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Verification of DOHaD theory in the offspring born to mother with preeclampsia, and establishment of early intervention for long term consequences due to preeclampsia.

Research Project

Project/Area Number 19K18637
Research Category

Grant-in-Aid for Early-Career Scientists

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

Principal Investigator

Ushida Takafumi  名古屋大学, 医学部附属病院, 病院講師 (90805152)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords妊娠高血圧腎症 / DOHaD / 早産児 / 脳障害 / 炎症 / 心血管障害
Outline of Research at the Start

妊娠高血圧腎症は妊娠により血圧上昇、蛋白尿を来す疾患である。近年の疫学調査により、妊娠高血圧腎症を発症した妊婦から生まれた児は、脳性麻痺や自閉症などのリスクが高いことや、将来心血管障害やメタボリック症候群などを発症しやすいことが明らかになってきた。我々は妊娠中の「異常炎症」による胎内環境の悪化が出生後の疾患リスクの上昇に関与するのではないかという仮説を立て、動物モデル(炎症誘発性妊娠高血圧腎症モデル)や臨床検体(早産児の在胎修正40週頭部MRI画像)を用いて検証することを研究目的とした。

Outline of Final Research Achievements

Growing evidence demonstrated that offspring born from mothers with hypertensive disorders of pregnancy (HDP) have increased risk for various complications such as cardiovascular disease, diabetes mellitus, and neurodevelopmental disorders. In this study, we demonstrated that abnormal maternal inflammation can contribute to increased risk of cardiovascular disease and metabolic disease in the offspring, and that the effects of inflammation may cross generations.
In addition, we evaluated the alterations of brain volume, brain injury score, and metabolism attributed to intrauterine exposure to HDP in very preterm infants. Our study contributed to the elucidation of mechanism of neurodevelopmental disorders.

Academic Significance and Societal Importance of the Research Achievements

妊娠高血圧症候群を発症した母から生まれた児は、将来様々な疾患のリスクが高いことが知られている。本研究ではモデル動物を用いて、母体の「異常炎症」が児の将来の心血管障害・糖尿病の発症機序の一つであること、またそれが次世代へ影響しうることを明らかにした。本研究は、母体の「異常炎症」を抑える治療を行うことで、児の長期的な予後の改善につながる可能性を示唆している。また、新生児の頭部MRI画像を用いることで神経学的後障害のハイリスク児を早期に抽出することができる可能性がある。これらの観点から、本研究により周産期・新生児医療における重要な知見が得られたと考える。

Report

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

    (14 results)

All 2022 2021 2020 2019

All Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 1 results) Presentation (5 results) (of which Int'l Joint Research: 2 results) Book (1 results)

  • [Journal Article] Aberrant inflammation in rat pregnancy leads to cardiometabolic alterations in the offspring and intrauterine growth restriction in the F2 generation2022

    • Author(s)
      Takafumi Ushida, Tiziana Cotechini, Nicole Protopappas, Aline Atallah, Charlotte Collyer, Shannyn K. Macdonald-Goodfellow, M. Yat Tse, Louise M. Winn, Stephen C. Pang, Michael A. Adams, Maha Othman, Tomomi Kotani, Hiroaki Kajiyama and Charles H. Graham
    • Journal Title

      Journal of Developmental Origins of Health and Disease

      Volume: -

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Hypertensive disorders of pregnancy and alterations in brain metabolites in preterm infants: A multi-voxel proton MR spectroscopy study2021

    • Author(s)
      Katsuki Satoru、Ushida Takafumi、Kidokoro Hiroyuki、Nakamura Noriyuki、Iitani Yukako、Fuma Kazuya、Imai Kenji、Nakano-Kobayashi Tomoko、Sato Yoshiaki、Hayakawa Masahiro、Natsume Jun、Kajiyama Hiroaki、Kotani Tomomi
    • Journal Title

      Early Human Development

      Volume: 163 Pages: 105479-105479

    • DOI

      10.1016/j.earlhumdev.2021.105479

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prevalence and risk factors of labor-onset hypertension: A multicenter study in Japan2021

    • Author(s)
      Ushida Takafumi、Kotani Tomomi、Imai Kenji、Nakano-Kobayashi Tomoko、Iitani Yukako、Nakamura Noriyuki、Moriyama Yoshinori、Yoshida Shigeru、Yamashita Mamoru、Kajiyama Hiroaki
    • Journal Title

