Elucidation of pathophysioalogy of preterm birth and new therapeutic strategy -Application of highly sensitive and reliable PCR system for detection of microorganisism in amniotic fluid-

• Project/Area Number: 17K11220
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: University of Toyama
• Principal Investigator: YONEDA NORIKO 富山大学, 学術研究部医学系, 助教 (80377283)
• Co-Investigator(Kenkyū-buntansha): 齋藤 滋 富山大学, 大学本部, 学長 (30175351)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 早産 / 子宮内感染 / 子宮内炎症 / PCR / 迅速高感度病原微生物検出法 / 羊水中病原微生物 / 腸内細菌叢

Outline of Final Research Achievements

Intrauterine infection has a high frequency in women with very preterm birth less than 28 weeks of gestation. However, previous report showed that antibiotic therapy for preterm labor is not effective. We examined the presence of infection in amniotic fluid in patients with preterm labor using highly sensitive and reliable PCR system and reported that appropriate antibiotic therapy improves the perinatal outcome. In addition, amniotic fluid sludge (AFS) is a high-intensity aggregates observed near the internal uterine os by transvaginal sonography in a　case of preterm labor. Using highly sensitive and reliable PCR system, we first reported that AFS showed intrauterine inflammation but not intrauterine infection in patients with preterm labor.

Academic Significance and Societal Importance of the Research Achievements

予後不良とされる妊娠28週未満の早産の原因となる、子宮内（羊水中）病原微生物を迅速高感度PCR法を用いて検出し、適切な抗菌薬治療をおこなうことで、早産児の予後の改善につながるため、社会的意義がある。

