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Establishment of a method for predicting the onset of preeclampsia and verification of the preventive effect of low-dose aspirin

Research Project

Project/Area Number 19K18653
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionShowa University

Principal Investigator

Tokunaka Mayumi  昭和大学, 医学部, 講師 (10643710)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords妊娠高血圧腎症 / アスピリン / 発症予測
Outline of Research at the Start

妊娠11~13週で血圧測定、既往歴、子宮動脈PI、血清中PlGFを測定し妊娠高血圧症候群の発症リスクのある妊婦を抽出できるとされる。マルチプレックスシステムを用いて網羅的なタンパク発現の高感度な定量的解析を、また母体血漿を用いてcell-free RNAを抽出し遺伝子発現解析を行うことで、より高感度なリスク評価法を検討する。その上でハイリスク群をアスピリン服用群と非服用群に二分し、妊娠20週頃の血液を同様に解析することで、アスピリン投与により変化するタンパク発現パターンの変化の病態生理を把握するとともに、アスピリン治療効果をモニターする分子マーカーの探索を行い、その精度を明らかにする。

Outline of Final Research Achievements

It was investigated that the usefulness of a method for extracting pregnant women at high risk of developing preeclampsia (PE) in early pregnancy in Japanese population. The combination of maternal background, mean blood pressure, bilateral uterine artery PI, and PlGF at 11-13 weeks of gestation resulted in a screening positive rate of 10% and a detection rate of 91% for preterm PE, compared with Europeans. The result was published as "Accuracy of the FMF Bayes theorem-based model for predicting preeclampsia at 11-13 weeks of gestation in a Japanese population" in Hypertension Research.
In addition, for the prediction of PE onset, it was shown that screening at two stages of pregnancy, at 11-13 weeks and at 19-24 weeks of gestation using maternal blood pressure and serum PlGF level/serum sFlt-1/PlGF ratio may be useful in Japanese population. Furthermore, low-dose aspirin intake was shown not to affect PE risk assessment biomarkers at 11-13 weeks of gestation.

Academic Significance and Societal Importance of the Research Achievements

妊娠初期に妊娠高血圧腎症発症ハイリスク妊婦を抽出し低用量アスピリンを投与することにより発症予防することの研究成果が欧州の多施設共同研究で示されたが日本人では十分検討されていない。そこでスクリーニング法とアスピリンによる予防効果をアジア人で確認する国際的共同研究を立ち上げた。この研究において妊娠11-13週に採血した検体を用い、ハイリスク妊婦を抽出するためのより感度の良いバイオマーカーの抽出を行った。妊娠初期のデータに妊娠中期の血清マーカーを組み合わせることで、より精度高く予測できることが示された。また、妊娠高血圧腎症発症予知スクリーニング実施時点でのアスピリン内服の影響がないことも確認できた。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (24 results)

All 2023 2022 2021 Other

All Int'l Joint Research (15 results) Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (7 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results)

  • [Int'l Joint Research] Chinese University of Hong Kong/Kwong Wah Hospital(その他の国・地域 Hong Kong)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] Nanjing Drum Tower Hospital/Angel Women & Children Hospital(中国)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] Chulalonglkorn University Hoapital/Siriraj Hospital/Chiang Mai Hospital(タイ)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] Philippine General Hospital/Harapan Kita Hospital/UKM Medical Centre(フィリピン)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] Hanoi O&G Hospital(ベトナム)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] Chinese University of Hong Kong/Kwong Wah Hospital(その他の国・地域 Hong Kong)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Nanjing Drum Tower Hospital/Angel Women & Children Hospital(中国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Chulalonglkorn University Hoapital/Siriraj Hospital/Chiang Mai Hospital(タイ)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Philippine General Hospital/Harapan Kita Hospital/UKM Medical Centre(フィリピン)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Hanoi O&G Hospital(ベトナム)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Chinese University of Hong Kong/Kwong Wah Hospital(その他の国・地域 Hong Kong)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] Nanjing Drum Tower Hospital/Angel Women & Children Hospital(中国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] Chulalonglkorn University Hoapital/Siriraj Hospital/Chiang Mai Hospital(タイ)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] Philippine General Hospital/Harapan Kita Hospital/UKM Medical Centre(フィリピン)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] Hanoi O&G Hospital(ベトナム)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Prediction of Preeclampsia2021

