Longitudinal influence of intrauterine growth restriction to the hypothalamus-pituitary-adrenal axis

• Project/Area Number: 18K07795
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Nagoya City University
• Principal Investigator: Iwata Sachiko 名古屋市立大学, 医薬学総合研究院(医学), 助教 (40465711)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 子宮内発育不全 / 新生児 / 早期産児 / 副腎機能 / 胎内プログラミング / 認知機能発達 / 副腎皮質 / 発達 / 認知機能 / 下垂体 / 視床 / 唾液 / 尿 / 視床下部‐下垂体‐副腎系機能 / 胎児期プログラミング

Outline of Final Research Achievements

This study aimed to elucidate the influence of intrauterine growth restriction to the hypothalamus-pituitary-adrenal axis in hospitalised newborns. We demonstrated that 1. cortisol levels of small for gestational age (SGA) infants were higher soon after birth and paradoxically lower after two weeks compared to those in their peers without intrauterine growth restriction, 2. myelination assessed using quantitative MRI was more matured in SGA infants, 3. higher prevalence of the autistic spectrum disorder was noted in SGA infants, 4. cot-side probes for cerebral structure, cerebral function and biological rhythms were developed for the assessment of SGA infants and other high risk infants using the near-infrared time-resolved spectroscopy and actigraphy.

Academic Significance and Societal Importance of the Research Achievements

SGA児のHPA系を単純な亢進や抑制で説明する試みには矛盾が絶えなかったが，本研究の結果から，SGA児のHPA系が胎内での亢進から生後の抑制に逆説的・ダイナミックに変化し，脳をはじめとする体組織も，未熟性よりも過成熟を呈する可能性が示唆された．生後のHPA系をも制御する胎内プログラミングを解明することで，１．SGA児特有の生体周期や高次脳機能の獲得プロセスを明らかにし，２．自閉症スペクトラム障害やその他の発達遅滞，高血圧・内分泌異常などの発症予測と予防策を確立し，３．ハイリスク児における外因性ステロイドホルモンの投与法に関する指針を提言できるように研究を発展させたい．

