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Development of a prediction model for the phenotype of preterm infants based on epigenetic memory.

Research Project

Project/Area Number 20K16916
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionThe University of Tokyo

Principal Investigator

Kashima Kohei  東京大学, 医学部附属病院, 講師 (10869077)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2020: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000)
KeywordsDNAメチル化 / 早産児 / エピゲノム記憶 / 炎症 / 早産 / 表現型予測 / 遺伝子発現 / エピジェネティクス
Outline of Research at the Start

早産児は周産期に栄養不良や低酸素に曝露され、生存のための適応を余儀なくされることが多い。この「適応過程で、疾病体質が形成される」のがDOHaDの概念であり、エピジェネティクスの関与が想定されているが、標的分子は十分に解明されていない。本研究では、代表者がこれまでの研究で得た知見から、早産児におけるエピゲノム記憶候補に焦点を絞り、血液等のエピゲノム・蛋白データを更に集積し、胎児期エピゲノム変化による中長期的な遺伝子発現・表現型への関連を明らかにする。早産児の病態・予後は胎児期の状態に大きく左右されるが、本研究によりエピゲノムデータからの表現型予測法開発に繋がり、臨床的にも大きく貢献が期待される。

Outline of Final Research Achievements

The objective of this study was to elucidate whether fetal epigenetic alteration predict the baby's traits among preterm infants by analyzing the association between fetal epigenetic alterations, gene expressions, and the baby's chronic traits. The coronavirus pandemic restricted the course of this study, and subsequently I was obliged to modify the goal. I published the results of "Identification of epigenetic memory candidates associated with gestational age at birth through analysis of methylome and transcriptional data". In addition, I found the epigenetic alterations associated with inflammation of placenta, by collaborationg with co-researchers. Now, I am preparing for submission of the results.

Academic Significance and Societal Importance of the Research Achievements

我が国の低出生体重児の出生率は10%に上り先進国の中でも一位である。新生児医療の進歩により低出生体重児の救命率が飛躍的に向上しているが、一方でこれらのハイリスク児は成人期に生活習慣病、骨粗鬆症、精神疾患をはじめとする慢性疾患に罹患しやすく、周産期の悪環境曝露により疾病体質が形成されるのではないかと言われている(DOHaD: Developmental Origin of Health and Diseases)。DOHaDの中で重要と想定されているのが、DNAメチル化などエピジェネティクスである。年々、早産児の長期フォローの重要性は高まっており、本成果は早産児の健康計画勘案に貢献すると考える。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (21 results)

All 2024 2023 2022 2021

All Journal Article (11 results) (of which Peer Reviewed: 9 results,  Open Access: 4 results) Presentation (10 results) (of which Int'l Joint Research: 3 results,  Invited: 8 results)

  • [Journal Article] The importance of designing a protector for a preterm and low birth weight infant with ectopia cordis2024

    • Author(s)
      Mukai Takeo、Ito Atsushi、Shitara Yoshihiko、Kashima Kohei、Kobayashi Mika、Shiraga Kazuhiro、Takazawa Shinya、Takahashi Naoto
    • Journal Title

      Clinical Case Reports

      Volume: 12 Issue: 1

    • DOI

      10.1002/ccr3.8403

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Treatments and outcomes of neonatal disseminated intravascular coagulation with and without neonatal asphyxia: A retrospective study using nationwide data in Japan2024

    • Author(s)
      Kitaoka Hiroki、Konishi Takaaki、Shitara Yoshihiko、Ito Atsushi、Kashima Kohei、Hashimoto Yohei、Matsui Hiroki、Kato Motohiro、Takahashi Naoto、Yasunaga Hideo
    • Journal Title

      Pediatrics & Neonatology

      Volume: 65 Issue: 2 Pages: 117-122

    • DOI

      10.1016/j.pedneo.2023.07.003

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Risk factors for anemia of prematurity among 30-35-week preterm infants2023

    • Author(s)
      Kitaoka Hiroki、Shitara Yoshihiko、Kashima Kohei、Ochiai Shingo、Chikai Hayato、Watanabe Keiko、Ida Hiroto、Kumagai Tadayuki、Takahashi Naoto
    • Journal Title

      FUKUSHIMA JOURNAL OF MEDICAL SCIENCE

      Volume: 69 Issue: 2 Pages: 115-123

    • DOI

      10.5387/fms.2022-21

    • ISSN
      0016-2590, 2185-4610
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of Milrinone on Neonates after Patent Ductus Arteriosus Ligation: A Retrospective Nationwide Database Study2023

    • Author(s)
      Kitaoka Hiroki、Konishi Takaaki、Shitara Yoshihiko、Ito Atsushi、Kashima Kohei、Fujita Asahi、Matsui Hiroki、Kato Motohiro、Takahashi Naoto、Yasunaga Hideo
    • Journal Title

      Neonatology

      Volume: 120 Issue: 6 Pages: 751-759

    • DOI

      10.1159/000533958

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Case report: A case of fetal umbilical vein varix presenting disseminated intravascular coagulation, polycythemia, and neonatal hepatitis in an extremely low birth weight infant2023

    • Author(s)
      Sekiguchi Mariko、Mukai Takeo、Shitara Yoshihiko、Kashima Kohei、Seyama Takahiro、Kumasawa Keiichi、Takahashi Naoto
    • Journal Title

