Research for the relationship between threshold of viability and fetal lung structure, and mechanism of fetal hypoplastic lungs

• Project/Area Number: 15591161
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Keio University
• Principal Investigator: IKEDA Kazushige Keio University, School of Medicine, Department of Pediatrics, Assistant Professor, 医学部, 専任講師 (00193194)
• Co-Investigator(Kenkyū-buntansha): HIDA Mariko Keio University, School of Medicine, Department of Pediatrics, Instructor, 医学部, 助手 (20276306)
• Project Period (FY): 2003 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,400,000 (Direct Cost: ¥3,400,000); Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000); Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000); Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
• Keywords: threshold of viability / premature infant / KL-6 / hypoplastic lung / cilia / fetus / 胎児 / atypical cilia / ラクトフェリン / 超低出生体重児 / 低形成肺 / FGF / 慢性肺疾患

Research Abstract

In Japan as well as western countries, the survival rate of extremely premature infants (ELBW) and very premature infants (VLBW) improved in the 1990s with the spread of new treatment methods such as surfactant therapy, new methods of mechanical ventilation represented by high frequency oscillatory ventilation (HFO), and prenatal steroid therapy. The Committee on Newborn Infants, Japan Society of Pediatrics has performed nation-wide surveys on the outcomes of ELBW and VLBW for reports on the current status of NICU and neonatal mortality in Japan at 5-year intervals. The mortality rate of infants weighing less than 1,000 g at birth significantly declined in the previous two decades from 55.3% in 1980 and 28.2% in 1990 to 17.8% in 2000. In view of this, the Ministry of Health, Labour and Welfare of the Japanese government changed the definition of the threshold of viability in the Maternal Protection Law from 24 weeks of gestation to 22 weeks of gestation in January, 1991. After this change, neonatologists in Japan have increasingly intervened in deliveries at 22-23 weeks' of gestation. To date, 15years have passed since intensive care for infants born at 22weeks' gestation was undertaken and efforts to improve the prognosis of such infants are continuing in Japan. The purpose of this project was as follows :
1.For test to validate 22 weeks gestation as threshold of viability
1)the analysis lung maturation of fetuses aborted at 21 weeks gestation
2)nation wide survey of short term prognosis born at 22-23 weeks gestation
3)nation wide survey of short term outcome of infants born weighing less than 500 grams
4)the analysis of urine steroid profile of preterm and term infants
2.experimental analysis
1)the relationship between intrauterine infection and KL-6 production in vitro
2)intaratracheal administration of lactoferrin to prevent pseudomonas pneumonia