Research Products

• [Journal Article] Foetal growth, birth transition, enteral nutrition and brain light scattering (2021)
  • Author(s): Iwata Osuke、Iwata Sachiko、Kurata Tsuyoshi、Tsuda Kennosuke、Kawase Koya、Kinoshita Masahiro、Lin Yung-Chieh、Saikusa Mamoru、Araki Yuko、Takashima Sachio、Oda Motoki、Ohmae Etsuko、Saitoh Shiji
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 21318-21318
  • DOI: 10.1038/s41598-021-00624-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Airway gas temperature within endotracheal tube can be monitored using rapid response thermometer (2021)
  • Author(s): Nakane Shigeharu、Tsuda Kennosuke、Kinoshita Masahiro、Kato Shin、Iwata Sachiko、Lin Yung-Chieh、Mizuno Mihoko、Saitoh Shinji、Iwata Osuke
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 9537-9537
  • DOI: 10.1038/s41598-021-88787-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Influence of mothers’ nighttime responses on the sleep?wake rhythm of 1-month-old infants (2021)
  • Author(s): Kuroda Momoka、Suetsugu Yoshiko、Iwata Sachiko、Kinoshita Masahiro、Fujita Fumie、Sato Yoko、Saitoh Shinji、Iwata Osuke、Morokuma Seiichi
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 24363-24363
  • DOI: 10.1038/s41598-021-03717-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Temporal inversion of the acid-base equilibrium in newborns: an observational study (2021)
  • Author(s): Mizutani Yuko、Kinoshita Masahiro、Lin Yung-Chieh、Fukaya Satoko、Kato Shin、Hisano Tadashi、Hida Hideki、Iwata Sachiko、Saitoh Shinji、Iwata Osuke
  • Journal Title: PeerJ Volume: 9 Pages: e11240-e11240
  • DOI: 10.7717/peerj.11240
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Revisions of clinical protocols using the Plan Do Check Act cycle improved outcomes of extremely preterm infants at 2?years (2021)
  • Author(s): Saikusa Mamoru、Kinoshita Masahiro、Tsuda Kennosuke、Hisano Tadashi、Okada Junichiro、Iwata Sachiko、Fujino Hiroshi、Maeno Yasuki、Yamashita Yushiro、Iwata Osuke
  • Journal Title: Acta Paediatrica Volume: in press Issue: 7 Pages: 1-10
  • DOI: 10.1111/apa.15840
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Temporal changes and control variables of growth differentiation factor 15 levels during the first week of life in hospitalised newborn infants (2021)
  • Author(s): Kinoshita Masahiro、Yatsuga Shuichi、Iwata Osuke、Okamura Hisayoshi、Morisaki Toshihiro、Iwata Sachiko、Hara Naoko、Shindo Ryota、Saikusa Mamoru、Harada Eimei、Tsuda Kennosuke、Yamashita Yushiro、Koga Yasutoshi
  • Journal Title: Mitochondrion Volume: 61 Pages: 25-30
  • DOI: 10.1016/j.mito.2021.09.002
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Validation of actigraphy in hospitalised newborn infants using video polysomnography (2021)
  • Author(s): Unno Mitsuaki、Morisaki Toshihiro、Kinoshita Masahiro、Saikusa Mamoru、Iwata Sachiko、Fukaya Satoko、Yamashita Yushiro、Nakayama Meiho、Saitoh Shinji、Iwata Osuke
  • Journal Title: Journal of Sleep Research Volume: 31 Issue: 1
  • DOI: 10.1111/jsr.13437
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Body temperature, heart rate and long-term outcome of cooled infants: an observational study (2021)
  • Author(s): Tsuda Kennosuke、Shibasaki Jun、Isayama Tetsuya、Takeuchi Akihito、Mukai Takeo、Ioroi Tomoaki、Takahashi Akihito、Sano Hiroyuki、Yutaka Nanae、Iwata Sachiko、Nabetani Makoto、Sobajima Hisanori、Hosono Shigeharu、Tamura Masanori、Iwata Osuke
  • Journal Title: Pediatric Research Volume: in press Issue: 4 Pages: 921-928
  • DOI: 10.1038/s41390-021-01502-w
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Promoting sound development of preterm infants in the name of developmental neuroscience: Beyond advanced life support and neuroprotection. (2021)
  • Author(s): Iwata O, Iwata S, Lin YC, Kato S, Mizutani Y, Hisano T, Kinoshita M, Fukaya S, Kawase K, Saitoh S.
  • Journal Title: Pediatr Neonatol. Volume: 62 Suppl 1 Pages: S10-S15
  • DOI: 10.1016/j.pedneo.2020.11.006
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Video-call based newborn triage system for local birth centres can be established without major instalment costs using commercially available smartphones. (2020)
  • Author(s): Okada J, Hisano T, Unno M, Tanaka Y, Saikusa M, Kinoshita M, Harada E, Iwata S, Iwata O.
  • Journal Title: Sci Rep. Volume: 10(1) Issue: 1 Pages: 7552-7552
  • DOI: 10.1038/s41598-020-64223-w
  • Peer Reviewed / Open Access
• [Journal Article] Peripartum depression and infant care, sleep and growth. (2020)
  • Author(s): Iwata S, Kinoshita M, Fujita F, Tsuda K, Unno M, Horinouchi T, Morokuma S, Saitoh S, Iwata O.
  • Journal Title: Sci Rep. Volume: 9(1) Issue: 1 Pages: 10186-10186
  • DOI: 10.1038/s41598-019-46563-4
  • Peer Reviewed / Open Access
• [Journal Article] Visual Function Scale for Identification of Infants with Low Respiratory Compliance (2019)
  • Author(s): Harada Eimei、Kinoshita Masahiro、Iwata Sachiko、Saikusa Mamoru、Tsuda Kennosuke、Shindou Ryota、Sahashi Takeshi、Kato Shin、Yamada Yasumasa、Saitoh Shinji、Iwata Osuke
  • Journal Title: Pediatrics & Neonatology Volume: - Issue: 6 Pages: 611-616
  • DOI: 10.1016/j.pedneo.2019.02.006
  • Peer Reviewed / Open Access
• [Journal Article] Intrauterine growth and the maturation process of adrenal function (2019)
  • Author(s): Iwata Sachiko、Kinoshita Masahiro、Okamura Hisayoshi、Tsuda Kennosuke、Saikusa Mamoru、Harada Eimei、Saitoh Shinji、Iwata Osuke
  • Journal Title: PeerJ Volume: - Pages: e6368-e6368
  • DOI: 10.7717/peerj.6368
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Body Temperature, Heart Rate, and Short-Term Outcome of Cooled Infants (2019)
  • Author(s): Tsuda Kennosuke、Iwata Sachiko、Mukai Takeo、Shibasaki Jun、Takeuchi Akihito、Ioroi Tomoaki、Sano Hiroyuki、Yutaka Nanae、Takahashi Akihito、Takenouchi Toshiki、Osaga Satoshi、Tokuhisa Takuya、Takashima Sachio、Sobajima Hisanori、Tamura Masanori、Hosono Shigeharu、Nabetani Makoto、Iwata Osuke
  • Journal Title: Therapeutic Hypothermia and Temperature Management Volume: 9 Issue: 1 Pages: 76-85
  • DOI: 10.1089/ther.2018.0019
  • Peer Reviewed / Open Access
• [Journal Article] Estimation of elevated intracranial pressure in infants with hydroce-phalus by using transcranial Doppler velocimetry with fontanel compression (2018)
  • Author(s): Yoshizuka Teiko、Kinoshita Masahiro、Iwata Sachiko、Tsuda Kennosuke、Kato Takenori、Saikusa Mamoru、Shindou Ryota、Hara Naoko、Harada Eimei、Takashima Sachio、Takeshige Nobuyuki、Saitoh Shinji、Yamashita Yushiro、Iwata Osuke
  • Journal Title: Scientific Reports Volume: - Issue: 1 Pages: 11824-11824
  • DOI: 10.1038/s41598-018-30274-3
  • Peer Reviewed / Open Access
• [Journal Article] Feeding-Induced Cortisol Response in Newborn Infants (2018)
  • Author(s): Kinoshita Masahiro、Iwata Sachiko、Okamura Hisayoshi、Tsuda Kennosuke、Saikusa Mamoru、Harada Eimei、Yamashita Yushiro、Saitoh Shinji、Iwata Osuke
  • Journal Title: The Journal of Clinical Endocrinology & Metabolism Volume: 103 Issue: 12 Pages: 4450-4455
  • DOI: 10.1210/jc.2018-01052
  • Peer Reviewed / Open Access / Int'l Joint Research