Research Products

• [Journal Article] Risk factors for spontaneous miscarriage above 12 weeks or premature delivery in patients undergoing cervical polypectomy during pregnancy. (2020)
  • Author(s): Fukuta K, Yoneda S, Yoneda N, Shiozaki A, Nakashima A, Minamisaka T, Imura J, Saito S.
  • Journal Title: BMC Pregnancy Childbirth Volume: 20(1) Issue: 1 Pages: 20-27
  • DOI: 10.1186/s12884-019-2710-z
  • Peer Reviewed / Open Access
• [Journal Article] Japan Environment and Children’s Study (JECS) Group. Fermented foods and preterm birth risk from a prospective large cohort study: the Japan Environment and Children's study. (2019)
  • Author(s): Ito M, Takamori A, Yoneda S, Shiozaki A, Tsuchida A, Matsumura K, Hamazaki K, Yoneda N, Origasa H, Inadera H, Saito S
  • Journal Title: Environ Health Prev Med. Volume: 24 Issue: 1 Pages: 25-25
  • DOI: 10.1186/s12199-019-0782-z
  • Peer Reviewed
• [Journal Article] 【胎盤・臍帯・羊水を再び考える】 羊水の新しい知見 特に感染/炎症との関連(解説/特集) (2019)
  • Author(s): 米田 哲,米田徳子,齋藤 滋
  • Journal Title: 周産期医学 Volume: 49(1) Pages: 40-45
• [Journal Article] 17OHP-C in patients with spontaneous preterm labor and intact membranes: is there an effect according to the presence of intra-amniotic inflammation? (2018)
  • Author(s): Yoneda S, Yoneda N, Shiozaki A, Yoshino O, Ueno T, Niimi H, Kitajima I, Tamura K, Kawasaki Y, Makimoto M, Yoshida T, Saito S.
  • Journal Title: Am J Reprod Immunol. Volume: 79 Issue: 3 Pages: 1-11
  • DOI: 10.1111/aji.12867
  • Peer Reviewed / Open Access
• [Journal Article] 【早産管理2018－至適娩出時期をめぐって】 (2018)
  • Author(s): 米田徳子， 米田 哲， 齋藤 滋
  • Journal Title: 周産期医学 Volume: 48(5) Pages: 521-526
• [Journal Article] Sludge reflects intra-amniotic inflammation with or without microorganisms. (2018)
  • Author(s): Yoneda N, Yoneda S, Niimi H, Ito M, Fukuta K, Ueno T, Ito M, Shiozaki A, Kigawa M, Kitajima I, Saito S.
  • Journal Title: Am J Reprod Immunol. Volume: 79(2) Issue: 2 Pages: 1-8
  • DOI: 10.1111/aji.12807
  • Peer Reviewed / Open Access
• [Journal Article] In which preterm labor-patients is intravenous maintenance tocolysis effective? (2018)
  • Author(s): Yoneda S, Yoneda N, Fukuta K, Shima T, Nakashima A, Shiozaki A, Yoshino O, Kigawa M, Yoshida T, Saito S.
  • Journal Title: J Obstet Gynaecol Res. Volume: 44(3) Issue: 3 Pages: 397-407
  • DOI: 10.1111/jog.13547
  • Peer Reviewed
• [Journal Article] 産科の薬物療法―update 各論 産科合併症の薬物療法 前期破水 (2018)
  • Author(s): 米田徳子,福田香織,齋藤 滋.
  • Journal Title: 周産期医学 Volume: 48(1) Pages: 47-49
• [Journal Article] 【早産リスクにどう向き合うか-最近の話題-】 切迫早産管理における羊水検査の意義(解説/特集) (2017)
  • Author(s): 米田 哲, 米田徳子, 齋藤 滋.
  • Journal Title: 産婦の実際 Volume: 66(7) Pages: 823-828
• [Journal Article] 切迫早産・早産と黄体ホルモン (2017)
  • Author(s): 安達知子,金山尚裕,中井章人,米田徳子
  • Journal Title: Progestin Insights Volume: 4 Pages: 1-5
• [Presentation] 迅速高感度PCR法を用いた切迫早産の適切な抗菌薬治療による周産期予後の検討 (2019)
  • Author(s): 米田徳子、米田 哲、須田尚美、山田清貴、草開 妙、田中智子、津田さやか、伊藤実香、塩﨑有宏、齋藤 滋
  • Organizer: 第55回日本周産期・新生児学会学術集会
• [Presentation] 迅速高感度PCR法で検出した胎盤擦過Ureaplasma,Mycoplasma感染例は周産期予後不良で，高度のCAMに関連する (2019)
  • Author(s): 米田徳子，米田 哲，生水貫人，津田さやか，塩崎有宏，齋藤 滋
  • Organizer: 第71回日本産科婦人科学会学術集会
• [Presentation] The relationship between intra-amniotic Infection/inflammation and ‘sludge’ in preterm labor (2019)
  • Author(s): Noriko Yoneda
  • Organizer: International Seminar. Prevention of Preterm Birth
• [Presentation] 早産と子宮内感染～病態解明と新たな治療戦略～ (2019)
  • Author(s): 米田徳子
  • Organizer: 道央圏周産期医療研修会
  • Invited
• [Presentation] 母体早発型妊娠高血圧腎症は,在胎34週未満早産児の長期神経発達予後不良に関連する． (2018)
  • Author(s): 米田 徳子, 米田 哲, 小林 睦, 草開 妙, 塩崎 有宏, 齋藤 滋．
  • Organizer: 第70回日本産科婦人科学会学術講演会
• [Presentation] 単胎自然早産児の長期神経発達予後不良因子は30週未満の早産である． (2018)
  • Author(s): 米田 徳子, 米田 哲, 古田 惇, 丸山 恵利子, 森田 恵子, 小野 洋輔, 田村 賢太郎, 伊藤 実香, 牧本 優美, 塩崎 有宏, 吉田 丈俊, 齋藤 滋．
  • Organizer: 第54回日本周産期・新生児医学会学術集会
• [Presentation] 早産の病態解明と新たな治療戦略－羊水中病原微生物の迅速高感度検出システムの臨床応用－． (2018)
  • Author(s): 米田徳子