      Frontiers in Pediatrics

      Volume: 11

    • DOI

      10.3389/fped.2023.1154820

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 【Late preterm・Early termを展望する】在胎週数とDNAメチル化変化2022

    • Author(s)
      鹿嶋晃平
    • Journal Title

      周産期医学

      Volume: 52 Pages: 464-467

    • Related Report
      2022 Research-status Report
  • [Journal Article] 【環境の影響とその遺伝・DOHaD】ヒト周産期異常症例で実際に観察される環境依存的エピゲノム変化とその遺残2022

    • Author(s)
      鹿嶋晃平, 河合智子
    • Journal Title

      遺伝子医学

      Volume: 12 Pages: 20-24

    • Related Report
      2022 Research-status Report
  • [Journal Article] Perinatal management of fetal congenital heart disease in the era of COVID-192022

    • Author(s)
      Hitomi Masuda, Ryo Inuzuka, Masatake Toshimitsu, Kohei Kashima, Hikoro Matsui
    • Journal Title

      Pediatrics international

      Volume: 64 Issue: 1

    • DOI

      10.1111/ped.14932

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Treatment of Extremely Preterm Infants With Birthweight Below 300 g: Case Series2021

    • Author(s)
      Yoshihiko Shitara, Satsuki Kakiuchi, Takeo Mukai, Kohei Kashima, Motohiro Kato, Naoto Takahashi
    • Journal Title

      Frontiers in Pediatrics

      Volume: 9 Pages: 758683-758683

    • DOI

      10.3389/fped.2021.758683

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Beckwith-Wiedemann syndrome with infantile hepatic hemangiomas2021

    • Author(s)
      足立夏帆, 入佐千晴, 鹿嶋晃平, 垣内五月, 西村力, 高見尚平, 渡辺美穂, 高橋尚人
    • Journal Title

      Journal of Japan Society of Perinatal and Neonatal Medicine

      Volume: 57 Issue: 2 Pages: 371-375

    • DOI

      10.34456/jjspnm.57.2_371

    • NAID

      130008085001

    • ISSN
      1348-964X, 2435-4996
    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of epigenetic memory candidates associated with gestational age at birth through analysis of methylome and transcriptional data2021

    • Author(s)
      Kashima Kohei, Kawai Tomoko, 共同筆頭著者、他22名
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 3381-3381

    • DOI

      10.1038/s41598-021-83016-3

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Epigenetic memory among preterm infants2023

    • Author(s)
      Kohei Kashima
    • Organizer
      The 22nd Congress of the Federation of Asia and Oceania Perinatal Societies
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 新生児医療とエピジェネティクス~早産児・低出生体重児におけるエピゲノム異常とその長期遺残~2022

    • Author(s)
      鹿嶋晃平
    • Organizer
      第58回日本周産期・新生児医学会学術集会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 出生直後から遷延する呼吸障害を呈したムコ多糖症II型の1例2022

    • Author(s)
      木本 豪, 垣内 五月, 衣斐 恭介, 久世 崇史, 片山 有里子, 杉本 美紀, 向井 丈雄, 設樂 佳彦, 伊藤 淳, 井上 毅信, 鹿嶋 晃平, 高橋 尚人
    • Organizer
      第58回日本周産期・新生児医学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] 新生児期に腸捻転を発症しNICU退院後に歌舞伎症候群と診断した2例2022

    • Author(s)
      杉本 美紀, 伊藤 淳, 井上 毅信, 衣斐 恭介, 片山 有里子, 木本 豪, 久世 嵩史, 小林 真美, 設楽 佳彦, 廣畑 晃司, 松岡 貴子, 向井 丈雄, 鹿嶋 晃平, 高橋 尚人
    • Organizer
      第58回日本周産期・新生児医学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] 新生児医療とエピジェネティクス~早産児・低出生体重児におけるエピゲノム異常と その長期遺残~2022

    • Author(s)
      鹿嶋晃平
    • Organizer
      第58回周産期・新生児医学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 早産児・低出生体重児における 血液検体での網羅的DNAメチル化・遺伝子発現解析を用いた エピジェネティック変化の探索2021

    • Author(s)
      鹿嶋晃平
    • Organizer
      第20回新生児栄養フォーラム
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 早産児に観察されるエピゲノム異常とその長期遺残2021

    • Author(s)
      鹿嶋晃平
    • Organizer
      日本人類遺伝学会第66回大会・第28回日本遺伝子診療学会大会 合同開催
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Epigenetic memory candidates associated with gestational age - a Japanese preterm infants’ study2021

    • Author(s)
      Kohei Kashima
    • Organizer
      The 16th Congress of Asian Society for Pediatric Research (ASPR)
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 早産児・低出生体重児における血液検体での網羅的DNAメチル化・遺伝子発現解析を用いたエピジェネティック変化の探索2021

    • Author(s)
      鹿嶋晃平
    • Organizer
      第20回新生児栄養フォーラム
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Epigenetic memory candidates associated with gestational age at birth - a Japanese preterm infants' study2021

    • Author(s)
      Kohei Kashima
    • Organizer
      The 16 th Congress of Asian Society of Pediatric Research
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited

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Published: 2020-04-28   Modified: 2025-01-30  

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