      Pregnancy Hypertension

      Volume: 26 Pages: 48-53

    • DOI

      10.1016/j.preghy.2021.08.118

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of maternal hypertensive disorders of pregnancy on brain volumes at term-equivalent age in preterm infants: A voxel-based morphometry study.2021

    • Author(s)
      Ushida T, Kidokoro H, Nakamura N, Katsuki S, Imai K, Nakano-Kobayashi T, Moriyama Y, Sato Y, Hayakawa M, Natsume J, Kajiyama H, Kotani T.
    • Journal Title

      Pregnancy hypertension

      Volume: 25 Pages: 143-149

    • DOI

      10.1016/j.preghy.2021.06.003

    • NAID

      120007190673

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Platelet counts during normal pregnancies and pregnancies complicated with hypertensive disorders2021

    • Author(s)
      Ushida Takafumi、Kotani Tomomi、Moriyama Yoshinori、Imai Kenji、Nakano-Kobayashi Tomoko、Kinoshita Fumie、Nakamura Noriyuki、Iitani Yukako、Yoshida Shigeru、Yamashita Mamoru、Kajiyama Hiroaki
    • Journal Title

      Pregnancy Hypertension

      Volume: 24 Pages: 73-78

    • DOI

      10.1016/j.preghy.2021.02.013

    • NAID

      120007175392

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Postpartum alterations following inflammation in rat pregnancy: a discovery proteomic analysis2021

    • Author(s)
      Ushida Takafumi、Kotani Tomomi、Moriyama Yoshinori、Hindmarch Charles C T、Cotechini Tiziana、Imai Kenji、Nakano-Kobayashi Tomoko、Kajiyama Hiroaki、Graham Charles H
    • Journal Title

      Reproduction

      Volume: 161 Issue: 5 Pages: 513-522

    • DOI

      10.1530/rep-20-0388

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Mortality and neurological outcomes in extremely and very preterm infants born to mothers with hypertensive disorders of pregnancy2021

    • Author(s)
      Nakamura Noriyuki、for the Neonatal Research Network of Japan、Ushida Takafumi、Nakatochi Masahiro、Kobayashi Yumiko、Moriyama Yoshinori、Imai Kenji、Nakano-Kobayashi Tomoko、Hayakawa Masahiro、Kajiyama Hiroaki、Kikkawa Fumitaka、Kotani Tomomi
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 1729-1729

    • DOI

      10.1038/s41598-021-81292-7

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Maternal low birth weight and hypertensive disorders of pregnancy2021

    • Author(s)
      Ushida Takafumi、Kotani Tomomi、Kinoshita Fumie、Imai Kenji、Nakano-Kobayashi Tomoko、Nakamura Noriyuki、Moriyama Yoshinori、Yoshida Shigeru、Yamashita Mamoru、Kajiyama Hiroaki
    • Journal Title

      Pregnancy Hypertension

      Volume: 23 Pages: 5-10

    • DOI

      10.1016/j.preghy.2020.10.010

    • NAID

      120007164845

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Presentation] Intrauterine exposure to hypertensive disorders of pregnancy and postnatal growth in extremely and very preterm infants2021

    • Author(s)
      Takafumi Ushida
    • Organizer
      The 22th World Congress of ISSHP
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Hypertensive disorders of pregnancy and alterations in brain metabolites in preterm infants: a multi-voxel proton MR spectroscopy study2021

    • Author(s)
      Satoru Katsuki, Takafumi Ushida
    • Organizer
      The 22th World Congress of ISSHP
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 妊娠高血圧症候群を発症した母から生まれた早産児における、修正満期MRIに よる脳容積および脳障害スコアの検討2020

    • Author(s)
      牛田貴文
    • Organizer
      日本産婦人科学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 母体妊娠高血圧症候群が児の神経学的予後に与える影響2019

    • Author(s)
      中村紀友喜、牛田貴文
    • Organizer
      第40回妊娠高血圧学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 妊娠高血圧腎症自体が将来の心血管障害やメタボリック症候群の発症の原因となる2019

    • Author(s)
      牛田貴文
    • Organizer
      第43回日本女性 栄養・代謝学会学術集会
    • Related Report
      2019 Research-status Report
  • [Book] 産科と婦人科2019

    • Author(s)
      牛田貴文
    • Total Pages
      6
    • Publisher
      診断と治療社
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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