  • Organizer: 平成30年度富山大学杉谷地区臨床研究発表会
• [Presentation] Because it’s a clinical study, It is interesting and useful. Part Ⅱ． (2018)
  • Author(s): Yoneda N.
  • Organizer: Pre-symposium lecture for yound doctors. The 31th annual meeting of the Korean Society of Perinatology
  • Int'l Joint Research
• [Presentation] 子宮内(羊水中)病原微生物の迅速高感度同定・定量検査により,抗菌薬治療後の菌量の減少を認めたが,子宮内炎症の改善に乏しく早産となった一例． (2018)
  • Author(s): 布村 晴香, 米田 徳子, 小野 洋輔, 津田 竜広, 森田 恵子, 伊藤 実香, 米田 哲, 塩崎 有宏, 齋藤 滋．
  • Organizer: 第70回日本産科婦人科学会学術講演会
• [Presentation] シンポジウム 早産1 Network Medicine 早産予防研究-頸管長短縮・頸管無力症への新たな挑戦 切迫早産有症状/無症状別、子宮頸管長別の、早産発生率(<35週)、及び早期娩出率(<7日) 多施設共同後向きコホート研究(PLASH-1 study)． (2018)
  • Author(s): 堀江 健司, 青木 宏明, 永松 健, 叶谷 愛弓, 兵頭 博信, 寺田 佳世子, 中井 章人, 米田 徳子, 齋藤 滋, 松田 義雄, 大口 昭英．
  • Organizer: 第54回日本周産期・新生児医学会学術集会
• [Presentation] 高度子宮頸管炎、子宮頸管長15mm以下の2因子が無症候性頸管長短縮例の早産リスク因子である (2018)
  • Author(s): 米田 哲,米田徳子,森田恵子,小野洋輔,伊藤実香,塩崎 有宏, 齋藤 滋．
  • Organizer: 第54回日本周産期・新生児医学会学術集会
• [Presentation] Pathology and novel management strategies for preterm labor from viewpoints of intra-amniotic inflammation and/or infection. Special lecture (invited speaker) (2018)
  • Author(s): Yoneda S, Yoneda N, Saito S.
  • Organizer: The 31th annual meeting of the Korean Society of Perinatology
  • Int'l Joint Research / Invited
• [Presentation] Because it’s a clinical study, It is interesting and useful. Part Ⅰ． (2018)
  • Author(s): Yoneda S.
  • Organizer: Pre-symposium lecture for yound doctors. The 31th annual meeting of the Korean Society of Perinatology
  • Int'l Joint Research / Invited
• [Presentation] 17-alpha-hydroxyprogesterone caproate combined maintenance tocolysis could prolong gestational period in case of preterm labor with mild intra-amniotic inflammation. (2018)
  • Author(s): Yoneda S, Yoneda N, Ito M, Ono Y, Shiozaki A, Saito S.
  • Organizer: 70th Annual congress of Japan Society of Obstetrics and Gynecology.
• [Presentation] Correlation between intracranial imaging by MRI and development at age of 3 in the children born from mothers with hypertensive disorders of pregnanacy or spontaneous preterm birth. (2018)
  • Author(s): Kusabiraki T, Yoneda N, Yoneda S, Kobayashi M, Fukuta K, Shiozaki A, Saito S.
  • Organizer: 70th Annual congress of Japan Society of Obstetrics and Gynecology
• [Presentation] Hypertensive disorder of pregnanacy (HDP)出生児における長期神経学的予後と修正40週時頭部MRI所見の検討. (2018)
  • Author(s): 草開 妙,米田徳子,米田 哲,小林 睦,福田香織,塩﨑有宏,川崎裕香子,牧本優美,吉田丈俊,齋藤 滋.
  • Organizer: 第5回中日本産婦人科セミナー
• [Presentation] The presence of pPROM and delivery before 29 weeks of gestation were independent risk for poor perinatal outcome in preterm labor patients with and without pPROM before 31 weeks of gestation． (2017)
  • Author(s): Yoneda N, Yoneda S, Fukuta K, Yoshie M, Shiozaki A, Saito S．
  • Organizer: 第69回日本産婦人科学会学術集会
• [Presentation] 32週未満の切迫早産の新生児短期予後不良因子は、CAMⅢ度と29週以前の早産である. (2017)
  • Author(s): 米田徳子,米田 哲,大北恭子,川口美保子,伊東雅美,福田香織,塩﨑有宏,齋藤 滋.
  • Organizer: 第52回日本周産期・新生児医学会
• [Presentation] The large yolk sac in the case of missed miscarriage is associated with abnormal chromosomal composition. (2017)
  • Author(s): Yoneda S, Yoneda N, Ito M, Shima T Nakashima A, Yoshino O, Shiozaki A, Saito S．
  • Organizer: 第69回日本産婦人科学会学術集会
• [Presentation] 病原微生物による子宮内炎症と慢性肺疾患発症についての検討． (2017)
  • Author(s): 田村賢太郎，猪又智実，川崎裕香子，牧本優美，米田徳子，米田 哲，吉田丈俊．
  • Organizer: 第52回日本周産期・新生児医学会
• [Presentation] 未破水切迫早産に対する長期tocolysisが必要な症例，不必要な症例に関した臨床的検討． (2017)
  • Author(s): 米田 哲，米田徳子，福田香織，伊東雅美，吉江正紀，塩崎有宏，齋藤 滋．
  • Organizer: 第52回日本周産期・新生児医学会
• [Presentation] 軽度の子宮内炎症を伴う未破水切迫早産例では、17-OHPCが妊娠期間延長に関与する? (2017)
  • Author(s): 米田 哲, 米田 徳子, 森田 恵子, 小野 洋輔, 伊藤 実香, 塩崎 有宏, 齋藤 滋．
  • Organizer: 第65回北日本産科婦人科学会総会・学術講演会
• [Book] Preterm Labor and Delivery. (2020)
  • Author(s): Noriko Yoneda, Satoshi Yoneda, Hideki Niimi, Isao Kitajima, PhD, Shigeru Saito
  • Total Pages: 252
  • Publisher: Springer Nature