Research Products

• [Journal Article] Recent outcomes of ultrapremature infants born at 22-23 weeks' gestation and infants born weighing less than 500 grams in Japan (2006)
  • Author(s): Ikeda, K, Hayashida S, Hokuto I, Kusuda S, Nishida H
  • Journal Title: NeoReview (in press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Recent outcomes of ultrapremature infants born at 22-23 weeks' gestation and infants born weighing less than 500 grams in Japan (2006)
  • Author(s): Ikeda, K, Hayashida S, Hokuto I, Kusuda S, Nishida H
  • Journal Title: Neo Review in press
• [Journal Article] Does intratracheal administration of lactoferrin prevents pseudomonas pneumonia? (2005)
  • Author(s): Ikeda K, Matsuzaki Y, Mori K, Naito Y, Hayashida S, Hokuto I
  • Journal Title: American Journal of Respiratory and Critical Care Medicine 171
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Iridic and retinal coloboma associated with prenatal methimazole exposure (2005)
  • Author(s): Aramaki M, Hokuto I, Matsumoto T, Ishimoto H, Inoue M, Kimura T, Oikawa Y, Ikeda K, Yoshimura Y, Takahashi T, Kosaki K.
  • Journal Title: Am J Med Genet A. 139・2 Pages: 156-158
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Does intaratracheal administration of lactrferrin prevent pseudomonas pneumonia? (2005)
  • Author(s): Ikeda K, Kurihara N, Matsuzaki Y, Mori K, Naito Y, Hayashida S, Hokuto I
  • Journal Title: American Journal of Respiratory and Critical Care Medicine 171・7(2)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Iridic and retinal coloboma associated with prenatal methimazole exposure (2005)
  • Author(s): Aramaki M, Hokuto I, Matsumoto T, Ishimoto H, Inoue M, Kimura T, Oikawa Y, Ikeda K, Yoshimura Y, Takahashi T, Kosaki K
  • Journal Title: Am J Med Genet A. 139(2) Pages: 156-158
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Does intratracheal administration of lactoferrin prevent pseudomonas pneumonia (2005)
  • Author(s): Ikeda K, Kurihara N, Matsuzaki Y, Mori K, Naito Y, Hayashida S, Hokuto I
  • Journal Title: American Journal of Respiratory and Critical Care Medicine 171・7(2)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Absent inner dynein arms in a fetus with familial hydrocephalus-situs abnormality (2004)
  • Author(s): Kosaki K, Ikeda K, Miyakoshi K, Ueno M, Kosaki R, Takahashi D, Tanaka M, Torikata C, Yoshimura Y, Takahashi T.
  • Journal Title: Am J Med Genet A. 129・3 Pages: 308-311
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Why is the serum KL-6 level increased in chronic lung disease of the newborn?-the relationship between risk factors and KL-6 production in pulmonary epithelial cells in vitro (2004)
  • Author(s): Ikeda K, Matsuzaki Y, Hayashida S, Mori K, Hokuto I
  • Journal Title: American Journal of Respiratory and Critical Care Medicine 169・7
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Absent inner dynein arms in a fetus with familial hydrocephalus-situs abnormality (2004)
  • Author(s): Kosaki K, Ikeda K, Miyakoshi K, Ueno M, Kosaki R, Takahashi D, Tanaka M, Torikata C, Yoshimura Y, Takahashi T
  • Journal Title: Am J Med Genet A. 129(3) Pages: 308-311
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Why is the serum KL-6 level increased in chronic lung disease of the newborn? - the relationship between risk factors and KL-6 production in pulmonary epithelial cells in vitro (2004)
  • Author(s): Ikeda K, Matsuzaki Y, Hayashida S, Mori K, Hokuto I
  • Journal Title: American Journal of Respiratory and Critical Care Medicine 169・7
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Pulmonary hypoplasia : prediction with use of MR imaging-measured fetal lung volume to US-estimated feral body weight. (2004)
  • Author(s): Tanigaki et al.
  • Journal Title: Radiology 232・3 Pages: 767-772
• [Journal Article] Abscent inner-dynein arms in a fetus with familial hydrocephalus-situs abnormality (2004)
  • Author(s): Kosaki et al.
  • Journal Title: Am J Med Genet 129A.3 Pages: 308-311
• [Publications] Tanigaki S, Miyakoshi K, Tanaka M, Hattori Y, Matsumoto T, Ueno K, Uehara K, Nishimura O, Minegishi K, Ishimoto H, Shinmoto H, Ikeda K, Yoshimura Y: "Prediction of pulmonary hypoplasia : The ratio of fetal lung volume obtained by magnetic resonance imaging to ultrasonographically estimated fetal body weight"Radiology. (in press). (2004)
• [Publications] Ikeda K, Matsuzaki Y, Hayashida S, Mori K, Hokuto I: "Why is the serum KL-6 level increased in chronic lung disease of the newborn? - the relation between risk factors and KL-6 production in pulmonary epithelial cells in vitro -"Am.J.Respir.Crit.Care Med.. (in press). (2004)
• [Publications] Mori K, Matsuzaki Y, Kurihara N, Tokieda T, Ikeda K, Tanaka T: "INTRAUTERINE EXPRESSION OF KL-6 DURING MID-TRIMESTER COMPARED WITH THE EXPRESSION OF SURFACTANT PROTEINS"Pediatr Res. 53・4. 435A (2003)