • Organizer: 第53回日本周産期・新生児医学会総会および学術集会
• [Presentation] 2Dトラッキング法によるAutoFSを用いた胎児心収縮能の検討 (2017)
  • Author(s): 長崎澄人, 鷹野真由美実, 上山怜, 佐久間淳也, 早田英二郎, 中田雅彦, 森田峰人
  • Organizer: 日本超音波医学会第90会学術集会