    • Author(s)
      Matsuoka Ryu、Takita Hiroko、Sekizawa Akihiko、Tokunaka Mayumi、Goto Minako、Saito Mizue、Hamada Shoko
    • Journal Title

      Donald School Journal of Ultrasound in Obstetrics and Gynecology

      Volume: 15 Issue: 3 Pages: 306-311

    • DOI

      10.5005/jp-journals-10009-1716

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Correction: Accuracy of the FMF Bayes theorem-based model for predicting preeclampsia at 11?13 weeks of gestation in a Japanese population2021

    • Author(s)
      Goto Minako、Koide Keiko、Tokunaka Mayumi、Takita Hiroko、Hamada Shoko、Nakamura Masamistu、Matsuoka Ryu、Sekizawa Akihiko、Poon Liona C.
    • Journal Title

      Hypertension Research

      Volume: - Issue: 6 Pages: 732-732

    • DOI

      10.1038/s41440-021-00653-x

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Preeclampsia Screening2023

    • Author(s)
      德中真由美
    • Organizer
      第2回日本産婦人科超音波研究会学術集会スポンサードセミナー
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 平均血圧値と血清PlGF、sFlt-1値による妊娠高血圧腎症発症予測の2段階スクリーニングモデルの作成とその有用性に関する検討2023

    • Author(s)
      栗木あかね 後藤未奈子 小出馨子 徳中真由美 瀧田寛子 山下有加 松岡隆 関沢明彦
    • Organizer
      第75回日本産科婦人科学会学術講演会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Impact of low-dose aspirin initiated since early pregnancy on the FMF Bayes theorem-based model for predicting preeclampsia at 11-13 weeks of gestation2022

    • Author(s)
      Mayumi Tokunaka, Minako Goto, Hiroko Takita, Tatsuya Arakaki, Shoko Hamada, Keiko Koide, Ryu Matsuoka, Akihiko Sekizawa
    • Organizer
      The 1st Annual Congress of the Japan Society of Ultrasound in Obstetrics and Gynecology
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Impact of low-dose aspirin initiated since early pregnancy on the FMF Bayes theorem-based model for predicting preeclampsia at 11-13 weeks of gestation2022

    • Author(s)
      Mayumi Tokunaka, Minako Goto, Hiroko Takita, Tatsuya Arakaki, Shoko Hamada, Keiko Koide, Ryu Matsuoka, Akihiko Sekizawa
    • Organizer
      32nd World Congress on Ultrasound in Obstetrics and Gynecology
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 妊娠初期からの低用量アスピリン内服の妊娠11-13週の妊娠高血圧腎症発症予測への影響2021

    • Author(s)
      徳中真由美 後藤未奈子 瀧田寛子 新垣達也  濱田尚子 小出馨子 松岡 隆 関沢明彦
    • Organizer
      第41回日本妊娠高血圧学会学術講演会
    • Related Report
      2021 Research-status Report
  • [Presentation] 妊娠高血圧症候群・胎児発育不全の予知・予防とアスピリンについて2021

    • Author(s)
      徳中真由美 後藤未奈子 瀧田寛子 新垣達也  濱田尚子 小出馨子 松岡 隆 関沢明彦
    • Organizer
      第41回日本妊娠高血圧学会学術講演会 シンポジウム3【妊娠高血圧症候群・胎児発育不全の予知・予防】
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Impact of low-dose aspirin initiated since early pregnancy on the FMF Bayes theorem-based model for predicting preeclampsia at 11-13 weeks of gestation2021

    • Author(s)
      Mayumi Tokunaka, Minako Goto, Hiroko Takita, Tatsuya Arakaki, Shoko Hamada, Keiko Koide, Ryu Matsuoka, Akihiko Sekizawa
    • Organizer
      The 1st Annual Congress of the Japan Society of Ultrasound in Obstetrics and Gynecology
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2024-01-30  

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